a stringlengths 138 8.15k | b stringlengths 138 8.15k | label int64 1 1 |
|---|---|---|
Exposure to high levels of particulate matter (PM) poses a major threat to human health.,Cigarette smoke is the most common irritant that causes chronic obstructive pulmonary disease (COPD); however, at least one-fourth of patients with COPD are nonsmokers, and their disease is largely attributed to air pollution.,The occurrence of pollution episodes in China has raised an emergent question of how PM leads to the pathogenesis of COPD.,In this paper, we show that deregulation of mitochondrial NADH dehydrogenase gene expression levels plays a key role in the aggravation of COPD during air pollutant exposure, which can be rescued by taurine and 3-MA treatments in both mammalian cells and animals.,Chronic obstructive pulmonary disease (COPD) has been linked to particulate matter (PM) exposure.,Using transcriptomic analysis, we demonstrate that diesel exhaust particles, one of the major sources of particulate emission, down-regulated genes located in mitochondrial complexes I and V and induced experimental COPD in a mouse model.,1-Nitropyrene was identified as a major toxic component of PM-induced COPD.,In the panel study, COPD patients were found to be more susceptible to PM than individuals with normal lung function due to an increased inflammatory response.,Mechanistically, exposure to PM in human bronchial epithelial cells led to a decline in CCAAT/enhancer-binding protein alpha (C/EBPα), which triggered aberrant expression of NADH dehydrogenase genes and ultimately led to enhanced autophagy.,ATG7-deficient mice, which have lower autophagy rates, were protected from PM-induced experimental COPD.,Using metabolomics analysis, we further established that treatment with taurine and 3-methyladenine completely restored mitochondrial gene expression levels, thereby ameliorating the PM-induced emphysema.,Our studies suggest a potential therapeutic intervention for the C/EBPα/mitochondria/autophagy axis in PM-induced COPD. | Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in those with chronic obstructive pulmonary disease (COPD).,Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD.,To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples from healthy nonsmokers, healthy smokers, and COPD patients.,BOEC from smokers and COPD patients showed increased DNA double-strand breaks and senescence compared to nonsmokers.,Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence.,Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence.,Treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or an ATM inhibitor (KU-55933) also rescued the senescent phenotype.,Using an in vivo mouse model of angiogenesis, we demonstrated that senescent BOEC from COPD patients are dysfunctional, displaying impaired angiogenic ability and increased apoptosis compared to cells from healthy nonsmokers.,Therefore, this study identifies epigenetic regulation of DNA damage and senescence as pathogenetic mechanisms linked to endothelial progenitors' dysfunction in smokers and COPD patients.,These defects may contribute to vascular disease and cardiovascular events in smokers and could therefore constitute therapeutic targets for intervention. | 1 |
Decorin, an extracellular matrix (ECM) proteoglycan, and TGF-β1 are both involved in lung ECM turnover.,Decorin and TGF-β1 expression are decreased respectively increased in COPD lung tissue.,Interestingly, they act as each other's feedback regulator.,We investigated whether single nucleotide polymorphisms (SNPs) in decorin and TGF-β1 underlie accelerated decline in FEV1 and development of COPD in the general population.,We genotyped 1390 subjects from the Vlagtwedde/Vlaardingen cohort.,Lung function was measured every 3 years for a period of 25 years.,We tested whether five SNPs in decorin (3'UTR and four intron SNPs) and three SNPs in TGF-β1 (3'UTR rs6957, C-509T rs1800469 and Leu10Pro rs1982073), and their haplotypes, were associated with COPD (last survey GOLD stage = II).,Linear mixed effects models were used to analyze genotype associations with FEV1 decline.,We found a significantly higher prevalence of carriers of the minor allele of the TGF-β1 rs6957 SNP (p = 0.001) in subjects with COPD.,Additionally, we found a significantly lower prevalence of the haplotype with the major allele of rs6957 and minor alleles for rs1800469 and rs1982073 SNPs in TGF-β1 in subjects with COPD (p = 0.030), indicating that this association is due to the rs6957 SNP.,TGF-β1 SNPs were not associated with FEV1 decline.,SNPs in decorin, and haplotypes constructed of both TGF-β1 and decorin SNPs were not associated with development of COPD or with FEV1 decline.,Our study shows for the first time that SNPs in decorin on its own or in interaction with SNPs in TGF-β1 do not underlie the disturbed balance in expression between these genes in COPD.,TGF-β1 SNPs are associated with COPD, yet not with accelerated FEV1 decline in the general population. | The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function.,The aims of this study were to investigate total mortality risks in GOLD stages 0-4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1-4.,Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits.,Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses.,Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0-4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group.,HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1-4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.,The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively.,The proportion of smokers among men was 50% and among women 40%.,Self reported comorbidity was present in 4.6% of the men and 6.6% of the women.,Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32-2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31-1.70).,The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98-1.29).,Among male smokers with stage 1; HR: 2.04 (1.34-3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38-7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.,Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2). | 1 |
GOLD guidelines classify COPD patients into A-D groups based on health status as assessed by COPD Assessment Test (CAT) or mMRC tools and exacerbations and recommend single or dual long-acting bronchodilators as maintenance therapy, with additional inhaled corticosteroids (ICS) if the disease remains uncontrolled.,We aimed to classify primary care COPD patients into A-D groups, assess usual treatment and adherence to guidelines, potential mismatches between CAT-and mMRC-based classification and described symptoms within groups.,A total of 257 primary care COPD patients were enrolled between 2015 and 2016 in Greece.,Physicians used structured interviews to collect cross-sectional data including demographics, symptoms, CAT, mMRC scores, and medications.,Patients were classified into A-D groups based on CAT and mMRC, and prevalence of symptoms and medication was estimated within A-D groups.,Interviews with physicians were also performed to explore additional issues about treatment and adherence to guidelines.,Mean (SD) age was 65 (12.3) years with 79% males.,The majority of patients reported uncontrolled symptoms (91% and 61% with ≥10 CAT or ≥2 mMRC scores, respectively).,Thirty-seven percentage had $2 exacerbations in the past year.,Group B was the largest followed by Groups D, A, and C.,Patients were classified as more severe by CAT than by mMRC.,In all groups, the majority were treated with combined long-acting beta agonist/ICS (> 50%).,When patients were asked to report their main symptoms, dyspnea and cough were the most important symptoms mentioned, and there was a great variation between the A-D groups.,However, Groups A-C reported mainly morning symptoms, whereas Group D suffered symptoms all day.,Physicians reported a significant number of barriers to implementing guidelines, eg, frequent lack of guideline updates, access to diagnostic procedures, and prescription-reimbursement issues.,Our study confirms poor adherence to guidelines regarding treatment with an overuse of ICS and important barriers to implementation.,A mismatch in classification occurs depending on the tool used, which can mislead clinicians in their choice of treatment. | 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 |
There is much description in the literature of how patients with chronic obstructive pulmonary disease (COPD) manage their breathlessness and engage in self-care activities; however, little of this is from the perspective of those with less severe disease, who are primarily managed in primary care.,This study aimed to understand the self-care experiences of patients with COPD who are primarily managed in primary care, and to examine the challenges of engaging in such behaviors.,Semistructured interviews were carried out with 15 patients with COPD as part of a larger project evaluating a self-management intervention.,Thematic analysis was supported by NVivo software (version 8, QSR International, Melbourne, Australia).,Three main themes are described, ie, experiencing and understanding symptoms of COPD, current self-care activities, and the importance of family perceptions in managing COPD.,Self-care activities evolved spontaneously as participants experienced symptoms of COPD.,However, there was a lack of awareness about whether these strategies would impact upon symptoms.,Perceptions of COPD by family members posed a challenge to self-care for some participants.,Health care professionals should elicit patients’ prior disease experiences and utilize spontaneous attempts at disease management in future self-management.,These findings have implications for promoting self-management and enhancing quality of life. | To unpack and interpret descriptions of experiences of social relationships during pulmonary rehabilitation (PR) for people living with chronic obstructive pulmonary disease (COPD).,Inspired by interpretive phenomenology, individual qualitative interviews were conducted twice with 18 persons from COPD rehabilitation units in two general hospitals.,Qualitative content analysis was performed.,Analysis of the interviews revealed the overarching theme of belonging.,The participants emphasised social integration in rehabilitation groups as well as support from peers and health-care personnel as important dimensions of social relationships with regard to PR.,Active participation in and engagement with the groups provided opportunities for patients to share their knowledge, encouraged mutual trust, and support and increased self-confidence, and motivation for self-care and further social participation.,Integration in the groups and perceived support during PR made coping and adaptation easier and had a positive effect on quality of life.,Patients' perspectives on PR were strongly influenced by certain facets of social relationships, such as social integration and social support.,Patients', peers' and health-care professionals' strategies to promote social support and social integration should be further explored in the future, both in different contexts and for longer periods of time. | 1 |
Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD.,While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with - according to Belgian market research data - up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting β2-adrenoreceptor agonist.,Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD.,However, historical habits appear difficult to change even in the light of recent scientific evidence.,We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter. | The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly. | 1 |
Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure.,We have shown previously that chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice.,These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke.,Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice.,We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure.,At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure.,Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure.,The remaining lung function measurements including quasistatic compliance were similar amongst all groups.,This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD.,These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways.,These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers. | COPD is a major cause of chronic morbidity and mortality throughout the world.,Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved.,We aimed to clarify the role of TNFRs in the development of pulmonary emphysema.,TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice.,After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined.,In addition, the relationship between apoptosis and emphysema was investigated.,Pulmonary emphysema-like changes disappeared with deletion of TNFR1.,However, slight improvements were attained with deletion of TNFR2.,Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice.,The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema.,In contrast, the inflammatory process has a less important role for the development of emphysema. | 1 |
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | 1 |
COPD is a common irreversible obstructive airway disease.,S100A1, ZAG, and adiponectin are important regulators of energy metabolism and body weight.,Therefore, the aim of this study was to assess resting metabolic rate (RMR) and its association with serum levels of S100A1, ZAG, and adiponectin in cachectic and noncachectic COPD patients.,Ninety men with COPD, aged 40-70 years, were enrolled in the study.,Patients were divided into the following two groups based on the unintentional weight loss of .7.5% in previous 6 months: noncachectic (n=45) and cachectic (n=45).,The groups were matched based on age and body mass index (BMI).,RMR was measured by indirect calorimetry method.,Anthropometric indices and body composition were also measured.,Serum levels of S100A1, ZAG, and adiponectin were measured by ELISA.,Cachectic patients had significantly higher RMR than controls (P<0.001).,Serum levels of ZAG, S100A1, and adiponectin were significantly higher in the cachexia group (P<0.0001).,RMR was not significantly associated with S100A1, ZAG, and adiponectin levels.,However, weight loss of patients was significantly associated with serum levels of ZAG and adiponectin (both, β=0.22, P=0.03).,Strong and positive association were found between the serum levels of S100A1 and ZAG (β=0.88, P<0.0001), S100A1 and adiponectin (β=0.86, P<0.0001), and also ZAG and adiponectin (β=0.83, P<0.0001).,The potential role of these factors in the wasting process is considerable.,Also, the association between serum levels of S100A1, ZAG, and adiponectin represents that these three proteins are probably related to specific functions. | The prognosis of Japanese patients with COPD who suffer repeated exacerbations is unclear, although Westerners with such episodes have a poor prognosis.,We conducted a 1-year prospective observational trial involving 90 Japanese patients with COPD: 58 nonexacerbators, 12 infrequent exacerbators, and 20 frequent exacerbators classified on the basis of exacerbation frequency (zero, one, and two or more exacerbations/year), respectively, during the previous year were observed prospectively for 1 year.,The characteristics of frequent exacerbators, the frequency of exacerbation, and the period until the first event were then compared among the groups.,A total of 78 patients completed the study.,Frequent exacerbators had a significantly higher risk of frequent exacerbation in the following year than the case for nonexacerbators (odds ratio [95% confidence interval] 2.94 [1.21-7.17], P=0.0340), but not in comparison with infrequent exacerbators (1.51 [0.49-4.63], P>0.05).,The mean annual frequency of exacerbations in the following year was significantly (P=0.0020) higher in the frequent exacerbators (1.4 exacerbations/year) than in the nonexacerbators (0.4), but not in the infrequent exacerbators (0.9, P>0.05).,The mean period until the first exacerbation was significantly shorter in the frequent exacerbators than in the infrequent or nonexacerbators (P=0.0012).,Independent risk factors for future frequent exacerbation included the presence of gastroesophageal reflux disease, more severe airflow obstruction, and use of inhaled corticosteroids.,Our present results indicate that Japanese COPD patients suffering frequent exacerbation have a poor prognosis.,The characteristics of Japanese and Western COPD patients suffering frequent exacerbation are similar. | 1 |
