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A low body mass index (BMI) is a poor prognostic marker of acute exacerbations and mortality in patients with COPD.,However, the impact of overweight and obesity on COPD-related outcomes is uncertain.,The aim of this study was to examine whether a high BMI is associated with the frequent exacerbator phenotype (≥2/year) in Taiwanese patients with COPD.,Data were obtained from the Taiwan Obstructive Lung Disease study, a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals in Taiwan.,Multivariate logistic regression models were used to explore the association between BMI and other factors with the frequency of COPD exacerbations in these patients.,Among the whole study cohort (n=1,096), 735 (67.1%) had no exacerbations and 148 (13.5%) were frequent exacerbators in the previous year.,The BMI values of the patients with 0, 1, and ≥2 exacerbations were 23.6, 23.5, and 22.6 kg/m2, respectively.,In all, 256 (23.4%) and 196 (17.9%) patients were overweight (27 kg/m2 > BMI ≥24 kg/m2) and obese (BMI ≥27 kg/m2), respectively.,Even after adjusting for multiple factors, overweight and obesity were associated with the frequency of exacerbations (odds ratio [95% confidence interval] 0.49 [0.28-0.87, P=0.015] and 0.49 [0.26-0.94, P=0.033], respectively).,Our results suggest that overweight and obesity are associated with a lower frequency of COPD exacerbations in Taiwan. | Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities.,The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities.,Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2-L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT.,A dose-response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV1] decline) was addressed with the Cochran-Armitage trend test.,Regression models were used to investigate possible relationships between CT body composition indices and comorbidities.,From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2-L3 to assess body composition.,CSA of VAT was increased (P<0.0001) and MT attenuation was reduced (indicating more muscle fat accumulation) in patients with COPD (P<0.002).,Progressively increasing CSA of VAT was not associated with adverse clinical outcomes.,The probability of exhibiting low 6MWD and accelerated FEV1 decline increased with progressively decreasing MT attenuation and CSA of MT.,In COPD, the probability of having diabetes (P=0.024) and gastroesophageal reflux (P=0.0048) at baseline increased in parallel with VAT accumulation, while the predicted MT attenuation increased the probability of cardiovascular comorbidities (P=0.042).,Body composition parameters did not correlate with coronary artery scores or with survival.,Ectopic fat accumulation is increased in COPD, and this was associated with relevant clinical outcomes and comorbidities. | 1 |
To assess whether hypercapnia may predict the prognosis in chronic obstructive pulmonary disease (COPD).,Prospective cohort study comparing the survival of patients with COPD and normocapnia to those with chronic hypercapnia.,Patients with consecutive COPD were enrolled between 1 May 1993 and 31 October 2006 at two medical centres.,Follow-up was censored on 31 October 2011.,A total of 275 patients with stable COPD and aged 40-85 years were enrolled.,Diagnosis of hypercapnia was confirmed by blood gas analysis.,Patients with near-terminal illness or comorbidities that affect PaCO2 (obstructive sleep apnoea, obesity-related hypoventilation, or neuromuscular disease) were excluded.,The outcome of 98 patients with normocapnia and 177 with chronic hypercapnia was analysed.,Overall survival.,Median survival was longer in patients with normocapnia than in those with hypercapnia (6.5 vs 5.0 years, p=0.016).,Multivariate COX regression analysis indicated that age (HR=1.043, 95% CI 1.012 to 1.076), Charlson Index, which is a measure of comorbidity (HR=1.172, 95% CI 1.067 to 1.288), use of medication (HR=0.565, 95% CI 0.379 to 0.842), body mass index (BMI) (HR=0.922, 95% CI 0.883 to 0.963), PaCO2 (HR=1.026, 95% CI 1.011 to 1.042), Cor pulmonale (HR=2.164, 95% CI 1.557 to 3.006), non-invasive positive-pressure ventilation (NPPV) (HR=0.615, 95% CI 0.429 to 0.881) and per cent of forced expiratory volume in 1 s (FEV1%) (HR=0.979, 95% CI 0.967 to 0.991), were independent risk factors for mortality.,Increased age, Charlson Index, chronic hypercapnia and Cor pulmonale, and decreased FEV1%, use of medication, BMI and NPPV, were associated with a poor prognosis in patients with COPD. | The use of noninvasive intermittent positive pressure ventilation (NIPPV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure remains controversial as long-term data are almost lacking.,The aim was to compare the outcome of 2-year home-based nocturnal NIPPV in addition to rehabilitation (NIPPV + PR) with rehabilitation alone (PR) in COPD patients with chronic hypercapnic respiratory failure.,Sixty-six patients could be analyzed for the two-year home-based follow-up period.,Differences in change between the NIPPV + PR and PR group were assessed by a linear mixed effects model with a random effect on the intercept, and adjustment for baseline values.,The primary outcome was health-related quality of life (HRQoL); secondary outcomes were mood state, dyspnea, gas exchange, functional status, pulmonary function, and exacerbation frequency.,Although the addition of NIPPV did not significantly improve the Chronic Respiratory Questionnaire compared to rehabilitation alone (mean difference in change between groups -1.3 points (95% CI: -9.7 to 7.4)), the addition of NIPPV did improve HRQoL assessed with the Maugeri Respiratory Failure questionnaire (-13.4% (-22.7 to -4.2; p = 0.005)), mood state (Hospital Anxiety and Depression scale -4.0 points (-7.8 to 0.0; p = 0.05)), dyspnea (Medical Research Council -0.4 points (-0.8 to -0.0; p = 0.05)), daytime arterial blood gases (PaCO2 -0.4 kPa (-0.8 to -0.2; p = 0.01); PaO2 0.8 kPa (0.0 to 1.5; p = 0.03)), 6-minute walking distance (77.3 m (46.4 to 108.0; p < 0.001)), Groningen Activity and Restriction scale (-3.8 points (-7.4 to -0.4; p = 0.03)), and forced expiratory volume in 1 second (115 ml (19 to 211; p = 0.019)).,Exacerbation frequency was not changed.,The addition of NIPPV to pulmonary rehabilitation for 2 years in severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL, mood, dyspnea, gas exchange, exercise tolerance and lung function decline.,The benefits increase further with time.,ClinicalTrials.Gov (ID NCT00135538). | 1 |
Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials. | Tele monitoring (TM) of patients with chronic obstructive pulmonary disease (COPD) has gained much interest, but studies have produced conflicting results.,Our aim was to investigate the effect of TM with the option of video consultations on exacerbations and hospital admissions in patients with severe COPD.,Patients with severe COPD at high risk of exacerbations were eligible for the study.,Of 560 eligible patients identified, 279 (50%) declined to participate.,The remaining patients were equally randomized to either TM (n=141) or usual care (n=140) for the 6-month study period.,TM comprised recording of symptoms, saturation, spirometry, and weekly video consultations.,Algorithms generated alerts if readings breached thresholds.,Both groups received standard care.,The primary outcome was number of hospital admissions for exacerbation of COPD during the study period.,Most of the enrolled patients had severe COPD (forced expiratory volume in 1 second <50%pred in 86% and ≥hospital admission for COPD in the year prior to enrollment in 45%, respectively, of the patients).,No difference in drop-out rate and mortality was found between the groups.,With regard to the primary outcome, no significant difference was found in hospital admissions for COPD between the groups (P=0.74), and likewise, no difference was found in time to first admission or all-cause hospital admissions.,Compared with the control group, TM group patients had more moderate exacerbations (ie, treated with antibiotics/corticosteroid, but not requiring hospital admission; P<0.001), whereas the control group had more visits to outpatient clinics (P<0.001).,Our study of patients with severe COPD showed that TM including video consultations as add-on to standard care did not reduce hospital admissions for exacerbated COPD, but TM may be an alternative to visits at respiratory outpatient clinics.,Further studies are needed to establish the optimal role of TM in the management of severe COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | Genome-wide association studies aim to correlate genotype with phenotype.,Many common diseases including Type II diabetes, Alzheimer’s, Parkinson’s and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits with hundreds of different loci that are associated with varied disease risk.,Identifying common features in the genes associated with each disease remains a challenge.,Furthermore, the role of post-transcriptional regulation, and in particular alternative splicing, is still poorly understood in most multigenic diseases.,We therefore compiled comprehensive lists of genes associated with Type II diabetes, Alzheimer’s, Parkinson’s and COPD in an attempt to identify common features of their corresponding mRNA transcripts within each gene set.,The SERPINA1 gene is a well-recognized genetic risk factor of COPD and it produces 11 transcript variants, which is exceptional for a human gene.,This led us to hypothesize that other genes associated with COPD, and complex disorders in general, are highly transcriptionally diverse.,We found that COPD-associated genes have a statistically significant enrichment in transcript complexity stemming from a disproportionately high level of alternative splicing, however, Type II Diabetes, Alzheimer’s and Parkinson’s disease genes were not significantly enriched.,We also identified a subset of transcriptionally complex COPD-associated genes (~40%) that are differentially expressed between mild, moderate and severe COPD.,Although the genes associated with other lung diseases are not extensively documented, we found preliminary data that idiopathic pulmonary disease genes, but not cystic fibrosis modulators, are also more transcriptionally complex.,Interestingly, complex COPD transcripts are more often the product of alternative acceptor site usage.,To verify the biological importance of these alternative transcripts, we used RNA-sequencing analyses to determine that COPD-associated genes are frequently expressed in lung and liver tissues and are regulated in a tissue-specific manner.,Additionally, many complex COPD-associated genes are spliced differently between COPD and non-COPD patients.,Our analysis therefore suggests that post-transcriptional regulation, particularly alternative splicing, is an important feature specific to COPD disease etiology that warrants further investigation. | 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. | A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use.,Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice.,We performed a systematic literature search in both Pubmed and Embase up to September 2010.,Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only.,Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies.,Of 7,028 articles screened, 13 studies comprising 15 indices were included.,Only 1 index had been explored for its application in daily practice.,We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation.,Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea.,The quality of the studies underlying the indices varied between fairly poor and good.,Statistical methods to assess the predictive abilities of the indices were heterogenic.,They generally revealed moderate to good discrimination, when measured.,Limitations: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity.,We identified 15 prognostic COPD indices.,Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation.,Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this. | 1 |
Maintaining and improving physical functioning is key to mitigating the cycle of deconditioning associated with chronic obstructive pulmonary disease (COPD).,We evaluated the impact of free combination of the long-acting anticholinergic tiotropium plus the long-acting β2-agonist olodaterol on physical functioning in a real-world clinical setting.,In this open-label noninterventional study, Global initiative for chronic Obstructive Lung Disease (GOLD) B-D patients with COPD aged ≥40 years were treated for 4-6 weeks with either tiotropium 5 μg + olodaterol 5 μg (both via Respimat® inhaler) or tiotropium 18 μg (HandiHaler®) + olodaterol 5 μg (Respimat®) once daily.,Physical functioning was assessed by the self-reported 10-item Physical Functioning Questionnaire (PF-10).,The primary end point was the percentage of patients achieving therapeutic success, defined as a 10-point increase in the PF-10 between baseline (visit 1) and weeks 4-6 (visit 2).,Secondary end points included absolute PF-10 scores, Physicians’ Global Evaluation, satisfaction with Respimat® and adverse events.,A total of 1,858 patients were treated: 1,298 (69.9%) with tiotropium 5 μg + olodaterol 5 μg and 560 (30.1%) with tiotropium 18 μg + olodaterol 5 μg.,At study end, 1,683 (92.6%) and 1,556 patients (85.6%) continued using tiotropium and olodaterol, respectively; 48.9% (95% confidence interval: 46.5, 51.3) achieved the primary end point.,Therapeutic success rates were significantly higher for maintenance-naïve patients compared to those who had received prior therapy (59.1% vs 44.5%; P<0.0001), largely driven by maintenance-treatment-naïve GOLD B (59.8%) and C (63.0%) patients.,Absolute physical functioning scores increased from an average baseline of 44.0 (standard deviation: 25.2) to 54.2 (standard deviation: 26.9) at visit 2.,Patients’ general condition improved from baseline to visit 2, and patients were largely satisfied with the Respimat® inhaler.,Adverse events were reported by 7.5% of patients; the most common were respiratory in nature.,Tiotropium + olodaterol improved physical functioning within 4-6 weeks in patients with moderate-to-very severe COPD.,GOLD B and C patients with no prior maintenance treatment demonstrated the greatest benefit. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
To systematically investigate the prevalence of pain, factors related with pain and pain management interventions in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis.,PubMed (MEDLINE), EMBASE, CINAHL and PsychINFO from 1966 to December 2013.,Studies were included if they presented clinical data on pain or symptom burden in patients with COPD, or pain as a domain of quality of life (QoL).,All types of study designs were included.,Of the 1571 articles that were identified, 39 met the inclusion criteria and were included in this review.,Fourteen studies focused on pain and symptom burden (including pain) in patients with COPD and 25 studies focused on QoL using a questionnaire that included a separate pain domain.,Reported pain prevalence in high-quality studies ranged from 32 to 60%.,Included studies report that pain is more prevalent in patients with COPD compared to participants from the general population.,Comorbidity, nutritional status, QoL and several symptoms were related to pain.,None of the included studies reported a significant relationship between lung function and pain prevalence or severity.,However, studies investigating pain in patients with moderate COPD reported higher pain prevalence compared to studies in patients with severe of very severe COPD.,Although literature on this topic is limited and shows substantial heterogeneity, pain seems to be a significant problem in patients with COPD and is related to several other symptoms, comorbidity and QoL.,Data synthesis suggests that pain is more prevalent in patients with moderate COPD compared to patients with severe or very severe COPD.,Further research is needed and should focus on determining a more accurate pain prevalence, investigating the relationship between pain prevalence, disease severity and comorbidity and explore implementation and efficacy of pain management interventions in patients with COPD. | The aim of this study was to describe the impact of chronic obstructive pulmonary disease (COPD) on health status in the Burden of Obstructive Lung Disease (BOLD) populations.,We conducted a cross-sectional, general population-based survey in 11 985 subjects from 17 countries.,We measured spirometric lung function and assessed health status using the Short Form 12 questionnaire.,The physical and mental health component scores were calculated.,Subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70, n = 2269) had lower physical component scores (44±10 versus 48±10 units, p<0.0001) and mental health component scores (51±10 versus 52±10 units, p = 0.005) than subjects without COPD.,The effect of reported heart disease, hypertension and diabetes on physical health component scores (-3 to -4 units) was considerably less than the effect of COPD Global Initiative for Chronic Obstructive Lung Disease grade 3 (-8 units) or 4 (-11 units).,Dyspnoea was the most important determinant of a low physical and mental health component scores.,In addition, lower forced expiratory volume in 1 s, chronic cough, chronic phlegm and the presence of comorbidities were all associated with a lower physical health component score.,COPD is associated with poorer health status but the effect is stronger on the physical than the mental aspects of health status.,Severe COPD has a greater negative impact on health status than self-reported cardiovascular disease and diabetes.,COPD is related to worse health status: impairment is greater than in self-reported cardiovascular diseases or diabeteshttp://ow.ly/p1cIx | 1 |
Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals.,We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes.,By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs).,The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls.,Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2.,Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins.,The eQTLs for IREB2 and CHRNA5 were not in LD.,Seventy-four additional eQTL SNPs were associated with COPD at p<0.01.,These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6.,Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus. | The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation. | 1 |
Assessment of airflow limitation (AFL) is crucial in the clinical evaluation of patients with chronic obstructive pulmonary disease (COPD).,However, in the absence of normative reference values among adult Australian Indigenous population, the implications of utilising the Global Lung Function Initiative (GLI-2012), Global Initiative for Chronic Obstructive Lung Disease (GOLD) and the Australian concise COPD-X recommended severity classifications is not known.,Moreover, spirometry values (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) are observed to be 20%-30% lower in an apparently healthy Indigenous population in comparison to Caucasian counterparts.,Adult Indigenous patients diagnosed to have COPD on spirometry (postbronchodilator (BD) FEV1/FVC <0.7 ((GOLD, (COPD-X)) and ≤lower limit of normal (others/mixed reference equations) for GLI-2012) were assessed for AFL severity classifications on Post-BD FEV1 values (mild, moderate, severe, very severe) as per the recommended classifications.,From a total of 742 unique patient records of Indigenous Australians, 253 were identified to have COPD via GOLD/COPD-X criteria (n=238) or GLI-2012 criteria (n=238) with significant agreeance between criteria (96%, κ=0.901).,Of these, the majority were classified as having moderate or severe/very-severe AFL with significant variability across classification criteria (COPD-X (40%-43%), GOLD (33%-65%), GLI-2012 (18%-75%)).,The FVC and FEV1 values also varied significantly between classification criterion (COPD-X/GOLD/GLI-2012) within the same AFL category, with COPD-X ‘moderate’ AFL almost matching ‘severe’ AFL categorisation by GOLD or GLI-2012.,Health professionals caring for Indigenous patients with COPD should be aware of the clinical implications and consequences of utilising various recommended AFL classifications in the absence of validated spirometry reference norms among adult Indigenous patients. | The trajectory of lung function decline among Indigenous patients with or without underlying chronic airway disease (COPD and concomitant bronchiectasis) and with use of inhaled pharmacotherapy, including inhaled corticosteroids (ICS), has not been reported in the past.,Adult Indigenous Australian patients identified to have undergone at least two or more lung function tests (LFTs) between 2012 and 2020 were assessed for changes in the lung function parameters (LFPs) between the first and last recorded LFTs.,Of the total 1350 patients identified to have undergone LFTs, 965 were assessed to fulfil session quality, 115 (n=58 females) were eligible to be included with two or more LFTs.,Among the 115 patients, 49% showed radiological evidence of airway diseases, and 77% were on airway directed inhaled pharmacotherapy.,Median time between LFTs was 1.5 years (IQR 0.86,5.85), with no significant differences in LFPs noted between first and last LFT.,Overall rate of change (mL/year) showed considerable variation for FVC (median −37.55 mL/year [IQR −159.88,92.67]) and FEV1 (−18.74 mL/year [−102.49,71.44]) with minimal change in FEV1/FVC (0.00 ratio/year [−0.03,0.01]).,When stratified by inhaled pharmacotherapy group, however, patients using ICS showed significantly greater rate of FEV1 decline (−48.64 mL/year [−110.18,62.5]) compared to those using pharmacotherapy with no ICS (15.46 mL/year [−73.5,74.62]) and those using no pharmacotherapy (−5.76 mL/year [−63.19,67.34]) (p=0.022).,Additionally, a greater proportion of these patients reached the threshold for excessive FEV1 decline (64%) compared to those using pharmacotherapy without ICS (44%) and those using no pharmacotherapy (52%).,Decline in LFPs occurs commonly among adult Indigenous population, especially, excessive so among those using inhaled pharmacotherapy containing ICS. | 1 |
There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers.,We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking.,This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort.,During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer.,Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively.,In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status. | Whether the use of inhaled corticosteroids (ICS) protects patients with chronic obstructive pulmonary disease (COPD) from lung cancer remains undetermined.,In this retrospective nationwide population-based cohort study, we extracted data of 13,686 female COPD patients (ICS users, n = 1,290, ICS non-users, n = 12,396) diagnosed between 1997 and 2009 from the Taiwan's National Health Insurance database.,These patients were followed-up until 2011, and lung cancer incidence was determined.,Cox regression analysis was used to estimate hazard ratios (HRs) for lung cancer incidence.,The time to lung cancer diagnosis was significantly different between ICS users and non-users (10.75 vs.,9.68 years, P < 0.001).,Per 100,000 person-years, the lung cancer incidence rate was 235.92 for non-users and 158.67 for users [HR = 0.70 (95% confidence interval {CI}: 0.46-1.09)].,After adjusting for patients' age, income, and comorbidities, a cumulative ICS dose > 39.48 mg was significantly associated with a lower risk of lung cancer [ICS users > 39.48 mg, HR = 0.45 (95% CI: 0.21-0.96)].,Age ≥ 60 years, pneumonia, diabetes mellitus, and hypertension decreased lung cancer risk, whereas pulmonary tuberculosis increased the risk.,Our results suggest that ICS have a potential role in lung cancer prevention among female COPD patients. | 1 |
