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Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Different inhalation devices are characterized by different techniques of use.,The untrained switching of device in chronic obstructive pulmonary disease (COPD) and asthma patients may be associated with inadequate inhalation technique and, consequently, could lead to a reduction in adherence to treatment and limit control of the disease.,The aim of this analysis was to estimate the potential economic impact related to errors in inhalation in patients switching device without adequate training.,An Italian real-practice study conducted in patients affected by COPD and asthma has shown an increase in health care resource consumption associated with misuse of inhalers.,Particularly, significantly higher rates of hospitalizations, emergency room visits (ER), and pharmacological treatments (steroids and antimicrobials) were observed.,In this analysis, those differences in resource consumption were monetized considering the Italian National Health Service (INHS) perspective.,Comparing a hypothetical cohort of 100 COPD patients with at least a critical error in inhalation vs 100 COPD patients without errors in inhalation, a yearly excess of 11.5 hospitalizations, 13 ER visits, 19.5 antimicrobial courses, and 47 corticosteroid courses for the first population were revealed.,In the same way, considering 100 asthma patients with at least a critical error in inhalation vs 100 asthma patients without errors in inhalation, the first population is associated with a yearly excess of 19 hospitalizations, 26.5 ER visits, 4.5 antimicrobial courses, and 21.5 corticosteroid courses.,These differences in resource consumption could be associated with an increase in health care expenditure for INHS, due to inhalation errors, of €23,444/yr in COPD and €44,104/yr in asthma for the considered cohorts of 100 patients.,This evaluation highlights that misuse of inhaler devices, due to inadequate training or nonconsented switch of inhaled medications, is associated with a decrease in disease control and an increase in health care resource consumption and costs. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | To estimate the incidence of pneumonia by COPD status and the excess cost of inpatient primary pneumonia in elders with COPD.,A retrospective, longitudinal study using claims linked to eligibility/demographic data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through 2007.,Incidence rates of pneumonia were calculated for elders with and without COPD and for elders with COPD and coexistent congestive heart failure (CHF).,Propensity-score matching with multivariate generalized linear regression was used to estimate the excess direct medical cost of inpatient primary pneumonia in elders with COPD as compared with elders with COPD but without a pneumonia hospitalization.,Elders with COPD had nearly six-times the incidence of pneumonia compared with elders without COPD (167.6/1000 person-years versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders with COPD and CHF compared with elders without COPD.,The incidence of inpatient primary pneumonia among elders with COPD was 54.2/1000 person-years compared with 7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to 11.0 for elders with COPD and CHF compared with elders without COPD.,The one-year excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697 ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was accrued during the quarter of the index hospitalization.,During months 13 through 24 following the index hospitalization, the excess direct medical cost was $ 5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01).,Pneumonia occurs more frequently in elders with COPD than without COPD.,The excess direct medical cost in elders with inpatient pneumonia extends up to 24 months following the index hospitalization and represents $28,638 in 2010 dollars. | 1 |
Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. | 1 |
It is reported that the iron-responsive element-binding protein 2 (IREB2) gene rs2568494 polymorphism might be associated with COPD risk.,The purpose of this meta-analysis was to collect all eligible studies to review the association between IREB2 gene rs2568494 polymorphism and susceptibility to COPD.,We carried out a comprehensive document search of electronic databases of PubMed, MEDLIN, Web of Science, and included 4 eligible studies that examined the association between IREB2 rs2568494 polymorphism and COPD susceptibility.,We performed a meta-analysis of these studies based on IREB2 rs2568494 genotypes.,After meta-analysis with fixed or random effects, no significant associations were found under the heterozygote model (GG/GA; OR=0.908, 95%CI: 0.790-1.043; P=0.172), homozygote model (GG/AA; OR=0.880, 95%CI: 0.497-1.557; P=0.661), dominant model (GG/AA+GA; OR=0.941, 95%CI: 0.748-1.182; P=0.599), or allelic model (G/A; OR=0.953, 95%CI: 0.770-1.179; P=0.655).,However, we found a significant correlation under the recessive model (AA/GA+GG; OR=1.384, 95%CI: 1.092-1.755; P=0.007).,The current results revealed that there was significant association between IREB2 gene rs2568494 polymorphism with susceptibility to COPD; the presence of allelic A might a genetic factor conferring susceptibility to COPD. | Several single nucleotide polymorphisms (SNPs) in an α-neuronal nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be associated with chronic obstructive pulmonary disease (COPD) in a study based on a Norwegian population.,However, results from subsequent studies have been controversial, particularly in studies recruiting Asians.,In the present study, we conducted a comprehensive search and meta-analyses to identify susceptibility SNPs for COPD in the CHRNA3/5 locus.,A comprehensive literature search was conducted to find studies that have reported an association between SNPs in the CHRNA3/5 locus and COPD risk.,Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each SNP were calculated with the major allele or genotype as the reference group.,The influence of individual studies on pooled measures was assessed, in addition to publication bias.,A total of 12 articles with 14 eligible studies were included in this analysis.,Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968.,Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10-1.18; rs8034191: OR = 1.29, 95%CI = 1.18-1.41; rs6495309: OR = 1.26, 95%CI = 1.09-1.45; rs16969968: OR = 1.27, 95%CI = 1.17-1.39) and genotype models.,Subgroup analysis conducted for rs1051730 showed a significant association between this SNP and COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10-1.18), but not Asians (OR = 1.23, 95%CI = 0.91-1.67).,Rs1051730 and rs6495309 were also significantly associated with COPD after adjusting for multiple variables, including age and smoking status.,Our results indicate that 4 SNPs in the CHRNA3/5 locus are associated with COPD risk.,Rs1051730 was particularly associated with COPD in non-Asians, but its role in Asians still needs to be verified.,Additional studies will be necessary to assess the effect of rs6495309 on COPD.,Although rs1051730 and rs6495309 were shown to be independent risk factors for COPD, validation studies should be performed. | 1 |
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD. | To investigate the magnitude of barriers in access to health services for chronic patients and the socioeconomic and demographic characteristics that affect them.,A cross-sectional study was conducted in 1,594 chronic patients suffering from diabetes, hypertension, COPD and Alzheimer.,Logistic regression analyses were carried out in order to explore the factors related to economic and geographical barriers in access, as well as the determinants of barriers due to waiting lists.,A total of 25% of chronic patients face geographical barriers while 63.5% and 58.5% of them are in front of economic and waiting list barriers, respectively.,Unemployed, low-income and low-educated are more likely to face economic barriers in access.,Moreover, women, low-income patients, and patients with lower health status are more likely to be in front of geographical barriers.,In addition, the probability of waiting lists occurrence is greater for unemployed, employees and low income patients.,Barriers in access can be mainly attributed to income decrease and unemployment.,In this context, health policy measures are essential for removing barriers in access.,Otherwise, inequalities may increase and chronic patients’ health status will be deteriorated.,These consequences imply adverse effects on health expenditure. | 1 |
Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations.,Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.,Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.,Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies.,Time to ACM was prespecified.,Additional vital status data collection and subsequent analyses were performed post hoc.,Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI.,For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI.,Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient’s COPD.,Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
Determine the effect of twice-daily chlorhexidine oral rinses on oral and lung microbiota biomass and respiratory symptoms.,Single centre.,Participants were aged 40-85 with chronic obstructive pulmonary disease (COPD) and chronic productive cough or COPD exacerbation within the last year.,Exclusions included antibiotics in the previous 2 months and/or those with less than four teeth.,Forty-four participants were recruited and 40 completed the study.,Participants were randomised 1:1 to twice-daily 0.12% chlorhexidine oral rinses versus placebo for 2 months along with daily diaries.,St.,George’s Respiratory Questionnaire (SGRQ), blood tests, oral rinse and induced sputum were collected at randomisation and the final visit.,Primary outcome was a change in oral and sputum microbiota biomass.,Secondary outcomes included: sputum and oral microbiota Shannon and Simpson diversity and taxonomy; inflammatory markers; Breathlessness, Cough and Sputum Scale and SGRQ scores.,Neither the oral microbiota nor the sputum microbiota biomass decreased significantly in those using chlorhexidine compared with placebo (oral microbiota mean log10 difference (SE)=−0.103 (0.23), 95% CI −0.59 to 0.38, p=0.665; sputum microbiota 0.80 (0.46), 95% CI −0.15 to 1.75, p=0.096).,Chlorhexidine decreased both oral and sputum microbiota alpha (Shannon) diversity (linear regression estimate (SE) oral: −0.349 (0.091), p=0.001; sputum −0.622 (0.169), p=0.001).,Chlorhexidine use did not decrease systemic inflammatory markers compared with placebo (C reactive protein (chlorhexidine 1.8±7.5 vs placebo 0.4±6.8, p=0.467), fibrinogen (22.5±77.8 vs 10.0±77.0, p=0.406) or leucocytes (0.2±1.8 vs 0.5±1.8, p=0.560)).,Chlorhexidine use decreased SGRQ scores compared with placebo (chlorhexidine −4.7±8.0 vs placebo 1.7±8.9, p=0.032).,We did not detect a significant difference in microbiota biomass due to chlorhexidine use.,Chlorhexidine decreased oral and sputum microbiota alpha diversity and improved respiratory health-related quality of life compared with placebo.,NCT02252588. | Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy. | 1 |
We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.,Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls.,A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.,Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD.,All parameters, except forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls.,Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls).,Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels.,Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients.,Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV1/FVC versus clusters I and II COPD patients.,The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.,www.clinicaltrials.gov.,NCT01360788 and NCT01072396. | The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures.,A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D.,The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS.,Age, gender, smoking status and socio-economic group were regarded as confounders.,The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023).,The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032).,No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity.,Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007).,The SGRQ Total score was significant between age groups (p = 0.0047).,No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed.,The results show that HRQL in COPD deteriorates with disease severity and with age.,These data show a relationship between HRQL and disease severity obtained by lung function. | 1 |
Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities.,We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks.,Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52.,Adverse events were also assessed.,In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years).,Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02-0.15) were small for all treatments.,Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score).,The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups.,Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%).,There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.,In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints.,Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful.,All treatments were well tolerated with no new or unexpected safety findings.,ClinicalTrials.gov NCT02536508.,Registered 27 August 2015.,The online version of this article (10.1186/s12931-019-1126-7) contains supplementary material, which is available to authorized users. | Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined.,The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without.,This is a retrospective cohort and population-based study in which we extracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision - Clinical Modification [ICD-9-CM] 491, 492, 496).,The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12 months on either inpatient or outpatient service claims submitted to TNHI.,Patients were excluded if they were younger than 40 years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.,X) before the index date.,These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined.,The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer.,Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled.,The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63-084).,The higher ICS dose is associated with lower risk of osteoporosis (0 mg to ≤20 mg, HR: 0.84, 95% CI: 0.69-1.04; >20 mg to ≤60 mg, HR: 0.78, 95% CI: 0.59-1.04; and >60 mg, HR: 0.72, 95% CI: 0.55-0.96; P for trend =0.0023) after adjusting for age, income, and medications.,The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P<0.001).,Female patients with COPD using ICS have a dose-response protective effect for osteoporosis. | 1 |
Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis.,In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release.,Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined.,The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD.,Primary adult lung fibroblasts were isolated from patients with or without COPD.,MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without inflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α.,MiR-503 expression was decreased in COPD lung fibroblasts.,The expression of miR-503 was positively correlated with %FVC, %FEV1, and %DLco as well as IL-6, -8, PGE2, HGF, KGF, and VEGF in the absence or presence of IL-1ß/TNF-α.,In addition, IL-8 and VEGF release from COPD lung fibroblasts were increased compared to those from control.,Exogenous miR-503 inhibited VEGF release from primary adult and fetal lung fibroblasts but not IL-8 release.,As expected, COPD fibroblasts proliferated more slowly than control fibroblasts.,MiR-503 did not affect proliferation of either control or COPD lung fibroblasts.,MiR-503 inhibition of VEGF protein production and mRNA was mediated by direct binding to the 3’ untranslated region of VEGF mRNA.,Endogenous miR-503 was differently regulated by exogenous stimulants associated with COPD pathogenesis, including IL-1ß/TNF-α, TGF-ß1 and PGE2.,Endogenous miR-503 inhibition augmented VEGF release by IL-1ß/TNF-α and TGF-ß1 but not by PGE2, demonstrating selectivity of miR-503 regulation of VEGF.,In conclusions, reduced miR-503 augments VEGF release from lung fibroblasts from patients with COPD.,Since VEGF contributes to disturbed vasculature in COPD, altered miR-503 production might play a role in modulating fibroblast-mediated vascular homeostasis in COPD. | Chronic obstructive pulmonary disease (COPD) is a multi-factor disease, in which metabolic disturbances played important roles.,In this paper, functional information was integrated into a COPD-related metabolic network to assess similarity between genes.,Then a gene prioritization method was applied to the COPD-related metabolic network to prioritize COPD candidate genes.,The gene prioritization method was superior to ToppGene and ToppNet in both literature validation and functional enrichment analysis.,Top-ranked genes prioritized from the metabolic perspective with functional information could promote the better understanding about the molecular mechanism of this disease.,Top 100 genes might be potential markers for diagnostic and effective therapies. | 1 |
Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs.,We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.,A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies.,Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61).,Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease.,There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia.,The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.,Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.,Long-term use of inhaled corticosteroids in COPD is associated with a significantly increased risk of side-effects, especially oral candidiasis, dysphonia, pneumonia, mycobacterial disease, diabetes and fractureshttps://bit.ly/3t0AGfO | Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity.,However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking.,A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted.,Patients with a diagnosis of COPD aged ≥40 years were followed up for 5 years from January 1, 2010.,CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time.,In addition, baseline factors predicting future risk of CAP and hospital admission with CAP were identified.,A total of 14,513 COPD patients were identified: 13.4% (n=1,938) had ≥1 CAP episode, of whom 18.8% suffered from recurrent (≥2) CAP.,Highest rates of both CAP and exacerbations were seen in winter.,A greater proportion of frequent, compared to infrequent, exacerbators experienced recurrent CAP (5.1% versus 2.0%, respectively, P<0.001); 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations.,Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission with CAP.,Other independent predictors of future CAP included lower body mass index, inhaled corticosteroid use, prior frequent exacerbations and comorbidities, including ischemic heart disease and diabetes.,CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission with CAP.,Highlighting this burden of COPD-associated CAP during the winter period informs us of the likely triggers and the need for more effective preventive strategies. | 1 |
Grouping COPD subjects into clinical phenotypes might be useful for the management of the disease, but the clinical implications of such classification are still not totally clear, especially regarding prognosis.,The primary objective of this study was to assess whether the mortality rates were different between four predefined clinical phenotypes.,This is a retrospective, observational study carried out at the COPD clinic of a University Hospital.,A total of 891 COPD patients were classified, according to the Spanish COPD guidelines, into the following four phenotypes: asthma-COPD overlap (ACO; 75 subjects), nonexacerbator (NONEX; 531 subjects), exacerbator with chronic bronchitis (EXCB; 194 subjects), and exacerbator with emphysema (EXEMPH; 91 subjects).,We compared the mortality outcomes between the phenotypes.,After a follow-up of 48.4±25.2 months, there were 194 deaths (21.8%).,There were significant differences in all-cause mortality between phenotypes.,The ACO phenotype had the best long-term prognosis, whereas EXEMPH had the highest risk of death.,NONEX and EXCB mortality figures were in between the other two groups.,We also found some differences in the causes of death, and patients with EXEMPH were at a higher risk of dying because of COPD itself.,The differences in mortality did not seem related to the classification into phenotypes in itself but to disparities in COPD severity and comorbidity load between groups.,Classifying COPD patients according to several predefined clinical phenotypes can identify clusters of subjects with different mortality outcomes.,Some phenotypes are associated with a specific cause of death.,The mechanisms that underlie these differences seem to be related to COPD severity and comorbidities. | The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described.,This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.,A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.,A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively.,Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%).,The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups.,Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01).,Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.,Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects.,The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research. | 1 |