Hyponatremia is prevalent and associated with mortality in patients with heart failure (HF).,The prevalence and prognostic implications of hyponatremia in acute exacerbation of chronic obstructive pulmonary (AECOPD) have not been established.,We included 313 unselected patients with acute dyspnea who were categorized by etiology of dyspnea according to established guidelines (derivation cohort).,Serum Na+ was determined on hospital admission and corrected for hyperglycemia, and hyponatremia was defined as [Na+]<137 mmol/L.,Survival was ascertained after a median follow-up of 816 days and outcome was analyzed in acute HF (n = 143) and AECOPD (n = 83) separately.,Results were confirmed in an independent AECOPD validation cohort (n = 99).,In the derivation cohort, median serum Na+ was lower in AECOPD vs. acute HF (138.5 [135.9-140.5] vs.,139.2 [136.7-141.3] mmol/L, p = 0.02), while prevalence of hyponatremia (27% [22/83] vs. 20% [29/143], p = 0.28) and mortality rate (42% [35/83] vs. 46% [66/143], p = 0.56) were similar.,By univariate Cox regression analysis, hyponatremia was associated with increased mortality in acute HF (HR 1.85 [95% CI 1.08, 3.16], p = 0.02), but not in AECOPD (HR 1.00 [0.47, 2.15], p = 1.00).,Analogous to the results of the derivation cohort, hyponatremia was prevalent also in the AECOPD validation cohort (25% [25/99]), but not associated with mortality.,The diverging effect of hyponatremia on outcome between AECOPD and acute HF was statistically significant (p = 0.04).,Hyponatremia is prevalent in patients with acute HF and AECOPD, but is associated with mortality in patients with acute HF only. | To identify if there is a dose-dependent risk of diabetes complications in patients treated with corticosteroids who have both diabetes and chronic obstructive pulmonary disorder (COPD).,A retrospective study of administrative claims data from the Australian Government Department of Veterans’ Affairs, from 1 July 2001 to 30 June 2008, of diabetes patients newly initiated on metformin or sulfonylurea.,COPD was identified by dispensings of tiotropium or ipratropium in the 6 months preceding study entry.,Total corticosteroid use (inhaled and systemic) in the 12 months after study entry was determined.,The outcome was time to hospitalization for a diabetes-related complication.,Competing risks and Cox proportional hazard regression analyses were conducted with adjustment for a number of covariates.,A total of 18,226 subjects with diabetes were identified, of which 5.9% had COPD.,Of those with COPD, 67.2% were dispensed corticosteroids in the 12 months from study entry.,Stratification by dose of corticosteroids demonstrated a 94% increased likelihood of hospitalization for a diabetes complication for those who received a total defined daily dose (DDD) of corticosteroids ≥0.83/day (subhazard ratio 1.94 [95% CI 1.14-3.28], P = 0.014), by comparison with those who did not receive a corticosteroid.,Lower doses of corticosteroid (<0.83 DDD/day) were not associated with an increased risk of diabetes-related hospitalization.,In patients with diabetes and COPD, an increased risk of diabetes-related hospitalizations was only evident with use of high doses of corticosteroids.,This highlights the need for constant revision of corticosteroid dose in those with diabetes and COPD, to ensure that the minimally effective dose is used, together with review of appropriate response to therapy. | 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) | The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care.,The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation.,Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care).,Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care.,The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32).,The program was accessed on 86% of the treatment days, especially the diary.,Patient adherence with the exercise scheme was low (21%).,Health care providers seem to play an important role in patients’ adherence to telehealth in usual care.,Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence. | 1 |
Although, to our knowledge, there has been no exhaustive or credible review of the evidence of the disease burden of COPD in China, COPD has become an increasing public health concern to the Chinese medical community.,The purpose of this article is to review the evidence and evaluate and clarify the disease burden of COPD in China with the aim of improving effective management.,We reviewed previous studies of COPD in China, which included data on prevalence, mortality, disease burden, risk factors, diagnosis, and management by searching related Web sites, including PubMed, ProQuest, and Thomson Reuters' Web of Knowledge, as well as major Chinese databases and government Web sites.,Reported COPD prevalence varied between 5% and 13% in different provinces/cities across China.,In 2008, COPD ranked fourth as a leading cause of death in urban areas and third in rural areas.,In addition, COPD accounted for 1.6% of all hospital admissions in China in that year.,The high prevalence of smoking and biomass fuel use acted as major contributors to the high occurrence of COPD in China.,Management of COPD in China should focus on adjusting the distribution of medical resources and on addressing public health policies to facilitate earlier diagnosis in rural areas, aim to reduce smoking prevalence, improve patients' self-management, and keep physicians' knowledge up to date and consistent with current guidelines.,COPD is one of the most challenging medical issues facing China because of its influence on both personal and public health and its impact on the economy.,Optimal management strategies should be adopted and strengthened immediately. | Gastro-oesophageal reflux disease (GORD) is common among chronic obstructive pulmonary disease (COPD) patients and may have a deleterious effect on COPD prognosis.,However, few studies have investigated whether GORD increases the risk of severe outcomes such as intensive care unit (ICU) admittance or mechanical ventilator use among COPD patients.,Propensity score matching by age, sex, comorbidities and COPD severity was used to match the 1,210 COPD patients with GORD sourced in this study to 2,420 COPD patients without GORD.,The Kaplan-Meier method was used to explore the incidence of ICU admittance and machine ventilation with the log rank test being used to test for differences.,Cox regression analysis was used to explore the risk of ICU admittance and mechanical ventilation use for patients with and without GORD.,During the 12-month follow-up, GORD patients and non-GORD patients had 5.22 and 3.01 ICU admittances per 1000 person-months, and 4.34 and 2.41 mechanical ventilation uses per 1000 person-month, respectively.,The log rank test revealed a difference in the incidence of ICU admittance and machine ventilation between the two cohorts.,GORD was found to be an independent predicator of ICU admittance (adjusted hazard ratio (HRadj) 1.75, 95% confidence interval (CI) 1.28-2.38) and mechanical ventilation (HRadj 1.92, 95% CI 1.35-2.72).,This is the first investigation to detect a significantly higher incidence rate and independently increased risk of admission to an ICU and mechanical ventilation use among COPD patients who subsequently developed GORD during the first year following their GORD diagnosis than COPD patients who did not develop GORD.,The online version of this article (doi:10.1186/s13054-015-0849-1) contains supplementary material, which is available to authorized users. | 1 |
Guidelines are critical for facilitating cost-effective COPD care.,Development and implementation in low-and middle-income countries (LMICs) is challenging.,To guide future strategy, an overview of current global COPD guidelines is required.,We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation.,Scoping review of national COPD management guidelines.,We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards.,LMICs guidelines were compared with those from high-income countries (HICs).,Of the 61 national COPD guidelines identified, 30 were from LMICs.,Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines.,Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities.,More than 90% of all guidelines included smoking cessation advice.,Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%).,LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05).,LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05).,Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation.,Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated.,Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources. | Caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function.,However, no systematic review has examined how the caregiver role has been operationalized in interventions to improve outcomes of individuals with COPD or the quality or effectiveness of these interventions.,The aims of this review were to 1) determine whether caregivers have been involved as part of interventions to improve outcomes of individuals with COPD; 2) determine the risk of bias within included intervention studies; and 3) examine the effectiveness of interventions that have involved caregivers in improving outcomes of individuals with COPD.,The electronic databases of Medline, Embase, PsycINFO, and Cochrane Library were searched from January 2000 to November 2015.,Experimental studies testing interventions that involved a caregiver to improve COPD patient outcomes were eligible.,Nine studies involving caregivers met inclusion criteria.,No studies reported any intervention components targeted solely at caregivers, with most instead including caregivers in dyadic or group education sessions about COPD delivered by health care professionals.,The risk of bias identified in included studies was mixed.,Seven of the nine studies were effective in improving a broad range of outcomes.,These findings highlight that there is an urgent need for methodologically rigorous interventions to examine the effectiveness of strategies to assist caregivers to provide direct care, encourage adherence to health care provider recommendations, act as a health care advocate, and provide emotional and psychosocial support to individuals with COPD. | 1 |
Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease.,An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly.,We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry.,We also studied 10 healthy never smokers (not exposed to smoking) as controls.,Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection) might be different in man and women, we stratified participant recruitment by sex.,Differentially expressed genes were validated by q-PCR.,Ontology enrichment was evaluated and interaction networks inferred.,Principal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking.,In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature) or smokers with normal spirometry (Smoking related signature), their ontologies and interaction networks.,The use of an experimental intervention (smoking exposure) to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females. | Recent investigations suggest that neutrophils play an important role in the immune response to lung cancer as well as chronic obstructive pulmonary disease (COPD).,The aim of this study was to evaluate the amount of neutrophils and markers of their activity in lung cancer and COPD and in coexistence of these two diseases.,In total, 267 persons were included in the study: 139 patients with lung cancer, 55 patients with lung cancer and COPD, 40 patients with COPD, and 33 healthy subjects.,Peripheral blood and BAL fluid samples were obtained for cell count analysis and determination of NE, MPO levels and ROS production.,NE and MPO levels in the serum and BAL fluid were determined by ELISA.,ROS production was analyzed by flow cytometer.,The percentage, cell count of neutrophils and neutrophil to lymphocyte ratio in the peripheral blood were significantly higher in lung cancer patients with or without COPD compared to COPD patients or healthy individuals (P < 0.05).,The percentage and cell count of neutrophils in BAL fluid were significantly lower in patients with lung cancer with or without COPD than in patients with COPD (P < 0.05).,However, BAL fluid and serum levels of both NE and MPO were significantly higher in patients with lung cancer than COPD patients or healthy individuals (P < 0.05).,Neutrophils produced higher amounts of ROS in patients with lung cancer with or without COPD compared with COPD patients or healthy individuals (P < 0.05).,The results from this study demonstrate higher degree of local and systemic neutrophilic inflammation in patients with lung cancer (with or without COPD) than in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease characterized by inflammatory cells activation and production of inflammatory mediators.,Methyl-CpG-binding domain protein 2 (MBD2) plays an important role in diverse immunological disorders by regulating immune cell functions, such as differentiation and mediator secretion.,However, the role of MBD2 in COPD remains unknown.,MBD2 protein expression in lung tissues of patients with COPD and cigarette smoke (CS)-exposed mice were evaluated by Western blot and immunohistochemistry.,The role of MBD2 in cigarette smoke extract (CSE)-induction of inflammatory mediator expression in the human bronchial epithelial (HBE) cell line was assessed by silencing MBD2 expression in vitro.,The involvement of signaling pathways in mediation of inflammation was tested with signaling inhibitors.,Compared with controls, MBD2 expression was distinctly reduced in the bronchial epithelium of both patients with COPD and CS-exposed mice.,Moreover, MBD2 expression was decreased in HBE after CSE stimulation in vitro.,Moreover, MBD2 knockdown enhanced interleukin (IL)-6 and IL-8 expression in HBE in the presence and absence of CSE treatment by the ERK signaling pathway.,MBD2 protein expression was reduced in the airway epithelium of COPD.,In HBE, this reduced expression was associated with increased levels of IL-6 and IL-8 mediated by the ERK pathway.,These results suggest that MBD2 could contribute to chronic airway inflammation in COPD. | Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration.,Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).,In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema.,Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models.,Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models.,These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments.,This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. | 1 |
The Global Initiative defines COPD for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status.,The World Health Organization (WHO) estimates that COPD will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and HIV/AIDS, by 2030.,The aim of this study was to determine the main structure feature of sputum potentially pathogenic microorganisms in subjects with COPD during the clinical stable state.,We employed a molecular genetics-based investigation of the bacteria community, including DNA isolation, PCR amplification and DGGE profiling.,PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers targeting the V3 region of the 16S rRNA gene was employed to characterize the overall COPD patient sputum microbiota composition, and some excised gel bands were cloned for sequencing.,Real-time PCR was further utilized to quantitatively analyze the subpopulation of microbiota using group-specific primers targeting Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa.,The DGGE profiles of two groups displayed significant differences between COPD and healthy groups (P < 0.05).,Real-time PCR revealed significant increases of Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa (P < 0.05) in the COPD group compared with the healthy group.,This study revealed strong relationship between alterations of sputum microbiota and COPD.,By determining the content of several types of bacteria, we can provide evidence to aid in the diagnosis and treatment of COPD. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD).,However, the anti-inflammatory mechanism of SFC remains unclear.,In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4+CD25+Foxp3+ regulatory T cells (Foxp3+Tregs) after SFC therapy.,Twenty-one patients with moderate or severe COPD received treatment with 50/500 μg of SFC twice a day for 12 weeks.,Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test.,The number of neutrophils, monocytes and lymphocytes in induced sputum were counted.,Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA.,The proportion of Foxp3+Tregs in the total CD4+ T cell of the peripheral blood was determined by flow cytometry.,The relationship between IL-17A levels and the percentage of Foxp3+Tregs was analyzed by statistical analysis.,After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased.,The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased.,Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged.,The proportion of Foxp3+Tregs in the total CD4+T cell population in the peripheral blood was drastically higher than that before treatment.,The level of IL-17A was negatively correlated with the proportion of Foxp3+Tregs in CD4+T cells.,SFC can reduce the levels of inflammatory factors and improve symptoms of COPD.,The levels of inflammatory factors are associated with the variation of Foxp3+Tregs in COPD.,This study was registered with http://www.chictr.org (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270 | 1 |