Latest evidence suggests that periodontitis is prevalent among patients with chronic obstructive pulmonary disease (COPD), while recent studies have also reported a potential benefit of periodontal treatment on several COPD outcomes.,This systematic review aims to determine the impact of periodontal treatment on exacerbation rate, lung function and quality of life of COPD patients.,A systematic search of electronic databases of PubMed, Scopus, Virtual Health Library, ScienceDirect, Wiley Online Library, Web of Science, ProQuest Dissertation and Theses Global and Google Scholar was conducted.,Search restricted to studies involving human subjects which were published from January 2000 to March 2020 in English language.,Distiller Systematic Review software was used for data management.,Risk of bias was assessed using Risk of Bias 2 (RoB2) and Risk of Bias for non-randomized studies of intervention (ROBINS-I) tools.,Overall quality of evidence was judged based on Grading of Recommendations Assessment, Development and Evaluation working group methodology.,Out of 1442 articles retrieved, 7 full text articles were included in the review.,Limited evidence suggests that periodontal treatment in patients with COPD and periodontitis is associated with reduced exacerbation frequency and a slower lung function decline rate, while its effects on quality of life remain unclear.,In addition, periodontal treatment in COPD is associated with lower hospitalization rates and reduced all-cause mortality.,Significant methodological differences were noted amongst included studies, while very low-to-moderate overall quality of evidence was demonstrated.,Although it is reasonable to advise COPD patients not to neglect their dental health, further studies are warranted to determine the role of periodontal therapy on COPD clinical outcomes.,Trial Registration: PROSPERO 2020 (CRD42020158481). https://www.crd.york.ac.uk/prospero/display_record.php?,ID=CRD42020158481,The online version contains supplementary material available at 10.1186/s12890-021-01429-2. | Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,The prevalence of COPD among cigarette smokers in the Middle East is not well studied.,A prospective descriptive study was performed in the north of Jordan.,Male cigarette smokers (≥10 pack-year) aged 35 years and older were recruited from the community.,They completed a questionnaire and a postbronchodilator spirometry.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (postbronchodilator forced expiratory volume in 1 second <70%) was used to define COPD.,A total of 512 subjects completed the study protocol.,According to the GOLD criteria, 42 subjects (8.2%) had COPD.,Of those, 27 subjects (64.3%) had symptomatic COPD.,Using the GOLD criteria, eight subjects (19%) with COPD had mild disease, 24 (57.1%) had moderate disease, eight (19%) had severe disease, and two (4.8%) had very severe disease.,Only 10.6% were aware of COPD as a smoking-related respiratory illness, and 6.4% had received counseling about risk for COPD by a physician.,Chronic bronchitis (cough for 3 months in 2 consecutive years) was reported by 15% of the subjects, wheezes by 44.1%, and dyspnea by 65.2%.,Subjects with COPD reported having more chronic bronchitis 18/42 (42.9%) and wheezing 28/42 (66.7%) than subjects without COPD.,The prevalence of COPD increased with increased number of pack-years smoked.,In conclusion, COPD prevalence among cigarette-smoking men in Jordan is lower than in the developed world.,COPD was largely underdiagnosed, despite the majority of participants being symptomatic and having moderate to severe disease. | 1 |
Since the introduction of the Quality and Outcomes framework, there has been some evidence of improvement in the management of chronic obstructive pulmonary disease (COPD) patients in the United Kingdom through increasing rates of smoking cessation advice and immunisations against influenza.,However, it is unknown whether disease-specific management criteria, disease outcomes and diagnosis have improved.,To describe changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009.,The study was done on a retrospective cohort using data from The Health Improvement Network UK primary care database.,We calculated age at diagnosis of COPD and death, total number of short-term oral corticosteroid courses and consultations, and proportion of patients with very severe COPD and on triple inhaled therapy for each year between 2000 and 2009.,We identified 92,576 patients with COPD.,The mean age at COPD diagnosis decreased from 68.1 years in 2000 to 66.7 years in 2009.,The mean age at death increased from 78.2 years in 2000 to 78.8 years in 2009.,The number of prescribed courses of oral corticosteroids increased from 0.6 in 2000 to 0.8 in 2009.,The number of consultations increased from 9.4 in 2004 to 11.3 in 2009.,The risk of having very severe COPD decreased from 9.4% in 2004 to 6.8% in 2009.,The likelihood of patients with very severe COPD receiving triple therapy increased from 25% in 2004 to 59% in 2009.,The trends suggest that management and outcomes observed in patients with COPD may have improved since the year 2000. | 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. | 1 |
Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population.,Drug therapies are symptomatic and inadequate to contrast disease progression and mortality.,Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets.,Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD.,Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD.,The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes.,Recent evidence corroborating the statement of the “aging theory for COPD” was also discussed. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
Vertebral compression fractures (VCF) are common in COPD patients, with osteoporosis being the main cause.,The clinical impact of VCF derives mostly from both pain and chest deformity, which may lead to ventilatory and physical activity limitations.,Surprisingly, the consequences of VCF on the quality outcomes of hospital care are poorly known.,To assess these indicators in patients hospitalized due to a COPD exacerbation (ECOPD) who also have VCF.,Clinical characteristics and quality care indicators were assessed in two one-year periods, one retrospective (exploratory) and one prospective (validation), in all consecutive patients hospitalized for ECOPD.,Diagnosis of VCF was based on the reduction of >20% height of the vertebral body evaluated in standard lateral chest X-ray (three independent observers).,From the 248 patients admitted during the exploratory phase, a third had at least one VCF.,Underdiagnosis rate was 97.6%, and patients with VCF had more admissions (normalized for survival), longer hospital stays, and higher mortality than patients without (4 [25th-75th percentiles, 2-8] vs 3 [1-6] admissions, P<0.01; 12 [6-30] vs 9 [6-18] days, P<0.05; and 50 vs 32.1% deaths, P<0.01, respectively).,The risk of dying in the two following years was also higher in VCF patients (odds ratio: 2.11 [1.2-3.6], P<0.01).,The validation cohort consisted of 250 patients who showed very similar results.,The logistic regression analysis indicated that both VCF and age were factors independently associated with mortality.,Although VCF is frequently underdiagnosed in patients hospitalized for ECOPD, it is strongly associated with a worse prognosis and quality care outcomes. | To systematically investigate the prevalence of pain, factors related with pain and pain management interventions in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis.,PubMed (MEDLINE), EMBASE, CINAHL and PsychINFO from 1966 to December 2013.,Studies were included if they presented clinical data on pain or symptom burden in patients with COPD, or pain as a domain of quality of life (QoL).,All types of study designs were included.,Of the 1571 articles that were identified, 39 met the inclusion criteria and were included in this review.,Fourteen studies focused on pain and symptom burden (including pain) in patients with COPD and 25 studies focused on QoL using a questionnaire that included a separate pain domain.,Reported pain prevalence in high-quality studies ranged from 32 to 60%.,Included studies report that pain is more prevalent in patients with COPD compared to participants from the general population.,Comorbidity, nutritional status, QoL and several symptoms were related to pain.,None of the included studies reported a significant relationship between lung function and pain prevalence or severity.,However, studies investigating pain in patients with moderate COPD reported higher pain prevalence compared to studies in patients with severe of very severe COPD.,Although literature on this topic is limited and shows substantial heterogeneity, pain seems to be a significant problem in patients with COPD and is related to several other symptoms, comorbidity and QoL.,Data synthesis suggests that pain is more prevalent in patients with moderate COPD compared to patients with severe or very severe COPD.,Further research is needed and should focus on determining a more accurate pain prevalence, investigating the relationship between pain prevalence, disease severity and comorbidity and explore implementation and efficacy of pain management interventions in patients with COPD. | 1 |
The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry.,Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis.,We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted.,Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD).,We then used logistic regression to investigate predictors of correct interpretation.,Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care.,Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality.,Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction.,Historical records for asthma diagnosis significantly decreased odds of correct interpretation.,The quality of the spirometry procedure undertaken in primary care is high.,However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care.,The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes. | Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of stroke than the general population.,Chronic inflammation associated with COPD is thought to contribute to this risk.,Exacerbations of COPD are associated with a rise in inflammation, suggesting that there may be an association between exacerbation frequency and the risk of stroke.,This study examined that association.,Using the UK Clinical Practice Research Datalink, COPD patients with a first stroke between January 2004 and December 2013 were identified as cases and matched on age, sex, and general practice to controls with COPD but without a stroke (6,441 cases and 19,323 controls).,Frequent exacerbators (FEs) were defined as COPD patients with ≥2 exacerbations, and infrequent exacerbators (IEs) have ≤1 exacerbation in the year prior to their stroke.,Conditional logistic regression was used to estimate the association between exacerbation frequency and stroke overall, and by stroke subtype (hemorrhagic, ischemic, or transient ischemic attack).,Exacerbations were also categorized into 0, 1, 2, or ≥3 exacerbations in the year prior to stroke.,There was no evidence that FE had an increased odds of stroke compared to IE (OR [odds ratio] =0.95, 95% CI [confidence interval] =0.89-1.01).,There was strong evidence that the risk of stroke decreased with each exacerbation of COPD experienced per year (Ptrend =0.003).,In the subgroup analysis investigating stroke subtype, FE had 33% lower odds of hemorrhagic stroke than IE (OR =0.67, 95% CI =0.51-0.88, P=0.003).,No association was found within other stroke types.,This study found no evidence of a difference in the odds of stroke between IE and FE, suggesting that exacerbation frequency is unlikely to be the reason for increased stroke risk among COPD patients.,Further research is needed to explore the association through investigation of stroke risk and the severity, duration, treatment of exacerbations, and concurrent treatment of cardiovascular risk factors. | 1 |
There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover.,Recently, activation of the WNT/β-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases.,We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of β-catenin in fibroblast phenotype and function.,We assessed the expression of WNT-pathway genes and the functional role of β-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD.,Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling.,Stimulation of fibroblasts with TGF-β1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and β-catenin mRNA expression.,The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF-β1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar.,Accordingly, TGF-β1 activated β-catenin signaling, as shown by an increase in transcriptionally active and total β-catenin protein expression.,Furthermore, TGF-β1 induced the expression of collagen1α1, α-sm-actin and fibronectin, which was attenuated by β-catenin specific siRNA and by pharmacological inhibition of β-catenin, whereas the TGF-β1-induced expression of PAI-1 was not affected.,The induction of transcriptionally active β-catenin and subsequent fibronectin deposition induced by TGF-β1 were enhanced in pulmonary fibroblasts from individuals with COPD.,β-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation.,WNT/β-catenin pathway expression and activation by TGF-β1 is enhanced in pulmonary fibroblasts from individuals with COPD.,This suggests an important role of the WNT/β-catenin pathway in regulating fibroblast phenotype and function in COPD. | Pulmonary emphysema is characterized by the irreversible loss of pulmonary alveoli.,Despite recent advances in the understanding this disease, its treatment remains palliative.,In this review, we will successively review the data suggesting (1) that alveolar regeneration systems are functional in the mammalian lung and have the potential to regrow lost alveoli, (2) that cigarette smoke, the main etiologic factor of emphysema, inhibits those systems under experimental conditions, and (3) that alveolar regeneration systems are dysfunctional in the human emphysematous lung and may be a target for therapeutic intervention in this disease.,Special emphasis will be put on the role of alveolar fibroblasts in those processes. | 1 |
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ. | In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result.,Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense.,Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity.,There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties.,We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker.,Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures.,Guided by sputum from healthy (1.5-2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression.,Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%.,Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel).,These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties.,These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions. | 1 |
To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population.,Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010.,Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping.,Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline.,And another 9SNPs were selected from HapMap website as HHIP tags.,In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses.,We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population.,And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations.,These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population.,Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.,The online version of this article (doi:10.1186/s12931-015-0209-3) contains supplementary material, which is available to authorized users. | In this review we consider the therapeutic potential of targeting Akt for the treatment of COPD.,Akt is a serine/threonine protein kinase that functions as a signaling intermediate linked to multiple signaling programs involved in survival, inflammation, and growth.,Akt is closely associated with key membrane-bound receptors and represents a convergent integration point for multiple stimuli implicated in COPD pathogenesis.,Persistent activation of Akt secondary to somatic mutations in regulatory oncogenes, such as PTEN, may explain why inflammation in COPD does not resolve when smoking is ceased.,Akt is also implicated in the systemic manifestations of COPD such as skeletal muscle wasting and metabolic disturbances.,Furthermore, targeting Akt may provide a useful means of limiting the severity and duration of disease exacerbations in COPD.,As such, Akt represents a particularly attractive therapeutic target for the treatment of COPD.,Interestingly, current knowledge suggests that both inhibitors and activators of Akt may be useful for treating different clinical subpopulations of COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | 1 |
To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.,COPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks.,The primary outcome was the annualized rate of moderate/severe COPD exacerbations.,In total, 1,765 patients were randomized.,There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%).,None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402).,There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084).,Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039).,There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077).,There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054).,EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066).,Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments.,Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses.,Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively.,Adverse events were otherwise similar across treatment groups.,FP/FORM did not reduce exacerbation rates versus FORM.,Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores.,Few efficacy differences were evident between FP/FORM 250/10 µg and FORM.,Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low.,Adverse events were otherwise similar between treatments. | Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease.,To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT).,Qualitative: patient focus group and interviews to address content validity.,Quantitative: secondary data analyses to test reliability and validity.,Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male.,Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure.,Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male.,Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score.,Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively.,Validity: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms).,RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05).,E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001).,Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD.,Further study of sensitivity to change is warranted. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression.,However, the effect on tissue structure and turnover is not well described.,There is an urgent clinical need for biomarkers of disease activity associated with disease progression.,Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity.,We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.,69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up.,Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).,Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001).,Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001).,Pro-C3 levels were unchanged.,At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.,Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity.,This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression. | Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | 1 |
Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD).,Oxidative stress from cigarette smoke and chronic inflammation is likely to induce this corticosteroid insensitivity.,Quercetin is a polyphenol that has been reported to be an active oxygen scavenger as well as a functional adenosine monophosphate-activated protein kinase (AMPK) activator.,The aim of this study was to investigate the effect of quercetin on corticosteroid responsiveness in COPD cells.,Corticosteroid sensitivity was examined in human monocytic U937 cells exposed to cigarette smoke extract (CSE) and peripheral blood mononuclear cells (PBMC) collected from patients with COPD.,Corticosteroid sensitivity was determined as the dexamethasone concentration causing 40% inhibition of tumor necrosis factor alpha-induced CXCL8 production (Dex-IC40) in the presence or absence of quercetin.,In U937 cells, treatment with quercetin activated AMPK and induced expression of nuclear factor erythroid 2-related factor 2, and consequently reversed CSE-induced corticosteroid insensitivity.,PBMC from patients with COPD showed corticosteroid insensitivity compared with those from healthy volunteers, and treatment with quercetin restored corticosteroid sensitivity.,In conclusion, quercetin restores corticosteroid sensitivity, and has the potential to be a novel treatment in combination with corticosteroids in COPD. | Cigarette smoking-induced oxidant-antioxidant imbalance is a factor that contributes to the pathogenesis of COPD through epithelial cell apoptosis.,Irisin is a skeletal muscle cell-derived myokine associated with physical activity.,Irisin is also known to decrease oxidant-induced apoptosis in patients with diabetes mellitus.,However, the correlation between irisin and emphysema in COPD and its role in epithelial cell apoptosis remains unknown.,Forty patients with COPD were enrolled in this study.,Pulmonary function tests and measurements of the percentage of low-attenuation area on high-resolution computed tomography images were performed, and the results were evaluated for correlation with serum irisin levels.,The effect of irisin on cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a transcription factor for antioxidants, was also examined in vitro.,Serum irisin levels were significantly correlated with lung diffusing capacity for carbon monoxide divided by alveolar volume (r=0.56, P<0.01) and percentage of low-attenuation area (r=−0.79, P<0.01).,Moreover, irisin significantly enhanced Nrf2 expression (P<0.05) and reduced cigarette-smoke extract-induced A549 cell apoptosis (P<0.05).,Decreased serum irisin levels are related to emphysema in patients with COPD and involved in epithelial apoptosis, resulting in emphysema.,Irisin could be a novel treatment for emphysema in patients with COPD. | 1 |
Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required. | 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 |