Background: The comorbidities and clinical signs of coronavirus disease 2019 (COVID-19) patients have been reported mainly as descriptive statistics, rather than quantitative analysis even in very large investigations.,The aim of this study was to identify specific patients’ characteristics that may modulate COVID-19 hospitalization risk.,Research design and methods: A pooled analysis was performed on high-quality epidemiological studies to quantify the prevalence (%) of comorbidities and clinical signs in hospitalized COVID-19 patients.,Pooled data were used to calculate the relative risk (RR) of specific comorbidities by matching the frequency of comorbidities in hospitalized COVID-19 patients with those of general population.,Results: The most frequent comorbidities were hypertension, diabetes mellitus, and cardiovascular and/or cerebrovascular diseases.,The RR of COVID-19 hospitalization was significantly (P < 0.05) reduced in patients with asthma (0.86, 0.77-0.97) or chronic obstructive pulmonary disease (COPD) (0.46, 0.40-0.52).,The most frequent clinical signs were fever and cough.,Conclusion: The clinical signs of hospitalized COVID-19 patients are similar to those of other infective diseases.,Patients with asthma or COPD were at lower hospitalization risk.,This paradoxical evidence could be related with the protective effect of inhaled corticosteroids that are administered worldwide to most asthmatic and COPD patients. | The effects of chronic inhaled and systemic corticosteroids use on COVID-19 susceptibility and severity are unclear.,Since many patients with chronic pulmonary diseases rely on corticosteroids to control disease, it is important to understand the risks of their use during the pandemic.,We aim to study if the use of inhaled or systemic corticosteroids affects the likelihood of developing COVID-19 infection.,We used the National Jewish Health electronic medical record research database to identify a cohort of all subjects who were tested for suspected COVID-19 between March 11 - June 23, 2020.,Testing results, medication use, and comorbidities were obtained from the medical record.,Following a comparison of different propensity score weighting methods, overlap propensity score weighting was used to analyze the association between medication use and COVID-19 diagnosis.,The cohort consisted of 928 patients, of which 12% tested positive.,The majority (66%) of patients had a history of chronic pulmonary diseases.,There was no significant association between inhaled corticosteroid use and testing positive for COVID-19.,Interestingly, systemic corticosteroid use was associated with a lower odds ratio (0.95, 95% CI: 0.91-0.99) of testing positive for COVID-19.,Similar results were noted when the analysis was restricted to those with any chronic pulmonary diseases, with asthma or with chronic obstructive pulmonary disease (COPD).,Our study supports the recommendation that patients with chronic pulmonary diseases, including asthma and COPD who require treatment with either inhaled or systemic corticosteroids, should continue their use during the COVID-19 pandemic. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a progressive and debilitating condition that affects individuals’ quality of life.,COPD self-management and supports provided by carers is key to the quality of life people living with COPD.,Health literacy (HL) and Patient Activation (PA) are main drivers of self-management practices (SMPs).,However, their contribution remains to be fully explored.,This study aimed to examine the level of self-management practices, and the relationship with socio-demographic factors, HL and PA among multi-morbid COPD patients from rural Nepal.,This is a cross-sectional study conducted between July 2018 and January 2019.,Patients completed a survey, including Self-management Practices questionnaire (SMPQ), five domains of the Health Literacy Questionnaire (HLQ), and Patient Activation Measure (PAM).,The relationship between HL, PAM, and SMPs was examined using univariate statistics.,Multivariable analysis was conducted to identify the factors associated with SMPs.,A total of 238 patients responded to the study.,The mean score of SMPQ was 45.31(SD = 9.00).,The HLQ and PAM scores were positively correlated with the total score of SMPQ.,Low level of SMPs were found to be positively associated with being uneducated (β = − 0.43, p = .001), having a low family income (β = − 5.22, p = .002), and, negatively associated with the presence of more than one co-morbidity (β = 3.58, p = 0.007) after controlling for other socio-demographic variables in the multivariable analysis.,The overall SMPs among this sample of Nepalese with COPD were low.,Our findings highlight the need to implement a self-management intervention program involving patient activation and health literacy-focused activities for COPD, creating a support system for patients from low-income families and low education. | Although many hospitals promote self-management to chronic obstructive pulmonary disease (COPD) patients post discharge from hospital, the clinical effectiveness of this is unknown.,We undertook a systematic review of the evidence as part of a Health Technology Assessment review.,A comprehensive search strategy with no language restrictions was conducted across relevant databases from inception to May 2012.,Randomized controlled trials of patients with COPD, recently discharged from hospital after an acute exacerbation and comparing a self-management intervention with control, usual care or other intervention were included.,Study selection, data extraction, and risk of bias assessment were undertaken by two reviewers independently.,Of 13,559 citations, 836 full texts were reviewed with nine randomized controlled trials finally included in quantitative syntheses.,Interventions were heterogeneous.,Five trials assessed highly supported multi-component interventions and four trials were less supported with fewer contacts with health care professionals and mainly home-based interventions.,Total sample size was 1,466 (range 33-464 per trial) with length of follow-up 2-12 months.,Trials varied in quality; poor patient follow-up and poor reporting was common.,No evidence of effect in favor of self-management support was observed for all-cause mortality (pooled hazard ratio =1.07; 95% confidence interval [0.74 to 1.55]; I2=0.0%, [n=5 trials]).,No clear evidence of effect on all-cause hospital admissions was observed (hazard ratio 0.88 [0.61, 1.27] I2=66.0%).,Improvements in St George’s Respiratory Questionnaire score were seen in favor of self-management interventions (mean difference =3.84 [1.29 to 6.40]; I2=14.6%), although patient follow-up rates were low.,There is insufficient evidence to support self-management interventions post-discharge.,There is a need for good quality primary research to identify effective approaches. | 1 |
Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation.,We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation.,COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily (tiotropium = 47, placebo = 44).,Study drug was administered for 5 weeks prior to, 8 weeks during, and 12 weeks following pulmonary rehabilitation.,Patients completed a questionnaire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit.,Patients who submitted an activity questionnaire at week 4 and on at least one subsequent visit were included in the analysis.,For each patient, the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration.,Patients (n = 46) had mean age of 67 years, mean baseline FEV1 of 0.84 L (33% predicted).,Mean (SE) increase in duration of activities (minutes during 2 weeks prior to each visit) from week 4 (prior to PR) to week 13 (end of PR) was 145 (84) minutes with tiotropium and 66 (96) minutes with placebo.,The increase from week 4 to week 25 (end of follow-up) was 262 (96) and 60 (93) minutes for the respective groups.,Increases in activity duration from week 4 to weeks 17, 21, and 25 were statistically significant with tiotropium.,No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant.,Tiotropium appears to amplify the effectiveness of pulmonary rehabilitation as seen by increases in patient self-reported participation in physical activities. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity stage classifies Chronic Obstructive Pulmonary Disease (COPD) into groups based on symptoms, exacerbations and forced expiratory volume in one second (FEV1).,This allows patients to change to less severe COPD stages, a novel aspect of assessment not previously evaluated.,We aimed to investigate the association between temporal changes in GOLD severity stage and outcomes in COPD patients.,This was a record-linkage study using patients registered with a Scottish regional COPD network 2000-2015.,Annual spirometry & symptoms were recorded and linked to healthcare records to identify exacerbations, hospitalisations and mortality.,Spirometry, modified Medical Research Council (mMRC) dyspnoea scale and acute exacerbations over the previous year were used to assign GOLD severity at each visit.,A time-dependent Cox model was used to model time to death.,Secondary outcomes were respiratory specific mortality and hospitalisations.,Effect sizes are expressed as Hazard Ratios HR (95%CI).,Four thousand, eight hundred and eighty-five patients (mean age 67.3 years; 51.3% female) with 21,348 visits were included.,During a median 6.6 years follow-up there were 1530 deaths.,For the secondary outcomes there were 712 respiratory deaths and 1629 first hospitalisations.,Across 16,463 visit-pairs, improvement in COPD severity was seen in 2308 (14%), no change in 11,010 (66.9%) and worsening in 3145 (19.1).,Compared to patients staying in GOLD stage A, those worsening had a stepwise increased mortality and hospitalisations.,Improving COPD severity classification was associated with reduced mortality and worsening COPD severity was associated with increased mortality and hospitalisations.,Change in GOLD group has potential as monitoring tool and outcome measure in clinical trials.,The online version of this article (10.1186/s12931-018-0960-3) contains supplementary material, which is available to authorized users. | This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St.,George’s Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations.,A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations.,These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance.,Sixty-seven trials were included in the analysis.,Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024).,Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant.,The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations.,Even in cases of non-significant relationships, results were in the expected direction with few exceptions.,The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies. | 1 |
Chronic respiratory diseases such as asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming increasingly prevalent in the Asia-Pacific region.,The Asia-Pacific Burden of Respiratory Diseases (APBORD) study was a cross-sectional, observational study which examined the disease and economic burden of AR, asthma, COPD, and rhinosinusitis across Asia-Pacific using 1 standard protocol.,Here we report symptoms, healthcare resource use (HCRU), work impairment, and associated cost in Taiwan.,Consecutive participants aged ≥ 18 years presenting to a physician with symptoms meeting the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled.,Participants and their treating physician completed surveys detailing respiratory symptoms, HCRU, work productivity, and activity impairment.,Costs including direct medical costs and indirect costs associated with lost work productivity were calculated.,The study enrolled 1001 patients.,AR was the most frequent primary diagnosis (31.2%).,A quarter of patients presented with a combination of respiratory diseases, with AR and asthma being the most frequent combination (14.1%).,Cough or coughing up phlegm was the primary reason for the medical visit for patients with asthma and COPD, whereas nasal symptoms (watery runny nose, blocked nose, and congestion) were the primary reasons for AR and rhinosinusitis.,Specialists were the most frequently used healthcare resource by patients with AR (26.1%), asthma (26.4%), COPD (26.6%), and rhinosinusitis (47.3%).,The mean annual cost per patient with a respiratory disease was US$4511 (SD 5395).,The cost was almost double for employed patients (US$8047, SD 6175), with the majority attributable to lost productivity.,Respiratory diseases have a significant impact on disease burden in Taiwan.,Treatment strategies that prevent lost work productivity could greatly reduce the economic burden of these diseases. | How well the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification prognosticates for Asian patients with COPD is unknown.,The authors aimed to study the predictive utility of the GOLD 2011 classification for exacerbations and mortality as compared with other multidimensional tools in an Asian population.,In all, 1,110 COPD patients were prospectively followed between March 2008 and March 2013.,They were classified using the 2011 and 2007 GOLD guidelines, modified Medical Research Council score, St.,George’s Respiratory Questionnaire (SGRQ), and Body mass index, Obstruction, Dyspnea (BOD) index.,Outcome measures were exacerbations and mortality.,Multivariable survival analyses and receiver operating characteristic (ROC) curves were used to assess the different classification systems.,Time-to-event analyses demonstrated earlier exacerbations in 2011’s GOLD D when compared with GOLD A (hazard ratio [HR] 0.54, 95% confidence interval [CI]: 0.31-0.95, P=0.032) and GOLD B (HR 0.62, 95% CI: 0.45-0.85, P=0.003) and higher mortality when compared with GOLD A (HR 0.37, 95% CI: 0.16-0.88, P=0.025) and GOLD B (HR 0.46, 95% CI: 0.31-0.70, P<0.001).,The areas under the ROC curve for GOLD 2011, GOLD 2007, modified Medical Research Council, St.,George’s Respiratory Questionnaire, and BOD index were 0.62, 0.59, 0.61, 0.60, and 0.61, respectively, for the prediction of exacerbations and 0.71, 0.70, 0.71, 0.71, and 0.72, respectively, for the prediction of mortality (ROC comparator, P>0.05).,The 2011 GOLD classification predicts exacerbations and mortality moderately well in Asian COPD patients.,Its prognostic utility is similar to that of other multidimensional systems. | 1 |
Effective self-management in chronic obstructive pulmonary disease (COPD) is crucial to reduce hospital admissions and improve outcomes for patients.,This includes early detection and treatment of exacerbations by patients themselves.,To explore patients’ current understanding and experience of managing and identifying COPD exacerbations at home.,A qualitative, interview-based study was carried out in patients’ homes.,Interviews were audio-recorded, transcribed and analysed using a grounded theory approach.,Forty-four patients (17 women, 27 men; age range 55-85 years), with moderate-to-very-severe COPD, were recruited to the interview study from primary and secondary care settings in Oxford, UK, during 2012-2013.,Patients identified exacerbations on the basis of measurable, ‘visible’ symptoms, such as cough and sputum and ‘invisible’ symptoms, such as chest sensations and bodily knowledge.,Most patients seemed to use a combination of these approaches when identifying exacerbations, according to the symptoms that had the most impact on their well-being.,Patients used additional self-management strategies during an exacerbation, such as self-medication (antibiotics and steroids) and monitored their recovery.,Contact with health-care professionals usually occurred when patients felt no longer able to manage themselves.,Patients use both assessment of objective biomarkers, which are aligned with medical knowledge, and subjective symptoms based on their experience, to identify and manage exacerbations of COPD.,Health-care professionals and clinicians should acknowledge this ‘expert patient’ knowledge and integrate this into patients’ care plans to facilitate early recognition and treatment of exacerbations. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
Rationale: Aberrant bronchial epithelium-fibroblast communication is essential for the airway remodeling that contributes to chronic obstructive pulmonary disease (COPD).,Exosomes have emerged as novel mediators of intercellular communication, but their role in cigarette smoke (CS)-induced COPD is unknown.,Here, we investigated the role of exosomal miR-21 in the dysfunctional epithelium-fibroblast cross-talk caused by CS.,Methods: Normal or CS extract (CSE)-treated human bronchial epithelial (HBE) cells were co-cultured with bronchial fibroblasts (MRC-5 cells).,Exosomes were obtained from culture media or serum by use of commercial kits.,The size distribution and concentration of exosomes were analyzed by nanoparticle tracking analysis using a ZetaView particle tracker from ParticleMetrix.,Inhibition of miR-21 levels by tail vein injection of antagomir-21 into mice exposed to CS was used to demonstrate the role of miR-21 in airway remodeling leading to COPD in animals.,Results: For MRC-5 cells, co-culture with CSE-treated HBE cells or with exosomes derived from CSE-treated HBE cells resulted in the myofibroblast differentiation phenotype.,Exosomal miR-21 was responsible for myofibroblast differentiation through hypoxia-inducible factor 1α (HIF-1α) signaling by targeting the von Hippel-Lindau protein (pVHL); HIF-1α transcriptionally regulated the α-SMA gene.,For mice, downregulation of miR-21 prevented CS-induced airway remodeling.,The levels of exosomal miR-21 were high in sera of smokers and COPD patients and inversely correlated with FEV1/FVC.,Conclusion: We demonstrate that CS triggers the modification of exosome components and identify miR-21 derived from bronchial epithelial cells as a mediator of myofibroblast differentiation through the pVHL/HIF-1α signaling pathway, which has potential value for diagnosis and treatment of COPD. | COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features.,In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry.,The severity of the airflow limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management.,However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1.,At present, there is a lack of reliable and simple blood biomarkers to confirm and further assess the diagnosis of COPD.,However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes.,Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and “frequent exacerbators”.,Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as “asthma COPD overlap syndrome”.,Several other phenotypes have been proposed, but require validation against clinical outcomes.,Defining phenotypes requires the assessment of multiple factors indicating disease severity, its impact, and its activity.,Recognition and validation of COPD phenotypes has an important role to play in the selection of evidence-based targeted therapy in the future management of COPD, but regardless of the diagnostic terms, patients with COPD should be assessed and treated according to their individual treatable characteristics. | 1 |
Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function.,Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined.,We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline.,We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points).,A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC.,Potential additional regions of interest were identified and followed up in two independent cohorts.,The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10−16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC).,This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts.,Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function.,It is possible that they influence COPD risk through lung development.,Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries. | Under-diagnosis of COPD is an important unmet medical need.,We investigated the characteristics and prognosis of hospitalised patients with undiagnosed COPD.,The PAC-COPD cohort included 342 COPD patients hospitalised for the first time for an exacerbation of COPD (2004-2006).,Patients were extensively characterised using sociodemographic, clinical and functional variables, and the cohort was followed-up through 2008.,We defined “undiagnosed COPD” by the absence of any self-reported respiratory disease and regular use of any pharmacological respiratory treatment.,Undiagnosed COPD was present in 34% of patients.,They were younger (mean age 66 vs. 68 years, p = 0.03), reported fewer symptoms (mMRC dyspnoea score, 2.1 vs.,2.6, p < 0.01), and had a better health status (SGRQ total score, 29 vs. 40, p < 0.01), milder airflow limitation (FEV1% ref., 59% vs. 49%, p < 0.01), and fewer comorbidities (two or more, 40% vs. 56%, p < 0.01) when compared with patients with an established COPD diagnosis.,Three months after hospital discharge, 16% of the undiagnosed COPD patients had stopped smoking (vs. 5%, p = 0.019).,During follow-up, annual hospitalisation rates were lower in undiagnosed COPD patients (0.14 vs.,0.25, p < 0.01); however, this difference disappeared after adjustment for severity.,Mortality was similar in both groups.,Undiagnosed COPD patients have less severe disease and lower risk of re-hospitalisation when compared with hospitalised patients with known COPD.,The online version of this article (doi:10.1186/1471-2466-15-4) contains supplementary material, which is available to authorized users. | 1 |
COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment.,Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation.,We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens.,COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015.,Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured.,Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality.,Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed.,Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined.,A total of 62 COPD patients were enrolled.,These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively.,Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria.,Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively.,Influenza was the most commonly detected viral pathogen.,Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar.,Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation.,Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035).,Increased serum PCT is associated with longer LOS in COPD exacerbation.,However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation. | Chronic Obstructive Pulmonary Disease (COPD) is defined as a disease characterized by persistent, progressive airflow limitation.,Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation.,In COPD fractional exhaled Nitric Oxide (FeNO) levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters.,Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones.,In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression.,FeNO measurements may be useful in clinical setting to identify the level of airway inflammation, per se and in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment.,Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD.,In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development. | 1 |
Blood eosinophils are a predictive marker for the use of inhaled corticosteroids (ICS).,However, there is concern over whether a single measure of blood eosinophils is sufficient for outlining a treatment plan.,Here, we evaluated the association between variability in blood eosinophils and the effects of ICS in stable COPD cohorts.,COPD patients in the Korean COPD Subtype Study and the Seoul National University Airway Registry from 2011 to 2018 were analyzed.,Based on blood eosinophils at baseline and at 1-year follow-up, the patients were classified into four groups with 250/μL as a cutoff value: consistently high (CH), consistently low (CL), variably increasing (VI), and variably decreasing (VD).,We compared rates of acute exacerbations (AEs) according to ICS use in each group after calibration of severity using propensity score matching.,Of 2,221 COPD patients, 618 were analyzed and a total of 125 (20%), 355 (57%), 63 (10%), and 75 (12%) patients were classified into the CH, CL, VI, and VD groups, respectively.,After calibration, we found that ICS users tended to have a lower AE rate in the CH group (RR 0.41, 95% CI 0.21-0.74) and VI group (RR 0.45, 95% CI 0.22-0.88), but not in the CL group (RR 1.42, 95% CI 1.08-1.89) and VD group (RR 1.71, 95% CI 1.00-2.96).,More than one-fifth of patients had an inconsistent blood eosinophil level after the 1-year follow-up, and the AE-COPD rate according to ICS differed based on variability in eosinophils.,Regular follow-up of blood eosinophils is required for COPD patients. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Pulmonary emphysema is characterized histologically by destruction of alveolar walls and enlargement of air spaces due to lung epithelial cell apoptosis.,Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member expressed in lung epithelial cells.,CADM1 generates a membrane-associated C-terminal fragment, αCTF, through A disintegrin- and metalloprotease-10-mediated ectodomain shedding, subsequently releasing the intracellular domain (ICD) through γ-secretase-mediated intramembrane shedding of αCTF. αCTF localizes to mitochondria and induces apoptosis in lung epithelial cells. αCTF contributes to the development and progression of emphysema as a consequence of increased CADM1 ectodomain shedding.,The purpose of this study was to examine whether the ICD makes a similar contribution.,The ICD was synthesized as a 51-amino acid peptide, and its mutant was synthesized by substituting seven amino acids and deleting two amino acids.,These peptides were labeled with fluorescein isothiocyanate and were introduced into various cell lines.,ICD peptide-derived fluorescence was well visualized in lung epithelial cells at the site of Mitotracker mitochondrial labeling, but was detected in locations other than mitochondria in other cell types.,Mutant peptide-derived fluorescence was detected in locations other than mitochondria, even in lung epithelial cells.,Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays revealed that transduction of the ICD peptide increased the proportion of apoptotic cells 2- to 5-fold in the lung epithelial cell lines, whereas the mutant peptide did not.,Abundance of the ICD was below the Western blot detection limit in emphysematous (n = 4) and control (n = 4) human lungs.,However, the ICD was detected only in emphysematous lungs when it was immunoprecipitated with anti-CADM1 antibody (4/4 vs.,0/4, P = 0.029).,As the abundance of ICD molecules was sparse but present, increased CADM1 shedding appeared to contribute to the development of emphysema by generating αCTF and the ICD in lung epithelial cells.,The online version of this article (doi:10.1186/s12929-015-0173-8) contains supplementary material, which is available to authorized users. | Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis.,Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer’s and Parkinson’s diseases, but little is known about iron accumulation in COPD.,We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction.,Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects.,Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay.,Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)).,The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues.,Futhermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity.,The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively).,In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction.,These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress. | 1 |
Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors.,We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD.,Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking.,Cases and controls were selected from the Obstructive Lung Disease in Northern Sweden (OLIN) studies.,In total, 37 genetic variants showed association with COPD (p < 0.05, uncorrected).,Several variants previously discovered to be associated with COPD from genetic genome-wide analysis studies were replicated using our sample.,Two high-risk variants were followed-up for functional characterization in a large eQTL mapping study of 1,111 human lung specimens.,The C allele of a synonymous variant, rs8040868, predicting a p.(,S45=) in the gene for cholinergic receptor nicotinic alpha 3 (CHRNA3) was associated with COPD (p = 8.8 x 10−3).,This association remained (p = 0.003 and OR = 1.4, 95 % CI 1.1-1.7) when analysing all available cases and controls in OLIN (n = 1,534).,The rs8040868 variant is in linkage disequilibrium with rs16969968 previously associated with COPD and altered expression of the CHRNA5 gene.,A follow-up analysis for detection of expression quantitative trait loci revealed that rs8040868-C was found to be significantly associated with a decreased expression of the nearby gene cholinergic receptor, nicotinic, alpha 5 (CHRNA5) in lung tissue.,Our data replicate previous result suggesting CHRNA5 as a candidate gene for COPD and rs8040868 as a risk variant for the development of COPD in the Swedish population.,The online version of this article (doi:10.1186/s12890-016-0309-y) contains supplementary material, which is available to authorized users. | Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression.,A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs).,PQTLs consistently replicated between the two cohorts.,Features of pQTLs were compared to previously reported expression QTLs (eQTLs).,Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests.,We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested.,Most pQTL SNPs were novel with low overlap to eQTL SNPs.,The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC).,Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.,Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins.,The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates.,Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema.,In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms.,Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group. | 1 |
Health-related quality of life (HRQoL) should be seen as a tool that provides an overall view of the general clinical condition of a COPD patient.,The aims of this study were to identify variables associated with HRQoL and whether they continue to have an influence in the medium term, during follow-up.,Overall, 543 patients with COPD were included in this prospective observational longitudinal study.,At all four visits during a 5-year follow-up, the patients completed the Saint George’s Respiratory Questionnaire (SGRQ), pulmonary function tests, the 6-min walk test (6MWT), and a physical activity (PA) questionnaire, among others measurements.,Data on hospitalization for COPD exacerbations and comorbidities were retrieved from the personal electronic clinical record of each patient at every visit.,The best fit to the data of the cohort was obtained with a beta-binomial distribution.,The following variables were related over time to SGRQ components: age, inhaled medication, smoking habit, forced expiratory volume in one second, handgrip strength, 6MWT distance, body mass index, residual volume, diffusing capacity of the lung for carbon monoxide, PA (depending on level, 13 to 35% better HRQoL, in activity and impacts components), and hospitalizations (5 to 45% poorer HRQoL, depending on the component).,Among COPD patients, HRQoL was associated with the same variables throughout the study period (5-year follow-up), and the variables with the strongest influence were PA and hospitalizations. | Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | 1 |
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended.,A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD.,Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks.,This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS.,A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD.,The methodologic quality and risk of bias of included studies were assessed.,Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks.,Meta-regression and sensitivity analyses were used to assess heterogeneity across studies.,Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network.,LAMA/LABA dual combinations were combined as a single treatment group to create a connected network.,Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks.,Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA.,In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD.,The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.,The online version contains supplementary material available at 10.1007/s12325-021-01703-z. | Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | 1 |
Health literacy (HL) is a person’s ability to practically apply a wide range of cognitive and non-cognitive skills in health-related decisions.,HL includes five domains: navigate/access, understand, communicate, evaluate, and use of health information and services.,Currently, no tool accurately captures and measures HL in adult patients with asthma and COPD, while utilizing all 5-HL domains.,Develop a comprehensive functional-based measurement tool for adult asthma and/or COPD patients, while assessing HL on routine actions required to manage their chronic respiratory condition(s).,We developed our HL tool based on a conceptualization of the link between HL and asthma and COPD management, during needs assessment stage including; a systematic review, which was followed by patient-oriented focus groups, and key-informant and respirologist interviews.,Preliminary face and content validation were obtained by patients’ and health professionals’ input prior to the pretesting stage.,The needs assessment information enabled us to develop passages in scenario-format and corresponding items to assess HL core domains, in addition to numeracy skills, across nine self-management topics: peak flow meters, prednisone use, pulmonary rehabilitation, action plans, flu shots, inhaler technique, lifestyle (nutrition and exercise), trigger control, and map navigation.,The tool was pretested with asthma and COPD patients to assess its relevance, clarity, and difficulty.,Our systematic review identified the deficiencies of existing HL tools that assessed the HL skills of asthma and COPD patients.,The patient-oriented focus groups (n=93) enabled us to identify self-management topics and develop items for our proposed HL tool, which were enriched by input from 45 key informants (eg, policy makers, clinicians, etc.) and 17 respiratory physicians.,Preliminary pretesting with a new cohort of participants (36 asthma and COPD patients and 39 key informants) aided in the refinement and finalized our tool.,The modified tool included passages and corresponding items related to asthma and COPD management was pretested with 75 asthma/COPD patients who completed the questionnaire and provided their feedback on the clarity, relevance, and difficulty of the tool.,The main barrier to self-management pertained to “communication” skills.,The flu shot was the most relevant topic (91.2%), while map navigation was the least relevant (63.9%).,Action plans were the most difficult topic, where only 55% knew when to utilize their action plans.,Numeracy items challenged COPD patients the most.,We summarized findings from the development and preliminary testing stages of a new asthma/COPD HL tool.,This tool will now be validated with a new cohort of patients.,Knowledge gained in this study has been applied to the final version of the tool, which is currently being validated. | Self-management is becoming increasingly important in COPD health care although it remains difficult to embed self-management into routine clinical care.,The implementation of self-management is understood as a complex interaction at the level of patient, health care provider (HCP), and health system.,Nonetheless there is still a poor understanding of the barriers and effective facilitators.,Comprehension of these determinants can have significant implications in optimizing self-management implementation and give further directions for the development of self-management interventions.,Data were collected among COPD patients (N=46) and their HCPs (N=11) in three general practices and their collaborating affiliated hospitals.,Mixed methods exploration of the data was conducted and collected by interviews, video-recorded consultations (N=50), and questionnaires on consultation skills.,Influencing determinants were monitored by 1) interaction and communication between the patient and HCP, 2) visible and invisible competencies of both the patient and the HCP, and 3) degree of embedding self-management into the health care system.,Video observations showed little emphasis on effective behavioral change and follow-up of given lifestyle advice during consultation.,A strong presence of COPD assessment and monitoring negatively affects the patient-centered communication.,Both patients and HCPs experience difficulties in defining personalized goals.,The satisfaction of both patients and HCPs concerning patient centeredness during consultation was measured by the patient feedback questionnaire on consultation skills.,The patients scored high (84.3% maximum score) and differed from the HCPs (26.5% maximum score).,Although the patient-centered approach accentuating self-management is one of the dominant paradigms in modern medicine, our observations show several influencing determinants causing difficulties in daily practice implementation.,This research is a first step unravelling the determinants of self-management leading to a better understanding. | 1 |
Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines.,The present study describes hospital resources, hospital factors related to case recruitment variability, patients’ characteristics, and adherence to guidelines.,An organisational database was completed by all participant hospitals recording resources and organisation.,Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified.,At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population.,Audited patients were reassessed 90 days after admission for survival and readmission rates.,A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death.,Median inpatient mortality was 5% (across-hospital range 0-35%).,Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%).,The overall mortality rate was 11.6% (0-50%).,Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment.,Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles.,The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes.,The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement. | 1 |
Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020.,It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation.,This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion.,The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood.,Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease.,Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD.,Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies.,The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD. | 1 |
Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features.,In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry.,The severity of the airflow limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management.,However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1.,At present, there is a lack of reliable and simple blood biomarkers to confirm and further assess the diagnosis of COPD.,However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes.,Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and “frequent exacerbators”.,Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as “asthma COPD overlap syndrome”.,Several other phenotypes have been proposed, but require validation against clinical outcomes.,Defining phenotypes requires the assessment of multiple factors indicating disease severity, its impact, and its activity.,Recognition and validation of COPD phenotypes has an important role to play in the selection of evidence-based targeted therapy in the future management of COPD, but regardless of the diagnostic terms, patients with COPD should be assessed and treated according to their individual treatable characteristics. | 1 |
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. | In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | 1 |
Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria.,This review aimed to identify the criteria used to diagnose sarcopenia and the prevalence and impact of sarcopenia on health outcomes in people with COPD.,This review was registered in PROSPERO (CRD42018092576).,Five electronic databases were searched to August 2018 to identify studies related to sarcopenia and COPD.,Study quality was assessed using validated instruments matched to study designs.,Sarcopenia prevalence was determined using authors' definitions.,Comparisons were made between people who did and did not have sarcopenia for pulmonary function, exercise capacity, quality of life, muscle strength, gait speed, physical activity levels, inflammation/oxidative stress, and mortality.,Twenty‐three studies (70% cross‐sectional) from Europe (10), Asia (9), and North and South America (4) involving 9637 participants aged ≥40 years were included (69.5% men).,Sarcopenia criteria were typically concordant with recommendations of hEuropean and Asian consensus bodies.,Overall sarcopenia prevalence varied from 15.5% [95% confidence interval (CI) 11.8-19.1; combined muscle mass, strength, and/or physical performance criteria] to 34% (95%CI 20.6-47.3; muscle mass criteria alone) (P = 0.009 between subgroups) and was greater in people with more severe [37.6% (95%CI 24.8-50.4)] versus less severe [19.1% (95%CI 10.2-28.0)] lung disease (P = 0.020), but similar between men [41.0% (95%CI 26.2-55.9%)] and women [31.9% (95%CI 7.0-56.8%)] (P = 0.538).,People with sarcopenia had lower predicted forced expiratory volume in the first second (mean difference −7.1%; 95%CI −9.0 to −5.1%) and poorer exercise tolerance (standardized mean difference −0.8; 95%CI −1.4 to −0.2) and quality of life (standardized mean difference 0.26; 95%CI 0.2-0.4) compared with those who did not (P < 0.001 for all).,No clear relationship was observed between sarcopenia and inflammatory or oxidative stress biomarkers.,Incident mortality was unreported in the literature.,Sarcopenia is prevalent in a significant proportion of people with COPD and negatively impacts upon important clinical outcomes.,Opportunities exist to optimize its early detection and management and to evaluate its impact on mortality in this patient group. | Osteoporosis is one of the systemic features of COPD.,A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear.,Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema.,The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis.,Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.,Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires.,Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA).,Twenty age-matched healthy volunteers were recruited as controls.,Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD.,Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05).,The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001).,Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables.,The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance.,The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05).,The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.,Radiographic emphysema is correlated with low BMD in current and former smokers with COPD.,IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD. | 1 |
Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler.,Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes.,In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated.,The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter.,Semi-structured, in-depth, qualitative interviews were carried out 2-4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI.,Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach.,Participants also rated the performance of the inhaler on several criteria, using a subjective 1-10 scale.,Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI.,It was frequently described as straightforward to operate and easy to use by interview participants.,Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler.,Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers.,Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers.,Overall average performance scores were >9 (out of 10) in participants with asthma and COPD.,The ELLIPTA DPI was associated with high patient satisfaction and was preferred to other inhalers by interview participants with asthma and COPD.,The development of an inhaler that is regarded as easy and intuitive to use may have positive implications for adherence to therapy in asthma and COPD.,Asthma: NCT01165138, NCT01431950.,COPD: NCT01053988, NCT01054885, NCT01009463, NCT01017952. | Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA) indicated for maintenance bronchodilator treatment of chronic obstructive pulmonary disease (COPD).,The efficacy of aclidinium was compared with tiotropium and glycopyrronium, using a network meta-analysis (NMA) of randomized controlled trials (RCTs) in moderate-to-severe COPD patients.,A systematic review was performed to identify RCTs evaluating aclidinium 400 μg twice daily (BID), glycopyrronium 50 μg once daily (OD), tiotropium 18 μg OD, or tiotropium 5 μg OD in adults with moderate-to-severe COPD.,The outcomes of interest were: trough forced expiratory volume in 1 second (FEV1); St George’s Respiratory Questionnaire (SGRQ) total score and proportion of patients achieving ≥4 unit change; Transition Dyspnea Index (TDI) focal score and proportion of patients achieving ≥1 point change.,The results were synthesized by means of a Bayesian NMA.,Twenty-one studies (22,542 patients) were included: aclidinium 400 μg BID (three studies); tiotropium 5 μg OD (three studies); tiotropium 18 μg OD (13 studies); and glycopyrronium 50 μg OD (two studies).,Regarding trough FEV1 at 24 weeks, aclidinium demonstrated comparable efficacy to tiotropium 5 μg (difference in change from baseline [CFB]), (0.02 L [95% credible interval CrI −0.05, 0.09]); tiotropium 18 μg (0.02 L [95% CrI −0.05, 0.08]); and glycopyrronium (0.00 L [95% CrI −0.07, 0.07]).,Aclidinium resulted in higher improvement in SGRQ score at 24 weeks, compared to tiotropium 5 μg (difference in CFB, −2.44 [95% CrI −4.82, −0.05]); and comparable results to tiotropium 18 μg (−1.80 [95% CrI −4.52, 0.14]) and glycopyrronium (−1.52 [95% CrI −4.08, 1.03]).,Improvements in TDI score were comparable for all treatments.,Maintenance treatment with aclidinium 400 μg BID is expected to produce similar improvements in lung function, health-related quality of life, and dyspnea compared to tiotropium 5 μg OD; tiotropium 18 μg OD; and glycopyrronium 50 μg OD. | 1 |
Chronic obstructive pulmonary disease (COPD) is an underdiagnosed cause of morbidity and mortality worldwide.,Prevalence of COPD has been shown to be highly associated with positive smoking history and increasing age.,Spirometry is the method used for diagnosing COPD.,However, identifying patients at risk of COPD to undergo spirometry tests has been challenging.,Therefore, there is a need for new cost-effective and feasible diagnostic screening procedures for use in primary care centers.,Our aim was to describe the prevalence and severity of undiagnosed COPD in a group of patients with respiratory infections attending urgent primary care, and to identify those variables in patients' history that could be used to detect the disease.,Patients of 40-75 years (n = 138) attending urgent primary care center with acute respiratory tract infection, positive smoking history and no previously known pulmonary disease underwent pre- and post bronchodilator spirometry testing four to five weeks after the acute infection.,Prevalence and severity of COPD were estimated following the Global Initiative for COPD (GOLD) criteria.,Variables such as sex, age, current smoking status, smoking intensity (pack years) and type of infection diagnosis were assessed for possible associations with COPD.,The prevalence of previously undiagnosed COPD in our study group was 27%, of which 45% were in stage 1 (FEV1 ≥ 80% of predicted), 53% in stage 2 (50 ≤ FEV1 < 80% of predicted), 3% in stage 3 (30 ≤ FEV1 < 50% of predicted) and 0% in stage 4 (FEV1 < 30% of predicted).,We found a significant association between COPD and age ≥ 55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack years > 20) (OR = 3.2 [95% CI 1.2-8.5]).,Sex, current smoking status and type of infection diagnosis were not shown to be significantly associated with COPD.,A middle-aged or older patient with any type of common respiratory tract infection, positive smoking history and no previously known pulmonary disease has an increased likelihood of having underlying COPD.,These patients should be offered spirometry testing for diagnosis of COPD. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population.,The study examined COPD patients with moderate COPD exacerbations.,COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.,This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation.,A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period.,A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs.,COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009).,COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.,21,524 patients with a moderate COPD exacerbation were identified.,Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation.,Annual costs averaged $594 per patient.,A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis.,The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04).,After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).,The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort.,However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05).,Total monthly COPD-related costs, as a result, did not differ between cohorts.,Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy.,Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness.,The pathologies of COPD are due to an abnormal immune response.,Invariant natural killer T (iNKT) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including COPD.,We have here analyzed the role of iNKT cells in a model of COPD induced by repeated intranasal administration of iNKT cell agonist α-galactosylceramide (α-GalCer).,Our results demonstrated that mice that received repeated intranasal administration of α-GalCer had molecular and inflammatory features of COPD including airway inflammation with significant increases in infiltration of macrophages and lymphocytes, CD8+ T cells, as well as proinflammatory cytokines IL-6 and TNF-α.,In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis.,Furthermore, neutralization of IL-4 reduced α-GalCer induced emphysema.,This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism. | Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure.,Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation.,In the current study, we investigate the role of iNKT cells in COPD pathogenesis.,The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls.,In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis.,The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17.,CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferonγ and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein.,In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD.,Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level. | 1 |