The incidence of chronic obstructive pulmonary disease (COPD) in China is very high.,This study aimed to assess the vulnerability of COPD patients in rural areas outside Xuzhou City, Jiangsu province, in order to provide helpful guidance for future research and public policies.,The vulnerability of 8,217 COPD patients was evaluated using a face-to-face questionnaire to obtain information on general characteristics, awareness, beliefs, medication usage, acute exacerbation of the disease, and economic burdens.,Direct economic burdens were calculated based on the questionnaire, and indirect economic burdens were estimated using local per capita income and life expectancy in 2008.,The years of potential life lost were calculated using loss of life years for each age group and multiplying by the number of deaths in a given age group.,Of the 8,217 patients, 7,921 (96.4%) had not heard of COPD, and 2,638 (32.1%) did not understand that smoking was a risk factor for COPD.,No patients had used inhalers, nebulizer drugs or oxygen therapy, either regularly or sporadically.,No patients had undergone pulmonary rehabilitation or surgical treatment, while 4,215 (51.3%) took theophylline to relieve dyspnea, and 3,418 (41.6%) used antibiotics to treat exacerbations.,A total of 2,925 (35.6%) patients had been admitted to hospital during the past year because of respiratory symptoms.,The average direct and indirect economic burdens on COPD patients were 1,090 and 20,605 yuan, respectively.,The vulnerability of patients in rural Xuzhou to COPD was high.,Their awareness of COPD was poor, their treatment during both the stable and acute exacerbation stages did not meet standards, and the economic burdens were large.,Interventions are therefore needed to improve the prevention and management of COPD in this population.,Further studies are required to verify these findings. | Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability.,The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea.,Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St.,Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI).,Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001).,Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ.,In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes.,ClinicalTrials.gov NCT00000606 | 1 |
Even with the dissemination of several clinical guidelines, chronic obstructive pulmonary disease (COPD) remains underdiagnosed and mismanaged by many primary care physicians (PCPs).,The objective of this study was to elucidate barriers to consistent implementation of COPD guidelines.,A cross-sectional study implemented in July 2008 was designed to assess attitudes and barriers to COPD guideline usage.,Five hundred US PCPs (309 family medicine physicians, 191 internists) were included in the analysis.,Overall, 23.6% of the surveyed PCPs reported adherence to spirometry guidelines over 90% of the time; 25.8% reported adherence to guidelines related to long-acting bronchodilator (LABD) use in COPD patients.,In general, physicians were only somewhat familiar with COPD guidelines, and internal medicine physicians were significantly more familiar than family physicians (P < 0.05).,In a multivariate model controlling for demographics and barriers to guideline adherence, we found significant associations with two tested guideline components.,Adherence to spirometry guidelines was associated with agreement with guidelines, confidence in interpreting data, ambivalence to outcome expectancy, and ability to incorporate spirometry into patient flow.,Adherence to LABD therapy guidelines was associated with agreement with guidelines and confidence in gauging pharmacologic response.,Adherence to guideline recommendations of spirometry use was predicted by agreement with the recommendations, self-efficacy, perceived outcome expectancy if recommendations were adhered to, and resource availability.,Adherence to recommendations of LABD use was predicted by agreement with guideline recommendations and self-efficacy.,Increasing guideline familiarity alone may have limited patient outcomes, as other barriers, such as low confidence and outcome expectancy, are more likely to impact guideline adherence. | Data on differences in clinical characteristics and management of COPD in different countries and settings are limited.,We aimed to characterize the profile of patients with COPD in a number of countries and their treatment in order to evaluate adherence to recommendations of international guidelines.,This was an observational, international, cross-sectional study on patients with physician-diagnosed COPD.,Demographic and clinical characteristics, risk factors, and treatment were collected by their physician via an internet web-based questionnaire developed for the study.,A total of 77 investigators from 17 countries provided data on 833 patients.,The countries with the highest number of patients included were: Argentina (128), Ecuador (134), Spain (162), and Hong Kong (153).,Overall, 79.3% were men and 81% former smokers, with a mean FEV1 = 42.7%, ranging from 34.3% in Hong Kong to 58.8% in Ecuador.,Patients reported a mean of 1.6 exacerbations the previous year, with this frequency being significantly and negatively correlated with FEV1(%) (r = −0.256; p < 0.0001).,Treatment with short-acting bronchodilators and theophyllines was more frequent in Ecuador and Hong Kong compared with Spain and Argentina, and in patients belonging to lower socioeconomic levels (p < 0.0001 for all comparisons).,Inadequacy of treatment with inhaled corticosteroids and theophyllines was high, with significant differences among countries.,Differences in the clinical characteristics and management of COPD were significant across countries.,Adherence to international guidelines appears to be low.,Efforts should be made to disseminate and adapt guidelines to the socioeconomic reality of different settings. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are often linked to respiratory infections.,However, it is unknown if COPD patients who experience frequent exacerbations have impaired humoral immunity.,The aim of this study was to determine if antibodies specific for common respiratory pathogens are associated with AECOPD.,Plasma was obtained from COPD patients when clinically stable.,AECOPD requiring hospitalisation were recorded.,IgG1 antibodies to H.,Influenzae outer membrane protein 6 (P6), pneumococcal surface protein C (PspC) and the VP1 viral capsid protein of rhinovirus were measured.,COPD patients who had an AECOPD (n = 32) had significantly lower anti-VP1 IgG1 antibody levels when stable compared to COPD patients who did not have an AECOPD (n = 28, p = 0.024).,Furthermore, the number of hospitalisations was inversely proportional to anti-VP1 antibody levels (r = −0.331, p = 0.011).,In contrast, antibodies specific for P6 and PspC were present at similar concentrations between groups.,Plasma IL-21, a cytokine important for B-cell development and antibody synthesis, was also lower in COPD patients who had an AECOPD, than in stable COPD patients (p = 0.046).,Deficient humoral immunity specific for rhinoviruses is associated with AECOPD requiring hospitalisation, and may partly explain why some COPD patients have an increased exacerbation risk following respiratory viral infections. | Nontypeable Haemophilus influenzae (NTHI) may play a role as an infectious trigger in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Few data are available regarding the influence of acute and persistent infection on tissue remodelling and repair factors such as transforming growth factor (TGF)-β.,NTHI infection in lung tissues obtained from COPD patients and controls was studied in vivo and using an in vitro model.,Infection experiments were performed with two different clinical isolates.,Detection of NTHI was done using in situ hybridization (ISH) in unstimulated and in in vitro infected lung tissue.,For characterization of TGF-β signaling molecules a transcriptome array was performed.,Expression of the TGF-pseudoreceptor BMP and Activin Membrane-bound Inhibitor (BAMBI) was analyzed using immunohistochemistry (IHC), ISH and PCR.,CXC chemokine ligand (CXCL)-8, tumor necrosis factor (TNF)-α and TGF-β expression were evaluated in lung tissue and cell culture using ELISA.,In 38% of COPD patients infection with NTHI was detected in vivo in contrast to 0% of controls (p < 0.05).,Transcriptome arrays showed no significant changes of TGF-β receptors 1 and 2 and Smad-3 expression, whereas a strong expression of BAMBI with upregulation after in vitro infection of COPD lung tissue was demonstrated.,BAMBI was expressed ubiquitously on alveolar macrophages (AM) and to a lesser degree on alveolar epithelial cells (AEC).,Measurement of cytokine concentrations in lung tissue supernatants revealed a decreased expression of TGF-β (p < 0.05) in combination with a strong proinflammatory response (p < 0.01).,We show for the first time the expression of the TGF pseudoreceptor BAMBI in the human lung, which is upregulated in response to NTHI infection in COPD lung tissue in vivo and in vitro.,The combination of NTHI-mediated induction of proinflammatory cytokines and inhibition of TGF-β expression may influence inflammation induced tissue remodeling. | 1 |
Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections.,The purpose of our study was to investigate innate immunity in stable COPD patients.,Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects.,Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology.,Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-β was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%).,ISGs were easily detectable in both groups.,In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects.,No difference was found with respect to MxA.,COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients.,Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts.,IFN-β expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs.,ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. | Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide.,The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th.,Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function.,More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function.,COPD and AECOPDs are characterized by an augmented inflammatory response.,Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management.,In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors.,Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis.,Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect.,Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities. | 1 |
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. | 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 |
Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines.,However, uptake of existing guidelines is poor.,A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches.,During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.,This article provides a summary of key changes in the GINA report, and their rationale.,The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.,This paper summarises key changes in the GINA global strategy report, a practical new resource for asthma carehttp://ow.ly/ObvYi | The abnormal regulation of neutrophil apoptosis may contribute to the ineffective resolution of inflammation in chronic lung diseases.,Multiple signalling pathways are implicated in regulating granulocyte apoptosis, in particular, NFκB (nuclear factor-kappa B) signalling which delays constitutive neutrophil apoptosis.,Although some studies have suggested a dysregulation in the apoptosis of airway cells in chronic obstructive pulmonary disease (COPD), no studies to date have directly investigated if NFκB is associated with apoptosis of airway neutrophils from COPD patients.,The objectives of this study were to examine spontaneous neutrophil apoptosis in stable COPD subjects (n = 13), healthy smoking controls (n = 9) and non-smoking controls (n = 9) and to investigate whether the neutrophil apoptotic process in inflammatory conditions is associated with NFκB activation.,Analysis of apoptosis in induced sputum was carried out by 3 methods; light microscopy, Annexin V/Propidium iodide and the terminal transferase-mediated dUTP nick end-labeling (TUNEL) method.,Activation of NFκB was assessed using a flow cytometric method and the phosphorylation state of IκBα was carried out using the Bio-Rad Bio-Plex phosphoprotein IκBα assay.,Flow cytometric analysis showed a significant reduction in the percentage of sputum neutrophils undergoing spontaneous apoptosis in healthy smokers and subjects with COPD compared to non-smokers (p < 0.001).,Similar findings were demonstrated using the Tunel assay and in the morphological identification of apoptotic neutrophils.,A significant increase was observed in the expression of both the p50 (p = 0.006) and p65 (p = 0.006) subunits of NFκB in neutrophils from COPD subjects compared to non-smokers.,These results demonstrate that apoptosis is reduced in the sputum of COPD subjects and in healthy control smokers and may be regulated by an associated activation of NFκB. | 1 |
H. haemolyticus is often misidentified as NTHi due to their close phylogenetic relationship.,Differentiating between the two is important for correct identification and appropriate treatment of infective organism and to ensure any role of H. haemolyticus in disease is not being overlooked.,Speciation however is not completely reliable by culture and PCR methods due to the loss of haemolysis by H. haemolyticus and the heterogeneity of NTHi.,Haemophilus isolates from COPD as part of the AERIS study (ClinicalTrials - NCT01360398) were speciated by analysing sequence data for the presence of molecular markers.,Further investigation into the genomic relationship was carried out using average nucleotide identity and phylogeny of allelic and genome alignments.,Only 6.3% were identified as H. haemolyticus.,Multiple in silico methods were able to distinguish H. haemolyticus from NTHi.,However, no single gene target was found to be 100% accurate.,A group of omp2 negative NTHi were observed to be phylogenetically divergent from H. haemolyticus and remaining NTHi.,The presence of an atypical group from a geographically and disease limited set of isolates supports the theory that the heterogeneity of NTHi may provide a genetic continuum between NTHi and H. haemolyticus. | Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction.,Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations.,Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome.,The role of the lung microbiome in the pathogenesis of COPD remains unknown.,The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora.,Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients.,The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid.,Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats.,Our results showed a significant increase in microbial diversity with the development of COPD.,The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria.,Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity.,However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators.,Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. | 1 |
The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.,From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort).,Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables.,Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort).,The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.,A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively.,In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02-1.11] for per 80 mg of budesonide).,Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline.,In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).,This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE.,ICS should be judiciously used in indicated COPD patients. | Diabetes damages major organ systems through disrupted glycemic control and increased inflammation.,The effects of diabetes on the lung have been of interest for decades, but the modest reduction in pulmonary function and its nonprogressive nature have limited its investigation.,A recent systematic review found that diabetes was associated with reductions in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide of the lung and increased FEV1/FVC.,They reported pooled results including few smokers.,This study will examine measures of pulmonary function in participants with extensive smoking exposure.,We examined pulmonary function in participants with a >10-pack-year history of smoking with and without diabetes with and without chronic obstructive pulmonary disease (COPD).,We measured pulmonary function, exercise capacity, and pulmonary-related quality of life in 10,129 participants in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study.,Participants with diabetes were observed to have reduced pulmonary function after controlling for known risk factors and also significant reductions in exercise capacity and quality of life across functional stages of COPD.,Pulmonary function in patients with ≥10 pack-years of smoking and diabetes is reduced, and this decrease is associated with significant reductions in activity-related quality of life and exercise capacity. | 1 |
Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD.,This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations.,Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium.,Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio.,Furthermore, triple therapy showed a promising signal in terms of improved survival.,The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia.,Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap. | It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | 1 |
Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19).,This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients.,A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea.,The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model.,Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively.,The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs.,45.2%, P < 0.001) and male (52.5% vs.,36.6%, P < 0.001) patients than the non-COPD group.,Relatively greater proportions of patients with COPD received intensive critical care (7.1% vs.,3.7%, P = 0.041) and mechanical ventilation (5.7% vs.,2.4%, P = 0.015).,Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11-2.93) after adjustment for age, sex, and Charlson Comorbidity Index score.,Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care.,COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea. | Coronavirus disease 2019 (COVID-19) was rapidly expanded worldwide within a short period.,Its relationship with chronic comorbidities is still unclear.,We aimed to determine the effects of chronic comorbidities on clinical outcomes of patients with and without COVID-19.,This was an analysis of 65,535 patients with suspicion of viral respiratory disease (38,324 SARS-CoV-2 positive and 27,211 SARS-CoV-2 negative) from January 01 to May 12, 2020 using the national administrative healthcare open data of Mexico.,SARS-CoV-2 infection was confirmed by reverse-transcriptase-polymerase-chain-reaction.,General characteristics and chronic comorbidities were explored.,Clinical outcomes of interest were hospital admission, pneumonia, intensive care unit admission, endotracheal intubation and mortality.,Prevalence of chronic comorbidities was 49.4%.,Multivariate logistic regression analysis showed that the effect of age, male sex, bronchial asthma, diabetes mellitus and chronic kidney disease on clinical outcomes was similar for both SARS-CoV-2 positive and negative patients.,Adverse clinical outcomes were associated with the time from symptoms onset to medical contact, chronic obstructive pulmonary disease, hypertension and obesity in SARS-CoV-2 positive patients, but with cardiovascular disease in SARS-CoV-2 negative patients (p value < 0.01 for all comparisons).,Chronic comorbidities are commonly found in patients with suspicion of viral respiratory disease.,The knowledge of the impact of comorbidities on adverse clinical outcomes can better define those COVID-19 patients at higher risk.,The different impact of the specific type of chronic comorbidity on clinical outcomes in patients with and without SARS-CoV-2 infection requires further researches.,These findings need confirmation using other data sources.,The online version contains supplementary material available at 10.1007/s11739-020-02597-5. | 1 |
Causes of death may be unique and different in Japanese patients with COPD because they are generally older, thinner, experience fewer exacerbations, and live longer than those in other countries.,We investigated the detailed mortality profile in the Hokkaido COPD cohort study, which completed a 10-year follow-up with a very low dropout rate.,We prospectively examined the 10-year natural history in 279 Japanese patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; and GOLD 4, 5%).,The majority of patients were male, and the average age at baseline was 69 years old.,About 95% of all patients had accurate mortality data.,The risk factors for mortality were also analyzed.,During the 10 years, 112 patients (40%) died.,Their median survival time was 6.1 years (interquartile range: 4.7-7.9 years), and age at death was 79 ± 6 years old (mean ± SD).,Respiratory diseases, including pneumonia, were the leading causes of death in 45 (40%), followed by lung cancer in 24 (21%), other cancers in 18 (16%), and cardiovascular diseases in 12 (11%).,In particular, lung cancer-related death was equally distributed across all COPD stages, with a higher proportion of lung cancer in the relatively younger generation (<64 years old).,Older age at baseline, lower BMI, and severer emphysema were significant risk factors for all-cause mortality.,The unique mortality profile observed in this study should be considered when designing strategies for the management of patients with COPD in any geographic region. | Given the heterogeneity of chronic obstructive pulmonary disease (COPD), personalized clinical management is key to optimizing patient outcomes.,Important treatment goals include minimizing disease activity and preventing disease progression; however, quantification of these components remains a challenge.,Growing evidence suggests that decline over time in forced expiratory volume in 1 s (FEV1), traditionally the key marker of disease progression, may not be sufficient to fully determine deterioration across COPD populations.,In addition, there is a lack of evidence showing that currently available multidimensional COPD indexes improve clinical decision-making, treatment, or patient outcomes.,The composite clinically important deterioration (CID) endpoint was developed to assess disease worsening by detecting early deteriorations in lung function (measured by FEV1), health status (assessed by the St George’s Respiratory Questionnaire), and the presence of exacerbations.,Post hoc and prospective analyses of clinical trial data have confirmed that the multidimensional composite CID endpoint better predicts poorer medium-term outcomes compared with any single CID component alone, and that it can demonstrate differences in treatment efficacy in short-term trials.,Given the widely acknowledged need for an individualized holistic approach to COPD management, monitoring short-term CID has the potential to facilitate early identification of suboptimal treatment responses and patients at risk of increased disease progression.,CID monitoring may lead to better-informed clinical management decisions and potentially improved prognosis. | 1 |
Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection.,Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy.,Lung specimens were not contaminated with upper airway taxa since they were obtained surgically.,The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing.,Data analyses were performed using QIIME, SourceTracker, and R.,Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways.,Each subject’s own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites.,Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject.,SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown.,An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue.,This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples.,In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease proposed in 2011 a new system to classify chronic obstructive pulmonary disease (COPD) patients into risk groups A-D, which considers symptoms and future exacerbation risk to grade disease severity.,The aim of this study was to investigate the agreement between COPD risk group classifications using COPD assessment test (CAT) or modified Medical Research Council (mMRC) and severity grades or past-year exacerbations.,Furthermore, physical activity across risk groups was examined.,87 patients with stable COPD were classified into risk groups A-D.,CAT and mMRC were completed.,Severity grades I-IV were determined using spirometry and the number of past-year exacerbations was recorded.,To test the interrater agreement, Cohen’s Kappa was calculated.,Daily physical activity was measured by the SenseWear Mini armband.,Using CAT, 65.5% of patients were in high-symptom groups (B and D).,With mMRC, only 37.9% were in B and D.,Using severity grades, 20.7% of patients were in high-exacerbation risk groups (C and D).,With past-year exacerbations, 9.2% were in C and D.,Interrater agreement between CAT and mMRC (κ = 0.21) and between severity grades and past-year exacerbations (κ = 0.31) was fair.,Daily steps were reduced in risk groups B and C + D compared to A (p < 0.01), using either classification.,When classifying COPD patients into risk groups A-D, the use of CAT or mMRC and severity grades or past-year exacerbations does not provide equal results.,Daily steps decreased with increasing COPD risk groups. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
Influencing the progression of COPD has long been an elusive goal of drug therapy.,Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®).,Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced.,The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD.,The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease.,With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted. | Data on differences in clinical characteristics and management of COPD in different countries and settings are limited.,We aimed to characterize the profile of patients with COPD in a number of countries and their treatment in order to evaluate adherence to recommendations of international guidelines.,This was an observational, international, cross-sectional study on patients with physician-diagnosed COPD.,Demographic and clinical characteristics, risk factors, and treatment were collected by their physician via an internet web-based questionnaire developed for the study.,A total of 77 investigators from 17 countries provided data on 833 patients.,The countries with the highest number of patients included were: Argentina (128), Ecuador (134), Spain (162), and Hong Kong (153).,Overall, 79.3% were men and 81% former smokers, with a mean FEV1 = 42.7%, ranging from 34.3% in Hong Kong to 58.8% in Ecuador.,Patients reported a mean of 1.6 exacerbations the previous year, with this frequency being significantly and negatively correlated with FEV1(%) (r = −0.256; p < 0.0001).,Treatment with short-acting bronchodilators and theophyllines was more frequent in Ecuador and Hong Kong compared with Spain and Argentina, and in patients belonging to lower socioeconomic levels (p < 0.0001 for all comparisons).,Inadequacy of treatment with inhaled corticosteroids and theophyllines was high, with significant differences among countries.,Differences in the clinical characteristics and management of COPD were significant across countries.,Adherence to international guidelines appears to be low.,Efforts should be made to disseminate and adapt guidelines to the socioeconomic reality of different settings. | 1 |
Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD).,Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions.,Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.,In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of a proprietary glycopyrronium (GP) MDI were evaluated compared with Placebo MDI and open-label tiotropium (TIO) in study patients with COPD.,Thirty-three study patients were enrolled and received single-dose administration of 4 of the 6 treatments (Placebo MDI, TIO 18 μg, or GP MDI at 14.4, 28.8, 57.6, and 115.2 μg ex-actuator) with an interval of 1 to 3 weeks between doses.,The primary efficacy endpoint was peak change in forced expiratory volume in 1 second (FEV1).,All 4 doses of GP MDI showed statistically superior efficacy compared with Placebo MDI for peak FEV1 (differences of 146 to 248 mL; P < .001), with a clear dose ordering of the response.,Statistically significant differences compared with Placebo MDI were noted at almost all doses for the secondary FEV1 parameters (P ≤ .049) except 24-hour trough FEV1 at 28.8 μg.,All doses were safe and well tolerated in this study; the most frequently reported adverse event was dry mouth (0-14.3% across doses; 9.5% for Placebo MDI, and 9.1% for TIO).,This study demonstrated superior bronchodilatory efficacy of GP MDI compared with Placebo MDI at all doses tested, and no serious adverse events were reported.,This study supports the further evaluation of GP MDI in study patients with COPD.,In addition, these findings indicate that the correct dosage of glycopyrronium is no more than 115.2 μg total daily dose, or 57.6 μg twice daily based on comparisons with the active comparator.,This clinical trial was registered on ClinicalTrials.gov, Identifier:NCT00871182. | Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326 | 1 |
Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events.,The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known.,A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD®) database.,Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk.,With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478).,For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol.,With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968).,This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk.,Boehringer Ingelheim and Pfizer.,Clinical trial registration number: ClinicalTrials.gov NCT00563381.,The online version of this article (doi:10.1007/s12325-015-0216-2) contains supplementary material, which is available to authorized users. | Acute respiratory failure (ARF) is a life-threatening event, which is frequently associated with the severe exacerbations of chronic obstructive pulmonary disease (COPD).,Hypoalbuminemia is associated with increased mortality in patients with COPD.,However, to date, little is known regarding whether or not hypoalbuminemia is a risk factor for developing ARF in COPD.,We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan.,A total of 42,732 newly diagnosed COPD patients (age ≥40 years) from 1997 to 2011 were enrolled.,Among them, 1,861 (4.36%) patients who had received albumin supplementation were defined as hypoalbuminemia, and 40,871 (95.6%) patients who had not received albumin supplementation were defined as no hypoalbuminemia.,Of 42,732 newly diagnosed COPD patients, 5,248 patients (12.3%) developed ARF during the 6 years follow-up period.,Patients with hypoalbuminemia were older, predominantly male, had more comorbidities, and required more steroid treatment and blood transfusions than patients without hypoalbuminemia.,In a multivariable Cox regression analysis model, being elderly was the strongest independent risk factor for ARF (adjusted hazard ratio [HR]: 4.63, P<0.001), followed by hypoalbuminemia (adjusted HR: 2.87, P<0.001).,However, as the annual average dose of albumin supplementation was higher than 13.8 g per year, the risk for ARF was the highest (adjusted HR: 11.13, 95% CI: 10.35-11.98, P<0.001).,Hypoalbuminemia is a strong risk factor for ARF in patients with COPD.,Therefore, further prospective studies are required to verify whether or not albumin supplementation or nutritional support may help to reduce the risk of ARF in patients with COPD. | 1 |
It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis.,We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers.,Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD).,All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software.,√Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe.,Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R2 = 0.78, P<0.0001).,The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not.,In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs. | Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population.,COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population.,To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.,We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI.,We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC).,EAT volume were compared between groups.,Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.,COPD patients had a higher EAT volume [143.7 (P25-75, 108.3-196.6) vs 129.1 (P25-75, 91.3-170.8) cm3, p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, p<0.001) and CRP (r = 0.32, p<0.001) but not with microalbuminuria (r = 0.12, p = 0.13).,In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV1%, 6 MWD, MMRC and HTN.,Multivariate analysis showed that only pack-years (B = 0.6, 95% CI: 0.5-1.3), BMI (B = 7.8, 95% CI: 5.7-9.9) and 6 MWD (B = −0.2, 95% CI: −0.3-−0.1), predicted EAT volume.,EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events.,EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events. | 1 |
Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis.,MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD).,Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically.,Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited.,450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12.,Due to missing data 33 subjects were excluded.,The remaining 417 participants were divided into 4 different groups.,Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD).,Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque.,This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors.,COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors.,Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting.,Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results. | This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | 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. | Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway inflammatory diseases that share some common features, although these diseases are somewhat different in etiologies, clinical features, and treatment policies.,The aim of this study is to investigate the common microRNA-mediated changes in bronchial epithelial cells of asthma and COPD.,The microRNA profiles in primary bronchial epithelial cells from asthma (AHBE) and COPD (CHBE) patients and healthy subjects (NHBE) were analyzed with next-generation sequencing (NGS) and the significant microRNA changes common in AHBE and CHBE were extracted.,The upregulation of hsa-miR-10a-5p and hsa-miR-146a-5p in both AHBE and CHBE was confirmed with quantitative polymerase chain reaction (qPCR).,Using bioinformatic methods, we further identified putative targets of these microRNAs, which were downregulated in both AHBE and CHBE: miR-10a-5p might suppress BCL2, FGFR3, FOXO3, PDE4A, PDE4C, and PDE7A; miR-146a-5p might suppress BCL2, INSR, PDE4D, PDE7A, PDE7B, and PDE11A.,We further validated significantly decreased expression levels of FOXO3 and PDE7A in AHBE and CHBE than in NHBE with qPCR.,Increased serum miR-146a-5p level was also noted in patients with asthma and COPD as compared with normal control subjects.,In summary, our study revealed possible mechanisms mediated by miR-10a-5p and miR-146a-5p in the pathogenesis of both asthma and COPD.,The findings might provide a scientific basis for developing novel diagnostic and therapeutic strategies. | 1 |
COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD).,We previously developed a score (‘2008 score’, based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs).,External validity of this score remained to be assessed.,To test the predictive properties of the ‘2008 score’ in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance.,Data from a cohort study in 1824 patients hospitalized in a medical ward for an AECOPD were analyzed.,Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed.,A new score was developed using multivariate logistic regression modeling in a randomly selected derivation population sample followed by testing in the remaining population (validation sample).,Robustness of results was assessed by case-by-case validation.,The 2008 score was characterized by a c-statistic at 0.77, a sensitivity of 69% and a specificity of 76% for prediction of in-hospital mortality.,The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78, a sensitivity of 77% and specificity of 66%.,A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AECOPD.,Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity.,The online version of this article (doi:10.1186/s12931-014-0099-9) contains supplementary material, which is available to authorized users. | 1 |
We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 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 |
Long-term maintenance therapy for COPD is evolving rapidly.,Dual bronchodilation with new long-acting muscarinic antagonist and long-acting beta-agonist (LAMA/LABA) fixed dose combination inhalers were introduced over the past 2 years.,In clinical trials, these inhalers significantly improved lung function (trough forced expiratory volume in 1 second), patient-reported outcomes, and quality of life measures compared with placebo, their respective monocomponents, and tiotropium.,The recorded adverse events of these new inhalers were also similar to those of their monocomponents or placebo.,There are concerns regarding long-term complications (weight gain, osteoporosis, cataract) and increased risk of community-acquired pneumonia with the use of inhaled corticosteroids (ICS).,The new LAMA/LABA inhalers could potentially reduce the use of ICS as part and parcel of maintenance therapy in COPD.,Recent studies compared these LAMA/LABA inhalers with ICS/LABA combination inhalers in moderate-to-severe COPD.,The results are promising and favor the LAMA/LABA inhalers, especially in the longer duration trials.,Furthermore, there is a clearer picture emerging as to the subgroup of COPD patients who may be able to successfully switch from their current ICS/LABA therapy to these new LAMA/LABA inhalers. | The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | 1 |
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 | It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | 1 |
COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking.,The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer.,We have investigated expression of these transcription factors and their “cellular localization” in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls.,An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01).,Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05).,In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4).,The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction. | Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity.,There are only limited data about its role in airway remodeling in COPD.,We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD).,This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.,Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls.,The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups.,Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3.,Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls.,TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs.,0.0 (0.0-7.0), p<0.05].,Percentage of vessels stained was also increased in these clinical groups.,Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.,Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD. | 1 |
In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses.,We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD.,Sixteen sedentary males with COPD were enrolled in this study.,Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured.,The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA).,Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated.,HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio.,Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=−0.53 (P<0.05).,Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=−0.77, r2=0.43, P<0.05).,Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD.,Moreover, greater lung function impairment was related to poorer heart rate dynamics.,Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients. | Asthma and COPD require different management strategies, but differentiation in primary care is difficult.,This primary care support initiative observed the impact of spirometry and clinical assessment on the diagnosis of airway disease.,Of 61 191 patients aged ≥40 years being treated for respiratory conditions within 1003 UK primary care practices, 43 203 underwent a diagnostic review including standardized spirometric assessment.,The proportion of patients in whom the diagnosis was changed by the additional information was determined.,The relationship of various patient characteristics was compared with the baseline and review diagnoses and with any change in diagnosis.,Asthma was initially diagnosed in 43% of patients, COPD in 35%, mixed disease in 9%, and other respiratory condition in 13%.,Patients initially diagnosed with asthma, mixed disease, or another condition were more likely to have their diagnosis changed at review (54%, 46%, and 63%, respectively) than those initially diagnosed with COPD (14%).,A change from asthma to COPD was associated with male gender, smoking, older age, and reduced lung function, the opposite being associated with a change from COPD to asthma.,In this study, a clinical review supplemented by additional information including spirometry highlights apparent mislabeling of significant numbers of patients with chronic obstructive disease in general practice with significant implications for individual treatment and healthcare provision.,This study shows that the addition of more clinical information can have a major effect on diagnostic tendency in patients with airway disease.,An initial diagnosis of COPD seems less likely to change following review than an asthma diagnosis.,While it is likely that greater information leads to a more accurate diagnosis, the differential effect of new information on diagnostic labeling highlights the insecurity of the diagnostic process in primary care in the UK. | 1 |
Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease.,We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort.,We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter.,Patients were dichotomized as frequent (≥2 AECOPD/year) or infrequent exacerbators.,Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline.,The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95 % CI, 1.24-7.14, p = 0.01).,The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]).,Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum.,However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test).,In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival.,The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989.,The online version of this article (doi:10.1186/s12931-015-0306-3) contains supplementary material, which is available to authorized users. | Patient-reported outcome (PRO) measures that quantify disease impact have become important measures of outcome in COPD research and treatment.,The objective of this literature review was to comprehensively evaluate psychometric properties of available PRO instruments and the ability of each of them to characterize pharmaceutical treatment effects from published clinical trial evidence.,Identified in this study were several PRO measures, both those that have been used extensively in COPD clinical trials (St George’s Respiratory Questionnaire and Chronic Respiratory Questionnaire) and new instruments whose full value is still to be determined.,This suggests a great need for more information about the patient experience of treatment benefit, but this also may pose challenges to researchers, clinicians, and other important stakeholders (eg, regulatory agencies, pharmaceutical companies) who develop new treatment entities and payers (including but not limited to health technology assessment agencies such as the National Institute for Health and Care Excellence and the Canadian Agency for Drugs and Technologies in Health).,The purpose of this review is to enable researchers and clinicians to gain a broad overview of PRO measures in COPD by summarizing the value and purpose of these measures and by providing sufficient detail for interested audiences to determine which instrument may be the most suitable for evaluating a particular research purpose. | 1 |
Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL.,The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.,We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015.,Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.,We included 603 patients.,Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%.,Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources.,Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources.,Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.,ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together.,Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended. | The association between asthma-chronic obstructive pulmonary diseases (COPD) overlap syndrome (ACOS) and tuberculosis (TB) has yet to be studied.,The newly diagnosed TB patients (age > 20 y) treated from January 2000 to December 2008 were included (ACOS cohort, n = 10 751; non-ACOS cohort, n = 42 966).,The non-ACOS cohort involved patients with confirmed absence of ACOS.,We calculated incidence rate ratios (IRRs) for TB in the ACOS and non-ACOS cohorts by using poisson regression analysis.,Cox proportional hazards regression models were used to determine the adjusted HR (aHR) for TB in the ACOS cohort compared with the non-ACOS cohort.,The aHR for TB was 2.41 (95% confidence interval [CI], 2.19-2.66) in the ACOS cohort.,The TB risk was significantly higher in the ACOS cohort than in the non-ACOS cohort when stratified by age, sex, comorbidities, and atopy.,Within the ACOS cohort, the aHR was higher among patients receiving SABAs+SAMAs, LABAs+LAMAs, and ICSs (aHR [95% CI]: 3.06 [2.75-3.41], 3.68 [2.93-4.61], and 2.79 [1.25-6.22], respectively; all P < .05).,Furthermore, patients with more than 15 outpatient visits and hospitalizations per year demonstrated the highest aHR (8.09; 95% CI, 6.85-9.56).,ACOS cohort potentially develop incident TB, regardless of the age,sex, comorbidities and atopy; even without receiving the inhalers.This risk is higher, especially in the ACOS cohort have a high frequency of medical services or receiving the inhalers such as SABAs+SAMAs, LABAs+LAMAs and ICSs. | 1 |
Patients with Chronic Obstructive Pulmonary Disease (COPD) and / or Obstructive Sleep Apnea (OSA) often complain about sleepiness, fatigue, anxiety and depression.,However, common screening questionnaires, like Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS) have not been previous evaluated in patients with overlap-coexisting COPD and OSA-syndrome versus patients with OSA alone.,Our study compared ESS, FSS and HADS between patients with overlap syndrome and patients with OSA, before and after treatment with Continuous Positive Airways Pressure (CPAP).,We examined 38 patients with coexisting COPD and OSA versus 38 patients with OSA-only and 28 subjects without respiratory disease, serving as controls.,All patients underwent pulmonary function tests (PFTs), oximetry and overnight polysomnography and completed the questionnaires, before and after 3 months of CPAP therapy.,The two patient groups did not differ significantly in terms of age, Body Mass Index (BMI), neck, waist and hip circumferences, and arterial blood pressure values.,They also had similar comorbidities.,They differed significantly, as expected, in PFTs (Forced Vital Capacity-FVC, 2.53±0.73 vs 3.08±0.85 lt, p = 0.005, Forced Expiratory Volume in 1sec-FEV1, 1.78±0.53 vs 2.60±0.73 lt/min, p<0.001) and in daytime oximetry (94.75±2.37 vs 96.13±1.56%, p = 0.007).,ESS, HADS-Anxiety and HADS-Depression scores did not differ statistically significant between these two groups, whereas overlap syndrome patients expressed significantly more fatigue (FSS) than OSA-only patients, a finding that persisted even after 3 months of CPAP therapy.,We conclude that sleepiness, anxiety and depression were similar in both groups, whereas fatigue was more prominent in patients with overlap syndrome than in sleep apneic patients and did not ameliorate after treatment. | The prevalence of erectile dysfunction (ED) in patients with chronic obstructive pulmonary disease (COPD) seemed high; however, large scale of population-based study was absent.,We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan.,The cohort included 29,042 male patients who were newly diagnosed with COPD.,Patients were recruited between 2000 and 2011, and the date of diagnosis was defined as the index date.,Each patient was randomly matched with 1 male person from the general population without COPD according to age and the index year.,The occurrence of ED was followed up until the end of 2011.,The hazard ratios of ED were estimated using the Cox proportional hazard model after adjusting for age, index year, comorbidities, and medications.,The overall incidence of ED was 1.88-fold greater in the COPD cohort than in the non-COPD cohort (24.9 vs 13.3/1000 person-years, 95% confidence interval [CI] = 1.61-2.18).,Compared with non-COPD patients, the hazard ratio increased with the number of emergency room visits and admissions for COPD from 1.51 (95% CI 1.29-1.77) to 5.46 (95% CI 3.03-9.84) and from 1.50 (95% CI 1.28-1.76) to 11.5 (95% CI 5.83-22.6), respectively.,Patients with COPD are at a significantly higher risk of developing ED compared with the general population regardless of age and presence of comorbidity.,The results also support that poor control of COPD status is a key factor affecting ED development. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with substantial health impact that may already become apparent in early disease.,This study aims to examine the features of subjects with COPD in a Dutch population-based sample and compare their physical status, mental status, and social status to non-COPD subjects.,This study made use of Longitudinal Aging Study Amsterdam (LASA) data.,Demographics, clinical characteristics, self-reported diseases, post-bronchodilator spirometry, physical, mental, and social status were assessed.,A number of 810 subjects (50.5% male, mean age 60.5 ± 2.9 years) were included.,Subjects with COPD (n = 68, mean FEV1 67.6 [IQR 60.4-80.4] %.) had a slower walking speed than non-COPD subjects, p = 0.033.,When compared to non-COPD subjects, COPD subjects gave a lower rating on their health (physical subscale of SF-12: 15 [IQR 16.0-19.0] vs.,18 [IQR 11.0-17.0] points) and life (EQ5D VAS: 75 [IQR 70.0-90.0] vs. 80 points [IQR 65.0-85.5]) surveys.,COPD subjects also had a more impaired disease-specific health status (CAT: 9.5 ± 5.9 vs.,6.7 ± 5.2, respectively), were less likely to have a partner (69% vs. 84%, respectively) and received emotional support less often (24% vs. 36%, respectively) compared to non-COPD subjects (All comparisons p < 0.001).,In a population-based sample, subjects with COPD had a reduced physical performance, a more impaired disease-specific health status and were more socially deprived compared to non-COPD subjects.,These impairments need to be taken into consideration when setting up a management program for patients with mild COPD.,Patients with early-stage chronic lung disease need holistic support to limit the physical, mental and social impacts of the condition.,There is more to chronic obstructive pulmonary disease (COPD) than persistent airflow limitation; systemic effects, including loss of muscle strength and higher risk of heart conditions, mental health and social problems can manifest from the early stages.,Frits Franssen at CIRO, the Netherlands, and co-workers interviewed 810 participants aged 55-65 from the Longitudinal Aging Study Amsterdam to investigate the physical, mental and social status of COPD sufferers and compare them with healthy controls.,Those with COPD were more likely to walk slower, tire easily and perceive themselves as having poor overall health.,Socially, COPD patients were less likely to have long-term partners and felt the need for more emotional support than their healthy peers. | Chronic obstructive pulmonary disease (COPD) is a chronic, progressively debilitating condition that is prevalent in the US and worldwide.,Patients suffer from progressive dyspnea and exercise intolerance.,Physical exercise is beneficial, but conventional pulmonary rehabilitation programs are underutilized.,There remains a need for novel interventions that improve symptoms, quality-of-life, and functional capacity.,Tai chi is an increasingly popular mind-body exercise that includes physical exercise, breathing training, mindful awareness, and stress management--components that are essential to the self-management of COPD.,There are, however, limited data on the effectiveness of tai chi as a therapeutic intervention in this population.,The Primary Aims are to evaluate the efficacy, safety, and feasibility of a 12-week tai chi program for patients with COPD.,We utilize a randomized controlled trial design, with participants assigned in a 2:1 ratio to either a group tai chi program (N = 63) or a time/attention-matched education control (N = 31).,Our primary outcomes are COPD-specific quality-of-life and exercise capacity.,Secondary outcomes include dyspnea, mood, functional status, self-efficacy, and lung function.,Cardiopulmonary exercise testing is done in a subset of patients (N = 50).,To explore optimal training duration, a subgroup of patients in tai chi are randomly assigned to complete an additional 12 weeks training (total 24 weeks) (Exploratory Aim 1).,To explore the impact of a simplified seated intervention including only a subset of tai chi’s training components, a third randomly assigned group (N = 31) receives a 12- week mind-body breathing program (N = 31) (Exploratory Aim 2).,Results of the BEAM study (Breathing, Education, Awareness, Movement) will provide preliminary evidence regarding the value of tai chi for improving quality of life and exercise capacity in patients with COPD, including information regarding optimal duration.,They will also inform the feasibility and potential benefit of an alternative mind-body breathing intervention, and provide insight regarding how isolated mind-body exercise components contribute to the overall effects of tai chi.,Should the results be positive, tai chi and related mind-body practices may offer a novel exercise option that is potentially accessible to a large proportion of patients with COPD.,This trial is registered in Clinical Trials.gov, ID number NCT01551953.,Date of Registration March 1 2012.,The online version of this article (doi:10.1186/1745-6215-15-337) contains supplementary material, which is available to authorized users. | 1 |
Hand grip strength (HGS) is a simple way of predicting the risk of cardiovascular disease and all-cause mortality in the general population.,However, the practical significance of grip strength in patients with COPD is uncertain.,The aim of this study was to compare HGS between subjects with and without COPD and to evaluate its clinical relevance in patients with COPD by using a national survey.,Data were collected from the Korean National Health and Nutrition Examination Survey.,The study included 421 adults with COPD and 2,542 controls who completed questionnaires, spirometry, and a HGS test.,HGS was compared between subjects with and without COPD, and the association between grip strength, lung function, and quality of life (QoL) was evaluated.,The mean HGS was 33.3±9.1 kg in the COPD group and 29.9±9.5 kg in the non-COPD group; adjusted HGS was 30.9±0.33 kg and 30.9±0.11 kg, respectively (P=0.99).,HGS was not related to forced vital capacity (β=0.04, P=0.70) or forced expiratory volume in 1 second (β=0.11, P=0.24) in multivariable analysis.,HGS was independently associated with the EQ-5D index, but the relationship was stronger in the COPD group (β=0.30, P<0.001) than in the non-COPD group (β=0.21, P<0.001).,The results were similar for each component of the EQ-5D, including mobility (β=−0.25, P<0.001), daily activity (β=−0.19, P=0.01), pain/discomfort (β=−0.32, P<0.001), and anxiety/depression (β=−0.16, P=0.01).,HGS was not different between subjects with and without COPD, but was associated with QoL - including mobility, daily activity, pain/discomfort, and anxiety/depression - in patients with COPD.,The HGS test could be used as a marker of QoL in patients with COPD and could assist risk stratification in clinical practice. | Dynamic hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease (COPD).,Given that most of these patients have respiratory and peripheral muscle weakness, dyspnea and functional exercise capacity may improve as a result of inspiratory muscle training (IMT).,The aim of the study was to analyze the effects of IMT on exercise capacity, dyspnea, and inspiratory fraction (IF) during exercise in patients with COPD.,Daily inspiratory muscle strength and endurance training was performed for 8 weeks in 10 patients with COPD GOLD II and III.,Ten patients with COPD II and III served as a control group.,Maximal inspiratory pressure (Pimax) and endurance time during resistive breathing maneuvers (tlim) served as parameter for inspiratory muscle capacity.,Before and after training, the patients performed an incremental symptom limited exercise test to maximum and a constant load test on a cycle ergometer at 75% of the peak work rate obtained in the pretraining incremental test.,ET was defined as the duration of loaded pedaling.,Following IMT, there was a statistically significant increase in inspiratory muscle performance of the Pimax from 7.75 ± 0.47 to 9.15 ± 0.73 kPa (P < 0.01) and of tlim from 348 ± 54 to 467 ± 58 seconds (P < 0.01).,A significant increase in IF, indicating decreased dynamic hyperinflation, was observed during both exercise tests.,Further, the ratio of breathing frequency to minute ventilation (bf/V′E) decreased significantly, indicating an improved breathing pattern.,A significant decrease in perception of dyspnea was also measured.,Peak work rate during the incremental cycle ergometer test remained constant, while ET during the constant load test increased significantly from 597.1 ± 80.8 seconds at baseline to 733.6 ± 74.3 seconds (P < 0.01).,No significant changes during either exercise tests were measured in the control group.,The present study found that in patients with COPD, IMT results in improvement in performance, exercise capacity, sensation of dyspnea, and improvement in the IF prognostic factor. | 1 |
Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes.,However, very little attention has been paid to the timing of the failure.,This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.,The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony.,The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation.,The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure.,However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate.,Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.,Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV.,Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation. | Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU).,Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population.,We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006.,Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses.,PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay.,Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission.,The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours.,The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively.,Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients.,Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L.,The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L.,The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80).,The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics.,Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.,The online version of this article (doi:10.1186/1471-2334-8-145) contains supplementary material, which is available to authorized users. | 1 |
The traditional classification of COPD, which relies solely on spirometry, fails to account for the complexity and heterogeneity of the disease.,Phenotyping is a method that attempts to derive a single or combination of disease attributes that are associated with clinically meaningful outcomes.,Deriving phenotypes entails the use of cluster analyses, and helps individualize patient management by identifying groups of individuals with similar characteristics.,We aimed to systematically review the literature for studies that had derived such phenotypes using unsupervised methods.,Two independent reviewers systematically searched multiple databases for studies that performed validated statistical analyses, free of definitive pre-determined hypotheses, to derive phenotypes among patients with COPD.,Data were extracted independently.,9156 citations were retrieved, of which, 8 studies were included.,The number of subjects ranged from 213 to 1543.,Most studies appeared to be biased: patients were more likely males, with severe disease, and recruited in tertiary care settings.,Statistical methods used to derive phenotypes varied by study.,The number of phenotypes identified ranged from 2 to 5.,Two phenotypes, with poor longitudinal health outcomes, were common across multiple studies: young patients with severe respiratory disease, few cardiovascular co-morbidities, poor nutritional status and poor health status, and a phenotype of older patients with moderate respiratory disease, obesity, cardiovascular and metabolic co-morbidities.,The recognition that two phenotypes of COPD were often reported may have clinical implications for altering the course of the disease.,This review also provided important information on limitations of phenotype studies in COPD and the need for improvement in future studies.,The online version of this article (doi:10.1186/s12931-015-0208-4) contains supplementary material, which is available to authorized users. | It is known that respiratory muscles undergo adaptation in response to overload stimuli during exercise training in stable COPD patients, thus resulting in significant increase of respiratory muscle function as well as the individual’s improvements.,The present article reviews the most updated evidence with regard to the use of respiratory muscle training (RMT) methods in COPD patients.,Basically, three types of RMT (resistive training, pressure threshold loading, and normocapnic hyperpnea) have been reported.,Frequency, duration, and intensity of exercise must be carefully considered for a training effect.,In contrast with the plentitude of existing data inherent to inspiratory muscle training (IMT), literature is still lacking in showing clinical and physiological studies related to expiratory muscle training (EMT).,In particular, while it seems that IMT is slightly superior to EMT in providing additional benefits other than respiratory muscle function such as a reduction in dyspnea, both the effects and the safety of EMT is still to be definitively elucidated in patients with COPD. | 1 |
Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life.,It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified.,The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified.,We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017.,We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission.,Of the 704 events, 65 were followed by readmission within 30 days.,Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively).,Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210).,In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296-17.041; P=0.019).,P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients. | Respiratory infection is the most common cause for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD).,The aim of this work was to study the etiology of the respiratory infection in order to assess the usefulness of the clinical and analytical parameters used for COPD identification.,We included 132 patients over a period of 2 years.,The etiology of the respiratory infection was studied by conventional sputum, paired serology tests for atypical bacteria, and viral diagnostic techniques (immunochromatography, immunofluorescence, cell culture, and molecular biology techniques).,We grouped the patients into four groups based on the pathogens isolated (bacterial versus. viral, known etiology versus unknown etiology) and compared the groups.,A pathogen was identified in 48 patients.,The pathogen was identified through sputum culture in 34 patients, seroconversion in three patients, and a positive result from viral techniques in 14 patients.,No significant differences in identifying etiology were observed in the clinical and analytical parameters within the different groups.,The most cost-effective tests were the sputum test and the polymerase chain reaction.,Based on our experience, clinical and analytical parameters are not useful for the etiological identification of COPD exacerbations.,Diagnosing COPD exacerbation is difficult, with the conventional sputum test for bacterial etiology and molecular biology techniques for viral etiology providing the most profitability.,Further studies are necessary to identify respiratory syndromes or analytical parameters that can be used to identify the etiology of new AE-COPD cases without the laborious diagnostic techniques. | 1 |
The use of inhaled corticosteroids (ICSs) in long-term treatment of COPD has been a debated topic for a long time.,According to the evidence produced till now, ICSs are presently advocated in combination with long-acting bronchodilators for high-risk symptomatic COPD patients with a history of frequent COPD exacerbations.,However, the heterogeneity of COPD patients in terms of prevalent underlying disease, with its associated biological and functional characteristics, and different types of exacerbation makes this recommendation highly questionable.,This review aims to discuss the usefulness of ICSs in the pharmacological management of COPD and trys to detect those aspects that may likely anticipate a beneficial response following their therapeutic use related to respiratory function, functional decline, prevention of exacerbation, and quality of life.,In this respect, the BERN acronym, meaning Bronchiolitis, Eosinophilia, Responsiveness to bronchodilator, and Non-smoker, may be of practical utility to select among COPD patients those that can take more advantage from ICS adoption when positive and vice versa when negative. | The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation.,However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood.,In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD.,Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα.,After 48-72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively.,Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36).,AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD.,In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD.,In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release.,In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts.,In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin.,This study shows that AA has disease-specific effects on inflammation and ECM protein deposition.,The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases.,The online version of this article (10.1186/s12931-018-0919-4) contains supplementary material, which is available to authorized users. | 1 |