The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD. | An increasing body of evidence suggests that the long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination appears to play an important role in maximizing bronchodilation, with studies to date indicating that combining different classes of bronchodilators may result in significantly greater improvements in lung function compared to the use of a single drug, and that these combinations are well tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,An inhaled, fixed-dose combination of two 24-hour bronchodilators, the LAMA umeclidinium and the LABA vilanterol, is under development as a once-daily treatment for COPD.,The efficacy of both mono-components has already been demonstrated.,The information currently available suggests that umeclidinium/vilanterol is an effective once-daily dual bronchodilator fixed-dose combination in the treatment of COPD.,However, it remains to be seen if it compares favorably with current therapies.,Moreover, the question remains whether umeclidinium/vilanterol fixed-dose combination, which significantly improves FEV1, is also associated with improvements in other outcome measures that are important to COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) patients often experience lower limb muscle dysfunction and wasting.,Exercise-based training has potential to improve muscle function and mass, but literature on this topic is extensive and heterogeneous including numerous interventions and outcome measures.,This review uses a detailed systematic approach to investigate the effect of this wide range of exercise-based interventions on muscle function and mass.,PUBMED and PEDro databases were searched.,In all, 70 studies (n = 2504 COPD patients) that implemented an exercise-based intervention and reported muscle strength, endurance, or mass in clinically stable COPD patients were critically appraised.,Aerobic and/or resistance training, high-intensity interval training, electrical or magnetic muscle stimulation, whole-body vibration, and water-based training were investigated.,Muscle strength increased in 78%, muscle endurance in 92%, and muscle mass in 88% of the cases where that specific outcome was measured.,Despite large heterogeneity in exercise-based interventions and outcome measures used, most exercise-based trials showed improvements in muscle strength, endurance, and mass in COPD patients.,Which intervention(s) is (are) best for which subgroup of patients remains currently unknown.,Furthermore, this literature review identifies gaps in the current knowledge and generates recommendations for future research to enhance our knowledge on exercise-based interventions in COPD patients. | We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients.,In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally.,Demographics, anthropometrics, lung function and clinical data were assessed.,Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband.,Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters.,Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns.,Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data.,Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all).,Daily physical activity measures and hourly patterns are heterogeneous in COPD.,Clusters of patients were identified solely based on physical activity data.,These findings may be useful to develop interventions aiming to promote physical activity in COPD. | 1 |
The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk.,We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC.,Outpatients with COPD were enrolled from January to June in 2012.,The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively.,Additionally, correlations between mMRC scores and each item of CAT scores were analyzed.,Classification of 257 patients using the CAT score vs mMRC scale was as follows.,By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D.,On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D.,The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510.,The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001).,The classification of COPD produced by the mMRC or CAT score was not identical.,Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document. | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences.,There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema).,The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD). | 1 |
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. | Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development.,However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis.,Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema.,For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (T L R2-R753Q, T L R4-D299G, and T L R4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not.,The presence of T L R4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations.,Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers.,Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development. | 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. | to evaluate the concurrent validity of the six-minute step test (6MST) in assessing exercise capacity of COPD patients using the six-minute walk test (6MWT) as a gold-standard.,The predictive validity of the 6MST was assessed to determine a cut-off point for identification of low exercise capacity.,thirty-two COPD patients (50-87 years old) with mild to very severe obstruction performed the 6MST and 6MWT twice.,Concurrent validity: a strong positive correlation (Pearson) between the number of ascents on the first (T1), second (T2) and the best of both (T1 or T2) tests during the 6MWT was observed.,Although a moderate negative correlation with BODE index and FEV1 was found, it was considered insufficient to test the validity, therefore ROC curves were not applied.,The predictive validity (ROC) of the 6MST to identify low physical capacity (compared with the 6MWT) using the performance of T1 or T2, or solely T1 was considered accurate, and the area under the curve was 0.8 (IC95% 0.62-0.98) and 0.85 (IC95% 0.70-0.99), respectively.,To classify patients, the cut-off points of 86 and 78 steps were chosen, with both values showing 90% of sensitivity and specificity of 64% and 68% for T1 or T2, or solely T1, respectively.,The number of steps on the 6MST was valid to verify exercise capacity in COPD patients and the cut-off point of 78 steps was able to identify patients with poor exercise tolerance.,Values under this cut-off point are considered to identify patients with a poorer prognosis. | 1 |
There is increasing recognition of asthma-COPD overlap syndrome (ACOS), which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well understood.,The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).,This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD.,Clinical data, including spirometry results, were retrieved from medical records.,For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire.,Of the 1,008 patients analyzed, 167 (16.6%) had syndromic features of ACOS.,Of the total number of patients, 93 and 42 (9.2% and 4.2%) also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV1), respectively, and therefore were identified as having ACOS.,Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV1 clinical variability), and 328 patients (32.5%, ≥12%/≥400 mL FEV1 clinical variability) had both the features.,Patients identified as having ACOS were of significantly younger age, had a shorter duration of COPD, lower number of pack-years, better lung function, milder dyspnea symptoms, and higher peripheral blood eosinophil values compared with patients with COPD alone.,The rate of exacerbations in the previous year was not significantly different between the ACOS and COPD groups.,Using a stepwise approach, as stated in the GINA/GOLD report, the proportions of patients identified as having ACOS were found to be 9.2% and 4.2% (depending on the FEV1 variability cutoff used) among the 1,008 outpatients medically treated for COPD in a real-life clinical setting. | The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | 1 |
In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.,Relevant studies were identified through MEDLINE searches.,Using random effects models, summary effects of specific previous conditions were evaluated separately and combined.,Stratified analyses were conducted based on smoking status, gender, control sources and continent.,A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies).,The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies).,Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).,Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer. | Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction.,Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies.,Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD.,Participants were recruited from all 48 contiguous U.S. states by random digit dialing.,Lifetime ETS exposure was ascertained by structured telephone interview.,We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD.,Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD.,The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21).,The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84).,The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure.,ETS exposure may be an important cause of COPD.,Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure. | 1 |
Patients with COPD have frequent exacerbations.,The role of respiratory viral infection is just emerging.,We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction.,Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction.,Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR.,One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited.,A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p < 0.0005.,Rhinovirus was most frequently detected.,The symptom of fever was associated with virus detection, p < 0.05.,Infection with more than one virus was only found in the exacerbated COPD patients.,Respiratory viral infection is associated with exacerbations of COPD.,Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected.,Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD.,Viruses were more commonly detected in those with more severe airways disease. | Although COPD exacerbations are known to occur more frequently in winter, there is little information on hospitalizations and cause-specific mortality.,This study aimed to examine seasonal variations in mortality and exacerbations in patients with COPD during the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial.,TIOSPIR was a large-scale, multicenter trial, which assessed the safety and efficacy of tiotropium delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ (2.5 or 5 μg once daily) inhaler in patients with COPD.,Patients were aged ≥40 years, with a smoking history ≥10 pack-years, and post-bronchodilator forced expiratory volume in 1 second ≤70% and forced expiratory volume in 1 second/forced vital capacity ≤0.70.,COPD exacerbations and deaths were monitored throughout the trial.,The data were pooled to examine seasonal patterns.,Southern hemisphere data were shifted by 6 months to align with northern hemisphere seasons.,TIOSPIR was conducted in 43 northern (n=15,968) and 7 southern (n=1,148) hemisphere (n=1,148) countries.,The median duration of treatment was 835 days, with a mean follow-up of 2.3 years.,Among 19,494 exacerbations, there were clear seasonal differences (winter, 6,646 [34.1%]; spring, 4,515 [23.2%]; summer, 3,198 [16.4%]; autumn, 5,135 [26.3%]).,Exacerbations peaked in early winter (December in the northern hemisphere and June in the southern hemisphere), respiratory hospitalizations in midwinter, and respiratory deaths in early spring.,Although winter poses a 2-fold hazard for COPD exacerbations vs summer, respiratory deaths peak in early spring.,These data suggest that seasonal intensification of preventive treatments may impact COPD morbidity and mortality.,NCT01126437. | 1 |
Determinar el impacto de un programa educativo para mejorar el manejo de la enfermedad pulmonar obstructiva crónica (EPOC) sobre la percepción de la calidad de vida, la capacidad de ejercicio, el grado de disnea y el riesgo clínico de los pacientes EPOC.,Estudio de intervención no controlado.,Centro de Atención Primaria.,Se invitó a participar a 193 pacientes con EPOC, de los que aceptaron 73 y 55 iniciaron el programa educativo.,Programa educativo de rehabilitación respiratoria con conceptos básicos de fisiopatología pulmonar/respiratoria, ejercicios de fisioterapia respiratoria, taller práctico de uso de los dispositivos de inhalación más frecuentes, comprensión de la enfermedad crónica y medidas de autocuidado en caso de exacerbación.,Se evaluaron la calidad de vida (cuestionario de evaluación de la EPOC), la capacidad de ejercicio (prueba de la marcha de los 6 minutos), el grado de disnea (la escala modificada de Borg) y el riesgo clínico (índice de BODE) mediante cuestionarios validados en castellano.,Un total de 43 (78,2%) participantes finalizaron el programa.,Se observó una mejora en la calidad de vida de una media de 3,3 puntos (IC95%: 1,76-4,84).,El 53,5% de los participantes obtuvieron una mejora clínicamente relevante.,Postintervención: los participantes también mejoraron su capacidad de ejercicio físico incrementando una media de 20,76 m (IC95%: 2,57-38,95) la distancia que caminaron durante 6 min.,También, se observaron mejoras en el grado de disnea y el riesgo clínico.,El programa educativo muestra una mejora estadísticamente significativa y clínicamente relevante para la calidad de vida, fatiga, sintomatología, capacidad de ejercicio, grado de disnea y riesgo clínico.,El programa es adaptable a la rutina asistencial de los centros de salud. | Understanding the breadth of patients’ support needs is important for the delivery of person-centered care, particularly in progressive long-term conditions such as chronic obstructive pulmonary disease (COPD).,Existing reviews identify important aspects of managing life with COPD with which patients may need support (support needs); however, none of these comprehensively outlines the full range of support needs that patients can experience.,We therefore sought to systematically determine the full range of support needs for patients with COPD to inform development of an evidence-based tool to enable person-centered care.,We conducted a systematic search and narrative review of the literature.,Medline (Ovid), EMBASE, PsycINFO, Cochrane Library, and CINAHL were systematically searched for papers which included data addressing key aspects of support need, as identified by patients with COPD.,Relevant data were extracted, and a narrative analysis was conducted.,Thirty-one papers were included in the review, and the following 13 domains (broad areas) of support need were identified: 1) understanding COPD, 2) managing symptoms and medication, 3) healthy lifestyle, 4) managing feelings and worries, 5) living positively with COPD, 6) thinking about the future, 7) anxiety and depression, 8) practical support, 9) finance work and housing, 10) families and close relationships, 11) social and recreational life, 12) independence, and 13) navigating services.,These 13 domains of support need were mapped to three of the four overarching categories of need commonly used in relevant national strategy documents (ie, physical, psychological, and social); however, support needs related to the fourth category (spiritual) were notably absent.,This review systematically identifies the comprehensive set of domains of support need for patients with COPD.,The findings provide the evidence base for a tool to help patients identify and express their support needs, which underpins a proposed intervention to enable the delivery of person-centered care: the Support Needs Approach for Patients (SNAP). | 1 |
Dyspnea is a predictor of mortality.,The effects of dyspnea severity and changes in dyspnea status on all-cause and cause-specific mortality remain unclear.,The Vlagtwedde/Vlaardingen study started in 1965 and subjects were re-examined every 3 years until 1989/1990.,Vital status of all 8,465 subjects on December 31st, 2008 was assessed.,Associations between mortality and dyspnea severity and changes in dyspnea status were investigated using Cox regression adjusted for gender, age, FEV1 %predicted, place of residence, smoking and BMI.,After 43 years of follow-up, 2,883 (39 %) of 7,360 subjects examined for dyspnea severity had died, 1,386 (19 %) due to cardiovascular disease, 267 (4 %) due to chronic obstructive pulmonary disease (COPD).,Subjects with moderate and severe dyspnea had increased all-cause and cardiovascular mortality [moderate: HR = 1.3 (95 % CI 1.2-1.5) and 1.4 (1.1-1.6), severe: 1.5 (1.1-2.0) and 1.9 (1.3-2.6) respectively] compared to asymptomatics.,Severe dyspnea was significantly associated with COPD mortality [3.3 (2.0-5.2)].,Subjects who lost dyspnea had hazard ratios for all-cause and cause-specific mortality comparable to asymptomatics.,Persistent dyspnea and dyspnea development were risk factors for all-cause, cardiovascular and COPD mortality [persistent: 2.0 (1.4-2.8), 1.9 (1.2-3.3) and 3.3 (1.2-8.9), development: 1.5 (1.2-1.8), 2.0 (1.5-2.6) and 3.8 (2.3-6.3) respectively].,Additionally, dyspnea effects on mortality were more pronounced in overweight/obese and older subjects and in subjects with better lung function.,These results show that dyspnea is associated with mortality in a severity-dependent manner.,Furthermore this study is the first showing that dyspnea remission normalizes mortality risk.,Having or developing dyspnea is a risk factor for mortality.,The online version of this article (doi:10.1007/s10654-012-9736-0) contains supplementary material, which is available to authorized users. | Patients with COPD use a higher proportion of their peak aerobic capacity during the performance of domestic activities of daily life (ADLs) compared to healthy peers, accompanied by a higher degree of task-related symptoms.,To date, the influence of body mass index (BMI) on the task-related metabolic demands remains unknown in patients with COPD.,Therefore, the aim of our study was to determine the effects of BMI on metabolic load during the performance of 5 consecutive domestic ADLs in patients with COPD.,Ninety-four COPD patients and 20 healhty peers performed 5 consecutive, self-paced domestic ADLs putting on socks, shoes and vest; folding 8 towels; putting away groceries; washing up 4 dishes, cups and saucers; and sweeping the floor for 4 min.,Task-related oxygen uptake and ventilation were assessed using a mobile oxycon, while Borg scores were used to assess task-related dyspnea and fatigue.,1.,Relative task-related oxygen uptake after the performance of domestic ADLs was increased in patients with COPD compared to healthy elderly, whereas absolute oxygen uptake is similar between groups; 2.,Relative oxygen uptake and oxygen uptake per kilogram fat-free mass were comparable between BMI groups; and 3.,Borg symptom scores for dyspnea en fatigue were comparable between BMI groups.,Patients with COPD in different BMI groups perform self-paced domestic ADLs at the same relative metabolic load, accompanied by comparable Borg symptom scores for dyspnea and fatigue. | 1 |
Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | We aimed to compare impulse oscillation system (IOS) and traditional pulmonary function tests (PFTs) for the assessment of the severity of chronic obstructive pulmonary disease (COPD), and to assess the use of IOS parameters to identify patients who were forced expiratory volume in 1 second (FEV1)%pred < 50%.,Patients with COPD (n = 215) were enrolled at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,All patients were assessed by traditional PFT and IOS.,Diagnostic performance of IOS parameters to determine indication for patients of FEV1%pred < 50% was assessed on receiver-operating characteristics (ROC) curve analysis.,Out of 215 patients, 18, 83, 78, and 36 patients were classified as grade 1, 2, 3, and 4, respectively, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity grading.,On Spearman correlation analysis, FEV1%pred, MMEF 75%-25%, and residual volume/total lung capacity (RV/TLC) correlated with total respiratory impedance (Z5)%pred, resistance at 5 Hz (R5)-resistance at 20 Hz (R20), R5-R20% R5, R5, R5%pred, frequency response (Fres), reactance area (Ax), and reactance at 5 Hz (X5).,On ROC curve analysis, the area under the curve (AUC) of X5 absolute value, Fres, Ax, Z5%pred, R5-R20, and R5-R20% R5 were 0.748, 0.755, 0.760, 0.705, 0.715, and 0.735, respectively, for COPD patients who required inhalational glucocorticoid therapy.,IOS parameters showed a good correlation with traditional pulmonary function parameters; reactance parameters showed a stronger correlation than that of the resistance parameters.,IOS can be used as an alternative method for pulmonary function assessment in patients with COPD with FEV1%pred < 50% who need inhalational glucocorticoid therapy.,Clinical trial registration number: ChiCTR-OCH-14004904. | 1 |
To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD).,Systematic review and network meta-analysis (NMA).,208 randomised clinical trials (RCTs) including 134 692 adults with COPD.,LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo.,The proportion of patients with moderate-to-severe exacerbations.,The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes.,NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol.,Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve).,NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%).,NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR).,Triamcinolone acetonide was the most harmful (SUCRA=81%).,NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol.,The most harmful agent was fluticasone/salmeterol (SUCRA=89%).,NMA was conducted for arrhythmia; no statistically significant differences between agents were identified.,Many inhaled agents are available for COPD, some are safer and more effective than others.,Our results can be used by patients and physicians to tailor administration of these agents.,PROSPERO # CRD42013006725. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
Epidemiological data demonstrate that the worldwide prevalence of chronic obstructive pulmonary disease is increasing.,These patients have an increased risk of mortality and morbidity and have constant limitations in airflow.,Comparing laparoscopic cholecystectomy (LC) in patients with chronic obstructive pulmonary disease (COPD) under spinal anesthesia (SA) and general anesthesia (GA).,We prospectively evaluated COPD patients who underwent laparoscopic cholecystectomy under general anesthesia (Group 1, n = 30) or spinal anesthesia (Group 2, n = 30) in our clinic between January 2016 and January 2018.,Patients with COPD were further divided into groups according to their preoperative stages (Stage 1-4).,Intraoperative vital findings, postoperative pain, complications, and length of hospitalization were compared between the general (GA) and spinal anesthesia (SA) groups.,The mean age of the patients in the GA group was 61.0 ± 6.7 years and was 61.0 ± 7.7 years in the SA group.,In the GA and SA groups, the mean ASA score was 2.8 ± 0.6 and 2.9 ± 0.6, respectively, the mean operation duration was 31.7 ± 5.1 and 30.6 ± 5.1 min, respectively, and the length of hospitalization was 3.2 ± 1.7 and 1.5 ± 0.5 days, respectively.,The partial carbon dioxide rates (PaCO2) at the postoperative 5th and 20th minutes were lower in the SA group than in the GA group.,Further, the requirement for postoperative analgesia was lower in the SA group, and the length of hospitalization was significantly shorter in the SA group.,There was no significant difference between the two groups in terms of operation duration.,Laparoscopic cholecystectomy is a rather safe procedure for COPD patients under general and spinal anesthesia.,However, spinal anesthesia is preferred over general anesthesia as it has better postoperative analgesia and causes no impairment of pulmonary functions.,The online version of this article (10.1186/s12893-018-0396-1) contains supplementary material, which is available to authorized users. | The incidence and prevalence of chronic obstructive pulmonary disease (COPD) is associated with increasing age.,Osteoarthritis is also a growing problem in the aging population, and total knee replacement (TKR) is a common surgical procedure for this population.,An increasing number of COPD patients are receiving TKR, but few studies have examined the complications and outcomes after TKR in COPD patients.,The purpose of this study was to investigate the complications, including mortality, wound infections, hospitalization readmission, pneumonia (PN), and cerebrovascular accidents (CVAs) in patients with COPD after receiving TKR.,The National Health Insurance operated by the government is a nationwide health care program with universal coverage in Taiwan.,It covers approximately 99% of the total Taiwanese population of 23 million people.,In this case-control study, we analyzed the longitudinally linked National Health Insurance Research Database, which consists of a cohort of 1,000,000 randomly selected enrollees retrospectively followed from 1996 to 2010.,This study analyzed patients who underwent TKR surgery between January 1, 2004 and December 31, 2009 by identifying the International Classification of Diseases, Ninth Revision, Clinical Modification code.,We separated patients into COPD and non-COPD groups.,Five study outcomes and complications were measured after TKR, including mortality for 1 and 3 years, wound infections for 1 and 2 years, hospitalization readmission for 30 and 90 days, PN for 30 and 90 days, and CVAs.,A total of 3431 patients who underwent TKR surgery were identified, including 358 patients with COPD and 3073 patients without COPD.,The COPD group had a higher percentage of 90-day PN (3.7% vs.,1.1%), 30-day readmission (7.0% vs.,4.0%), 30-day CVA (1.7% vs.,0.6%), 90-day CVA (3.9% vs.,2.1%), and 3-year mortality (3.9% vs.,2.1%) than the non-COPD group.,COPD was associated with 90-day PN (adjusted hazard ratio[HR)] = 2.12, P = 0.030) after adjusting for sex, cardiovascular disease, and CVA occurrence.,Patients with COPD had a higher risk of PN after TKR than patients without COPD, but no significant differences were found for CVAs and mortality. | 1 |