Administrative databases are widely available and have been extensively used to provide estimates of chronic disease prevalence for the purpose of surveillance of both geographical and temporal trends.,There are, however, other sources of data available, such as medical records from primary care and national surveys.,In this paper we compare disease prevalence estimates obtained from these three different data sources.,Data from general practitioners (GP) and administrative transactions for health services were collected from five Italian regions (Veneto, Emilia Romagna, Tuscany, Marche and Sicily) belonging to all the three macroareas of the country (North, Center, South).,Crude prevalence estimates were calculated by data source and region for diabetes, ischaemic heart disease, heart failure and chronic obstructive pulmonary disease (COPD).,For diabetes and COPD, prevalence estimates were also obtained from a national health survey.,When necessary, estimates were adjusted for completeness of data ascertainment.,Crude prevalence estimates of diabetes in administrative databases (range: from 4.8% to 7.1%) were lower than corresponding GP (6.2%-8.5%) and survey-based estimates (5.1%-7.5%).,Geographical trends were similar in the three sources and estimates based on treatment were the same, while estimates adjusted for completeness of ascertainment (6.1%-8.8%) were slightly higher.,For ischaemic heart disease administrative and GP data sources were fairly consistent, with prevalence ranging from 3.7% to 4.7% and from 3.3% to 4.9%, respectively.,In the case of heart failure administrative estimates were consistently higher than GPs’ estimates in all five regions, the highest difference being 1.4% vs 1.1%.,For COPD the estimates from administrative data, ranging from 3.1% to 5.2%, fell into the confidence interval of the Survey estimates in four regions, but failed to detect the higher prevalence in the most Southern region (4.0% in administrative data vs 6.8% in survey data).,The prevalence estimates for COPD from GP data were consistently higher than the corresponding estimates from the other two sources.,This study supports the use of data from Italian administrative databases to estimate geographic differences in population prevalence of ischaemic heart disease, treated diabetes, diabetes mellitus and heart failure.,The algorithm for COPD used in this study requires further refinement. | Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor.,This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy.,The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique.,One-year follow-ups with three visits were performed.,The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques.,Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group.,The main outcome measure was adherence to the medication regimen.,Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count.,Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group).,When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046).,Number needed to treat is 6.37.,In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%.,The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment; activity (OR = 1.03) and impact (OR = 1.03) scales of the Saint George Respiratory Questionnaire.,Application of the multifactorial intervention designed for this study (COPD information, dose reminders, audio-visual material, motivational aspects and training in inhalation techniques) resulted in an improvement in therapeutic adherence in COPD patients with scheduled inhalation therapy.,Current Controlled Trials ISRCTN18841601. | 1 |
We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD.,We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects.,Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages.,Multiplex ELISA measured BAL cytokines.,Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles.,We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups.,However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects.,BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs.,The mouse-model of COPD showed similar increase in mRNA for M2 markers.,Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance.,There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD. | Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity.,There are only limited data about its role in airway remodeling in COPD.,We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD).,This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.,Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls.,The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups.,Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3.,Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls.,TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs.,0.0 (0.0-7.0), p<0.05].,Percentage of vessels stained was also increased in these clinical groups.,Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.,Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD. | 1 |
Efficient management of COPD represents an international challenge.,Effective management strategies within the means of limited health care budgets are urgently required.,This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET).,Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET.,The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy.,Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR).,Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores.,Home-based DM was associated with improved mortality and quality-adjusted life expectancy.,DM and UM were associated with equivalent direct costs (DM reduced costs by EUR −37 per patient per year) in the pooled analysis.,DM was associated with lower costs in France (EUR −806 per patient per year) and Spain (EUR −51 per patient per year), but higher costs in Germany (EUR 391 per patient per year).,Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM.,Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany.,Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis.,DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained.,The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers. | Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | 1 |
Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality.,We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema.,We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema.,As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted.,The overall prevalence of emphysema was 52%.,Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1 (P < 0.001).,The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96).,In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001).,The odds of emphysema were not statistically different between males and females.,In conclusion, body height is a strong, independent risk factor for emphysema in COPD. | The COPD assessment test (CAT) score is a key component of the multifactorial assessment of COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines of 2014.,Nevertheless, little is known regarding the differences among COPD categories in terms of clinical parameters such as pulmonary function or radiological findings.,Thus, our aims in this study were to evaluate the associations between CAT scores and pulmonary clinical parameters, and to investigate factors that could discriminate between a “less symptomatic group” (categories A and C) and a “more symptomatic group” (categories B and D) among stable COPD patients.,We enrolled 200 outpatients at Chiba University Hospital.,Study subjects were assessed by CAT, pulmonary function testing, and multidetector computed tomography (MDCT).,We assessed possible correlations between these indices.,CAT scores were negatively correlated with percentage of the forced expiratory volume in 1 second predicted value (FEV1 %predicted) and percentage of the diffusing capacity for carbon monoxide per liter of lung volume predicted value (DLCO/VA [%predicted]) results and positively correlated with low attenuation volume percentage (LAV%) and residual volume to total lung capacity ratios (RV/TLC).,In the “more symptomatic group” (category B or D), the mean DLCO/VA (%predicted) was significantly lower and the mean LAV% and RV/TLC was significantly higher than those in the “less symptomatic group” (category A or C), respectively.,Interestingly, those in category B had higher mean LAV% compared to those in category C.,CAT scores were significantly correlated with pulmonary function parameters and emphysematous changes on MDCT.,The new GOLD classification system would be a step toward a phenotypic approach, especially taking into account the degree of emphysema and hyperinflation. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients.,Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) regulate goblet cell differentiation.,This study aimed to (1) investigate DNA methylation and expression of SPDEF and FOXA2 during goblet cell differentiation and (2) compare this in airway epithelial cells from patients with COPD and controls during mucociliary differentiation.,To assess DNA methylation and expression of SPDEF and FOXA2 during goblet cell differentiation, primary airway epithelial cells, isolated from trachea (non-COPD controls) and bronchial tissue (patients with COPD), were differentiated by culture at the air-liquid interface (ALI) in the presence of cytokine interleukin (IL)-13 to promote goblet cell differentiation.,We found that SPDEF expression was induced during goblet cell differentiation, while FOXA2 expression was decreased.,Importantly, CpG number 8 in the SPDEF promoter was hypermethylated upon differentiation, whereas DNA methylation of FOXA2 promoter was not changed.,In the absence of IL-13, COPD-derived ALI-cultured cells displayed higher SPDEF expression than control-derived ALI cultures, whereas no difference was found for FOXA2 expression.,This was accompanied with hypomethylation of CpG number 6 in the SPDEF promoter and also hypomethylation of CpG numbers 10 and 11 in the FOXA2 promoter.,These findings suggest that aberrant DNA methylation of SPDEF and FOXA2 is one of the factors underlying mucus hypersecretion in COPD, opening new avenues for epigenetic-based inhibition of mucus hypersecretion.,The online version of this article (doi:10.1186/s13148-017-0341-7) contains supplementary material, which is available to authorized users. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) share common risk factors.,However, there is limited information about COPD and CKD.,This is case-cohort study was carried out using the Taiwanese National Health Insurance Research Database to evaluate the correlation between COPD and CKD.,We identified cases aged older than 40 years who had an inpatient hospitalization with a first-time COPD diagnosis between 1998 and 2008.,Control were selected from hospitalized patients without COPD or CKD and were matched according to age, gender, and year of admission at a 2:1 ratio.,Cox proportional hazards model was used to assess the association of CKD and COPD.,The overall incidence of CKD was higher in the COPD group (470.9 per 104 person-years) than in the non-COPD group (287.52 per 104 person-years).,The adjusted hazard ratio of case was 1.61 (P < 0.0001) times that of control.,COPD was found to be associated with kidney disease from our follow-up.,To detect CKD early, early diagnosis of CKD in patients with COPD and prompt initiation of monitoring and treatment are imperative. | The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | 1 |
COPD is a multi-pathogenesis disease mainly caused by smoking.,A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages.,This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.,COPD models were built in the C57BL/6 mouse by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE).,The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E) staining.,The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS) of CD206, CD86 and CD68 on the lung tissue paraffin section.,The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer.,The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR).,The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β) in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.,The COPD model is well established, which is confirmed by the lung function test and lung H&E staining.,The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05).,The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer.,The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05) in CES-treated M2 macrophages, which is detected by RT-PCR.,The protein levels of TGF-β/Smad pathway-related markers are all increased in alveolar M2 macrophages of the model group.,This study found an increased deposition of alveolar M2 macrophages in the mouse COPD model and an increased expression level of TGF-β/Smad pathway in M2 macrophages, both in vitro and in vivo, induced by CSE and/or CS exposure, indicating that M2 macrophages might contribute to COPD through changing of phenotype and TGF-β/Smad pathway. | Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown.,We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS.,CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells.,CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium.,CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice.,The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis.,Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages.,These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers. | 1 |
In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society.,Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE).,In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis.,We searched the terms “chronic obstructive pulmonary disease,” “pulmonary embolism,” “exacerbations,” and “thromboembolic” in PubMed database and collected the results up to April 2018.,The language was limited to English.,We thoroughly examined the titles and abstracts of all studies that met our search strategy.,The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review.,The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria.,Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department.,PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms.,However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation.,Obesity and lower limb asymmetry were described as independent predictors for PE.,Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation.,According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay.,Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated. | It is generally accepted that people with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE).,While it is plausible that the risk of arterial and venous thrombotic events is greater still in certain subgroups of patients with COPD, such as those with more severe airflow limitation or more frequent exacerbations, these associations, in particular those between venous events and COPD severity or exacerbation frequency, remain largely untested in large population cohorts.,A total of 3,594 patients with COPD with a first VTE event recorded during January 1, 2004 to December 31, 2013, were identified from the Clinical Practice Research Datalink dataset and matched on age, sex, and general practitioner practice (1:3) to patients with COPD with no history of VTE (n=10,782).,COPD severity was staged by degree of airflow limitation (ie, GOLD stage) and by COPD medication history.,Frequent exacerbators were defined as patients with COPD with ≥ 2 exacerbations in the 12-month period prior to their VTE event (for cases) or their selection as a control (for controls).,Conditional logistic regression was used to estimate the association between disease severity or exacerbation frequency and VTE.,After additional adjustment for nonmatching confounders, including body mass index, smoking, and heart-related comorbidities, there was evidence for an association between increased disease severity and VTE when severity was measured either in terms of lung function impairment (odds ratio [OR]moderate:mild =1.16; 95% confidence intervals [CIs] =1.03, 1.32) or medication usage (ORsevere:mild/moderate =1.17; 95% CIs =1.06, 1.26).,However, there was no evidence to suggest that frequent exacerbators were at greater risk of VTE compared with infrequent exacerbators (OR =1.06; 95% CIs =0.97, 1.15).,COPD severity defined by airflow limitation or medication usage, but not exacerbation frequency, appears to be associated with VTE events in people with COPD.,This finding highlights the disconnect between disease activity and severity in COPD. | 1 |
Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | The aims of this study were: (1) to compare the discriminative ability of a disease-specific instrument, the St.,George's Respiratory Questionnaire (SGRQ) to generic instruments (i.e., EQ-5D and SF-36); and (2), to evaluate the strength of associations among clinical and health-related quality of life (HRQL) measures in chronic obstructive pulmonary disease (COPD).,We analyzed data collected from 120 COPD patients in a Veterans Affairs hospital.,Patients self-completed two generic HRQL measures (EQ-5D and SF-36) and the disease-specific SGRQ.,The ability of the summary scores of these HRQL measures to discriminate COPD disease severity based on Global Obstructive Lung Disease (GOLD) stage was assessed using relative efficiency ratios (REs).,Strength of correlation was used to further evaluate associations between clinical and HRQL measures.,Mean total scores for PCS-36, EQ-VAS and SGRQ were significantly lower for the more severe stages of COPD (p < 0.05).,Using SGRQ total score as reference, the summary scores of the generic measures (PCS-36, MCS-36, EQ index, and EQ-VAS) all had REs of <1.,SGRQ exhibited a stronger correlation with clinical measures than the generic summary scores.,For instance, SGRQ was moderately correlated with FEV1 (r = 0.43), while generic summary scores had trivial levels of correlation with FEV1 (r < 0.2).,The SGRQ demonstrated greater ability to discriminate among different levels of severity stages of COPD than generic measures of health, suggestive that SGRQ may provide COPD studies with greater statistical power than EQ-5D and SF-36 summary scores to capture meaningful differences in clinical severity. | 1 |
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. | 1 |
Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | Introduction.,Chronic obstructive pulmonary disease (COPD) is associated with comorbidities such as cardiovascular disease, metabolic disease, osteoporosis, and anxiety and/or depression.,Although pulmonary rehabilitation programs are proven to be beneficial in patients with COPD, it is unclear whether comorbidities influence pulmonary rehabilitation outcomes.,The aim of the present review was to investigate to what extent the presence of comorbidities can affect pulmonary rehabilitation outcomes.,Methods.,The systematic literature search (Pubmed, EMBASE, and PEDro) resulted in 4 articles meeting the inclusion criteria.,The odds ratios (95% confidence intervals) of the logistic regression analyses, with comorbidities as independent variables and pulmonary rehabilitation outcomes (dyspnea, functional exercise capacity, and quality of life) as dependent variables, were used for data extraction.,Results.,Patients with anxiety and/or depression less likely improve in dyspnea.,Osteoporosis is associated with less improvements in functional exercise capacity, while cardiovascular disease does not seem to negatively impact on this outcome.,Patients with cardiovascular comorbidity will experience less positive changes in quality of life.,Conclusion.,Evidence from literature suggests that comorbidities can have a negative influence on pulmonary rehabilitation outcomes.,Screening for comorbidities in pulmonary rehabilitation settings seems useful to readdress the right patients for individually tailored pulmonary rehabilitation. | 1 |
The percentage of α1-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies.,We aimed to estimate the prevalence of PiZZ in COPD patients from 20 European countries with available data, according to the number of PiZZ and COPD individuals in each country.,A systematic review was conducted to select European countries with reliable data on the prevalence of PiZZ and COPD.,We created a database with the following data: 1) total population and population aged ≥40 years according to the Eurostat database; 2) number and 95% CI of PiZZ patients aged ≥40 years; 3) application of a conversion factor of genetic penetrance of 60%; 4) number of COPD individuals, with 95% CI, aged ≥40 years; and 5) calculation of the PiZZ/COPD ratio.,Finally, results were presented using an Inverse Distance Weighted Interpolation map.,We found 36 298 (95% CI 23 643-56 594) PiZZ individuals at high risk and 30 849 709 (95% CI 21 411 293-40 344 496) COPD patients, with a PiZZ/COPD ratio of 0.12% (range 0.08-0.24%), and a prevalence of 1 out of 408 in Northern, 1 out of 944 in Western, 1 out of 1051 in Central, 1 out of 711 in Southern, and 1 out of 1274 in Eastern Europe.,These data may be useful to plan strategies for future research and diagnosis, and to rationalise the available therapeutic resources.,There is a significant number of PiZZ individuals at high risk of COPD, as well as an impressive number of patients with COPD in Europe.,The ratio between PiZZ and COPD ranges between 0.08% and 0.24%, with wide differences among countries.https://bit.ly/2VrOzUv | The alpha-1 antitrypsin (AAT) haplotype Pi*S, when inherited along with the Pi*Z haplotype to form a Pi*SZ genotype, can be associated with pulmonary emphysema in regular smokers, and less frequently with liver disease, panniculitis, and systemic vasculitis in a small percentage of people, but this connection is less well established.,Since the detection of cases can allow the application of preventive measures in patients and relatives with this congenital disorder, the objective of this study was to update the prevalence of the SZ genotype to achieve accurate estimates of the number of Pi*SZ subjects worldwide, based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) selection of studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals.,Studies fulfilling these criteria were used to develop tables and maps with an inverse distance-weighted (IDW) interpolation method, to provide numerical and geographical information of the Pi*SZ distribution worldwide.,A total of 262 cohorts from 71 countries were included in the analysis.,With the data provided by these cohorts, a total of 1,490,816 Pi*SZ were estimated: 708,792 in Europe; 582,984 in America and Caribbean; 85,925 in Africa; 77,940 in Asia; and 35,176 in Australia and New Zealand.,Remarkably, the IDW interpolation maps predicted the Pi*SZ prevalence throughout the entire world even in areas lacking real data.,These results may be useful to plan strategies for future research, diagnosis, and management of affected individuals. | 1 |
Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD).,We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD.,The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database.,Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group.,Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex.,Patients who had used hypnotics within 1 month meant active users.,The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models.,Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively.,After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11-17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68-14.2) compared with the adjusted ORs of those who never used hypnotics.,The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD. | The possible relationship between chronic inflammatory diseases and their co-morbidities has become an increasing focus of research.,Both chronic periodontitis and chronic obstructive pulmonary disease are neutrophilic, inflammatory conditions characterized by the loss of local connective tissue.,Evidence suggests an association and perhaps a causal link between the two diseases.,However, the nature of any relationship between them is unclear, but if pathophysiologically established may have wide-reaching implications for targeted treatments to improve outcomes and prognosis.,There have been a number of epidemiological studies undertaken demonstrating an independent association between chronic periodontitis and chronic obstructive pulmonary disease.,However, many of them have significant limitations, and drawing firm conclusions regarding causality may be premature.,Although the pathology of both these diseases is complex and involves many cell types, such as CD8 positive cells and macrophages, both conditions are predominantly characterized by neutrophilic inflammation.,Increasingly, there is evidence that the two conditions are underpinned by similar pathophysiological processes, especially centered on the functions of the neutrophil.,These include a disturbance in protease/anti-protease and redox state balance.,The association demonstrated by epidemiological studies, as well as emerging similarities in pathogenesis at the level of the neutrophil, suggest a basis for testing the effects of treatment for one condition upon the severity of the other.,Although the evidence of an independent association between chronic periodontitis and chronic obstructive pulmonary disease grows stronger, there remains a lack of definitive studies designed to establish causality and treatment effects.,There is a need for future research to be focused on answering these questions. | 1 |
Sarcopenia is characterized by a progressive and generalized decrease of strength and muscle mass.,Muscle mass loss is prevalent in patients with chronic obstructive pulmonary disease (COPD) as a result of both the disease and aging.,Some methods have been proposed to assess body composition (and therefore identify muscle mass loss) in this population.,Despite the high accuracy of some methods, they require sophisticated and costly equipment.,The purpose of this study was to infer the occurrence of muscle mass loss measured by a sophisticated method (dual energy X-ray absorptiometry [DEXA]) using a more simple and affordable equipment (dynamometer).,Fifty-seven stable subjects with COPD were evaluated for anthropometric characteristics, lung function, functional exercise capacity, body composition, and peripheral muscle strength.,A binary logistic regression model verified whether knee-extension strength (measured by dynamometry) could infer muscle mass loss (from DEXA).,Patients with decreased knee-extension strength were 5.93 times more likely to have muscle mass loss, regardless of sex, disease stage, and functional exercise capacity (P=0.045).,Knee-extension dynamometry was able to infer muscle mass loss in patients with COPD. | Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis.,Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects.,The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.,In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital.,The primary outcomes were changes in 6-min walk distance (6-MWD) and the St.,George Respiratory Questionnaire (SGRQ) score.,Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength.,At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment.,In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant.,At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group.,Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021).,Ghrelin treatment was well tolerated.,In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.,UMIN Clinical Trial Registry C000000061 | 1 |
Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined.,We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function.,NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome.,Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation.,Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001).,This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002).,Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01).,Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes.,Consistent results were observed regardless of the method of quantifying sputum NETs.,Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD.,NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity. | There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. | 1 |
The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed.,We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II).,Blood was taken once in Control I and 4 times (every month) in Control II.,In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively.,Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I.,In Control II, the similar differences as compared to Control I were observed throughout the study.,Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E.,COPD is accompanied by oxidative stress.,A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters. | ► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences. | 1 |
Omega-3 fatty acid is an emerging hotspot on anti-inflammation and chronic obstructive pulmonary disease (COPD) is known as a chronic inflammatory disease.,The effect of Omega-3 fatty acid supplement on patients with COPD remains mixed for insufficient evidence.,This systematic review and meta-analysis is based on neat randomized controlled trials trying to give a clearer impression on the effect of Omega-3 on patients with COPD.,This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements.,Randomized clinical trials (RCTs) published in electronic databases including Medline, Embase, Cochrane Library, ClinicalTrials.gov and China National Knowledge Infrastructure (CNKI) by May 10, 2021 were searched.,Data extracted from 6 predetermined domains (nutritional condition, lipid composition, inflammatory biomarker, lung function, physical endurance and quality of life [QoL]) were reviewed and analyzed.,A total of 8 RCTs evaluating 418 patients (age, mean [SD] = 67.3 [10.2] years) were included.,Statistical differences were found in 3 parameters of 3 domains - weight (Wt) (0.25 [95% CI, 0.02 to 0.48], P = 0.03) in nutritional condition, low-density lipoprotein (LDL) (0.70 [95% CI, 0.30 to 1.10], P = 0.00) in lipid composition and interleukin-6 (IL-6) level (−0.32 [95% CI, −0.60 to −0.05], P = 0.02) in inflammatory biomarker - while no significant difference was found in lung function, physical endurance or QoL.,Comparing with placebo, Omega-3 intake was associated with more weight-gaining, LDL increase and IL-6 reduction.,These results should be interpreted cautiously for the quality and quantity of available evidence are limited. | The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation.,However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood.,In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD.,Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα.,After 48-72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively.,Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36).,AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD.,In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD.,In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release.,In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts.,In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin.,This study shows that AA has disease-specific effects on inflammation and ECM protein deposition.,The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases.,The online version of this article (10.1186/s12931-018-0919-4) contains supplementary material, which is available to authorized users. | 1 |
Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited.,The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass.,Eighty‐one COPD patients with low muscle mass, admitted to out‐patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega‐3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training.,The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid.,Intention‐to‐treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048).,After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001).,Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (−18%,P = 0.005).,High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction.,Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo. | Fat-free mass (FFM) depletion has been shown to be a better predictor of mortality than BMI in chronic obstructive pulmonary disease (COPD) patients.,The specific aim of the current study was to assess the nutritional status of stable COPD patients in relation to fat free mass index profiles.,We investigated 65 male moderate-to-severe stable COPD patients.,A self-reported questionnaire was applied about general characteristics and smoking history.,Nutritional intake was assessed by using a 54-item quantitative food frequency questionnaire.,Weight, height, mid-upper arm circumference (MUAC), waist circumference (WC), handgrip strength and body composition measurements were taken by a trained dietitian.,The data were analyzed with SPSS 15.0 software.,The mean age of the patients was 62.1 ± 8.9 years.,Among all of the patients 13.8% was underweight (BMI < 21 kg/m2) and 18.5% had a low fat-free mass index (FFMI < 16 kg/m2).,The percentages of the patients who did not meet the daily recommended intakes (RNI) were highest for magnesium (93.8%) and calcium (92.3%).,Mean daily consumptions of milk-yogurt, red meat and fruits were significantly low in the low FFMI group compared to normal FFMI group (for all; p < 0.05).,Patients with normal FFMI had significantly higher weight, height, WC, MUAC, handgrip strength, fat and fat-free mass than the patients with low FFMI (for all; p < 0.05).,Dieticians should be aware of COPD patients with low FFMI in order to evaluate the nutritional intake and therefore plan nutritional strategies to improve prognosis of the disease. | 1 |
A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity.,Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant.,We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies.,Stata/SE 15.0 was used to perform all data analysis.,A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816.,Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%).,Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%).,Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial.,Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group.,Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate.,Instead, the hospitalization rate and mortality increased with theophylline.,Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients.,PROSPERO RegistrationCRD42021224952. | Peripheral blood eosinophilic counts are susceptible to many factors and have variability over time.,There are limited studies on association of blood eosinophilia with long-term mortality of chronic obstructive pulmonary disease (COPD) patients and these results remain controversial.,Our aims were to explore the association of blood eosinophilia at index hospitalization and stability of blood eosinophilia stability over 5 years with all-cause mortality of patients hospitalized for acute exacerbation of COPD (AECOPD).,Eight hundred twenty-nine patients hospitalized for AECOPD between 2013 and 2014 were included in this study and grouped into two groups according to blood eosinophil with 150 cells/μL used as the cutoff value to form eosinophilic and non-eosinophilic groups.,Two hundred forty-one COPD inpatients with at least three blood eosinophils measured from different hospitalizations were used for analysis of longitudinally eosinophilic stability and divided into three groups according to the same cutoff value: predominantly (PE), intermittently (IE) and rarely (RE) eosinophilic groups.,Cox regression analysis was used to determine the association of blood eosinophilia and all-cause mortality.,In patients hospitalized for AECOPD, 261 (31.5%) at baseline and 41 (17%) based on at least three measurements of blood eosinophils had increased blood eosinophils.,For all-cause mortality, eosinophilic COPD patients at index hospitalization had a lower all-cause mortality compared with non-eosinophilic COPD patients (hazard ratio 0.77, 95% confidence interval 0.6-0.99, P=0.04).,In patients readmitted for AECOPD by longitudinal eosinophil stability, with the RE group used as reference, the PE group was associated with a lower all-cause mortality of AECOPD patients (hazard ratio 0.43, 95% confidence interval 0.22-0.85, P=0.016), compared to the IE group (hazard ratio 0.72, 95% confidence interval 0.47-1.11, P=0.133).,Patients with increased eosinophils (using eosinophil 150 cells/μL as a cutoff value), especially predominantly increased eosinophil levels based on multiple measurements, had a lower risk of all-cause mortality.,Blood eosinophilia can be used as a biomarker in hospitalized COPD exacerbations for predicting the risk of all-cause mortality.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/RroTKw3Hisg | 1 |
Alpha-1 antitrypsin deficiency (AATD), mainly due to the PI*ZZ genotype in SERPINA1, is one of the most common inherited diseases.,Since it is associated with a high disease burden and partially prevented by smoking cessation, identification of PI*ZZ individuals through genotyping could improve health outcomes.,We examined the frequency of the PI*ZZ genotype in individuals with and without diagnosed AATD from UK Biobank, and assessed the associations of the genotypes with clinical outcomes and mortality.,A phenome-wide association study (PheWAS) was conducted to reveal disease associations with genotypes.,A polygenic risk score (PRS) for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio was used to evaluate variable penetrance of PI*ZZ.,Among 458 164 European-ancestry participants in UK Biobank, 140 had the PI*ZZ genotype and only nine (6.4%, 95% CI 3.4-11.7%) of them were diagnosed with AATD.,Those with PI*ZZ had a substantially higher odds of COPD (OR 8.8, 95% CI 5.8-13.3), asthma (OR 2.0, 95% CI 1.4-3.0), bronchiectasis (OR 7.3, 95%CI 3.2-16.8), pneumonia (OR 2.7, 95% CI 1.5-4.9) and cirrhosis (OR 7.8, 95% CI 2.5-24.6) diagnoses and a higher hazard of mortality (2.4, 95% CI 1.2-4.6), compared to PI*MM (wildtype) (n=398 424).,These associations were stronger among smokers.,PheWAS demonstrated associations with increased odds of empyema, pneumothorax, cachexia, polycythaemia, aneurysm and pancreatitis.,Polygenic risk score and PI*ZZ were independently associated with FEV1/FVC <0.7 (OR 1.4 per 1-sd change, 95% CI 1.4-1.5 and OR 4.5, 95% CI 3.0-6.9, respectively).,The important underdiagnosis of AATD, whose outcomes are partially preventable through smoking cession, could be improved through genotype-guided diagnosis.,Only 6.4% of those with genotype-defined alpha-1 antitrypsin deficiency had been diagnosed with this serious disease in UK Biobank.,Genotype-guided diagnosis could help to identify the thousands of people in the UK with this partially preventable disease. https://bit.ly/3dMu5Ng | Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD).,Although the exact cause is not firmly established, physical inactivity and oxidative stress are among the proposed underlying mechanisms.,Here, we assess the impact of COPD pathophysiology on mitochondrial DNA (mtDNA) integrity, biogenesis, and cellular oxidative capacity in locomotor muscle of COPD patients and healthy controls.,We hypothesized that the high oxidative stress environment of COPD muscle would yield a higher presence of deletion-containing mtDNA and oxidative-deficient fibers and impaired capacity for mitochondrial biogenesis.,Vastus lateralis biopsies were analyzed from 29 COPD patients and 19 healthy age-matched controls for the presence of mtDNA deletions, levels of oxidatively damaged DNA, mtDNA copy number, and regulators of mitochondrial biogenesis as well the proportion of oxidative-deficient fibers (detected histologically as cytochrome c oxidase-deficient, succinate dehydrogenase positive (COX−/SDH+ )).,Additionally, mtDNA copy number and mitochondrial transcription factor A (TFAM) content were measured in laser captured COX−SDH+ and normal single fibers of both COPD and controls.,Compared to controls, COPD muscle exhibited significantly higher levels of oxidatively damaged DNA (8-hydroxy-2-deoxyguanosine (8-OHdG) levels = 387 ± 41 vs. 258 ± 21 pg/mL) and higher prevalence of mtDNA deletions (74 vs. 15 % of subjects in each group), which was accompanied by a higher abundance of oxidative-deficient fibers (8.0 ± 2.1 vs.,1.5 ± 0.4 %).,Interestingly, COPD patients with mtDNA deletions had higher levels of 8-OHdG (457 ± 46 pg/mL) and longer smoking history (66.3 ± 7.5 years) than patients without deletions (197 ± 29 pg/mL; 38.0 ± 7.3 years).,Transcript levels of regulators of mitochondrial biogenesis and oxidative metabolism were upregulated in COPD compared to controls.,However, single fiber analyses of COX−/SDH+ and normal fibers exposed an impairment in mitochondrial biogenesis in COPD; in healthy controls, we detected a marked upregulation of mtDNA copy number and TFAM protein in COX−/SDH+ compared to normal fibers, reflecting the expected compensatory attempt by the oxidative-deficient cells to increase energy levels; in contrast, they were similar between COX−/SDH+ and normal fibers in COPD patients.,Taken together, these findings suggest that although the signaling factors regulating mitochondrial biogenesis are increased in COPD muscle, impairment in the translation of these signals prevents the restoration of normal oxidative capacity.,Single fiber analyses provide the first substantive evidence that low muscle oxidative capacity in COPD cannot be explained by physical inactivity alone and is likely driven by the disease pathophysiology. | 1 |
Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily).,The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles.,This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.,Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks).,Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately.,In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure.,Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted).,The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]).,The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group.,Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium.,Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.,This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. | In Europe, administration of an inhaled corticosteroid (ICS) combined with a long-acting β2 agonist is approved in chronic obstructive pulmonary disease (COPD) patients with a pre-bronchodilator FEV1 < 60% predicted normal, a history of repeated exacerbations, and who have significant symptoms despite regular bronchodilator therapy.,Minimal data are available on the use of the fluticasone propionate/salmeterol xinafoate combination (FSC) in the real-life COPD setting and prescription compliance with the licensed specifications.,A French observational study was performed to describe the COPD population prescribed with FSC, prescription modalities, and the coherence of prescription practices with the market authorized population.,Data were collected for patients initiating FSC treatment (500 μg fluticasone propionate, 50 μg salmeterol, dry powder inhaler) prescribed by a general practitioner (GP) or a pulmonologist, using physician and patient questionnaires.,A total of 710 patients were included, 352 by GPs and 358 by pulmonologists.,Mean age was over 60 years, and 70% of patients were male.,More than half were retired, and overweight or obese.,Approximately half were current smokers and one-third had cardiovascular comorbidities.,According to both physician evaluation and GOLD 2006 classification, the majority of patients (>75%) had moderate to very severe COPD.,Strict compliance by prescribing physicians with the market-approved population for dry powder inhaler SFC in COPD was low, notably in ICS-naïve patients; all three conditions were fulfilled in less than a quarter of patients with prior ICS and less than 7% of ICS-naïve patients.,Prescription of dry powder inhaler SFC by GPs and pulmonologists has very low conformity with the three conditions defining the licensed COPD population.,Prescription practices need to be improved and systematic FEV1 evaluation for COPD diagnosis and treatment management should be emphasized. | 1 |
Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | 1 |
Ambient air pollution can contribute to the development and exacerbation of COPD.,However, the influence of air pollution on objective COPD phenotypes, especially from imaging, is not well studied.,We investigated the influence of long-term exposure to air pollution on lung function and quantitative imaging measurements in a Korean cohort of participants with and without COPD diagnosis.,Study participants (N = 457 including 296 COPD cases) were obtained from the COPD in Dusty Areas (CODA) cohort.,Annual average concentrations of particulate matter less than or equal to 10 μm in diameter (PM10) and nitrogen dioxide (NO2) were estimated at the participants’ residential addresses using a spatial air pollution prediction model.,All the participants underwent volumetric computerized tomography (CT) and spirometry measurements and completed survey questionnaires.,We examined the associations of PM10 and NO2 with FVC, FEV1, emphysema index, and wall area percent, using linear regression models adjusting for age, gender, education, smoking, height, weight, and COPD medication.,The age of study participants averaged 71.7 years.,An interquartile range difference in annual PM10 exposure of 4.4 μg/m3 was associated with 0.13 L lower FVC (95% confidence interval (CI), − 0.22- -0.05, p = 0.003).,Emphysema index (mean = 6.36) was higher by 1.13 (95% CI, 0.25-2.02, p = 0.012) and wall area percent (mean = 68.8) was higher by 1.04 (95% CI, 0.27-1.80, p = 0.008).,Associations with imaging phenotypes were not observed with NO2.,Long-term exposure to PM10 correlated with both lung function and COPD-relevant imaging phenotypes in a Korean cohort. | Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity.,It contributes to the current persistent one-size-fits-all treatment.,To replace this treatment by more personalized, precision medicine, new insights are required.,We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs.,The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution.,Forty seven patients were assessed.,FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of −0.25±0.61 L, p≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p=0.02), and airway resistance.,As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters.,Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI.,FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups.,It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations. | 1 |
Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years.,Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers.,However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways.,In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly.,Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis.,Nebulizers should be considered for patients unable to use handheld inhalers properly.,What follows is a review of issues associated with COPD and its treatment in the elderly patient. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | The introduction of microCT has made it possible to show that the terminal bronchioles are narrowed and destroyed before the onset of emphysematous destruction in COPD.,This report extends those observations to the cellular and molecular level in the centrilobular phenotype of emphysematous destruction in lungs donated by persons with very severe COPD (n = 4) treated by lung transplantation with unused donor lungs (n = 4) serving as controls.,These lung specimens provided companion samples to those previously examined by microCT (n = 61) that we examined using quantitative histology (n = 61) and gene expression profiling (n = 48).,The histological analysis showed that remodeling and destruction of the bronchiolar and alveolar tissue is associated with macrophage, CD4, CD8, and B cell infiltration with increased formation of tertiary lymphoid organs.,Moreover, gene set enrichment analysis showed that genes known to be expressed by natural killer (NK), lymphoid tissue inducer (LTi), and innate lymphoid cell 1 (ILC1) cells, but not ILC2 or ILC3 cells, were enriched in the expression profiles associated with CD4, CD8, and B cell infiltration.,Based on these findings, we postulate that the centrilobular phenotype of emphysematous destruction COPD is driven by a Th1 response activated by infiltrating ILC1, NK, and LTi cells. | 1 |
The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated.,Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown.,Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status.,Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals.,We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2O2 in cultured myoblasts and/or myotubes.,Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes.,Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022).,Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress.,Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles.,We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models. | Strength training and neuromuscular electrical stimulation (NMES) are effective training modalities for improving muscle function, exercise performance and health status in individuals with COPD.,The aim of the present study was to analyze the metabolic load of these training modalities at baseline, half-way, and at the end of an eight-week interdisciplinary pulmonary rehabilitation program in a subgroup of individuals with COPD of the DICES trial.,Of 24 individuals with COPD (FEV1: 34 ± 2% predicted, men: 58%, age: 66 (61-68) years), peak oxygen uptake (VO2), peak minute ventilation (VE), heart rate, oxygen saturation and symptom scores were assessed during HF-NMES (75 Hz), LF-NMES (15 Hz) and strength training at three moments during their pulmonary rehabilitation program.,Intervention-related peak VO2 did not change over time during HF-NMES, LF-NMES or strength training.,Intervention-related peak VE did not change over time during strength training or LF-NMES and increased slightly, but significantly over time during HF-NMES.,Peak VO2 and VE were significantly higher during strength training compared to HF-NMES or LF-NMES.,Oxygen saturation significantly decreased after the first measurements during HF-NMES and strength training group to baseline, while no significant changes in oxygen saturation were observed during the other measurements.,Heart rate significantly increased compared to baseline in all groups at all moments and was significantly higher after strength training compared to HF-NMES or LF-NMES.,Median end scores (points) for dyspnea, fatigue and muscle pain ranged from 1 to 3, from 0.5 to 2 and from 0 to 6 after HF-NMES, from 2 to 3, from 2 to 5 and from 0 to 9 after LF-NMES and from 2 to 5, from 1.5 to 4 and from 0 to 28 after strength training respectively.,To conclude, the metabolic load and symptom scores remain acceptable low over time with increasing training loads during HF-NMES, LF-NMES or strength training.,Trial registration:NTR2322 | 1 |
Some patients share characteristics of both COPD and asthma.,As yet, there is no gold standard to identify patients with the so-called asthma-COPD overlap syndrome (ACOS).,To describe the differences between ACOS patients and the remaining COPD patients, and to compare the clinical characteristics of patients diagnosed with ACOS by two different criteria: previous diagnosis of asthma before the age of 40 years; and the diagnostic criteria of the Spanish guidelines of COPD.,Multicenter, observational, cross-sectional study performed in 3,125 COPD patients recruited in primary care and specialized outpatient clinics.,Patients with COPD and a history of asthma before the age of 40 years were diagnosed with ACOS and compared to the remaining COPD patients.,Subsequently, ACOS patients were subdivided based on whether they fulfilled the Spanish guidelines of the COPD diagnostic criteria or not, and they were compared.,ACOS was diagnosed in 15.9% of the patients.,These patients had different basal characteristics compared to the remaining COPD patients, including a higher frequency of women and more exacerbations despite lower tobacco exposure and better lung function.,They were more likely to have features of asthma, such as a positive bronchodilator test, higher peripheral eosinophilia, and higher total immunoglobulin E.,Within the ACOS group, only one-third fulfilled the diagnostic criteria of the Spanish guidelines of COPD; these individuals were not significantly different from the remaining ACOS patients, except for having more exacerbations and poorer lung function.,ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs.,This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO).,This retrospective matched cohort study selected patients from Optum’s de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing).,Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting β2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date.,Outcomes included time-to-first (Kaplan-Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM).,Propensity score matching was used to adjust for potential confounders.,Each cohort included 3929 matched patients.,Kaplan-Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05).,UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p < 0.001; proportion with PDC ≥ 0.8: 22.0% vs 16.4%; p< 0.001) and significantly lower mean on-treatment COPD-related total medical costs ($867 vs $1095 PPPM; p = 0.028), driven by lower outpatient visit costs.,These findings provide valuable information for physicians considering UMEC/VI or TIO as initial maintenance therapy options for patients with COPD.,The online version contains supplementary material available at 10.1186/s12890-021-01612-5. | Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | 1 |
With increasing availability of different treatments for chronic obstructive pulmonary disease (COPD), we sought to understand patient preferences for COPD treatment in the UK, USA, and Germany using a discrete choice experiment (DCE).,Qualitative research identified six attributes associated with COPD maintenance treatments: ease of inhaler use, exacerbation frequency, frequency of inhaler use, number of different inhalers used, side effect frequency, and out-of-pocket costs.,A DCE using these attributes, with three levels each, was designed and tested through cognitive interviews and piloting.,It comprised 18 choice sets, selected using a D-efficient experimental design.,Demographics and disease history were collected and the final DCE survey was completed online by participants recruited from panels in the UK, USA and Germany.,Responses were analyzed using mixed logit models, with results expressed as odds ratios (ORs).,Overall, 450 participants (150 per country) completed the DCE; most (UK and Germany, 97.3%; USA, 98.0%) were included in the final analysis.,Based on relative attribute importance, avoidance of side effects was found to be most important (UK: OR 11.65; USA: OR 7.17; Germany: OR 11.45; all p<0.0001), followed by the likelihood of fewer exacerbations (UK: OR 2.22; USA: OR 1.63; Germany: OR 2.54; all p<0.0001) and increased ease of use (UK: OR 1.84; USA: OR 1.84; Germany: OR 1.60; all p<0.0001).,Number of inhalers, out-of-pocket costs, and frequency of inhaler use were found to be less important.,Preferences were relatively consistent across the three countries.,All participants required a reduction in exacerbations to accept more frequent inhaler use or use of more inhalers.,When selecting COPD treatment, individuals assigned the highest value to the avoidance of side effects, experiencing fewer exacerbations, and ease of inhaler use.,Ensuring that patients’ preferences are considered may encourage treatment compliance. | The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. | 1 |
The field of biomarker research has almost reached unmanageable proportions in chronic obstructive pulmonary disease (COPD).,The developments of new technology platforms have generated a huge information data base, both cross sectionally and increasingly, longitudinally.,The knowledge emerging provides an enormous potential for understanding the disease pathophysiology, for developing markers specific for long-term outcomes, and for developing new therapeutic strategies.,However, the excitement must be tempered with an understanding of the limitations of the data collection techniques, and of the variations in disease state, activity, impact, and progression.,Nevertheless, the most crucial aspect in interpreting the current literature is the recognition of the relatively superficial characterization of what is a complex group of pathological processes with a common end point of airflow limitation.,The current review explores some of these issues together with those areas where real progress appears to have been made, and provides caution on interpretation. | Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD.,The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.,EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers).,EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.,EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs.,7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03].,In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively).,No differences were observed among current smokers with different disease severity.,EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.,Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD.,The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies. | 1 |
Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD).,AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism.,However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema.,Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury.,To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM).,Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C.,AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence.,Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells.,Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice.,This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement.,Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs.,In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema. | Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema.,In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations.,Six unused donor lungs served as controls.,Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1).,The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate.,The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09).,The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1).,An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05).,TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05).,A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r2 = 0.8).,A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r2 = 0.99),Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease.,The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease.,Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types. | 1 |
Previous studies have demonstrated the potential beneficial effect of N-acetylcysteine (NAC) in chronic obstructive pulmonary disease (COPD).,However, the required dose and responder phenotype remain unclear.,The current study investigated the effect of high-dose NAC on airway geometry, inflammation, and oxidative stress in COPD patients.,Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy.,Twelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were randomized to receive NAC 1800 mg or placebo daily for 3 months and were then crossed over to the alternative treatment for a further 3 months.,Significant correlations were found between image-based resistance values and glutathione levels after treatment with NAC (P = 0.011) and glutathione peroxidase at baseline (P = 0.036).,Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC (P = 0.02), changes in glutathione peroxidase levels (P = 0.035), and reduction in lobar functional residual capacity levels (P = 0.00084).,In the limited set of responders to NAC therapy, the changes in airway resistance were in the same order as changes induced by budesonide/formoterol.,A combination of glutathione, glutathione peroxidase, and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy.,The findings of this small pilot study need to be confirmed in a larger pivotal trial. | Noninvasive ventilation (NIV) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients.,Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention.,In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV1 30.5 [±5.1] %pred, PaO2 65 [±6] mmHg, PaCO2 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV1 29.5 [±9.0] %pred, PaO2 59 [±13] mmHg, PaCO2 55.4 [±7.7] mmHg) for 6 months.,We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes.,In both groups there was a nonsignificant change in FEV1 (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg).,PaCO2 dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS).,Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients.,Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion.,There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO2.,Improved ventilation-perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases.,We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation-perfusion match and hence better blood gases and lung function.,Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation.,These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do.,Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment.,To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population. | 1 |
To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis of randomised controlled trials.,PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.,Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible.,Efficacy and safety outcomes of interest were also available.,Data were collected independently.,Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals.,Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).,21 trials (19 publications) were included.,Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS).,Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91).,Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy.,The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).,Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.,Prospero CRD42018077033. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in the United States.,Exacerbations- acute worsening of COPD symptoms-can be mild to severe in nature.,Increased healthcare resource use is common among patients with frequent exacerbations, and exacerbations are a major cause of the high 30-day hospital readmission rates associated with COPD.,This review provides a concise overview of the literature regarding the impact of COPD exacerbations on both the patient and the healthcare system, the recommendations for pharmacologic management of COPD, and the strategies employed to improve patient care and reduce hospitalizations and readmissions.,COPD exacerbations significantly impact patients’ health-related quality of life and disease progression; healthcare costs associated with severe exacerbation-related hospitalization range from $7,000 to $39,200.,Timely and appropriate maintenance pharmacotherapy, particularly dual bronchodilators for maximizing bronchodilation, can significantly reduce exacerbations in patients with COPD.,Additionally, multidisciplinary disease-management programs include pulmonary rehabilitation, follow-up appointments, aftercare, inhaler training, and patient education that can reduce hospitalizations and readmissions for patients with COPD.,Maximizing bronchodilation by the appropriate use of maintenance therapy, together with multidisciplinary disease-management and patient education programs, offers opportunities to reduce exacerbations, hospitalizations, and readmissions for patients with COPD. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function.,Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD).,Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study.,Mean annual decline in FEV1 % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status.,Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line).,AQP5 abundance and localization were assessed by immunoblots and confocal immunofluoresence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization.,Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers.,Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results.,In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid.,Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD.,A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress.,These results suggest that AQP5 may be an important candidate gene for COPD. | Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes.,In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies.,Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765.,One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD).,We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers).,We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10−35 and <10−8 respectively).,Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone.,Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10−6).,In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10−20) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968.,This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior.,This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue. | 1 |
The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined.,This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype.,A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited.,Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]).,The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions.,A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included.,In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations.,Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%).,Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006).,The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001).,Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001).,One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease.,The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) has significant systemic effects beyond the lungs amongst which muscle wasting is a prominent contributor to exercise limitation and an independent predictor of morbidity and mortality.,The molecular mechanisms leading to skeletal muscle dysfunction/wasting are not fully understood and are likely to be multi-factorial.,The need to develop therapeutic strategies aimed at improving skeletal muscle dysfunction/wasting requires a better understanding of the molecular mechanisms responsible for these abnormalities.,Microarrays are powerful tools that allow the investigation of the expression of thousands of genes, virtually the whole genome, simultaneously.,We aim at identifying genes and molecular pathways involved in skeletal muscle wasting in COPD.,We assessed and compared the vastus lateralis transcriptome of COPD patients with low fat free mass index (FFMI) as a surrogate of muscle mass (COPDL) (FEV1 30 ± 3.6%pred, FFMI 15 ± 0.2 Kg.m−2) with patients with COPD and normal FFMI (COPDN) (FEV1 44 ± 5.8%pred, FFMI 19 ± 0.5 Kg.m−2) and a group of age and sex matched healthy controls (C) (FEV1 95 ± 3.9%pred, FFMI 20 ± 0.8 Kg.m−2) using Agilent Human Whole Genome 4x44K microarrays.,The altered expression of several of these genes was confirmed by real time TaqMan PCR.,Protein levels of P21 were assessed by immunoblotting.,A subset of 42 genes was differentially expressed in COPDL in comparison to both COPDN and C (PFP < 0.05; −1.5 ≥ FC ≥ 1.5).,The altered expression of several of these genes was confirmed by real time TaqMan PCR and correlated with different functional and structural muscle parameters.,Five of these genes (CDKN1A, GADD45A, PMP22, BEX2, CGREF1, CYR61), were associated with cell cycle arrest and growth regulation and had been previously identified in studies relating muscle wasting and ageing.,Protein levels of CDKN1A, a recognized marker of premature ageing/cell cycle arrest, were also found to be increased in COPDL.,This study provides evidence of differentially expressed genes in peripheral muscle in COPD patients corresponding to relevant biological processes associated with skeletal muscle wasting and provides potential targets for future therapeutic interventions to prevent loss of muscle function and mass in COPD.,The online version of this article (doi:10.1186/s12931-014-0139-5) contains supplementary material, which is available to authorized users. | Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management.,Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease.,Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics.,To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management.,To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction.,An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people).,Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena.,(1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering.,The results indicate the high potential of a systems approach to address COPD heterogeneity.,Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD. | 1 |
Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide.,Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.,The objective of this study was to assess IL-1 α and β expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation.,Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1α and β.,Here, we demonstrate an underappreciated role for IL-1α expression in COPD.,While a strong correlation existed between IL-1α and β levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1α-dependent, and IL-1β- and caspase-1-independent in a murine model of cigarette smoke exposure.,As IL-1α was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1α+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation.,IL-1α/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.,This study provides compelling evidence that IL-1α is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1α/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD. | Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins.,We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) over one year and examined the relationships between these systemic markers in COPD.,Fifty-eight stable COPD patients completed a baseline and one-year visit.,Serum IL-6, plasma CRP, and plasma TNF-α were measured.,Repeatability was expressed by intraclass correlation coefficient (Ri) and the Bland-Altman method.,Pearson correlations were used to determine the relationships between the systemic markers at both visits.,There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001) between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α).,CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively).,There were no other significant associations between the systemic markers at either of the visits.,Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients.,We have also shown that a robust and repeatable association between IL-6 and CRP exists. | 1 |
Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Using the COPD Diagnostic Questionnaire (CDQ) as a selection tool for spirometry could potentially improve the efficiency and accuracy of chronic obstructive pulmonary disease (COPD) diagnosis in at-risk patients.,To identify an optimal single cut point for the CDQ that divides primary care patients into low or high likelihood of COPD, with the latter group undergoing spirometry.,Former or current smokers aged 40-85 years with no prior COPD diagnosis were invited to a case-finding appointment with the practice nurse at various general practices in Sydney, Australia.,The CDQ was collected and pre- and post-bronchodilator spirometry was performed.,Cases with complete CDQ data and spirometry meeting quality standards were analysed (1,054 out of 1,631 patients).,CDQ cut points were selected from a receiver operating characteristic (ROC) curve.,The area under the ROC curve was 0.713.,A cut point of 19.5 had the optimal combination of sensitivity (63%) and specificity (70%) with two-thirds below this cut point.,A cut point of 14.5 corresponded to a sensitivity of 91%, specificity of 35% and negative predictive value of 96%, and 31% of patients below this cut point.,The CDQ can be used to select patients at risk of COPD for spirometry using one cut point.,We consider two possible cut points.,The 19.5 cut point excludes a higher proportion of patients from undergoing spirometry with the trade-off of more false negatives.,The 14.5 cut point has a high sensitivity and negative predictive value, includes more potential COPD cases but has a higher rate of false positives. | To describe the item-selection and item-reduction for the Lung Function Questionnaire (LFQ), being developed to help clinicians identify patients appropriate for diagnostic evaluation for chronic obstructive pulmonary disease (COPD) using spirometry.,Item selection and reduction were based on information from 387 ≥40-year-old respondents to the third National Health and Nutrition Examination Survey who had self-reported chronic bronchitis.,Item reduction involved stepwise logistic regression.,The accuracy of the final subset of items for identifying individuals with airflow obstruction (forced expiratory volume in one second/forced vital capacity <0.70) versus those without it was assessed with receiver operating characteristic analysis.,Content and face validity were assessed using focus groups of primary care physicians (n = 16) and interviews with COPD patients (n = 16).,The model with all five items (age; smoking history; the presence of wheeze, dyspnea, and phlegm) compared with models with combinations of fewer items had the highest classification accuracy (area under the curve [AUC] = 0.720) with sensitivity and specificity of 73.2% and 58.2%, respectively.,The presence of three or more factors yielded the highest AUC, a result suggesting that three or more affirmative answers is the most appropriate criterion indicating presence of airflow obstruction.,The five-item LFQ retained sufficient accuracy, sensitivity, and specificity in identifying individuals with COPD for further validation testing. | 1 |
This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.,A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed.,Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment.,Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.,ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead.,Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period.,The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs.,0.53, p < 0.001).,Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs.,0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs.,0.12, p = 0.03).,Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators.,ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients’ characteristics. | COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited.,This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.,This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group.,The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.,Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25-75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).,According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group.,Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P<0.05).,Using logistic regression, exacerbation hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0, P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.,Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life.,Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays.,The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients.,We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations.,78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George’s Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test.,Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time.,Correlations between the CAT and other measurements were examined.,After 7 days’ therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001).,Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001).,The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05).,The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = -0.101, P > 0.05).,No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).,The CAT is associate with the changes of systemic inflammation following COPD exacerbations.,Moreover, the CAT is responsive to the treatments, similar to other measures such as SGRQ, mMRC dyspnea scale and pulmonary function.,Therefore, the CAT is a potentially useful instrument to assess the efficacy of treatments following COPD exacerbations. | Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) frequent exacerbators (FE) suffer increased morbidity and mortality compared to infrequent exacerbators (IE).,The association between the oral and sputum microbiota and exacerbation phenotype is not well defined.,The objective of this study was to determine key features that differentiate the oral and sputum microbiota of FEs from the microbiota of IEs during periods of clinical stability.,We recruited 11 FE and 11 IE who had not used antibiotics or systemic corticosteroids in the last 1 month.,Subjects provided oral wash and sputum samples, which underwent 16S V4 MiSeq sequencing and qPCR of 16S rRNA.,Data were analyzed using Dada2 and R.,FE and IE were similar in terms of age, FEV1 percent predicted (FEV1pp), pack-years of tobacco exposure, and St.,George’s Respiratory Questionnaire score.,16S copy numbers were significantly greater in sputum vs. oral wash (p = 0.01), but phenotype was not associated with copy number.,Shannon diversity was significantly greater in oral samples compared to sputum (p = 0.001), and IE samples were more diverse than FE samples (p < 0.001).,Sputum samples from FE had more Haemophilus and Moraxella compared to IE sputum samples, due to dominance of these COPD-associated taxa in three FE sputum samples.,Amplicon sequencing variant (ASV)-level analysis of sputum samples revealed one ASV (Actinomyces) was significantly more abundant in IE vs.,FE sputum (padj = 0.048, Wilcoxon rank-sum test), and this persisted after controlling for FEV1pp.,Principal coordinate analysis using Bray-Curtis distance with PERMANOVA analyses demonstrated clustering by anatomic site, phenotype, inhaled corticosteroid use, current tobacco use, COPD severity, and last professional dental cleaning.,FE have less diverse oral and sputum microbiota than IE.,Actinomyces was significantly more abundant in IE sputum than FE sputum.,The oral and sputum microbiota of COPD subjects cluster based on multiple clinical factors, including exacerbation phenotype.,Even during periods of clinical stability, the frequent exacerbator phenotype is associated with decreased alpha diversity, beta-diversity clustering, and changes in taxonomic abundance.,The online version of this article (10.1186/s12931-019-1080-4) contains supplementary material, which is available to authorized users. | Induced and spontaneous sputum are used to evaluate the airways microbiota.,Whether the sputum types can be used interchangeably in microbiota research is unknown.,Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation.,COPD patients from Bergen, Norway, were followed between 2006/2010, examined during the stable state and exacerbations. 30 patients delivered 36 sample pairs.,DNA was extracted by enzymatic and mechanical lysis methods.,The V3-V4 region of the 16S rRNA gene was PCR-amplified and prepared for paired-end sequencing.,Illumina Miseq System was used for sequencing, and Quantitative Insights Into Microbial Ecology (QIIME) and Stata were used for bioinformatics and statistical analyses.,Approximately 4 million sequences were sorted into 1004 different OTUs and further assigned to 106 different taxa.,Pair-wise comparison of both taxonomic composition and beta-diversity revealed significant differences in one or both parameters in 1/3 of sample pairs.,Alpha-diversity did not differ.,Comparing abundances for each taxa identified, showed statistically significant differences between the mean abundances in induced versus spontaneous samples for 15 taxa when disease state was considered.,This included potential pathogens like Haemophilus and Moraxella.,When studying microbiota in sputum samples one should take into consideration how samples are collected and avoid the usage of both induced and spontaneous sputum in the same study. | 1 |
Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques.,Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique.,Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known.,To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques.,A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database.,Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”.,COPD-related events were recorded during an outcome year of follow-up.,The primary outcome measure was an incidence rate ratio (IRR) comparing the rate of exacerbations between study cohorts.,A secondary outcome compared average daily use of short-acting beta agonist (SABA).,The final study sample contained 8,225 patients in each cohort (mean age 67 [SD, 10], 57% males, 37% current smokers).,Patients in the similar-devices cohort had a lower rate of exacerbations compared with those in the mixed-devices cohort (adjusted IRR 0.82, 95% confidence interval [CI] 0.80-0.84) and were less likely to be in a higher-dose SABA group (adjusted proportional odds ratio 0.54, 95% CI 0.51-0.57).,COPD patients who were prescribed one or more additional inhaler devices requiring similar inhalation techniques to their previous device(s) showed better outcomes than those who were prescribed devices requiring different techniques. | The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are episodes of symptom worsening which have significant adverse consequences for patients.,Exacerbations are highly heterogeneous events associated with increased airway and systemic inflammation and physiological changes.,The frequency of exacerbations is associated with accelerated lung function decline, quality of life impairment and increased mortality.,They are triggered predominantly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,A proportion of patients appear to be more susceptible to exacerbations, with poorer quality of life and more aggressive disease progression than those who have infrequent exacerbations.,Exacerbations also contribute significantly to healthcare expenditure.,Prevention and mitigation of exacerbations are therefore key goals of COPD management. | COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | 1 |
Exacerbations are important outcomes in COPD both from a clinical and an economic perspective.,Most studies investigating predictors of exacerbations were performed in COPD patients participating in pharmacological clinical trials who usually have moderate to severe airflow obstruction.,This study was aimed to investigate whether predictors of COPD exacerbations depend on the COPD population studied.,A network of COPD health economic modelers used data from five COPD data sources - two population-based studies (COPDGene® and The Obstructive Lung Disease in Norrbotten), one primary care study (RECODE), and two studies in secondary care (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoint and UPLIFT) - to estimate and validate several prediction models for total and severe exacerbations (= hospitalization).,The models differed in terms of predictors (depending on availability) and type of model.,FEV1% predicted and previous exacerbations were significant predictors of total exacerbations in all five data sources.,Disease-specific quality of life and gender were predictors in four out of four and three out of five data sources, respectively.,Age was significant only in the two studies including secondary care patients.,Other significant predictors of total exacerbations available in one database were: presence of cough and wheeze, pack-years, 6-min walking distance, inhaled corticosteroid use, and oxygen saturation.,Predictors of severe exacerbations were in general the same as for total exacerbations, but in addition low body mass index, cardiovascular disease, and emphysema were significant predictors of hospitalization for an exacerbation in secondary care patients.,FEV1% predicted, previous exacerbations, and disease-specific quality of life were predictors of exacerbations in patients regardless of their COPD severity, while age, low body mass index, cardiovascular disease, and emphysema seem to be predictors in secondary care patients only. | The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | 1 |
There is an ongoing demand for easily accessible biomarkers that reflect the physiological and pathophysiological mechanisms of COPD.,To test if an exercise challenge could help to identify clinically relevant metabolic biomarkers in COPD.,We performed two constant-load exercise challenges separated by 4 weeks including smokers with COPD (n=23/19) and sex- and age-matched healthy smokers (n=23/20).,Two hours after a standardized meal venous blood samples were obtained before, 5 mins after the start, at the end of submaximal exercise, and following a recovery of 20 mins.,Data analysis was performed using mixed- effects model, with the metabolite level as a function of disease, time point and interaction terms and using each individual's resting level as reference.,Exercise duration was longer in healthy smokers but lactate levels were comparable between groups at all four time points.,Glucose levels were increased in COPD.,Glutamine was lower, while glutamate and arginine were higher in COPD.,Branched-chain amino acids showed a stronger decline during exercise in healthy smokers.,Carnitine and the acyl-carnitines C16 and C18:1 were increased in COPD.,These metabolite levels and changes were reproducible in the second challenge.,Higher serum glucose, evidence for impaired utilization of amino acids during exercise and a shift of energy metabolism to enhanced consumption of lipids could be early signs for a developing metabolic syndrome in COPD.,In COPD patients, deviations of energy and nitrogen metabolism are amplified by an exercise challenge. | Glucocorticoid (GC) resistance is a major barrier in COPD treatment.,We have shown increased expression of the drug efflux pump, Pgp1 in cytotoxic/pro-inflammatory lymphocytes in COPD.,Loss of lymphocyte co-stimulatory molecule CD28 (lymphocyte senescence) was associated with a further increase in their pro-inflammatory/cytotoxic potential and resistance to GC.,We hypothesized that lymphocyte senescence and increased Pgp1 are also associated with down-regulation of the GC receptor (GCR).,Blood was collected from 10 COPD and 10 healthy aged-matched controls.,Flow cytometry was applied to assess intracellular pro-inflammatory cytokines, CD28, Pgp1, GCR, steroid binding and relative cytoplasm/nuclear GCR by CD28+ and CD28null T, NKT-like cells.,GCR localization was confirmed by fluorescent microscopy.,COPD was associated with increased numbers of CD28nullCD8+ T and NKT-like cells.,Loss of CD28 was associated with an increased percentage of T and NKT-like cells producing IFNγ or TNFα and associated with a loss of GCR and Dex-Fluor staining but unchanged Pgp1.,There was a significant loss of GCR in CD8 + CD28null compared with CD8 + CD28+ T and NKT-like cells from both COPD and controls (eg, mean ± SEM 8 ± 3% GCR + CD8 + CD28null T-cells vs 49 ± 5% GCR + CD8 + CD28+ T-cells in COPD).,There was a significant negative correlation between GCR expression and IFNγ and TNFα production by T and NKT-like cells(eg, COPD: T-cell IFNγ R = −.615; ) and with FEV1 in COPD (R = −.777).,COPD is associated with loss of GCR in senescent CD28null and NKT-like cells suggesting alternative treatment options to GC are required to inhibit these pro-inflammatory/cytotoxic cells. | 1 |
The prevalence of disabilities is rising steadily, reflecting an aging population and an increasing burden of chronic conditions affecting quality of life.,There are scant national data on the prevalence of disability among individuals with chronic obstructive pulmonary disease (COPD).,The main objective was to estimate the prevalence of common disabilities among US-based individuals diagnosed with COPD.,Data from the BRFSS, a national telephone survey examining health-related behaviors in 2016-2017 were analyzed.,The study population consisted of individuals with self-reported COPD (N = 38352 in 2016 and N = 35423 in 2017).,The prevalence of disabilities in hearing, vision, cognition, mobility, and independent living were obtained and adjusted with sampling weights.,Healthcare access measures were described by type of disability.,Mobility disability had the highest prevalence of 45.9 (44.8-47.0) % in 2016 and 48.4 (47.3-49.5) % in 2017 among respondents with COPD.,The prevalence of disabilities was highest among those 45-64 years old, except for hearing and cognition.,Hearing disabilities were most prevalent among males with COPD while cognitive and mobility disabilities were most prevalent among females with COPD.,While differences in the prevalence of disabilities were observed, access to health care was similar by disability type and age group among respondents.,Contrary to expectation, the highest prevalence of disabilities was found not to be among those 65 years old and above.,Further research is needed to explain this age-specific shift in the burden of disability, as long-term care planning and prevention support systems should be informed by the demographical patterns of disabilities among individuals with COPD. | This report updates surveillance results for COPD in the United States.,For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed.,In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD.,From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019).,In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD.,From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001).,In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD.,Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033).,There were 133,575 deaths (63.1 per 100,000) from COPD in 2010.,The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163).,Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001).,Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed.,Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research.,The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls.,Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups.,Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO.,Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values.,To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile.,While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters.,Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r = −0.52, p = 0.005 and r = −0.61, p = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r = −0.25, p = 0.47 and r = −0.15, p = 0.96, respectively), and may be driving overall associations in the general cohort.,In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO.,These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD. | 1 |
The fractal dimension characterizing the cumulative size distribution of low attenuation area (LAA) clusters, identified with a fixed threshold such as − 950 Hounsfield Units (HU), on computed tomography (CT) sensitively detects parenchymal destruction in chronic obstructive pulmonary disease (COPD) even when the percent LAA (LAA%), a standard emphysema index, is unchanged.,This study examines whether the cumulative size distribution of LAA clusters, defined with thresholds of the 15th, 25th, and 35th percentiles of a CT density histogram instead of the fixed-threshold of − 950 HU, exhibits a fractal property and whether its fractal dimension (D’15, D’25, and D’35, respectively) provides additional structural information in emphysematous lungs that is difficult to detect with the conventional − 950-HU-based fractal dimension (D950).,Chest inspiratory CT scans and pulmonary functions were cross-sectionally examined in 170 COPD subjects.,A proxy for the inspiration level at CT scan was obtained by dividing CT-measured total lung volume (CT-TLV) by physiologically measured total lung capacity.,Moreover, long-term (> 5 years) changes in D950 and the new fractal dimensions were longitudinally evaluated in 17 current and 42 former smokers with COPD.,D950, but not D’15, D’25, or D’35 was weakly correlated with the proxy for the inspiration.,D950, D’25, and D’35 but not D’15 correlated with LAA% and diffusion capacity.,In the long-term longitudinal study, LAA% was increased and D950 and D’35 were decreased in both current and former smokers, while D’25 was decreased only in current smokers and D’15 was not changed in either group.,The longitudinal changes in D’25 but not those in LAA%, D950, D’15, and D’35 were greater in current smokers than in former smokers.,This greater change in D’25 in current smokers was confirmed after adjusting the change in CT-TLV and the baseline D’25.,D’25 reflects diffusion capacity in emphysematous lungs and is robust against inspiration levels during CT scans.,This new fractal dimension might provide additional structural information that is difficult to detect with the conventional D950 and LAA% and allow for more sensitive evaluation of emphysema progression over time.,The online version of this article (10.1186/s12890-018-0714-5) contains supplementary material, which is available to authorized users. | The progression of chronic obstructive pulmonary disease (COPD) considerably varies among patients.,Those with emphysema identified by quantitative computed tomography (CT) are associated with the rapid progression assessed by forced expiratory volume in one second (FEV1).,However, whether the rate of the decline in lung function is independently affected by the regional distribution or the severity of emphysema in the whole lung is unclear.,We followed up 131 male patients with COPD for a median of 3.7 years.,We measured wall area percent (WA%) in right apical segmental bronchus, total lung volume, percent low attenuation volume (LAV%), and the standard deviation (SD) of LAV% values from CT images of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal emphysema heterogeneity.,Annual changes in FEV1 were then determined using a random coefficient model and relative contribution of baseline clinical parameters, pulmonary function, and CT indexes including LAV%, SD-LAV, and WA% to annual changes in FEV1 were examined.,The mean (SD) annual change in FEV1 was −44.4 (10.8) mL.,Multivariate random coefficient model showed that higher baseline FEV1, higher LAV%, current smoking, and lower SD-LAV independently contributed to an excessive decline in FEV1, whereas ratio of residual volume to total lung capacity, ratio of diffusing capacity to alveolar ventilation, and WA% did not, after adjusting for age, height, weight, and ratio of CT-measured total lung volume to physiologically-measured total lung capacity.,A more homogeneous distribution of emphysema contributed to an accelerated decline in FEV1 independently of baseline pulmonary function, whole-lung emphysema severity, and smoking status.,In addition to whole-lung analysis of emphysema, CT assessment of the cranial-caudal distribution of emphysema might be useful for predicting rapid, progressive disease and for developing a targeted strategy with which to prevent disease progression. | 1 |