The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant.,Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID.,This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St.,George’s Respiratory Questionnaire (SGRQ).,Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR).,CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months.,A 15-point Global Rating of Change scale (GRC) was completed at each follow-up.,A five-point GRC was used as second anchor at 12 months.,Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID.,The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency.,In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up.,Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ).,MCID estimates for improvement ranged − 3.1 to − 1.4 for CAT, − 0.6 to − 0.3 for CCQ, and − 10.3 to − 7.6 for SGRQ.,Absolute higher - though not significant - MCIDs were observed for CAT and CCQ directly after PR.,Significantly absolute lower MCID estimates were observed for CAT (difference − 1.4: CI -2.3 to − 0.5) and CCQ (difference − 0.2: CI -0.3 to −0.1) using a five-point GRC.,The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values.,However, the design of the anchor question was likely to influence the MCID of CAT and CCQ.,RIMTCORE trial #DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer).,The online version of this article (10.1186/s12955-018-0950-7) contains supplementary material, which is available to authorized users. | COPD is considered a complex disease and global problem that is predicted to be the third most common cause of death by 2030.,While managing this chronic condition, primary health care practitioners are faced with the ongoing challenge of achieving good quality of life and overall “wellness” for those affected.,As such, a practical tool for monitoring quality of life in a clinical setting is required.,However, due to the wide variety of general and disease-specific tools from which to choose, primary health care practitioners are given minimal guidance as to which tool may be most appropriate.,To address these challenges, the International Primary Care Respiratory Group (IPCRG) proposed the creation of a user’s guide for primary health care practitioners to assess “wellness” in COPD patients in an everyday clinical setting.,This short report outlines the process by which the IPCRG Users’ Guide to COPD “Wellness” Tools was developed.,It also describes why this guide has the potential to be of great value in guiding primary health care practitioners to improve patient wellness. | 1 |
Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease.,To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations.,This was a 2-year prospective cohort study of COPD patients.,Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared.,Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002).,For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001).,Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation.,In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices. | To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes. | 1 |
Pulmonary rehabilitation is effective in all stages of COPD.,The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden.,Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers.,Multivariable logistic regression examined associations with having received rehabilitation in the previous year.,In primary care, nurse-based asthma/COPD clinics were common (87%), with additional separate access to other rehabilitation professionals.,In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%).,In total, 36% of the patients met an asthma/COPD nurse in the previous year.,Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%), occupational therapists (3% vs 10%), nutritionists (5% vs 13%), and counselors (1% vs 4%).,A higher COPD Assessment Test score and frequent exacerbations were associated with higher utilization of all rehabilitation professionals.,Pulmonary rehabilitation resources are available but underutilized, and receiving rehabilitation is more common in severe COPD.,Treatment recommendations need to be better implemented, especially in mild and moderate COPD. | Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement.,The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT).,Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1) <50% of predicted value from 27 secondary care respiratory units in Sweden.,Correlation analyses and multiple linear regression models were performed using EQ-5D index, EQ-5D visual analog scale (VAS), and CAT scores as response variables.,Having more comorbid conditions was associated with a worse HRQL as assessed by all instruments.,Chronic bronchitis was significantly associated with a worse HRQL as assessed by EQ-5D index (adjusted regression coefficient [95% confidence interval] −0.07 [−0.13 to −0.02]), EQ-5D VAS (−5.17 [−9.42 to −0.92]), and CAT (3.78 [2.35 to 5.20]).,Musculoskeletal symptoms were significantly associated with worse EQ-5D index (−0.08 [−0.14 to −0.02]), osteoporosis with worse EQ-5D VAS (−4.65 [−9.27 to −0.03]), and depression with worse EQ-5D index (−0.10 [−0.17 to −0.04]).,In stratification analyses, the associations of musculoskeletal symptoms, osteoporosis, and depression with HRQL were limited to female patients.,The instruments EQ-5D and CAT complement each other and emerge as useful for assessing HRQL in patients with COPD.,Chronic bronchitis, musculoskeletal symptoms, osteoporosis, and depression were associated with worse HRQL.,We conclude that comorbid conditions, in particular chronic bronchitis, depression, osteoporosis, and musculoskeletal symptoms, should be taken into account in the clinical management of patients with severe COPD. | 1 |
COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function.,Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy.,This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID.,CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings.,Three definitions of CID (D1-D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV1), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD).,In D1 and D2, either TDI or CCQ was evaluated along with FEV1 and AECOPD, whereas in D3, all 4 parameters were included.,ClinicalTrials.gov number: NCT01985334.,Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments.,The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30-0.55]; D2: OR 0.41 [95% CI: 0.31-0.55]; D3: OR 0.39 [95% CI: 0.29-0.52]).,Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56-1.02]; D2: OR 0.75 [95% CI: 0.56-1.00]; D3: OR 0.67 [95% CI: 0.51-0.89]).,In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice. | Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | 1 |
‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) clinical trials evaluating hard endpoints (mortality, hospitalized exacerbations) require a large number of subjects and prolonged observational periods.,We hypothesized that a composite endpoint of respiratory outcomes (CERO) can help evaluate safety and benefit in COPD trials.,Retrospective analysis of 5992 patients enrolled in the 4-year UPLIFT® trial, a randomized trial of tiotropium versus placebo in patients with moderate-to-severe COPD.,Patients were permitted to continue using their usual COPD medications except for other anticholinergics.,The CERO included deaths, respiratory failure, hospitalized exacerbations, and trial dropout due to COPD worsening.,The incidence rates (IRs) per 100 patient-years and risk ratios (RRs and 95 % CI) were determined at years 1 to 4.,The effect of treatments on CERO was similarly assessed.,A power analysis helped calculate the sample size needed to achieve outcome differences between treatments.,The CERO IRs at years 1 to 4 for tiotropium versus placebo were 16, 13, 11, and 11, and 21, 16, 14, and 13, respectively.,The RRs of CERO between tiotropium and placebo at the same time points were: RR-year 0.76 (0.67, 0.86), 0.80 (0.72, 0.88), 0.81 (0.74, 0.89), and 0.84 (0.77, 0.92).,Using the IRs and RRs, the sample size (alpha = 0.05 two-sided, 90 % power) for studies of 1, 2, 3, and 4 years would be 1546, 1392, 1216, and 1504 per treatment group, respectively, with 575, 810, 930, 1383 required events, respectively, for hypothetical, event-driven studies.,A composite endpoint incorporating relatively infrequent serious or significant COPD-related safety outcomes could be useful in clinical trials.,In UPLIFT®, CERO events were significantly reduced in patients receiving tiotropium compared with placebo.,NCT00144339.,The online version of this article (doi:10.1186/s12931-016-0361-4) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome characterized by varying degrees of airflow limitation and diffusion impairment.,There is increasing evidence to suggest that COPD is also characterized by systemic inflammation.,The primary goal of this study was to identify soluble proteins in plasma that associate with the severity of airflow limitation in a COPD cohort with stable disease.,A secondary goal was to assess whether unique markers associate with diffusion impairment, based on diffusion capacity of carbon monoxide (DLCO), independent of the forced expiratory volume in 1 second (FEV1).,A cross sectional study of 73 COPD subjects was performed in order to examine the association of 25 different plasma proteins with the severity of lung function impairment, as defined by the baseline measurements of the % predicted FEV1 and the % predicted DLCO.,Plasma protein concentrations were assayed using multiplexed immunobead-based cytokine profiling.,Associations between lung function and protein concentrations were adjusted for age, gender, pack years smoking history, current smoking, inhaled corticosteroid use, systemic corticosteroid use and statin use.,Plasma concentrations of CCL2/monocyte chemoattractant protein-1 (CCL2/MCP-1), CCL4/macrophage inflammatory protein-1β (CCL4/MIP -1β), CCL11/eotaxin, and interleukin-13 (IL-13) were inversely associated with the % FEV1.,Plasma concentrations of soluble Fas were associated with the % DLCO, whereas CXCL9/monokine induced by interferon-γ (CXCL9/Mig), granulocyte- colony stimulating factor (G-CSF) and IL-13 showed inverse relationships with the % DLCO.,Systemic inflammation in a COPD cohort is characterized by cytokines implicated in inflammatory cell recruitment and airway remodeling.,Plasma concentrations of IL-13 and chemoattractants for monocytes, T lymphocytes, and eosinophils show associations with increasing severity of disease.,Soluble Fas, G-CSF and CXCL9/Mig may be unique markers that associate with disease characterized by disproportionate abnormalities in DLCO independent of the FEV1. | 1 |
Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (“over-perception”).,Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function.,Learned associations influence brain mechanisms of sensory perception.,We hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations.,In 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during a breathlessness-related word-cue task (using functional magnetic resonance imaging), and clinical and psychological measures of breathlessness.,Changes in ratings of breathlessness word cues positively correlated with changes in activity in the insula and anterior cingulate cortex.,Changes in ratings of breathlessness-anxiety negatively correlated with activations in attention regulation and motor networks.,Baseline activity in the insula, anterior cingulate cortex and prefrontal cortex correlated with improvements in breathlessness and breathlessness-anxiety.,Pulmonary rehabilitation is associated with altered neural responses related to learned breathlessness associations, which can ultimately influence breathlessness perception.,These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.,Pulmonary rehabilitation improves breathlessness by recalibrating the brain's sensory perception networkshttp://ow.ly/crhy30cQerx | Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain.,The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD.,Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated.,Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging.,Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD.,After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus.,Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD.,In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction.,We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. | 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD).,However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood.,The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD.,We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD.,All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results.,The percentages of the total CSA less than 5 mm2 and equal to 5-10 mm2 over the lung area (%CSA<5 and %CSA5-10, respectively) were measured.,The %CSA<5 steadily decreased in relation to the increase of COPD severity.,In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731).,Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. | 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. | Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).,Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks.,At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured.,Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo.,Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo).,However, inclusion of contaminated samples did not affect the overall trend of the outcome.,Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils.,Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo.,Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant.,This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population.,In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo.,Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo. | 1 |
Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD).,Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection.,Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation.,However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed.,We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD.,To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors.,Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors.,Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation.,Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects.,In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72-96 h post-infection.,Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response. | The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation.,The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD.,Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited.,Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses.,A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected.,The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%).,A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients.,Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population.,In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population.,The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare. | 1 |
Nuclear Factor (NF)-κB is positioned to provide the interface between COPD and carcinogenesis through regulation of chronic inflammation in the lungs.,Using a tetracycline-inducible transgenic mouse model that conditionally expresses activated IκB kinase β (IKKβ) in airway epithelium (IKTA), we found that sustained NF-κB signaling results in chronic inflammation and emphysema by 4 months.,By 11 months of transgene activation, IKTA mice develop lung adenomas.,Investigation of lung inflammation in IKTA mice revealed a substantial increase in M2-polarized macrophages and CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs).,Depletion of alveolar macrophages in IKTA mice reduced Tregs, increased lung CD8+ lymphocytes, and reduced tumor numbers following treatment with the carcinogen urethane.,Alveolar macrophages from IKTA mice supported increased generation of inducible Foxp3+ Tregs ex vivo through expression of TGFβ and IL-10.,Targeting of TGFβ and IL-10 reduced the ability of alveolar macrophages from IKTA mice to induce Foxp3 expression on T cells.,These studies indicate that sustained activation of NF-κB pathway links COPD and lung cancer through generation and maintenance of a pro-tumorigenic inflammatory environment consisting of alternatively activated macrophages and regulatory T cells. | •COPD is a risk factor for lung cancer beyond their shared aetiology.,•Both are driven by oxidative stress.,•Both are linked to cellular aging, senescence and telomere shortening.,•Both have been linked to genetic predisposition.,•Both show altered epigenetic regulation of gene expression.,COPD is a risk factor for lung cancer beyond their shared aetiology.,Both are driven by oxidative stress.,Both are linked to cellular aging, senescence and telomere shortening.,Both have been linked to genetic predisposition.,Both show altered epigenetic regulation of gene expression.,Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden.,Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking.,Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging.,In the majority of smokers, the burden of smoking may be dealt with by the body’s defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms.,However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great.,Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation.,Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments. | 1 |