The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR).,Focus groups were carried out with patients (n = 26) and HCPs (n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology.,A questionnaire was used to assess technology use, PR experience, and general health status.,Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time.,A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements.,Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR.,Patients and HCPs identified similar key elements for P-TR.,The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes. | 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. | 1 |
Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD).,Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results.,Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).,To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.,We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/−10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.,The analysis included 16,936 genotyped and imputed SNPs.,No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3×10−5.,The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81×10−5), CNTN5 (P = 4.37×10−4), and TRPV4 (P = 1.58×10−3).,Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4).,The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38×10−4), and ESR1 (P = 5.42×10−4) among ever-smokers.,Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population.,Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population. | The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes.,Whether they are associated with emphysema is not known.,Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people.,The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined.,Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001).,Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema.,Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002).,SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers. | 1 |
Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of COPD.,This study aims to estimate the prevalence of COPD and its correlates through a community-based survey in Pokhara Metropolitan City, a semi-urban area of Western Nepal.,A cross-sectional household survey was conducted among 1459 adults ≥40 years.,COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as a post-bronchodilator ratio of forced expiratory volume in 1st second (FEV1) to forced vital capacity (FVC) <0.70 with the presence of symptoms.,COPD was also defined by the lower limit of normal (LLN) threshold - FEV1/FVC < LLN cut-off values with the presence of symptoms.,Study participants were interviewed about sociodemographic and behavioural characteristics and respiratory symptoms.,Descriptive statistics and logistic regression analysis were applied.,Spirometry reports were acceptable in 1438 participants.,The mean age of the participants was 55 (±10) years, and, 54% were female.,The prevalence of GOLD-defined COPD was 8.5% (95% CI: 7.1-10.0) and based on the LLN threshold of 5.4% (95% CI: 4.2-6.6).,The multivariate logistic regression showed that increasing age, low body mass index, illiterate, current or former smoker, and biomass fuel smoke increased the odds of COPD in both the definitions.,COPD is highly prevalent at community level and often underdiagnosed.,Strategies aiming at early diagnosis and treatment of COPD, especially for the elderly, illiterate, and reducing exposure to smoking and biomass fuel smoke and childhood lung infection could be effective. | Socioeconomic status (SES) is a strong social determinant of health.,There remains a limited understanding of the association between SES and COPD prevalence among low- and middle-income countries where the majority of COPD-related morbidity and mortality occurs.,We examined the association between SES and COPD prevalence using data collected in Argentina, Bangladesh, Chile, Peru, and Uruguay.,We compiled lung function, demographic, and SES data from three population-based studies for 11,042 participants aged 35-95 years.,We used multivariable alternating logistic regressions to study the association between COPD prevalence and SES indicators adjusted for age, sex, self-reported daily smoking, and biomass fuel smoke exposure.,Principal component analysis was performed on monthly household income, household size, and education to create a composite SES index.,Overall COPD prevalence was 9.2%, ranging from 1.7% to 15.4% across sites.,The adjusted odds ratio of having COPD was lower for people who completed secondary school (odds ratio [OR] =0.73, 95% CI 0.55-0.98) and lower with higher monthly household income (OR =0.96 per category, 95% CI 0.93-0.99).,When combining SES factors into a composite index, we found that the odds of having COPD was greater with lower SES (interquartile OR =1.23, 95% CI 1.05-1.43) even after controlling for subject-specific factors and environmental exposures.,In this analysis of multiple population-based studies, lower education, lower household income, and lower composite SES index were associated with COPD.,Since household income may be underestimated in population studies, adding household size and education into a composite index may provide a better surrogate for SES. | 1 |
Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes. | 1 |
Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people.,The relevance of frailty to chronic respiratory disease and its management is unknown.,To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation.,816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015.,Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation.,Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex.,209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail.,Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01).,Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission.,However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001).,After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty.,Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion.,However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term. | To validate a Portuguese-language version of the COPD assessment test (CAT) for use in Brazil and to assess the reproducibility of this version.,This was multicenter study involving patients with stable COPD at two teaching hospitals in the city of Fortaleza, Brazil.,Two independent observers (twice in one day) administered the Portuguese-language version of the CAT to 50 patients with COPD.,One of those observers again administered the scale to the same patients one week later.,At baseline, the patients were submitted to pulmonary function testing and the six-minute walk test (6MWT), as well as completing the previously validated Portuguese-language versions of the Saint George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (MMRC) dyspnea scale, and hospital anxiety and depression scale (HADS).,Inter-rater and intra-rater reliability was excellent (intraclass correlation coefficient [ICC] = 0.96; 95% CI: 0.93-0.97; p < 0.001; and ICC = 0.98; 95% CI: 0.96-0.98; p < 0.001, respectively).,Bland Altman plots showed good test-retest reliability.,The CAT total score correlated significantly with spirometry results, 6MWT distance, SGRQ scores, MMRC dyspnea scale scores, and HADS-depression scores.,The Portuguese-language version of the CAT is a valid, reproducible, and reliable instrument for evaluating patients with COPD in Brazil.,Realizar a validação e verificar a reprodutibilidade da versão em português do Brasil do COPD Assessment Test (CAT).,Estudo multicêntrico, no qual foram selecionados pacientes com DPOC estável em dois hospitais de ensino na cidade de Fortaleza, CE.,A versão do CAT foi aplicada duas vezes a 50 pacientes com DPOC por dois observadores independentes no mesmo dia.,Após uma semana, esse mesmo questionário foi aplicado novamente aos mesmos pacientes por um dos observadores.,No primeiro dia, os pacientes foram submetidos à prova de função pulmonar e ao teste de caminhada de seis minutos (TC6) e responderam as versões validadas de qualidade de vida relacionada à saúde (QVRS).,(SGRQ), escala de dispneia Modified Medical Research Council (MMRC) e hospital anxiety and depression scale (HADS).,As reprodutibilidades interobservador e intraobservador foram excelentes (coeficiente de correlação intraclasse [CCI] = 0,96; IC95%: 0,93-0,97; p < 0,001; e CCI = 0,98; IC95%: 0,96-0,98; p < 0,001, respectivamente).,As disposições gráficas de Bland Altman demonstraram boa confiabilidade teste-reteste.,Houve correlações significativas do escore total do CAT com os resultados de espirometria, TC6, SGRQ, escala de dispneia MMRC e HADS-depressão.,A versão brasileira do CAT é um instrumento válido, reprodutível e confiável para a avaliação dos pacientes com DPOC na população brasileira. | 1 |
Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD).,Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation.,We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD.,Twenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV1 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection).,AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum.,There was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum.,Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge.,ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum.,In mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation.,The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD.,Netherlands Trial Register (NTR): NTR1283 | COPD represents one of the leading causes of mortality in the general population.,This study aimed at evaluating the relationship between airway hyperresponsiveness (AHR) and COPD and its relevance for clinical practice.,We performed a MEDLINE search that yielded a total of 1919 articles.,Eligible studies were defined as articles that addressed specific aspects of AHR in COPD, such as prevalence, pathogenesis, or prognosis.,AHR appears to be present in at least one out of two individuals with COPD.,The occurrence of AHR in COPD is influenced by multiple mechanisms, among which impairment of factors that oppose airway narrowing plays an important role.,The main determinants of AHR are reduction in lung function and smoking status.,We envision a dual role of AHR: in suspected COPD, specific determinants of AHR, such as reactivity and the plateau response, may help the physician to discriminate COPD from asthma; in definite COPD, AHR may be relevant for the prognosis.,Indeed, AHR is an independent predictor of mortality in COPD patients.,Smoking cessation has been shown to reduce AHR.,Further studies are needed to elucidate whether this functional change is associated with improvement in lung function and respiratory symptoms. | 1 |
Bronchodilators are central in the symptomatic management of chronic obstructive pulmonary disease (COPD).,Long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are the main classes of long-acting bronchodilators.,To date, tiotropium is the only once-daily LAMA available for the treatment of COPD.,Glycopyrronium is a novel LAMA, currently in development for COPD.,Phase II studies have shown that glycopyrronium 50 μg once daily provides clinically significant 24-hour bronchodilation with a rapid onset of action, which is faster than that of tiotropium, and a favorable safety and tolerability profile.,The Phase III GLycopyrronium bromide in COPD airWays (GLOW) program has now confirmed the long-term efficacy and tolerability of glycopyrronium 50 μg once daily.,The three studies included in this program have further shown that the effect of glycopyrronium versus placebo is similar to that of tiotropium in reducing dyspnea and the risk of exacerbations, as well as improving lung function, exercise tolerance, and health status in patients with COPD.,The safety profile of glycopyrronium is also similar to that of tiotropium in terms of overall incidence of adverse events and muscarinic side effects.,Glycopyrronium could be an alternative choice to tiotropium, and like tiotropium, has the potential to be used as a monotherapy or combination therapy.,Phase II studies have shown that a fixed-dose combination of glycopyrronium and the 24-hour LABA indacaterol, produces rapid and sustained bronchodilation compared with indacaterol monotherapy in patients with COPD.,Phase III studies are currently ongoing to assess the long-term efficacy and safety of this combination. | Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD).,The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.,This study was performed as a systematic literature review.,Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action.,In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status.,Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance.,Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.,Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD. | 1 |
COPD is characterized by a pulmonary and systemic inflammatory process.,Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations.,The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count.,We performed a systematic literature review using the PRISMA statement.,Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls.,Compared with controls, COPD patients had significantly higher NLR values.,We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients.,Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively).,Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity.,The NLR is an independent predictor of in-hospital and late mortality after exacerbation.,In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR. | Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker.,However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD).,This study was aimed to evaluate the usefulness of NLR in patients with COPD.,NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28).,NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period.,The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression.,NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001).,NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs.,11.5 ± 8.8, p < 0.001).,NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale.,NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079).,Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization.,NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD. | 1 |
Cytotoxic lymphocytes are increased in the airways of COPD patients.,Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.,Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function.,BAL lymphocyte subsets were determined using flow cytometry.,In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years.,Within the COPD group, NK cells - but not iNKT or NKT-like cells - were significantly elevated also in subjects that had quit smoking.,In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells.,Rate of lung function decline did not significantly affect any of the results.,In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD.,Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.,Clinicaltrials.gov identifier NCT02729220.,The online version of this article (10.1186/s12931-018-0940-7) contains supplementary material, which is available to authorized users. | Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.,To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.,3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.,An analysis of risk of COPD was carried out using ever smoking controls (n=4784).,Associations with %predicted FEV1 were tested in cases.,We followed-up signals of interest (p<10−5) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.,Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10−6, preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10−6).,In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10−6).,We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5.,No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10−7).,This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study. | 1 |
Rationale: People living with both chronic obstructive pulmonary disease (COPD) and frailty have high potential to benefit from pulmonary rehabilitation but face challenges completing programs.,However, research to understand ways to optimize participation in this group is lacking.,Objectives: To explore the experiences, needs, and preferences of people with COPD and frailty referred for outpatient pulmonary rehabilitation.,Methods: Semistructured interviews with people with COPD and physical frailty, purposively sampled by age, living status, level of frailty, and completion of pulmonary rehabilitation.,Thematic analysis with a critical realist perspective was used, involving relevant stakeholders with clinical, academic, and lived experience for interpretive rigor.,Results: Nineteen people with COPD and frailty were interviewed, with a median age of 78 years (range, 58-88).,Nine did not complete their pulmonary rehabilitation program.,Four themes were identified: striving to adapt to multidimensional loss, tensions of balancing support with independence, pulmonary rehabilitation as a challenge worth facing, and overcoming unpredictable disruptions to participation.,Participants described constantly adapting to their changing health and resulting multidimensional losses (e.g., functional abilities, relationships, confidence).,This involved traversing between independence and seeking support, set against a mismatch between their needs and what support is available.,People with COPD and frailty can be highly motivated to participate in pulmonary rehabilitation, despite the physical and mental demands it entails, and report a range of benefits.,Yet in the context of changeable health, they must often overcome multiple unpredictable disruptions to completing rehabilitation programs.,Participant determination and flexibility of services can facilitate ongoing attendance, but for some, these unpredictable disruptions erode their motivation to attend.,Conclusions: People with COPD and frailty experience accumulating, multidimensional loss.,This group are motivated to complete pulmonary rehabilitation but often require additional support and flexibility owing to fluctuating and unpredictable health.,Person-centered approaches should be considered to minimize disruptive health events and support pulmonary rehabilitation participation and completion.,Service adaptations could allow more flexibility to meet the changing needs of this group and enable communication around how pulmonary rehabilitation might align with their priorities. | People living with both chronic obstructive pulmonary disease (COPD) and frailty have high potential to benefit from exercise-based interventions, including pulmonary rehabilitation, but face challenges completing them.,Research to understand ways to optimise exercise-based interventions in this group is lacking.,We aimed to understand how exercise-based interventions might improve outcomes for people living with both COPD and frailty.,This realist review used database searches and handsearching until October 2019 to identify articles of relevance to exercise-based interventions for people living with COPD and frailty.,A scoping search explored what is important about the context of living with COPD and frailty, and what mechanisms might be important in how exercise-based interventions result in their intended outcomes.,Through discussion with stakeholders, the review scope was refined to areas deemed pertinent to improving care.,We retained articles within this refined scope and identified additional articles through targeted handsearching.,Data were extracted and synthesised in a narrative, prioritised by relevance and rigour.,Of 344 records identified, 35 were included in the review and 20 informed the final synthesis.,Important contextual factors to consider included: negative beliefs about themselves and exercise-based interventions; heterogenous presentation and comorbidities; decreased reserves and multidimensional loss; and experiencing unpredictable health and disruptions.,In these circumstances, mechanisms that may help maximise outcomes from exercise-based interventions included: trusting relationships; creating a shared understanding of needs; having the capacity to address multidimensional concerns; being able to individualise approaches to needs and priorities; and flexible approaches to intervention delivery.,Mixed-methods research and explicit theorising were often absent.,Building trusting relationships, understanding priorities, using individualised and multidisciplinary approaches, and flexible service delivery can improve the value of exercise-based interventions for people living with both COPD and frailty.,Development and evaluation of new and adapted interventions should consider these principles. | 1 |
Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
The aim of this study was to determine the influence of selected physiological, psychological and situational factors on experience of fatigue, and functional limitations due to fatigue in patients with stable chronic obstructive pulmonary disease (COPD).,In total 101 patients with COPD and 34 control patients were assessed for experience of fatigue, functional limitation due to fatigue (Fatigue Impact Scale), physiological [lung function, 6-minute walk distance (6MWD), body mass index (BMI), dyspnoea, interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hs-CRP), surfactant protein D], psychological (anxiety, depression, insomnia), situational variables (age, sex, smoking, living alone, education), and quality of life.,Fatigue was more common in patients with COPD than in control patients (72% versus 56%, p < 0.001).,Patients with COPD and fatigue had lower lung function, shorter 6MWD, more dyspnoea, anxiety and depressive symptoms, and worse health status compared with patients without fatigue (all p < 0.01).,No differences were found for markers of systemic inflammation.,In logistic regression, experience of fatigue was associated with depression [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.28-2.25) and insomnia (OR 1.75, 95% CI 1.19-2.54).,In linear regression models, depression, surfactant protein D and dyspnoea explained 35% (R2) of the variation in physical impact of fatigue.,Current smoking and depression explained 33% (R2) of the cognitive impact of fatigue.,Depression and surfactant protein D explained 48% (R2) of the psychosocial impact of fatigue.,Experiences of fatigue and functional limitation due to fatigue seem to be related mainly to psychological but also to physiological influencing factors, with depressive symptoms, insomnia problems and dyspnoea as the most prominent factors.,Systemic inflammation was not associated with perception of fatigue but surfactant protein D was connected to some dimensions of the impact of fatigue | Cough is a prevalent symptom that impacts quality of life in COPD.,The aim of this study was to assess the relationship between cough-specific quality of life, abdominal muscle endurance, fatigue, and depression in stable patients with COPD.,Twenty-eight patients with COPD (mean age 60.6±8.7 years) referred for pulmonary rehabilitation participated in this cross-sectional study.,Sit-ups test was used for assessing abdominal muscle endurance.,Leicester Cough Questionnare (LCQ) was used to evaluate symptom-specific quality of life.,Fatigue perception was evaluated with Fatigue Impact Scale (FIS).,Beck Depression Inventory (BDI) was used for assessing depression level.,The LCQ total score was significantly associated with number of sit-ups; BDI score; FIS total; physical, cognitive, and psychosocial scores (P<0.05).,Scores of the LCQ physical, social, and psychological domains were also significantly related with number of sit-ups, FIS total score, and BDI score (P<0.05).,FIS total score and number of sit-ups explained 58% of the variance in LCQ total score (r=0.76, r2=0.577, F(2-20)=12.296, P<0.001).,Chronic cough may adversely affect performance in daily life due to its negative effect on fatigue and decrease abdominal muscle endurance in patients with COPD.,Decreased cough-related quality of life is related with increased level of depression in COPD patients.,Effects of increased abdominal muscle endurance and decreased fatigue in COPD patients with chronic cough need further investigation. | 1 |