Respiratory inhalers, which directly deliver medication to the airway, are important for controlling symptoms and preventing exacerbations of chronic obstructive pulmonary disease (COPD).,The inhaler misuse rate of patients with COPD in Taiwan is unclear.,In this study, the inhaler techniques and patient characteristics associated with incorrect inhaler techniques among patients with COPD were evaluated.,This cross-sectional study enrolled 298 patients with COPD (mean age 72.10 years) who used at least one inhaler device.,The following five types of inhalers were included: metered-dose inhaler (MDI) with spacer, Diskus®, Turbuhaler®, Respimat®, and Breezhaler®.,The inhaler technique was evaluated step by step.,Misuse of an individual inhaler was defined as an error in at least one step.,The sociodemographic characteristics, vision, hearing ability, type and number of inhalers, and inhaler-related knowledge of these patients were recorded.,The misuse rates of the five types of inhalers ranged from 65.00% to 87.89%.,The Respimat inhaler was the most likely to be assembled incorrectly.,The steps that were most commonly performed incorrectly were “breathing out fully” and “holding breath”.,In the logistic regression analysis, poor hearing was related to misuse of the MDI with spacer (adjusted odds ratio [aOR] 9.85; 95% CI 1.40-69.30); the number of acute exacerbations was related to misuse of Breezhaler (aOR 4.07; 95% CI 1.50-11.08).,Incorrect inhaler-related knowledge was significantly associated with misuse in handling the MDI with spacer (aOR 9.58; 95% CI 2.14-42.80), Respimat (aOR 5.14; 95% CI 2.07-12.76), and Breezhaler (aOR 6.98; 95% CI 1.95-25.08).,The misuse rates were high for all five types of inhaler.,Poor hearing and the number of acute exacerbations were device-specific factors related to the misuse of inhalers.,Inhaler-related knowledge was significantly associated with misuse, emphasizing the importance of inhaler education. | Tiotropium (Spiriva) is an inhaled muscarinic antagonist for patients with chronic obstructive pulmonary disease (COPD), and is available in two forms: the HandiHaler and the Respimat inhaler.,The aim of this study was to investigate the handling of and preference for each device immediately after switching from the HandiHaler to the Respimat and 2-3 years after the switch.,The study comprised two surveys.,A questionnaire was first administered to 57 patients with COPD (male:female 52:5, mean age 73.6±7.1 years) 8 weeks after switching from the HandiHaler (18 μg) to the Respimat (5 μg).,A second similar but simplified questionnaire was administered to 39 of these patients who continued to use the Respimat and were available for follow-up after more than 2 years.,Pulmonary function was also measured during each period.,In the first survey, 17.5% of patients preferred the HandiHaler, and 45.6% preferred the Respimat.,There were no significant changes in pulmonary function or in the incidence of adverse events after the switch.,In the second survey, performed 2-3 years later, the self-assessed handling of the Respimat had significantly improved, and the number of patients who preferred the Respimat had increased to 79.5%.,The efficacy of the Respimat was similar to that of the HandiHaler.,This was clear immediately after the switch, even in elderly patients with COPD who were long-term users of the HandiHaler.,The preference for the Respimat increased with continued use. | 1 |
Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | The objective of this study was to measure health-related quality of life (HRQL) in outpatients with chronic obstructive pulmonary disease (COPD) and to assess differences in HRQL according to age, gender, and severity of COPD.,A total of 9405 patients (79% men, mean age 68 years) participated in a cross-sectional study.,HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12).,Severity of COPD was graded into three levels according to forced expiratory volume in one second value.,COPD severity was mild in 33.8% of cases, moderate in 49.3% and severe in 16.8%.,The mean physical component summary (PCS-12) and mental component summary (MCS-12) scores were 36.8 ± 10.4 and 47.2 ± 11.2, respectively.,General health and physical functioning domains were those with the lowest scores.,The mean MCS-12 scores were significantly higher in men (47.9 ± 10.9) than in women (44.1 ± 11.8) (P < 0.001).,Patients older than 60 years rated HRQL worse than patients aged 40-59 years.,There were statistically significant differences according to severity of disease in the mean scores of all domains of the PCS-12 and MCS-12 scales.,The present findings show the influence of female gender, older age and moderate-to-severe of airflow limitation on HRQL in outpatients with COPD attended in daily practice. | 1 |
Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD).,Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology.,We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.,Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined.,Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD.,Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.,Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression.,Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR.,ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased.,Healthy smokers were intermediate between healthy nonsmokers and patients with COPD.,Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects.,MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release.,Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation.,Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD. | Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression.,However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established.,Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema.,We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.,Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity.,Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice.,Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice.,Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression.,Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS.,Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated.,Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.,Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression.,Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation. | 1 |
COPD is often associated with various comorbidities that may influence its outcomes.,Pneumonia, cardiovascular disease (CVD), and cancer are the major causes of death in COPD patients.,The objective of this study is to investigate the influence of comorbidities on COPD by using the Taiwan National Health Insurance database.,We retrospectively analyzed the database in 2006 of one million sampling cohort.,Newly diagnosed patients with COPD with a controlled cohort that was matched by age, sex, and Charlson comorbidity index (CCI) were included for analysis.,In total, 1,491 patients with COPD were included for analysis (61.8% male).,Patients with COPD had higher incidences of pneumonia (25.7% vs 10.4%; P<0.0001), CVD (15.1% vs 10.5%; P<0.0001), and mortality rate (26.6% vs 15.8%; P<0.001) compared with the control group in the 4-year follow-up.,In patients with COPD, CCI ≥3 have a higher incidence of pneumonia (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.23-2.09; P<0.0001), CVD (HR 1.73; 95% CI 1.24-2.41; P=0.001), and mortality (HR 1.12; 95% CI 1.12-1.83; P=0.004).,Among the major comorbidities of COPD, hyperlipidemia was associated with decreased incidence of pneumonia (HR 0.68; 95% CI 0.5-0.93; P=0.016) and mortality (HR 0.64; 95% CI 0.46-0.90; P=0.009), but was not associated with increased risk of CVD (HR 1.10; 95% CI 0.78-1.55; P=0.588).,Our results demonstrate that COPD is associated with increased incidence of pneumonia, CVD, and mortality.,In patients with COPD, higher CCI is associated with increased incidence of pneumonia, CVD, and mortality.,However, COPD with hyperlipidemia is associated with decreased incidence of pneumonia and mortality. | COPD is a long-term condition associated with considerable disability with a clinical course characterized by episodes of worsening respiratory signs and symptoms associated with exacerbations.,Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal conditions in the general population and has emerged as a comorbidity of COPD.,GERD may be diagnosed by both symptomatic approaches (including both typical and atypical symptoms) and objective measurements.,Based on a mix of diagnostic approaches, the prevalence of GERD in COPD ranges from 17% to 78%.,Although GERD is usually confined to the lower esophagus in some individuals, it may be associated with pulmonary microaspiration of gastric contents.,Possible mechanisms that may contribute to GERD in COPD originate from gastroesophageal dysfunction, including altered pressure in the lower esophageal sphincter (which normally protect against GERD) and changes in esophageal motility.,Proposed respiratory contributions to the development of GERD include respiratory medications that may alter esophageal sphincter tone and changes in respiratory mechanics, with increased lung hyperinflation compromising the antireflux barrier.,Although the specific cause and effect relationship between GERD and COPD has not been fully elucidated, GERD may influence lung disease severity and has been identified as a significant predictor of acute exacerbations of COPD.,Further clinical effects could include a poorer health-related quality of life and an increased cost in health care, although these factors require further clarification.,There are both medical and surgical options available for the treatment of GERD in COPD and while extensive studies in this population have not been undertaken, this comorbidity may be amenable to treatment. | 1 |
Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations.,However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available.,Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.,A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed.,The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate.,Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible.,The usefulness of formally scheduled regular follow-up visits was assessed.,Two different databases (resources and clinical database) were constructed.,Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes.,Exacerbations and survival served as the main endpoints.,This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting.,Results from such audits can guide health information systems development and implementation in real-world settings. | To analyze the accuracy of diagnosis in a population receiving inhaled therapies due to respiratory diseases in a primary care setting.,Noninterventional, multicenter, cross-sectional, observational epidemiologic study methodology.,A total of 9752 subjects were evaluated.,Of these, 4188 (42.9%) patients were diagnosed with asthma, 4175 (42.8%) with chronic obstructive pulmonary disease (COPD), and 1389 had a diagnosis of disease of unknown origin.,Of those over the age of 40 years, 4079 (50.9%) had COPD and 2877 (35.9%) had asthma.,Sixty percent of the subjects were men, and the proportion of men was higher in patients with COPD (83.2%) than in the group with asthma (39.8%, P < 0.0001).,Of subjects with COPD, 17.3% had mild, 55.3% had moderate, 24.1% had severe, and 3.2% had very severe disease.,With regard to the level of severity of asthma, 34.9% of subjects had intermittent, 34.6% had mild persistent, 27.1% had moderate persistent, and 3.5% had severe persistent disease.,Only 13.9% of patients in the COPD group had all the characteristics of COPD based on the Global Initiative for Chronic Obstructive Lung Disease criteria and an absence of the characteristics of asthma.,The majority of patients receiving inhaled therapy in primary care did not have an accurate diagnosis according to current international guidelines for COPD and asthma.,More initiatives for improving diagnostic accuracy in respiratory diseases must be implemented in primary care. | 1 |
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes.,Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.,Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time.,Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time.,Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile.,Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.,Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL).,Delivered dose was 88% of the nominal dose for both formulation strengths.,The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL.,Nebulization times were 1-2.5 minutes with no apparent increasing trend with use over a 60-day period.,The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1-0.2 μm) after 60-day simulated use.,Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.,Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition.,The unit dose vial mitigates medication misuse and ensures dose uniformity.,Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD. | Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy.,Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices.,The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs.,This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy.,In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI.,In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases.,Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation.,The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management.,However, the evidence on the benefit of self-management in COPD is conflicting.,Whether this could be due to other unmet needs of patients have not been investigated.,Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD.,We conducted a qualitative study with doctors and patients in Malaysia.,We used convenience sampling to recruit patients until data saturation.,Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide.,The interviews were audio-recorded, transcribed verbatim and checked by the interviewers.,Data were analysed using a thematic approach.,The themes were similar for both the patients and doctors.,Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management.,Knowledge about COPD was generally poor.,Patients were not familiar with the term chronic obstructive pulmonary disease or COPD.,The word ‘asthma’ was used synonymously with COPD by both patients and doctors.,Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness.,Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care.,In conclusion, our study showed that knowledge of COPD is generally poor.,There was mislabelling of COPD as asthma by both patients and physicians.,This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD.,The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation.,Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit. | This study aims to (i) evaluate the association between anxiety and depressive symptoms and health-related quality of life (HRQoL); and (ii) identify the effect modifiers of this relationship in patients with chronic obstructive pulmonary disease (COPD).,A total of 337 clinically stable COPD patients answered the St.,George's Respiratory Questionnaire (SGRQ) (assessing HRQoL) and the Hospital Anxiety and Depression Scale (HADS).,Socio-demographic information, lung function, and other clinical data were collected.,Most patients (93%) were male; they had a mean (SD) age of 68 (9) years and mild to very severe COPD (post-bronchodilator FEV1 52 (16)% predicted).,Multivariate analyses showed that anxiety, depression, or both conditions were associated with poor HRQoL (for all SGRQ domains).,The association between anxiety and total HRQoL score was 6.7 points higher (indicating a worse HRQoL) in current workers than in retired individuals.,Estimates for patients with "both anxiety and depression" were 5.8 points lower in stage I-II than in stage III-IV COPD, and 10.2 points higher in patients with other comorbidities than in those with only COPD.,This study shows a significant association between anxiety, depression, or both conditions and impaired HRQoL.,Clinically relevant factors affecting the magnitude of this association include work status, COPD severity, and the presence of comorbidities. | 1 |
Several studies suggest that there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases.,On the other hand, increased sympathetic tone has been described in several respiratory diseases.,Our objective was to determine whether hypertension mediated by sympathetic overactivity is a mechanism that explains the association between COPD and cardiovascular diseases.,Prospective nested case-control observational study; 67 COPD patients were matched 1:1 by sex and age to controls with smoking history. 24 hour-blood pressure monitoring, urinary catecholamines and their metabolites measurement, echocardiography, carotid ultrasound examination, nocturnal oximetry and retinography were performed.,classic cardiovascular risk factors and comorbidities were similarly distributed between cases and controls.,No significant differences for blood pressure variables (difference for mean systolic blood pressure: -0·13 mmHg; 95% CI: -4·48,4·20; p = 0·94; similar results for all blood presssure variables) or catecholamines values were found between both groups.,There was a tendency for lower left ventricle ejection fraction in the COPD cases, that approached statistical significance (64·8 ± 7·4 vs 67·1 ± 6·2, p = 0·05).,There were no differences in the retinal arteriovenous ratio, the carotid intima-media thickness, or the number of carotid plaques, between cases and controls.,Fibrinogen values were higher in the COPD group (378·4 ± 69·6 vs 352·2 ± 45·6 mg/dL, p = 0·01) and mean nocturnal oxygen saturation values were lower for COPD patients (89·0 ± 4·07 vs 92·3 ± 2·2%, p < 0·0001).,Hypertension induced by sympathetic overactivity does not seem to be a mechanism that could explain the association between COPD and cardiovascular disease. | Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | 1 |
Guidelines are critical for facilitating cost-effective COPD care.,Development and implementation in low-and middle-income countries (LMICs) is challenging.,To guide future strategy, an overview of current global COPD guidelines is required.,We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation.,Scoping review of national COPD management guidelines.,We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards.,LMICs guidelines were compared with those from high-income countries (HICs).,Of the 61 national COPD guidelines identified, 30 were from LMICs.,Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines.,Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities.,More than 90% of all guidelines included smoking cessation advice.,Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%).,LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05).,LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05).,Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation.,Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated.,Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources. | Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.,To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.,A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted.,COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected.,Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis.,All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.,Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities.,Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations.,CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations.,All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001).,CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.,This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities.,Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities. | 1 |
Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | Alveolar apoptosis is increased in the emphysematous lung.,However, mechanisms involved are not fully understood.,Recently, we demonstrated that levels of TRAIL receptor 1 and 2, levels of p53, and Bax/Bcl-xL ratio were elevated in the lung of subjects with emphysema, despite smoking cessation.,Thus, we postulate that due to chronic pulmonary oxidative stress, the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis.,A549 cells were exposed to rTRAIL, cigarette smoke extract, and/or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment.,In addition, freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours.,Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates.,Both cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis.,Moreover, following exposure to rTRAIL, caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects.,Alveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress.,This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation. | 1 |
Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens.,This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management.,Both adult-onset asthma and COPD are complex diseases arising from gene-environment interactions.,Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma.,While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD.,Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness.,In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes).,Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation.,The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly.,Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy.,Each of these is associated with error due to overlap and convergence of clinical characteristics.,The management of chronic stable asthma and COPD is similarly convergent.,New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and risk factors.,Short-acting beta-agonists provide effective symptom relief in airway diseases.,Inhalers combining a long-acting beta-agonist and corticosteroid are now widely used for both asthma and COPD.,Written action plans are a cornerstone of asthma management although evidence for self-management in COPD is less compelling.,The current management of chronic asthma in adults is based on achieving and maintaining control through step-up and step-down approaches, but further trials of back-titration in COPD are required before a similar approach can be endorsed.,Long-acting inhaled anticholinergic medications are particularly useful in COPD.,Other distinctive features of management include pulmonary rehabilitation, home oxygen, and end of life care. | Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology.,Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome.,We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype.,We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study.,PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity.,PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location.,PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques. | 1 |
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