Inhaled corticosteroid/long-acting β2-agonist combinations (ICS/LABA) have emerged as first line therapies for chronic obstructive pulmonary disease (COPD) patients with exacerbation history.,No randomized clinical trial has compared exacerbation rates among COPD patients receiving budesonide/formoterol combination (BFC) and fluticasone/salmeterol combination (FSC) to date, and only limited comparative data are available.,This study compared the real-world effectiveness of approved BFC and FSC treatments among matched cohorts of COPD patients in a large US managed care setting.,COPD patients (≥40 years) naive to ICS/LABA who initiated BFC or FSC treatments between 03/01/2009-03/31/2012 were identified in a geographically diverse US managed care database and followed for 12 months; index date was defined as first prescription fill date.,Patients with a cancer diagnosis or chronic (≥180 days) oral corticosteroid (OCS) use within 12 months prior to index were excluded.,Patients were matched 1-to-1 on demographic and pre-initiation clinical characteristics using propensity scores from a random forest model.,The primary efficacy outcome was COPD exacerbation rate, and secondary efficacy outcomes included exacerbation rates by event type and healthcare resource utilization.,Pneumonia objectives included rates of any diagnosis of pneumonia and pneumonia-related healthcare resource utilization.,Matching of the identified 3,788 BFC and 6,439 FSC patients resulted in 3,697 patients in each group.,Matched patients were well balanced on age (mean = 64 years), gender (BFC: 52% female; FSC: 54%), prior COPD-related medication use, healthcare utilization, and comorbid conditions.,During follow-up, no significant difference was seen between BFC and FSC patients for number of COPD-related exacerbations overall (rate ratio [RR] = 1.02, 95% CI = [0.96,1.09], p = 0.56) or by event type: COPD-related hospitalizations (RR = 0.96), COPD-related ED visits (RR = 1.11), and COPD-related office/outpatient visits with OCS and/or antibiotic use (RR = 1.01).,The proportion of patients diagnosed with pneumonia during the post-index period was similar for patients in each group (BFC = 17.3%, FSC = 19.0%, odds ratio = 0.92 [0.81,1.04], p = 0.19), and no difference was detected for pneumonia-related healthcare utilization by place of service.,This study demonstrated no difference in COPD-related exacerbations or pneumonia events between BFC and FSC treatment groups for patients new to ICS/LABA treatment in a real-world setting.,ClinicalTrials.gov identifier NCT01921127. | 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 |
Cultural differences affect the administration and results of health status questionnaires.,“Cross cultural adaptation” ensures retention of psychometric properties such as validity and reliability at an item and/or scale level.,To develop a Malaysian version of St George’s respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia.,SGRQ-C was translated to Bahasa Malaysia using a standard protocol.,240 COPD patients were included in the study.,All patients were followed-up for six months.,Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated.,The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively.,Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, − 0.82, 0.72 and − 0.42 respectively.,Correlation coefficient between the subscales and other clinical and health status measures ranged from r = − 0.35 to r = − 0.87.,The MCID was reported as 5.07 (− 2.54-12.67).,The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients.,It can be recommended as a reliable quality of life measure for future research. | Chronic obstructive pulmonary disease (COPD) is one global disease.,Lung function gradually declines.,Medication does not fully reverse the airflow limitation.,Qigong’s role in COPD rehabilitation has been assessed.,We aimed to assess the effects of Qigong practised by COPD patients.,Eligible articles were obtained through a systematic search.,The databased were search on October 8, 2017, and the date range of the searches in the electronic databases had no upper limit.,The Cochrane risk-of-bias tool was used to evaluate the quality of the eligible studies.,Mean differences with 95% confidence intervals were utilized to analyse the results.,Ten included studies contained 993 participants.,Statistical improvements occurred in the 6-min walk distance (6MWD) (MD, 30.57 m; 95% CI, 19.61-41.53 m; P < 0.00001); forced expiratory volume in 1 s (FEV1) (MD, 0.32 L; 95% CI, 0.09-0.56 L; P < 0.001); forced vital capacity rate of 1 s (FEV1/FVC) (MD, 2.66%; 95% CI, 1.32-2.26%; P = 0.0001); forced expiratory volume in 1 s/predicted (FEV1/pre) (MD, 6.04; CI, 2.58-9.5; P = 0.006); Monitored Functional Task Evaluation (MD, 0.88; 95% CI, 0.78-0.99; P < 0.00001); COPD Assessment Test for exercise (MD, − 5.54; 95% CI, − 9.49 to − 1.59; P = 0.006); Short Form-36 Health Quality Survey (SF-36)-General Health (MD, 5.22; 95% CI, 3.65-6.80; P < 0.00001); and Short Form-36 Health Quality Survey (SF-36)-Mental Health (MD, − 1.21; 95% CI, − 2.75 to 0.33; P = 0.12).,In this meta-analysis of RCTs between ten included studies, we found that Qigong can improve COPD patients in lung function, exercise capacity and quality of life who were in the stable stage.,The online version of this article (10.1186/s12906-019-2639-9) contains supplementary material, which is available to authorized users. | 1 |
Smoking cessation in chronic obstructive pulmonary disease (COPD) reduces accelerated forced expiratory volume in 1 s decline, but impact on key health outcomes is less clear.,We studied the relationship of smoking status to mortality and hospitalisation in a UK primary care COPD population.,Using patient-anonymised routine data in the Hampshire Health Record Analytical Database, we identified a prevalent COPD cohort, categorising patients by smoking status (current, ex- or never-smokers).,Three outcomes were measured over 3 years (2011-2013): all-cause mortality, respiratory-cause unplanned hospital admission and respiratory-cause emergency department attendance.,Survival analysis using multivariable Cox regression after multiple imputation was used to estimate hazard ratios for each outcome by smoking status, adjusting for measured confounders (including age, lung function, socioeconomic deprivation, inhaled medication and comorbidities).,We identified 16 479 patients with COPD, mean±sd age 70.1±11.1 years.,Smoking status was known in 91.3%: 35.1% active smokers, 54.3% ex-smokers, 1.9% never-smokers.,Active smokers predominated among younger patients.,Compared with active smokers (n=5787), ex-smokers (n=8941) had significantly reduced risk of death, hazard ratio (95% confidence interval) 0.78 (0.70-0.87), hospitalisation, 0.82 (0.74-0.89) and emergency department attendance, 0.78 (0.70-0.88).,After adjusting for confounders, ex-smokers had significantly better outcomes, emphasising the importance of effective smoking cessation support, regardless of age or lung function.,Many COPD patients smoke: better outcomes in ex-smokers suggest many deaths and admissions avoidable if smokers quithttp://ow.ly/l85u30aizmK | Chronic obstructive pulmonary disease (COPD) is a known risk factor for lung cancer and a leading cause of mortality in the U.S., but its impact may not be fully appreciated, especially among low-income populations in the southeast where COPD prevalence and lung cancer incidence are elevated.,We conducted a prospective study among 26,927 low-income adults age 40-79 in the Southern Community Cohort Study who had a Center for Medicare and Medicaid Services (CMS) encounter prior to enrollment and were followed for a median of over 6 years.,Using a validated algorithm for assessing COPD from CMS claims data, we estimated COPD prevalence and potential misreporting.,From Cox proportional hazard models, we computed overall and lung cancer-specific mortality according to COPD status.,The overall prevalence of CMS-diagnosed COPD was 16%, but was twice as high among whites as blacks.,Only 35% of these individuals, however, self-reported having COPD, with underreporting significantly greater for blacks than whites.,Smoking-adjusted all-cause mortality was increased by 1.7-fold and lung cancer mortality by 2.3-fold among those with a CMS COPD diagnosis, with similar patterns in blacks and whites, but no excess was found among those self-reporting COPD and without CMS confirmation.,The prevalence of COPD in this low-income population may be greater than previously recognized and misreporting is common.,COPD is associated with elevated lung cancer mortality, even among those not self-reporting the condition. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD).,Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies.,This study investigated subjects with AATD to determine the relationship between specific phenotypes and TNFα polymorphisms.,424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis.,A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function.,Four single nucleotide polymorphisms (SNPs) tagging TNFα were genotyped using TaqMan® genotyping technologies and compared between subjects affected by each phenotype and those unaffected.,Plasma TNFα levels were measured in all PiZZ subjects.,All SNPs were in Hardy-Weinberg equilibrium.,A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes.,TNFα plasma level showed no phenotypic or genotypic associations.,Variation in TNFα is associated with chronic bronchitis in AATD. | 1 |
Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem.,Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment.,This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action.,Several dietary options can be considered in terms of COPD prevention and/or progression.,Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD.,Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health. | Prescription of mucoactive drugs for chronic obstructive pulmonary disease (COPD) is increasing.,This development in clinical practice arises, at least in part, from a growing understanding of the important role that exacerbation frequency, systemic inflammation and oxidative stress play in the pathogenesis of respiratory disease.,S-carboxymethylcysteine (carbocisteine) is the most frequently prescribed mucoactive agent for long-term COPD use in the UK.,In addition to its mucoregulatory activity, carbocisteine exhibits free-radical scavenging and anti-inflammatory properties.,These characteristics have stimulated interest in the potential that this and other mucoactive drugs may offer for modification of the disease processes present in COPD.,This article reviews the pharmacology, in vivo and in vitro properties, and clinical trial evidence for carbocisteine in the context of guidelines for its use and the current understanding of the pathogenic processes that underlie COPD. | 1 |
Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk.,We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC.,Outpatients with COPD were enrolled from January to June in 2012.,The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively.,Additionally, correlations between mMRC scores and each item of CAT scores were analyzed.,Classification of 257 patients using the CAT score vs mMRC scale was as follows.,By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D.,On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D.,The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510.,The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001).,The classification of COPD produced by the mMRC or CAT score was not identical.,Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document. | 1 |
Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications.,Patients of interest were those that have been diagnosed with COPD.,MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers.,We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality.,Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).,CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance.,Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts. | 1 |
Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations.,We assessed risk factors for bacterial colonisation in COPD.,Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis.,Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥102 colony-forming units (CFU)/mL on quantitative bacterial culture.,Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load.,A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated.,Bacterial colonisation was demonstrated in 58 (48.7%) patients.,Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour.,Thirty-six patients (62% of those colonised) had a high bacterial load.,More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture.,In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001).,Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum.,Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs.,Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised. | Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation.,Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.,We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers).,All subjects underwent a complete medical history and pulmonary function testing.,SP-D was measured by Enzyme-Linked ImmunoSorbent Assay.,Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding.,The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.,Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01).,In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046).,To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs.,These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.,Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung.,Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro.,Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD.,Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD.,Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis. | 1 |
The investigation of complex disease heterogeneity has been challenging.,Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes.,We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD).,We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants.,Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches.,Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease severity, and genetic mechanisms. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting.,Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course.,However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment.,Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon.,This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained. | Chronic obstructive pulmonary disease (COPD) is predicted to become a major cause of death worldwide.,Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies.,In the present study, we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union, focusing on prevalence, severity, frequency of exacerbations and mortality, as well as on differences between the studies' methods.,This systematic review was based on a search for the relevant literature in the Science Citation Index database via the Web of Science and on COPD mortality rates issued from national statistics.,Analysis was finally based on 65 articles and Eurostat COPD mortality data for 21 European countries.,Epidemiological characteristics of COPD varied widely from country to country.,For example, prevalence estimates ranged between 2.1% and 26.1%, depending on the country, the age group and the methods used.,Likewise, COPD mortality rates ranged from 7.2 to 36.1 per 105 inhabitants.,The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD, severity scales, methods of investigation and target populations.,Nevertheless, to a large extent, several recent international guidelines or research initiatives, such as GOLD, BOLD or PLATINO, have boosted a substantial standardization of methodology in data collection and have resulted in the availability of more comparable epidemiological estimates across countries.,On the basis of such standardization, severity estimates as well as prevalence estimates present much less variation across countries.,The contribution of these recent guidelines and initiatives is outlined, as are the problems remaining in arriving at more accurate COPD epidemiological estimates across European countries.,The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures, interventions and patient management in various health care systems.,Therefore, the recent initiatives for standardizing data collection should be enhanced to result in COPD epidemiological estimates of improved quality.,Moreover, establishing international guidelines for reporting research on COPD may also constitute a major contribution. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Guidelines recommend the use of simple but comprehensive tools such as COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ) to assess health status in COPD patients.,We aimed to compare the ability of CAT and CCQ to predict exacerbation in COPD patients.,We organized a multicenter prospective cohort study that included COPD patients.,The relationships between CAT, CCQ, and other clinical measurements were analyzed by correlation analysis, and the impact of CAT and CCQ scores on exacerbation was analyzed by logistic regression analyses and receiver operating characteristic curve.,Among 121 COPD patients, CAT and CCQ score correlated with other symptom measures, lung function and exercise capacity as well.,Compared with patients who did not experience exacerbation, those who experienced exacerbation (n=45; 38.2%) exhibited more severe airflow limitation, were more likely to have a history of exacerbation in the year prior to enrollment, and demonstrated higher CAT scores.,CCQ scores were not significantly associated with exacerbations.,A CAT score of ≥15 was an independent risk factor for exacerbation (adjusted odds ratio [aOR], 2.40; 95% CI, 1.03-6.50; P=0.04).,Furthermore, CAT scores of ≥15 demonstrated an increased predictive ability for exacerbation compared with currently accepted guidelines for the use of CAT (≥10) and CCQ (≥1) in the assessment of COPD patients (area under the curve for CAT ≥15, CAT ≥10, and CCQ ≥1 was 0.61±0.04, 0.53±0.03, and 0.50±0.03, respectively; P=0.03).,A CAT score of ≥15 indicates increased risk of exacerbation in COPD patients, whereas there is no evidence for increased risk based on CCQ score. | 1 |
Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects.,We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes.,We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta.,We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted).,Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry.,We assessed predictive performance of models by area under the curve.,In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth.,The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations.,Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts.,The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]).,The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes.,The polygenic risk score was associated with a reduced lung growth pattern.,A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth.,US National Institutes of Health, Wellcome Trust. | Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | 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. | Pulmonary Daoyin (PD) (evolved from ancient Chinese daoyin skills), is a rehabilitation technology that combines specially designed movements of the arms and body and controlled breathing exercises, to improve the physiological and psychological status of patients with chronic respiratory disease.,Pulmonary rehabilitation is effective for patients with chronic obstructive pulmonary disease (COPD), and the efficacy of PD is unknown.,The aim of this study is to investigate the effect of a PD program in enhancing activity tolerance, patient-reported outcomes and satisfaction with the effectiveness on patients with COPD.,The multi-center, randomized controlled trial was conducted from November 2011 to June 2012 in local communities in cities of the 11 research centers in China.,It included COPD patients (moderate to very severe) who were recruited from an outpatient clinic.,A randomized controlled study included 464 COPD patients who were randomly allocated either to the PD group, participating in a 3-month, ten times-weekly supervised PD-based pulmonary rehabilitation program, or to a control group continuing with regular medical treatment alone.,Data were gathered using the 6-minute walking distance (6MWD) test, COPD patient-reported outcomes (COPD-PRO) and Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD), which was filled out at baseline and 3 months post-intervention.,SAS 9.2 was used for statistical analysis.,Of the 464 patients in the study, 461 were included in the full analysis set (FAS); 429 were in the per-protocol analysis set (PPS).,After 3-month intervention, there was a significant difference between the two groups in 6MWD (FAS; P=0.049; PPS; P=0.041), total score and all domains of COPD-PRO (FAS; P=0.014; PPS; P=0.003) and ESQ-COPD (FAS; P=0.038; PPS; P<0.001).,The PD program was able to improve the activity tolerance level and satisfaction of COPD patients because of its effectiveness. | 1 |
We studied if pre-bronchodilator FEV1/FEV6 determinations with microspirometers by GPs improve the diagnostic process for COPD in a 6-8 month clustered randomised controlled trial in Dutch general practices (http://www.trialregister.nl: NTR4041).,GPs allocated to microspirometry (MI) used COPD-6® microspirometers in patients ≥50 years old with a smoking history and respiratory complaints that could indicate undiagnosed COPD and ask to refer patients for full spirometry if MI was positive (FEV1/FEV6 <0.73).,Introduction of the COPD-6® was postponed in the usual care (UC) group.,GPs of both study arms were asked to list all patients that fulfilled study criteria and at the end of the study we screened the electronic medical record system for number of patients that fulfilled study criteria and visited their GP within the study period.,Main end point was a documented diagnostic conclusion of COPD within 3 months after the patient’s visit.,We used multilevel logistic regression with correction for relevant covariates.,Next, we described the process of care. 21 practices (88 GPs) participated and 416 possible undiagnosed COPD patient visited these practices in the study period. 78 (of 192 visiting) subjects were listed by MI GPs and diagnostic conclusions were documented in 77%, compared to 61 listed (of 224 visiting) subjects and 44% with documented diagnostic conclusions by UC GPs (Odds Ratio: OR: 4.3, 95%CI: 1.6-11.5).,Microspirometry improved the diagnostic process for possible underlying COPD in patients who consulted their GP with respiratory symptoms, but the majority of possible undiagnosed COPD patients remained unrecognised by GPs.,A quick, simple test that can be used by family doctors may help identify patients suffering from chronic obstructive pulmonary disease (COPD).,The small, inexpensive microspirometry (MI) kit enables doctors conducting routine appointments to measure the volume of air expelled from patients’ lungs.,Lisette van den Bemt at Radboud University Medical Center, the Netherlands, and co-workers worked with two groups of doctors in local practices.,Both groups were asked to identify patients over 50 with a smoking history, respiratory problems and no diagnose of asthma and COPD, and start a diagnostic process for COPD.,One group was given microspirometers to aid diagnoses.,Of 192 patients visiting the MI doctors, 78 were identified and 77 per cent were later listed as COPD or COPD was ruled out.,In the other group, 61 out of 224 patients were identified with only 44 per cent listed. | Aging is an important risk factor for most chronic diseases.,Patients with COPD develop more comorbidities than non-COPD subjects.,We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD.,We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain).,We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups.,Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups.,We divided the groups into 5 incremental age categories and compared their comorbidity networks.,We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups.,In addition, we replicated the analysis in the smokers’ subgroup to correct for the confounding effect of cigarette smoking.,Subjects with COPD had more comorbidities and died at a younger age compared to controls.,Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network’s density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older.,The findings persisted after adjusting for smoking.,Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age. | 1 |
Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally.,Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD.,Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality.,Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes.,In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels.,To date, only limited evidence exists to support the effectiveness of these interventions.,We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term. | 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. | Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | 1 |
The understanding of certain data often requires the collection of similar data from different places to be analysed and interpreted.,Interoperability standards and ontologies, are facilitating data interchange around the world.,However, beyond the existing networks and advances for data transfer, data sharing protocols to support multilateral agreements are useful to exploit the knowledge of distributed Data Warehouses.,The access to a certain data set in a federated Data Warehouse may be constrained by the requirement to deliver another specific data set.,When bilateral agreements between two nodes of a network are not enough to solve the constraints for accessing to a certain data set, multilateral agreements for data exchange are needed.,We present the implementation of a Multi-Agent System for multilateral exchange agreements of clinical data, and evaluate how those multilateral agreements increase the percentage of data collected by a single node from the total amount of data available in the network.,Different strategies to reduce the number of messages needed to achieve an agreement are also considered.,The results show that with this collaborative sharing scenario the percentage of data collected dramaticaly improve from bilateral agreements to multilateral ones, up to reach almost all data available in the network. | Today, many different tools are developed to execute and visualize physiological models that represent the human physiology.,Most of these tools run models written in very specific programming languages which in turn simplify the communication among models.,Nevertheless, not all of these tools are able to run models written in different programming languages.,In addition, interoperability between such models remains an unresolved issue.,In this paper we present a simulation environment that allows, first, the execution of models developed in different programming languages and second the communication of parameters to interconnect these models.,This simulation environment, developed within the Synergy-COPD project, aims at helping and supporting bio-researchers and medical students understand the internal mechanisms of the human body through the use of physiological models.,This tool is composed of a graphical visualization environment, which is a web interface through which the user can interact with the models, and a simulation workflow management system composed of a control module and a data warehouse manager.,The control module monitors the correct functioning of the whole system.,The data warehouse manager is responsible for managing the stored information and supporting its flow among the different modules.,This simulation environment has been validated with the integration of three models: two deterministic, i.e. based on linear and differential equations, and one probabilistic, i.e., based on probability theory.,These models have been selected based on the disease under study in this project, i.e., chronic obstructive pulmonary disease.,It has been proved that the simulation environment presented here allows the user to research and study the internal mechanisms of the human physiology by the use of models via a graphical visualization environment.,A new tool for bio-researchers is ready for deployment in various use cases scenarios. | 1 |
To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution.,After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression.,We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups.,After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups.,The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM.,Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets. | 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. | 1 |
The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users. | Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce.,Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.,The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months.,The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over.,Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization.,Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting.,The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.,The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up.,The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82).,Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]).,Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. | 1 |
Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
Symptomatic patients with chronic obstructive pulmonary disease (COPD) and low exacerbation risk still have disease instability, which can be improved with better bronchodilation.,We evaluated two long-acting bronchodilators individually and in combination on reducing exacerbation risk and the potential impact of concurrent medication in these patients.,Integrated post hoc intent-to-treat (ITT) analysis of data from two large 24-week, randomized placebo (PBO)-controlled trials (NCT01313637, NCT01313650).,Symptomatic patients with moderate-to-very-severe COPD with/without an exacerbation history were randomized (2:3:3:3) to once-daily: PBO, umeclidinium/vilanterol (UMEC/VI 62.5/25 μg [NCT01313650] or 125/25 μg [NCT01313637]), UMEC (62.5 [NCT01313650] or 125 μg [NCT01313637]) or VI (25 μg) via the ELLIPTA inhaler.,Medication subgroups were segmented by treatment status at screening: a) maintenance-naïve or on maintenance medications, b) inhaled corticosteroid [ICS]-free or ICS-treated, c) low or high albuterol use based on median run-in use (< 3.6 or ≥ 3.6 puffs/day).,Time to first moderate/severe exacerbation (Cox proportional hazard model) and change from baseline in trough forced expiratory volume in 1 s (FEV1; mixed model repeated measures) were analyzed.,Safety was also assessed.,Of 3021 patients (ITT population; UMEC/VI: n = 816; UMEC: n = 825; VI: n = 825; PBO: n = 555), 36% had a recent exacerbation history, 33% were maintenance-naïve, 51% were ICS-free.,Mean baseline albuterol use was 5.1 puffs/day.,In the ITT population, UMEC/VI, UMEC, and VI reduced the risk of a first exacerbation versus PBO by 58, 44, and 39%, respectively (all p < 0.05).,UMEC/VI provided significant risk reductions versus PBO in all subgroups.,VI had no benefit versus PBO in maintenance-naïve, ICS-free, and low rescue use patients and was significantly less effective than UMEC/VI in these subgroups.,UMEC had no significant benefit versus PBO in maintenance-naïve and ICS-free patients.,All bronchodilators improved FEV1 versus PBO, and UMEC/VI significantly improved FEV1 versus both monotherapies across all populations studied (p < 0.05).,All bronchodilators were similarly well tolerated.,Results suggest that UMEC/VI reduces exacerbation risk versus PBO more consistently across medication subgroups than UMEC or VI, particularly in patients with no/low concurrent medication use.,Confirmed prospectively, these findings may support first-line use of dual bronchodilation therapy in symptomatic low-risk patients.,The online version of this article (10.1186/s12931-019-1027-9) contains supplementary material, which is available to authorized users. | It has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.,Define and subsequently validate “modified” control criteria (MCC) of COPD.,Prospective observational study in COPD patients with a 1-year follow-up.,Control was defined as the presence of low clinical impact and clinical stability.,To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color.,Stability was assessed by clinical changes and exacerbations in the last 3 months.,The COPD assessment test score and their changes were also evaluated as alternative control criteria.,To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established.,Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.,We included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%.,The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%).,Similar percentages were found using COPD assessment test scores.,The time to the first combined event was significantly greater in controlled patients using MCC criteria (P<0.001, all cases).,The predictive capacity of risk was similar in MCC-B (c-statistic [C]=0.639) and MCC-F (C=0.637) and higher than OCC (C=0.589).,The new MCC identified a higher number of controlled COPD patients.,These patients have a better quality of life and lower risk of poor outcomes.,The concept of control and the new MCC could be a useful tool to optimize therapy. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,It is well established that patients with mild to moderate disease represent the majority of patients with COPD, and patients with mild COPD already have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with healthy non-smoking individuals.,However, this subpopulation is both underdiagnosed and undertreated.,In addition, most clinical trials include cohorts of patients with worse lung function and quality of life, which are very different from the milder patients usually seen in primary care.,Clinical trials have shown that mild-moderate COPD patients present an improvement in lung function after treatment with long-acting bronchodilators (LABD).,Inhaled therapy has also shown benefits in terms of symptoms, health-related quality of life (HRQL) and exacerbation prevention in this population.,Early intervention might have also a positive effect to prevent functional impairment.,Nevertheless, there is scarce evidence from randomised clinical trials and real-life studies about the importance of pharmacological treatment in early stages of COPD to improve long-term outcomes.,New concepts such as clinically important deterioration may help to investigate the impact of interventions on the natural history of the disease. | Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management.,We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program.,Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.,We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017.,Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.,We included 13 randomized trials (801 participants).,Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])).,Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [− 6.85 to − 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])).,Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate.,Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.,Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation.,Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months.,Therefore, we recommend early supervised PR to patients with COPD-related exacerbations.,PR should be initiated during hospital admission or within 4 weeks after hospital discharge.,The online version of this article (10.1186/s12890-018-0718-1) contains supplementary material, which is available to authorized users. | 1 |
Reports regarding gender-related differences in COPD expression have provided conflicting results.,In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted intervals) and comparisons were performed using univariate logistic regressions.,For a given age and level of airflow obstruction, women with COPD had higher BOD scores due to more pronounced dyspnea and lower BMI, suggesting worse prognosis, and were more likely to exhibit anxiety, suggesting the need for specific assessment and care. | Dyspnea while performing the activities of daily living has been suggested to be a better measurement than peak dyspnea during exercise.,Furthermore, the inspiratory capacity (IC) has been shown to be more closely related to exercise tolerance and dyspnea than the FEV1, because dynamic hyperinflation is the main cause of shortness of breath in patients with COPD.,However, breathlessness during exercise is measured in most studies to evaluate this relationship.,To evaluate the correlation between breathlessness during daily activities and airflow limitation or static hyperinflation in COPD.,We examined 167 consecutive outpatients with stable COPD.,The Baseline Dyspnea Index (BDI) was used to evaluate dyspnea with activities of daily living.,The relationship between the BDI score and the clinical measurements of pulmonary function was then investigated.,The Spearman rank correlation coefficients (Rs) between the BDI score and the FEV1(L), FEV1(%pred) and FEV1/FVC were 0.60, 0.56 and 0.56, respectively.,On the other hand, the BDI score also correlated with the IC, IC/predicted total lung capacity (TLC) and IC/TLC (Rs = 0.45, 0.46 and 0.47, respectively).,Although all of the relationships studied were strongly correlated, the correlation coefficients were better between dyspnea and airflow limitation than between dyspnea and static hyperinflation.,In stepwise multiple regression analyses, the BDI score was most significantly explained by the FEV1 (R2 = 26.2%) and the diffusion capacity for carbon monoxide (R2 = 14.4%) (Cumulative R2 = 40.6%).,Static hyperinflation was not a significant factor for clinical dyspnea on the stepwise multiple regression analysis.,Both static hyperinflation and airflow limitation contributed greatly to dyspnea in COPD patients. | 1 |
The changes in the microbial community structure during acute exacerbations of severe chronic obstructive pulmonary disease (COPD) in hospitalized patients remain largely uncharacterized.,Therefore, further studies focused on the temporal dynamics and structure of sputum microbial communities during acute exacerbation of COPD (AECOPD) would still be necessary.,In our study, the use of molecular microbiological techniques provided insight into both fungal and bacterial diversities in AECOPD patients during hospitalization.,In particular, we examined the structure and varieties of lung microbial community in 6 patients with severe AECOPD by amplifying 16S rRNA V4 hyper-variable and internal transcribed spacer (ITS) DNA regions using barcoded primers and the Illumina sequencing platform.,Sequence analysis showed 261 bacterial genera representing 20 distinct phyla, with an average number of genera per patient of >157, indicating high diversity.,Acinetobacter, Prevotella, Neisseria, Rothia, Lactobacillus, Leptotrichia, Streptococcus, Veillonella, and Actinomyces were the most commonly identified genera, and the average total sequencing number per sputum sample was >10000 18S ITS sequences.,The fungal population was typically dominated by Candia, Phialosimplex, Aspergillus, Penicillium, Cladosporium and Eutypella.,Our findings highlight that COPD patients have personalized structures and varieties in sputum microbial community during hospitalization periods. | Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively.,They share many similarities in epidemiological and clinical characteristics as well as inflammatory pathologies.,Importantly, both conditions are accompanied by systemic co-morbidities that are largely overlooked in both basic and clinical research.,Therefore, consideration of these complications may maximise the efficacy of prevention and treatment approaches.,Here, we examine both the intestinal involvement in COPD and the pulmonary manifestations of IBD.,We also review the evidence for inflammatory organ cross-talk that may drive these associations, and discuss the current frontiers of research into these issues. | 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. | The use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.,Using claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.,This was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006-2010).,Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest.,A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics.,Daily ICS use was classified into low, medium, and high doses (1 μg-499 μg, 500 μg-999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.,Among 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year).,ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27-1.49) for low-dose users, 1.69 (1.52-1.88) for medium-dose users, and 2.57 (1.98-3.33) for high-dose users (P < 0.01 versus no use and between doses).,The use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level.,This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation.,This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation.,Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD.,Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes.,Fourteen studies including 167 COPD patients met the inclusion criteria.,Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation.,These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine.,These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment.,The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD. | 1 |
In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification categorized chronic obstructive pulmonary disease (COPD) patients into 4 groups.,A report demonstrated that the mortality in Group B was higher than that in Group C.,Ischemic heart disease and cancer were suggested to be the cause.,The aim of the present study was to test the hypothesis that interstitial lung abnormalities (ILAs) are more prevalent in Group B than Group C and that they may be responsible for the higher mortality in Group B.,Patients were selected based on their pulmonary function test results.,The inclusion criterion was a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of ＜70% after the inhalation of a bronchodilator.,Patients without a smoking history or computed tomography (CT) scan were excluded.,The medical records of the patients were retrospectively reviewed, and the selected patients were categorized into Groups A to D.,High-resolution CT scans were used to investigate the presence of ILAs and determine the low attenuation area (LAA).,Among the 349 COPD patients, ILAs were detected in 10.3% of the patients in Group A, 22.5% of the patients in Group B, 5.6% of the patients in Group C, and 23.1% of the patients in Group D.,In Group B, the frequency of ILAs was significantly higher and the area affected by the ILAs was significantly greater in comparison to Group C.,Among the patterns of interstitial abnormalities, the area of honeycombing in Group B was significantly greater than that in Group C.,Furthermore, among the patients in Group B, the LAA in the ILA-positive patients was significantly greater than that in the ILA-negative patients.,In Group B, the area occupied by ILAs-especially honeycombing-was greater than that in Group C.,This contributed to the preserved %FEV1 and possibly to the poorer prognosis of the patients in Group B. | COPD patients with community-acquired pneumonia (CAP) have worse clinical outcomes, as compared to those without COPD.,Cardiovascular disease (CVD) is a common comorbidity for COPD patients.,Whether COPD with comorbid CVD will increase the risk of CAP is not well investigated.,The incidence and factors associated with CAP in COPD patients with and without CVD were analyzed.,The medical records of patients with newly diagnosed COPD between 2007 and 2010 were reviewed.,The patients’ characteristics, medical history of CVD, occurrence of CAP, and type of medication were recorded.,Kaplan-Meier curves were used to assess the differences in cumulative incidence of CAP.,Cox’s proportional hazards regression model was used to determine the adjusted hazard ratios with 95% confidence intervals in relation to factors associated with CAP in COPD patients with and without CVD.,Among 2,440 patients, 475 patients (19.5%) developed CAP during the follow-up period.,COPD patients who developed CAP were significantly older, had lower forced expiratory volume in 1 second, frequent severe exacerbation and comorbid CVD, as well as received inhaled corticosteroid (ICS)-containing therapy than those without CAP.,The cumulative incidence of CAP was higher in COPD patients with CVD compared to those without CVD.,Patients who received ICS-containing therapy had significantly increased risk of developing CAP compared to those who did not.,For patients with COPD, comorbid CVD is an independent risk factor for developing CAP.,ICS-containing therapy may increase the risk of CAP among COPD patients. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world.,The underlying pathophysiological mechanisms have been the focus of extensive research in the past.,The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue.,Both types of cells express chemokines and chemokine receptors, making them sensitive to modifications of concentration gradients.,Cigarette smoke exposure and recurrent exacerbations, directly and indirectly, impact the expression of chemokines and chemokine receptors.,Here, we provide an overview of the evidence regarding chemokines involvement in COPD, and we hypothesize that a dysregulation of this tightly regulated system is critical in COPD evolution, both at a stable state and during exacerbations.,Targeting chemokines and chemokine receptors could be highly attractive as a mean to control both chronic inflammation and bronchial remodeling.,We present a special focus on the CXCL8-CXCR1/2, CXCL9/10/11-CXCR3, CCL2-CCR2, and CXCL12-CXCR4 axes that seem particularly involved in the disease pathophysiology. | Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disorder characterized by the progressive obstruction of airflow and is currently the fourth leading cause of death in the world.,The pathogenesis of COPD is thought to involve bacterial infections and inflammations.,Owing to advancement in sequencing technology, evidence is emerging that supports an association between the lung microbiome and COPD.,However, few studies have looked into the expression profile of the bacterial communities in the COPD lungs.,In this study, we analyzed the sputum microbiome of four moderate and four severe COPD male patients both at the DNA and RNA level, using next generation sequencing technology.,We found that bacterial composition determined by 16S rRNA gene sequencing may not directly translate to the set of actively expressing bacteria as defined by transcriptome sequencing.,The two sequencing data agreed on Prevotella, Rothia, Neisseria, Porphyromonas, Veillonella, Fusobacterium and Streptococcus being among the most differentially abundant genera between the moderate and severe COPD samples, supporting their association with COPD severity.,However, the two sequencing analyses disagreed on the relative abundance of these bacteria in the two COPD groups, implicating the importance of studying the actively expressing bacteria for enriching our understanding of COPD.,Though we have described the metatranscriptome profiles of the lung microbiome in moderate and severe COPD, further investigations are required to determine the functional basis underlying the relationship between the microbial species in the lungs and pathogenesis of COPD. | 1 |
Skeletal muscle dysfunction leads to reduction in activity in patients with COPD.,As an essential part of the management of COPD, pulmonary rehabilitation (PR) alleviates dyspnea and fatigue, improves exercise tolerance and health-related quality of life, and reduces hospital admissions and mortality for COPD patients.,Exercise is the key component of PR, which is composed of exercise assessment and training therapy.,To evaluate PR’s application in clinical practice, this article summarizes the common methods of exercise measurement and exercise training for patients with COPD.,Exercise assessments should calculate patients’ symptoms, endurance, strength, and health-related quality of life.,After calculation, detailed exercise therapies should be developed, which may involve endurance, strength, and respiratory training.,The detailed exercise training of each modality is mentioned in this review.,Although various methods and therapies of PR have been used in COPD patients, developing an individualized exercise training prescription is the target.,More studies are warranted to support the evidence and examine the effects of long-term benefits of exercise training for patients with COPD in each stage. | Chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure (HF) in clinical practice since they share the same pathogenic mechanism.,Both conditions incur significant morbidity and mortality.,Therefore, the prognosis of COPD and HF combined is poorer than for either disease alone.,Nevertheless, usually only one of them is diagnosed.,An active search for each condition using clinical examination and additional tests including plasma natriuretic peptides, lung function testing, and echocardiography should be obtained.,The combination of COPD and HF presents many therapeutic challenges.,The beneficial effects of selective β1-blockers should not be denied in stable patients who have HF and coexisting COPD.,Additionally, statins, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers may reduce the morbidity and mortality of COPD patients.,Moreover, caution is advised with use of inhaled β2-agonists for the treatment of COPD in patients with HF.,Finally, noninvasive ventilation, added to conventional therapy, improves the outcome of patients with acute respiratory failure due to hypercapnic exacerbation of COPD or HF in situations of acute pulmonary edema.,The establishment of a combined and integrated approach to managing these comorbidities would seem an appropriate strategy.,Additional studies providing new data on the pathogenesis and management of patients with COPD and HF are needed, with the purpose of trying to improve quality of life as well as survival of these patients. | 1 |
The complexity of breathlessness in advanced disease requires a diversity of measures ideally tailored to the individual patient needs.,‘Breathlessness services’ have been systematically developed and tested to provide specific interventions and support for patients and their carers.,The aim of this article is (1) to identify and describe components of breathlessness services and (2) to describe the clinical model of one specific service in more detail.,This article is based on a systematic review evaluating randomized controlled trials (RCTs) and quasi-RCTs which examine the effectiveness of services aiming to improve breathlessness of patients with advanced disease.,The Munich Breathlessness Service (MBS) is described in detail as an example of a recently set-up specialist service.,Five service models were identified which were tested in six RCTs.,Services varied regarding structure and composition with face-to-face meetings, some with additional telephone contacts.,Service duration was median 6 weeks (range 2-12 weeks).,Involved professions were nurses, various therapists and, in two models, also physicians.,The breathing-thinking-functioning model was targeted by various service components.,The MBS is run by a multi-professional team mainly with physicians and physiotherapists.,Patients are seen weekly over 5-6 weeks with an individualized management plan.,Breathlessness services are a new model for patients with advanced disease integrating symptom management and early access to palliative care. | Objectives To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD.,Design Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months.,Interviews were transcribed and analysed both thematically and as narratives.,Participants 21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients.,Setting Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9.,Results Eleven patients died during the study period.,Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together).,Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.”,Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition.,Professional carers’ familiarity with the patients’ condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease.,Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population.,Conclusions Our findings challenge current assumptions underpinning provision of end of life care for people with COPD.,The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care.,Careful assessment of possible supportive and palliative care needs should be triggered at key disease milestones along a lifetime journey with COPD, in particular after hospital admission for an exacerbation. | 1 |
Cytotoxic lymphocytes are increased in the airways of COPD patients.,Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.,Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function.,BAL lymphocyte subsets were determined using flow cytometry.,In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years.,Within the COPD group, NK cells - but not iNKT or NKT-like cells - were significantly elevated also in subjects that had quit smoking.,In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells.,Rate of lung function decline did not significantly affect any of the results.,In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD.,Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.,Clinicaltrials.gov identifier NCT02729220.,The online version of this article (10.1186/s12931-018-0940-7) contains supplementary material, which is available to authorized users. | Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.,Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.,In smokers with normal lung function, the expression of CD25+CD4+ was increased, whereas the proportions of FoxP3+ and CD127+ were unchanged compared to never-smokers.,Among CD4+ cells expressing high levels of CD25, the proportion of FoxP3+ cells was decreased and the percentage of CD127+ was increased in smokers with normal lung function.,CD4+CD25+ cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.,The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells.,Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25+ helper T-cell population in smokers and stable COPD.,Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development. | 1 |
This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT).,Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database.,MITT was defined as subjects with ≥1 overlapping days’ supply of three COPD medications (ICS, LABA, and LAMA).,Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up.,In addition, analyses were stratified by number of inhalers.,In total, 14,635 MITT users were identified (mean age, 62 years).,Mean PDC for MITT at 12 months was 0.37%.,Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively.,The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT.,Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up.,Patients with COPD had low adherence to and persistence with MITT in a real-world setting.,Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT.,Reducing the number of inhalers may improve overall adherence to intended triple therapy. | Increasing availability of therapeutic options for COPD may drive new treatment pathways.,This study describes COPD treatment in France, focusing on identifying initial treatment modifications in patients with COPD who either initiated long-acting bronchodilator (LABD)-based therapy or escalated to triple therapy (long-acting muscarinic antagonist [LAMA] + long-acting β2-agonist [LABA] + inhaled corticosteroid [ICS]).,This retrospective analysis of patients with COPD in a large general practitioner database (IQVIA Longitudinal Patient Database) in France included two cohorts: Cohort 1 - new initiators of LABD-based therapy (LAMA, LABA, LAMA + LABA, LAMA + ICS, LABA + ICS or LAMA + LABA + ICS); Cohort 2 - patients escalating to triple therapy from mono- or dual-bronchodilator-based maintenance treatment.,Both cohorts were indexed on the date of initiation/escalation (January 2008-December 2013), and the first treatment modification (at class level) within the 18-month post-index observational period was described.,Five mutually exclusive outcomes were defined: continuous use (no modification), discontinuation (permanent [≥91 days with no restart] or temporary [≥91 days with subsequent restart]), switch, and augmentation (Cohort 1 only).,Exploratory analysis of Cohort 1 explored potential drivers of treatment initiation.,Overall, 5,065 patients initiated LABD-based therapy (Cohort 1), and 501 escalated to triple therapy (Cohort 2).,In Cohort 1, 7.0% of patients were continuous users, 46.5% discontinued permanently, 28.5% discontinued temporarily, 2.8% augmented (added LAMA and/or LABA and/or ICS), and 15.2% switched therapy.,In Cohort 2, 18.2% of patients were continuous users, 7.2% discontinued permanently, 27.9% discontinued temporarily, and 46.7% switched therapy.,Exploratory analyses showed that time since COPD diagnosis was first recorded, pre-index exacerbation events, and concomitant medical conditions were potential drivers of initial maintenance treatment choices.,Discontinuation among new initiators of LABD-based therapy was high in France, whereas few switched or augmented treatment.,In comparison, permanent discontinuation within 18 months was low in patients escalating to triple therapy. | 1 |
To systematically investigate the prevalence of pain, factors related with pain and pain management interventions in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis.,PubMed (MEDLINE), EMBASE, CINAHL and PsychINFO from 1966 to December 2013.,Studies were included if they presented clinical data on pain or symptom burden in patients with COPD, or pain as a domain of quality of life (QoL).,All types of study designs were included.,Of the 1571 articles that were identified, 39 met the inclusion criteria and were included in this review.,Fourteen studies focused on pain and symptom burden (including pain) in patients with COPD and 25 studies focused on QoL using a questionnaire that included a separate pain domain.,Reported pain prevalence in high-quality studies ranged from 32 to 60%.,Included studies report that pain is more prevalent in patients with COPD compared to participants from the general population.,Comorbidity, nutritional status, QoL and several symptoms were related to pain.,None of the included studies reported a significant relationship between lung function and pain prevalence or severity.,However, studies investigating pain in patients with moderate COPD reported higher pain prevalence compared to studies in patients with severe of very severe COPD.,Although literature on this topic is limited and shows substantial heterogeneity, pain seems to be a significant problem in patients with COPD and is related to several other symptoms, comorbidity and QoL.,Data synthesis suggests that pain is more prevalent in patients with moderate COPD compared to patients with severe or very severe COPD.,Further research is needed and should focus on determining a more accurate pain prevalence, investigating the relationship between pain prevalence, disease severity and comorbidity and explore implementation and efficacy of pain management interventions in patients with COPD. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
Dual bronchodilation combining a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials.,The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year.,Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments.,The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population).,The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units).,Improvements in health status and lower rescue medication use were also observed with IND/GLY.,The safety profile of the study medication was similar to that observed in previous studies.,IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments.,ClinicalTrials.gov number: NCT01985334.,The online version of this article (doi:10.1186/s12931-017-0622-x) contains supplementary material, which is available to authorized users. | In 2013, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) updated the management strategy on COPD based on severity using a combined assessment of symptoms, degree of airflow limitation, and number of exacerbations.,This study quantified prevalence and incidence of COPD in the United Kingdom and estimated disease severity by GOLD 2013 categories A/B (low risk) and C/D (high risk).,The Clinical Practice Research Datalink was used to identify COPD patients ≥40 years.,Patient characteristics were described, and prevalence was calculated on December 31, 2013.,Five-year incidence (2009-2013) was estimated, with rates standardized using 2011 UK population age and sex.,To classify patients by GOLD categories, spirometry results, the modified British Medical Research Council grade, and history of exacerbations were used.,The prevalent cohort comprised 49,286 patients with COPD with mean age 70 years; 51.0% were male.,Overall prevalence was 33.3 per 1,000 persons (95% confidence interval [CI]: 33.1-33.6); 66.4% were classified as GOLD A/B and 33.6% as C/D.,The standardized prevalence of GOLD A/B was 21.9 per 1,000 persons (95% CI: 21.7-22.1) and of C/D was 11.1 (95% CI: 10.9-11.2).,A total of 27,224 newly diagnosed COPD patients were identified with mean age 67 years at diagnosis; 53.0% were male.,Incidence was 2.2 per 1,000 person-years (95% CI: 2.2-2.3); 68.7% were classified in categories A/B and 31.3% in C/D, of which 17.2% did not receive COPD maintenance medication.,A third of COPD patients in the UK are considered high risk (GOLD 2013 categories C/D), and a third of patients are diagnosed for the first time at these severe stages.,Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD in the UK is warranted. | 1 |
Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD. | The prevalence of chronic obstructive pulmonary disease (COPD) in females appears to be increasing.,Recent studies have revealed that the percentage of women with COPD in Greece is approximately 12.5%.,To evaluate the burden of COPD among males and females in Greece through a nationwide cross-sectional survey and to explore sex differences regarding functional characteristics and exacerbation frequency.,Data collection was completed in a 6-month period.,The present study followed a nationwide sampling approach of respiratory medicine physicians.,The sampling approach included three steps: 1) estimation of expected incidence and prevalence of COPD cases in each prefecture of Greece and in total; 2) estimation of expected incidence of COPD cases per physician in each prefecture; and 3) creation of a frame of three different sampling zones.,Following this sampling, data were provided by 199 respiratory physicians.,The participating physicians provided data from 6,125 COPD patients.,Female patients represented 28.7% of the study participants.,Female COPD patients were, on average, 5 years younger than male COPD patients.,Never smokers accounted for 9.4% within female patients, compared to 2.7% of males (P<0.001).,Female patients were characterized by milder forms of the disease.,Comorbidities were more prevalent in men, with the exception of gastroesophageal reflux (14.6% versus 17.1% for men and women, respectively, P=0.013).,Female COPD patients had a higher expected number of outpatient visits per year (by 8.9%) than males (P<0.001), although hospital admissions did not differ significantly between sexes (P=0.116).,Females had fewer absences from work due to COPD per year, by 19.0% (P<0.001), compared to males.,The differences observed between male and female COPD patients provide valuable information which could aid the prevention and management of COPD in Greece. | 1 |
To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009.,A total of 45,837 male residents were observed for a median period of 19.1 years.,Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019.,During follow-up, 268 participants died from COPD.,The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41-0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59-0.68).,These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years.,Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality. | Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment.,The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status.,Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD.,Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD.,Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems.,It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism.,In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group).,After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species.,Later, the comparisons of individual lipids were performed between controls and patients with COPD.,Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers.,Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated.,Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD.,Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change.,In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers.,Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity.,Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years.,Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD.,Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD. | 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. | The changes in grading of disease severity and treatment recommendations for patients with COPD in the 2017 GOLD strategy may present an opportunity for reducing treatment burden for the patients and costs to the health care system.,The aim of this study was to assess the implications of the GOLD 2017 grading system in terms of change in distribution across GOLD groups A-D for existing patients in UK primary care and estimate the potential cost savings of implementing GOLD 2017 treatment recommendations in UK primary care.,Using electronic health record data from the Clinical Practice Research Datalink (CPRD), patients aged ≥35 years with spirometry-confirmed COPD, receiving care during 2016, were included.,The cohort was graded according to the GOLD 2017 groups (A-D), and treatment costs were calculated, according to corresponding recommendations, to observe the difference in actual vs predicted costs.,When applying GOLD 2013 criteria, less than half of the cohort (46%) was assigned to GOLD A or B, as compared to 86% when applying the GOLD 2017 grading.,The actual mean annual maintenance treatment cost was £542 per patient vs a predicted £389 for treatment according to the 2017 GOLD strategy.,There is a potential to make significant cost savings by implementing the grading and treatment recommendations from the 2017 GOLD strategy. | 1 |
The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs.,We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data.,COPD was confirmed by spirometry.,BMI was used to stratify patients into four categories: underweight (BMI <18.5 kg/m2), normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2).,Of the 1,320 patients with COPD with mild to moderate airflow obstruction, 27.8% had a BMI ≥25 kg/m2.,Compared with normal-weight patients, obese patients tended to experience fewer exacerbations (incidence rate ratio [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not significant in a multivariable analysis.,COPD-related health-care utilization and medical expenses were higher among underweight patients than the other groups.,After adjustment, the risk of COPD-related hospitalization was highest among underweight and higher among overweight patients vs normal-weight patients (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight, and obese groups, respectively; P = 0.01).,Decreased weight tends to negatively influence prognosis of COPD with mild to moderate airflow obstruction, whereas higher BMI was not significantly related to worse outcomes. | COPD affects over 13 million Americans, and accounts for over half a million hospitalizations annually.,The Hospital Readmission Reduction Program, established by the Affordable Care Act requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals with excess readmissions for COPD as of 2015.,This study sought to develop a predictive readmission scale to identify COPD patients at higher readmission risk.,Demographic and clinical data on 339,389 patients from New York and California (derivation cohort) and 258,113 patients from Washington and Florida (validation cohort) were abstracted from the State Inpatient Database (2006-2011), and the Readmission After COPD Exacerbation (RACE) Scale was developed to predict 30-day readmission risk.,Thirty-day COPD readmission rates were 7.54% for the derivation cohort and 6.70% for the validation cohort.,Factors including age 40-65 years (odds ratio [OR] 1.17; 95% CI, 1.12-1.21), male gender (OR 1.16; 95% CI, 1.13-1.19), African American (OR 1.11; 95% CI, 1.06-1.16), 1st income quartile (OR 1.10; 95% CI, 1.06-1.15), 2nd income quartile (OR 1.06; 95% CI, 1.02-1.10), Medicaid insured (OR 1.83; 95% CI, 1.73-1.93), Medicare insured (OR 1.45; 95% CI, 1.38-1.52), anemia (OR 1.05; 95% CI, 1.02-1.09), congestive heart failure (OR 1.06; 95% CI, 1.02-1.09), depression (OR 1.18; 95% CI, 1.14-1.23), drug abuse (OR 1.17; 95% CI, 1.09-1.25), and psychoses (OR 1.19; 95% CI, 1.13-1.25) were independently associated with increased readmission rates, P<0.01.,When the devised RACE scale was applied to both cohorts together, it explained 92.3% of readmission variability.,The RACE Scale reliably predicts an individual patient’s 30-day COPD readmission risk based on specific factors present at initial admission.,By identifying these patients at high risk of readmission with the RACE Scale, patient-specific readmission-reduction strategies can be implemented to improve patient care as well as reduce readmissions and health care expenditures. | 1 |
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies.,Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking.,Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions.,Exosomal miRNAs have been studied in relation to many diseases.,However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF.,Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts.,Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration.,Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL.,NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers.,Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively.,Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls.,Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets. | Microparticles (MPs) are small membrane vesicles of 0.1-1 µm which are released by cells following chemical, physical, and apoptotic stimuli.,MPs represent more than a miniature version of the cell.,Their composition and function depend not only on cellular origin, but also on stimuli.,Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by nearly irreversible lung destruction which results in airway limitation.,We investigated the presence and source of MPs in sputum of COPD patients to evaluate if changes in MP number and origin may reflect the pathophysiological conditions of disease and may serve as potential biomarkers for diagnostic and prognostic use.,Induced sputum samples were collected from 18 male subjects and liquefied with Sputasol.,MPs obtained were immunolabeled for leukocyte (CD11a), granulocyte (CD66b), monocyte-macrophage (CD11b), platelets and megakaryocytic cells (CD41), endothelial cells (CD31), and red blood cells (CD235ab) and analyzed by cytofluorimetry.,There was a negative correlation between CD31-MPs and forced expiratory volume in 1 second (R=−53, P<0.05) and CD66b-MP level was correlated with worse performance index of COPD such as the Body mass index airflow Obstruction, Dyspnea, and Exercise capacity (BODE); they were negatively correlated with 6-minute walking test: 0.65 and −0.64, respectively (P<0.05).,CD235ab-MPs showed a negative correlation with body mass index (R=−0.86, P<0.05), while there was a positive correlation with dyspnea index (R=0.91, P<0.05).,The main finding of this study was that MPs were detected in the sputum of patients affected by COPD.,The phenotype of some of them was related to the main COPD parameters.,These results suggest that MPs could be implicated in the pathogenesis of COPD. | 1 |
Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality.,Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations.,However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate.,The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.,We comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.,Eleven RCTs and one retrospective study including a total of 2,151 cases were carried out.,Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24-0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45-0.78; P<0.01).,Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months.,In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance.,The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50).,Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).,Prophylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner.,However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance.,Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks. | To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations.,Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included.,Repeated-measures t-tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after.,After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005).,These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed.,No pre-post differences were detected in the number of exacerbations not requiring admission.,Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA.,Clinical trials with a larger number of patients are needed in order to confirm these results. | 1 |
Chronic obstructive pulmonary disease (COPD) airways are characterised by thickening of airway smooth muscle, partly due to airway smooth muscle cell (ASMC) hyperplasia.,Metabolic reprogramming involving increased glycolysis and glutamine catabolism supports the biosynthetic and redox balance required for cellular growth.,We examined whether COPD ASMCs show a distinct metabolic phenotype that may contribute to increased growth.,We performed an exploratory intracellular metabolic profile analysis of ASMCs from healthy nonsmokers, healthy smokers and COPD patients, under unstimulated or growth conditions of transforming growth factor (TGF)-β and fetal bovine serum (FBS).,COPD ASMCs showed impaired energy balance and accumulation of the glycolytic product lactate, glutamine, fatty acids and amino acids compared to controls in unstimulated and growth conditions.,Fatty acid oxidation capacity was reduced under unstimulated conditions.,TGF-β/FBS-stimulated COPD ASMCs showed restoration of fatty acid oxidation capacity, upregulation of the pentose phosphate pathway product ribose-5-phosphate and of nucleotide biosynthesis intermediates, and increased levels of the glutamine catabolite glutamate.,In addition, TGF-β/FBS-stimulated COPD ASMCs showed a higher reduced-to-oxidised glutathione ratio and lower mitochondrial oxidant levels.,Inhibition of glycolysis and glutamine depletion attenuated TGF-β/FBS-stimulated growth of COPD ASMCs.,Changes in glycolysis, glutamine and fatty acid metabolism may lead to increased biosynthesis and redox balance, supporting COPD ASMC growth.,A metabolic shift in airway smooth muscle cells of COPD patients may support their increased growth and survivalhttp://ow.ly/XVkb30eUTLJ | Goblet cell hyperplasia is a classic but variable pathologic finding in COPD.,Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described.,We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.,We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers.,Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue.,Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane.,Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.,Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects.,COPD subjects had a greater GCD than nonsmokers.,When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD.,When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD.,This finding was also seen in those with CB in the COPD group alone.,In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates.,All other covariates were not significant predictors of GCD or MVD.,Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction.,This provides clinical and pathologic correlation for smokers with and without COPD. | 1 |
Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis.,Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM.,Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD.,This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014.,The primary outcome of interest was all-cause mortality.,We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population.,Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization.,Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM.,Moreover, metformin users had similar survival to COPD patients without DM.,This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard.,Our findings suggest a potential role of metformin in the management of DM in COPD.,The online version of this article (10.1186/s12931-019-1035-9) contains supplementary material, which is available to authorized users. | 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 |
The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
The prevalence of chronic obstructive pulmonary disease (COPD), a common and preventable chronic disease, is on the increase, and so are the financial and social burdens associated with it.,The management of COPD is particularly challenging, as patients have complex health and social needs requiring life-long monitoring and treatment.,In order to address these issues and reduce the burden imposed by COPD, the development of innovative disease management models is vital.,Nurses are in a key position to assume a leading role in the management of COPD since they frequently represent the first point of contact for patients and are involved in all stages of care.,Although evidence is still limited, an increasing number of studies have suggested that nurse-led consultations and interventions for the management of COPD have the potential to impact positively on the health and quality of life of patients.,The role of nurses in the management of COPD around the world could be significantly expanded and strengthened.,Providing adequate educational opportunities and support to nurses, as well as addressing funding issues and system barriers and recognising the importance of the expanding roles of nurses, is vital to the well-being of patients with long-term medical conditions such as COPD and to society as a whole, in order to reduce the burden of this disease. | Antibiotic and oral corticosteroid prescribing rate in patients suffering from acute exacerbations of chronic obstructive pulmonary disease (COPD) or asthma in general practice are only sparsely described.,Our aim was to identify predictors for such prescribing when results from CRP testing, spirometry, and pulse oximetry are available.,Patients aged 40 years or more diagnosed with asthma, COPD or both, the previous five years from seven general practice offices in Norway, were invited to a baseline examination and asked to visit their GPs during exacerbations the following 12 months.,At all visits, symptoms, chest findings, and results from spirometry, pulse oximetry and CRP testing were registered.,Out of the 376 who took part in baseline examination, 95 patients with an exacerbation were included in the analysis.,Based on the diagnosis made by GPs, 46 patients (48.4%) were only registered with asthma, and 49 (51.6%) with COPD (or both diagnosis). 11 patients had taken antibiotics and 16 had taken systemic corticosteroids prior to their visit to their GPs.,After excluding those already treated, antibiotics were prescribed in 34.9% and systemic corticosteroids in 42.5% of patients diagnosed with COPD compared to 14.6% and 30.8% respectively in patients only diagnosed with asthma (P = 0.02, P = 0.2).,In the COPD group, antibiotic prescribing was not significantly associated with purulence or other respiratory symptoms, but increased phlegm was a significant predictor of antibiotic prescribing in the whole sample (P = 0.04).,Prolonged expiration, wheezes and diminished breath sounds also predicted the prescribing of both antibiotics and systemic corticosteroids in the whole sample with P values < 0.01.,The prescribing rate of antibiotics and systemic corticosteroids also increased with increasing CRP value (P = 0.001 and P = 0.01, respectively) and with decreasing oxygen saturation (P = 0.01 and P = 0.003, respectively).,FEV1/FVC < 0.7 at baseline was as significant predictor in patients with COPD and in the whole sample of patients regarding treatment with antibiotics (P = 0.004 and P = 0.001, respectively) and treatment with systemic corticosteroids (P = 0.004 and P = 0.001, respectively).,Chest findings, raised CRP value and decreased oxygen saturation were stronger predictors of prescribing of antibiotics and systemic corticosteroids than were respiratory symptoms.,Further evaluation of the importance of these findings to guide treatment of asthma and COPD exacerbations is warranted. | 1 |
Sleep disturbance has been termed the forgotten dimension of chronic obstructive pulmonary disease (COPD), but it is clinically important as most patients are affected.,This study examined the incremental burden of illness associated with sleep disturbance in COPD, with reference to health status and disease impact, and the degree of concordance between physicians and patients in reporting night-time COPD symptoms.,Real-world data from >2,500 patients with COPD consulting for routine care were derived from respiratory Disease-Specific Programs conducted in Europe, the USA, and China.,Night-time COPD symptom burden was assessed from patient and physician perspectives.,Patients completed the Jenkins Sleep Evaluation Questionnaire (JSEQ), COPD assessment test (CAT), and EuroQol five-dimension questionnaire (EQ-5D).,A regression approach was used to analyze the relationship between sleep disturbance (JSEQ score) and health status (EQ-5D score), adjusting for confounding variables.,Frequency of night-time symptoms was high and was higher when reported by patients than physicians (69.7% and 65.7%, respectively).,According to the JSEQ, 73.3% of patients had trouble falling asleep, 75.3% experienced night-time awakenings, 70.6% had trouble staying asleep, and 67.7% woke after a usual amount of sleep feeling worn out.,Over half (52.7%) of patients received maintenance treatment where night-time symptom relief was stated by the physician as a treatment aim.,A one unit increase in JSEQ score was associated with increased CAT score (0.7 units in Europe and the USA; 0.2 units in China).,Sleep disturbance was significantly associated with worse health status (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.18, 1.36, P<0.001 for Europe; OR: 1.23, 95% CI: 1.12, 1.38, P<0.001 for the USA; and OR: 1.19, 95% CI: 1.10, 1.28, P<0.001 for China).,Night-time symptoms and sleep disturbance are common among patients with COPD, and sleep disturbance has a detrimental impact on COPD symptoms and health status. | Past research has suggested significant relationships between symptoms and health outcomes among patients with COPD.,However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment.,As a result, the aim of this study was to document the burden of COPD symptoms among those who are currently treated with the standard-of-care (SOC) medications in both the US and Western Europe.,Data from the 2013 US (N=75,000) and 2011 (N=57,512)/2013 (N=62,000) European (France, Germany, Italy, Spain, and UK; 5EU) National Health and Wellness Survey (NHWS) were used.,The NHWS is a health survey administered to a demographically representative sample of the adult population in each country.,A total of 1,666 and 2,006 patients with self-reported physician diagnosis of COPD in the 5EU and US, respectively, were being treated with the appropriate SOC (based on self-reported medication use) and were included in the analyses.,Symptoms (eg, dyspnea, coughing, wheezing) were reported descriptively and summed to create a symptom score (with higher score indicating more frequent symptoms).,The relationships between the symptom score and patient outcomes (eg, health status using the Short Form-36 version 2 [SF-36v2], work productivity and activity impairment [WPAI], and self-reported health care resource use) were explored using regression modeling.,Nearly all patients (99.7% and 99.8% in the 5EU and US, respectively) reported experiencing symptoms and >80% reported experiencing at least one symptom “often”.,Increasing symptom scores were associated with poorer health status (unstandardized beta [b] =−0.87 and −0.78 for mental component summary and physical component summary, respectively, in the US and b =−0.67 and −0.79 in the 5EU, respectively; all P<0.05).,Increasing symptom scores were also associated with greater work impairment (b =0.09 and 0.06 for the US and 5EU, respectively), activity impairment (b =0.05 and 0.06, respectively), and health care resource utilization (eg, hospitalizations: b =0.05 and 0.06, respectively) (all P<0.05).,Approximately 70% of patients reported some level of non-adherence.,Greater non-adherence was significantly associated with more frequent symptoms, poorer health status, and greater work impairment and health care resource use (all P<0.05).,Patients with COPD who are using the appropriate SOC still experience symptoms, which have a significant effect on both humanistic and economic outcomes. | 1 |
Genome-wide association studies (GWAS) and candidate gene studies have identified a number of risk loci associated with the smoking-related disease COPD, a disorder that originates in the airway epithelium.,Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome, enriched, in part, at known GWAS/candidate gene loci.,Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n = 10) and healthy smokers (n = 7).,The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS to confer risk for COPD.,Smoker BC have 676 genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation.,Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10−4 compared to chance), including 4 genes (NFKBIB, LTBP4, EGLN2 and TGFB1) associated with risk for COPD.,These observations provide the first direct connection between known genetic risks for smoking-related lung disease and airway BC, the population of lung cells that undergo the earliest changes associated with smoking. | Smoking and COPD are associated with decreased mucociliary clearance, and healthy smokers have shorter cilia in the large airway than nonsmokers.,We hypothesized that changes in cilia length are consistent throughout the airway, and we further hypothesized that smokers with COPD have shorter cilia than healthy smokers.,Because intraflagellar transport (IFT) is the process by which cilia of normal length are produced and maintained, and alterations in IFT lead to short cilia in model organisms, we also hypothesized that smoking induces changes in the expression of IFT-related genes in the airway epithelium of smokers and smokers with COPD.,To assess these hypotheses, airway epithelium was obtained via bronchoscopic brushing.,Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject and Affymetrix microarrays were used to evaluate IFT gene expression in nonsmokers and healthy smokers in 2 independent data sets from large and small airway as well as in COPD smokers in a data set from the small airway.,In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers.,The gene expression data confirmed that a set of 8 IFT genes were down-regulated in smokers in both data sets; however, no differences were seen in COPD smokers compared to healthy smokers.,These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers.,Strategies to normalize cilia length may be an important avenue for novel COPD therapies. | 1 |
Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy.,It is unknown whether socioeconomic deprivation associates with rates of completion of PR or the magnitude of clinical benefits bequeathed by PR.,PR services across England and Wales enrolled patients to the National PR audit in 2015.,Deprivation was assessed using Index of Multiple Deprivation (IMD) derived from postcodes.,Study outcomes were completion of therapy and change in measures of exercise performance and health status.,Univariate and multivariate analyses investigated associations between IMD and these outcomes.,210 PR programmes enrolled 7413 patients.,Compared with the general population, the PR sample lived in relatively deprived neighbourhoods.,There was a statistically significant association between rates of completion of PR and quintile of deprivation (70% in the least and 50% in the most deprived quintiles).,After baseline adjustments, the risk ratio (95% CI) for patients in the most deprived relative to the least deprived quintile was 0.79 (0.73 to 0.85), p<0.001.,After baseline adjustments, IMD was not significantly associated with improvements in exercise performance and health status.,In a large national dataset, we have shown that patients living in more deprived areas are less likely to complete PR.,However, deprivation was not associated with clinical outcomes in patients who complete therapy.,Interventions targeted at enhancing referral, uptake and completion of PR among patients living in deprived areas could reduce morbidity and healthcare costs in such hard-to-reach populations. | Singing group participation may benefit patients with chronic obstructive pulmonary disease (COPD).,Previous studies are limited by small numbers of participants and short duration of generally hospital-based singing group intervention.,This study examines the feasibility of long-term participation in a community singing group for patients with COPD who had completed pulmonary rehabilitation (PR).,This was a feasibility cohort study.,Patients with COPD who had completed PR and were enrolled in a weekly community exercise group were recruited to a new community-based singing group which met weekly for over 1 year.,Measurements at baseline, 4 months and 1 year comprised comprehensive pulmonary function tests including lung volumes, 6 min walk test (6MWT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and hospital admission days for acute exacerbation of COPD (AECOPD) for 1 year before and after the first singing group session.,There were 28 participants with chronic lung disease recruited from 140 people approached.,Five withdrew in the first month. 21 participants meeting Global Initiative for Chronic Obstructive Lung Disease criteria for COPD completed 4-month and 18 completed 1-year assessments.,The mean attendance was 85%.,For the prespecified primary outcome measure, total HADS score, difference between baseline and 12 months was −0.9, 95% CI −3.0 to 1.2, p=0.37.,Of the secondary measures, a significant reduction was observed for HADS anxiety score after 1 year of −0.9 (95% CI −1.8 to −0.1) points, p=0.038 and an increase in the 6MWT at 1 year, of 65 (95% CI 35 to 99) m compared with baseline p<0.001.,Our findings support the feasibility of long-term participation in a community singing group for adults with COPD who have completed PR and are enrolled in a weekly community exercise group and provide evidence of improved exercise capacity and a reduction in anxiety.,ACTRN12615000736549; Results. | 1 |
Since the introduction of the Quality and Outcomes framework, there has been some evidence of improvement in the management of chronic obstructive pulmonary disease (COPD) patients in the United Kingdom through increasing rates of smoking cessation advice and immunisations against influenza.,However, it is unknown whether disease-specific management criteria, disease outcomes and diagnosis have improved.,To describe changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009.,The study was done on a retrospective cohort using data from The Health Improvement Network UK primary care database.,We calculated age at diagnosis of COPD and death, total number of short-term oral corticosteroid courses and consultations, and proportion of patients with very severe COPD and on triple inhaled therapy for each year between 2000 and 2009.,We identified 92,576 patients with COPD.,The mean age at COPD diagnosis decreased from 68.1 years in 2000 to 66.7 years in 2009.,The mean age at death increased from 78.2 years in 2000 to 78.8 years in 2009.,The number of prescribed courses of oral corticosteroids increased from 0.6 in 2000 to 0.8 in 2009.,The number of consultations increased from 9.4 in 2004 to 11.3 in 2009.,The risk of having very severe COPD decreased from 9.4% in 2004 to 6.8% in 2009.,The likelihood of patients with very severe COPD receiving triple therapy increased from 25% in 2004 to 59% in 2009.,The trends suggest that management and outcomes observed in patients with COPD may have improved since the year 2000. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE‚ sElf-management anD support proGrammE) in improving quality of life and clinical outcomes.,We compared daily use of EDGE with usual care for 12 months.,The primary outcome was COPD-specific health status measured with the St George’s Respiratory Questionnaire for COPD (SGRQ-C).,A total of 166 patients were randomized (110 EDGE, 56 usual care).,All patients were included in an intention to treat analysis.,The estimated difference in SGRQ-C at 12 months (EDGE−usual care) was −1.7 with a 95% CI of −6.6 to 3.2 (P=.49).,The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care.,Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03).,The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively.,The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention.,However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6pmfIJ9KK) | In patients with COPD progressive dyspnoea leads to a sedentary lifestyle.,To date, no studies exist investigating the effects of Nordic Walking in patients with COPD.,Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages.,Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity.,Sixty COPD patients were randomised to either Nordic Walking or to a control group.,Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV1: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention.,Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD).,Assessment time points in both groups: baseline, after three, six and nine months.,After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s2) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01).,Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01).,These significant improvements were sustained six and nine months after baseline.,In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points.,Nordic Walking is a feasible, simple and effective physical training modality in COPD.,In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.,Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632 | 1 |
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