India has 18% of the global population and an increasing burden of chronic respiratory diseases.,However, a systematic understanding of the distribution of chronic respiratory diseases and their trends over time is not readily available for all of the states of India.,Our aim was to report the trends in the burden of chronic respiratory diseases and the heterogeneity in their distribution in all states of India between 1990 and 2016.,Using all accessible data from multiple sources, we estimated the prevalence of major chronic respiratory diseases and the deaths and disability-adjusted life-years (DALYs) caused by them for every state of India from 1990 to 2016 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016.,We assessed heterogeneity in the burden of chronic obstructive pulmonary disease (COPD) and asthma across the states of India.,The states were categorised into four groups based on their epidemiological transition level (ETL).,ETL was defined as the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa.,We also assessed the contribution of risk factors to DALYs due to COPD.,We compared the burden of chronic respiratory diseases in India against the global average in GBD 2016.,We calculated 95% uncertainty intervals (UIs) for the point estimates.,The contribution of chronic respiratory diseases to the total DALYs in India increased from 4·5% (95% UI 4·0-4·9) in 1990 to 6·4% (5·8-7·0) in 2016.,Of the total global DALYs due to chronic respiratory diseases in 2016, 32·0% occurred in India.,COPD and asthma were responsible for 75·6% and 20·0% of the chronic respiratory disease DALYs, respectively, in India in 2016.,The number of cases of COPD in India increased from 28·1 million (27·0-29·2) in 1990 to 55·3 million (53·1-57·6) in 2016, an increase in prevalence from 3·3% (3·1-3·4) to 4·2% (4·0-4·4).,The age-standardised COPD prevalence and DALY rates in 2016 were highest in the less developed low ETL state group.,There were 37·9 million (35·7-40·2) cases of asthma in India in 2016, with similar prevalence in the four ETL state groups, but the highest DALY rate was in the low ETL state group.,The highest DALY rates for both COPD and asthma in 2016 were in the low ETL states of Rajasthan and Uttar Pradesh.,The DALYs per case of COPD and asthma were 1·7 and 2·4 times higher in India than the global average in 2016, respectively; most states had higher rates compared with other locations worldwide at similar levels of Socio-demographic Index.,Of the DALYs due to COPD in India in 2016, 53·7% (43·1-65·0) were attributable to air pollution, 25·4% (19·5-31·7) to tobacco use, and 16·5% (14·1-19·2) to occupational risks, making these the leading risk factors for COPD.,India has a disproportionately high burden of chronic respiratory diseases.,The increasing contribution of these diseases to the overall disease burden across India and the high rate of health loss from them, especially in the less developed low ETL states, highlights the need for focused policy interventions to address this significant cause of disease burden in India.,Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India. | It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD).,We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use.,We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno.,We defined COPD as a post-bronchodilator FEV1/FVC < 70%.,Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001).,Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%).,Rather, we found that PARs of COPD varied by setting.,In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively).,In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%.,The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking.,This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas. | 1 |
Bronchoscopic lung volume reduction using coils (LVRC) is a well-known treatment option for severe emphysema.,The purpose of this study was to identify quantitative computed tomography (QCT) and clinical parameters associated with positive treatment outcome.,The CT scans, pulmonary function tests (PFT), and 6-minute walk test (6-MWT) data were collected from 72 patients with advanced emphysema prior to and at 3 months after LVRC treatment.,The procedure involved placing 10 coils unilaterally.,Various QCT parameters were derived using Apollo imaging software (VIDA).,Independent predictors of clinically relevant outcome (Δ6-MWT ≥ 26 m, ΔFEV1 ≥ 12%, ΔRV ≥ 10%) were identified through stepwise linear regression analysis.,The response outcome for Δ6-MWT, for ΔFEV1 and for ΔRV was met by 55%, 32% and 42%, respectively.,For Δ6-MWT ≥ 26 m a lower baseline 6-MWT (p = 0.0003) and a larger standard deviation (SD) of low attenuation cluster (LAC) sizes in peripheral regions of treated lung (p = 0.0037) were significantly associated with positive outcome.,For ΔFEV1 ≥ 12%, lower baseline FEV1 (p = 0.02) and larger median LAC sizes in the central regions of treated lobe (p = 0.0018) were significant predictors of good response.,For ΔRV ≥ 10% a greater baseline TLC (p = 0.0014) and a larger SD of LAC sizes in peripheral regions of treated lung (p = 0.007) tended to respond better.,Patients with lower FEV1 and 6-MWT, with higher TLC and specific QCT characteristics responded more positively to LVRC treatment, suggesting a more targeted CT-based approach to patient selection could lead to greater efficacy in treatment response. | Noninvasive ventilation (NIV) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients.,Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention.,In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV1 30.5 [±5.1] %pred, PaO2 65 [±6] mmHg, PaCO2 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV1 29.5 [±9.0] %pred, PaO2 59 [±13] mmHg, PaCO2 55.4 [±7.7] mmHg) for 6 months.,We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes.,In both groups there was a nonsignificant change in FEV1 (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg).,PaCO2 dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS).,Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients.,Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion.,There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO2.,Improved ventilation-perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases.,We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation-perfusion match and hence better blood gases and lung function.,Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation.,These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do.,Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment.,To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality.,We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.,Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death.,Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits.,Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.,In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.,COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.,The online version of this article (10.1186/s12890-018-0573-0) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a progressive, chronic respiratory disease with a significant socioeconomic burden.,Exacerbations, the sudden and sustained worsening of symptoms, can lead to hospitalization and reduce quality of life.,Major limitations of previous telemonitoring interventions for COPD include low compliance, lack of consensus on what constitutes an exacerbation, limited numbers of patients, and short monitoring periods.,We developed a telemonitoring system based on a digital health platform that was used to collect data from the 1-year EDGE (Self Management and Support Programme) COPD clinical trial aiming at daily monitoring in a heterogeneous group of patients with moderate to severe COPD.,The objectives of the study were as follows: first, to develop a systematic and reproducible approach to exacerbation identification and to track the progression of patient condition during remote monitoring; and second, to develop a robust algorithm able to predict COPD exacerbation, based on vital signs acquired from a pulse oximeter.,We used data from 110 patients, with a combined monitoring period of more than 35,000 days.,We propose a finite-state machine-based approach for modeling COPD exacerbation to gain a deeper insight into COPD patient condition during home monitoring to take account of the time course of symptoms.,A robust algorithm based on short-period trend analysis and logistic regression using vital signs derived from a pulse oximeter is also developed to predict exacerbations.,On the basis of 27,260 sessions recorded during the clinical trial (average usage of 5.3 times per week for 12 months), there were 361 exacerbation events.,There was considerable variation in the length of exacerbation events, with a mean length of 8.8 days.,The mean value of oxygen saturation was lower, and both the pulse rate and respiratory rate were higher before an impending exacerbation episode, compared with stable periods.,On the basis of the classifier developed in this work, prediction of COPD exacerbation episodes with 60%-80% sensitivity will result in 68%-36% specificity.,All 3 vital signs acquired from a pulse oximeter (pulse rate, oxygen saturation, and respiratory rate) are predictive of COPD exacerbation events, with oxygen saturation being the most predictive, followed by respiratory rate and pulse rate.,Combination of these vital signs with a robust algorithm based on machine learning leads to further improvement in positive predictive accuracy.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6olpMWNpc) | 1 |
Current evidence suggests that interval exercise training (IET) and continuous exercise training (CET) produce comparable benefits in exercise capacity, cardiorespiratory fitness and symptoms in patients with chronic obstructive pulmonary disease (COPD).,However, the effects of these modalities have only been reviewed in patients with COPD.,This meta-analysis compares the effectiveness of IET versus CET on exercise capacity, cardiorespiratory fitness and exertional symptoms in patients with chronic respiratory diseases (CRDs).,Methods: PubMed, CINHAL, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and Nursing and Allied health were searched for randomised controlled trials from inception to September 2020.,Eligible studies included the comparison between IET and CET, reporting measures of exercise capacity, cardiorespiratory fitness and symptoms in individuals with CRDs.,Results: Thirteen randomised control trials (530 patients with CRDs) with fair to good quality on the PEDro scale were included.,Eleven studies involved n = 446 patients with COPD, one involved n = 24 patients with cystic fibrosis (CF) and one n = 60 lung transplantation (LT) candidates.,IET resulted in greater improvements in peak work rate (WRpeak) (2.40 W, 95% CI: 0.83 to 3.97 W; p = 0.003) and lower exercise-induced dyspnoea (−0.47, 95% CI: −0.86 to 0.09; p = 0.02) compared to CET; however, these improvements did not exceed the minimal important difference for these outcomes.,No significant differences in peak values for oxygen uptake (VO2peak), heart rate (HRpeak), minute ventilation (VEpeak), lactate threshold (LAT) and leg discomfort were found between the interventions.,Conclusions: IET is superior to CET in improving exercise capacity and exercise-induced dyspnoea sensations in patients with CRDs; however, the extent of the clinical benefit is not considered clinically meaningful. | Many trials supporting the benefits of pulmonary rehabilitation (PR) have used specialist exercise equipment, such as treadmills and cycle ergometers.,However, access to specialist equipment may not be feasible in some settings.,There is growing interest in delivering PR programmes with minimal, low-cost equipment, but uncertainty remains regarding their efficacy compared with programmes using specialist equipment.,Using propensity score matching, 318 consecutive patients with COPD undergoing supervised PR using minimal equipment (PR-min) were compared 1:1 with a control group of 318 patients with COPD who underwent supervised PR using specialist equipment (PR-gym).,A non-inferiority analysis was performed for the primary outcome (incremental shuttle walk (ISW)) and secondary outcomes (Chronic Respiratory Disease Questionnaire (CRQ)-domain and total scores).,Similar improvements in ISW and CRQ-domains were observed in PR-min and PR-gym groups (mean difference ISW: 3 m (95% CI −16 to 9); CRQ-total: 0.9 (95% CI −2.7 to 4.5)).,The 95% CI between group differences for ISW and CRQ-total did not cross the predefined non-inferiority margins.,However, completion rates were lower in PR-min compared with PR-gym (64% vs 73%; p=0.014).,In patients with COPD, PR delivered using minimal equipment produces clinically significant benefits in exercise capacity and health-related quality of life that are non-inferior to rehabilitation delivered using specialist equipment.,This study provides support for the provision of PR using minimal exercise equipment, particularly in areas where access to specialist exercise equipment is limited. | 1 |
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. | The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described.,This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.,A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.,A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively.,Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%).,The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups.,Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01).,Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.,Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects.,The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research. | 1 |
Appropriate use of antibiotics in the management of hospitalised patients with COPD exacerbations is defined within the GOLD strategy.,This paper analyses the factors associated with antibiotic prescribing in patients to better understand how prescribing may be improved.,The European COPD audit was a study of clinical care in 384 hospitals from 13 European countries between 2010 and 2011 enrolling 16018 patients.,Those admitted to hospital due to a clinician-made diagnosis of exacerbation of COPD at the time of discharge were audited.,We defined antibiotic prescribing compliance as consistent with the GOLD 2010 recommendations.,Two different multivariate models were used to evaluate factors associated with the prescription of antibiotics and the guideline-compliant prescriptions.,Overall 86% of admissions were given antibiotics but only 61.4% cases met the GOLD recommendations.,Antibiotics were more likely to be given in hospital and at discharge if received prior to admission.,Antibiotic prescription was more likely in patients who met the GOLD recommendations and in those with radiological consolidation but there was also a significant use of antibiotics in patients who did not meet either criterion.,Patients cared for on a Respiratory Ward were more likely to receive GOLD compliant antibiotic management.,The present study describes the audited in-hospital antibiotic prescription for COPD exacerbation across different European countries.,In general, there is an apparent overuse of antibiotics likely to be associated with both patient and practice-related variables. | Antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent in hospitals and the community.,Acute exacerbations of COPD (AE-COPD) often result in administration of antibiotics although more than half of exacerbations are associated with detection of respiratory viruses and potentially pathogenic bacteria can only be detected in 20-30% of cases.,There is a paucity of placebo-controlled clinical trials and up to today no single study has been powered sufficiently to prove the efficacy of antibiotic treatment in AE-COPD.,Most studies so far did not include current standards of care comprising administration of systemic corticosteroids.,A total of 980 patients with moderate acute exacerbations will be included in 22 German centers (hospitals and private practices).,Patients will receive a standardized treatment for exacerbation including systemic corticosteroids, inhaled bronchodilators and supplementary oxygen if needed and will be randomized to additional treatment with placebo or antibiotic (oral sultamicillin) for five days.,The primary endpoint is clinical failure defined by need for additional antibiotic treatment until day 30.,Secondary endpoints will assure that management of AE-COPD without antibiotics does not result either in increased occurrence of relapse, new exacerbations, prolonged recovery, or unwanted long-term consequences.,ABACOPD will be the first sufficiently powered double-blind placebo-controlled study in the field to systematically assess the question whether antibiotics, known to increase antibiotic resistance, are really needed in a well-defined patient cohort receiving state-of-the art treatment in all other aspects.,ClinicalTrials.gov: NCT01892488. | 1 |
Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.,Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD.,COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis).,Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.,Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001).,Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001).,Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095).,Late diagnosis was also associated with higher direct costs than early diagnosis.,Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis.,The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD. | The six-second spirometry has been proposed as an alternative to diagnose airflow limitation, although its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unknown.,The purpose of this study was to determine the prognostic value of the postbronchodilator forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio and FEV6 in COPD patients.,The study population consisted of 2,614 consecutive stable patients with COPD.,The patients were monitored for an average period of 4.3 years regarding mortality, hospitalizations by COPD exacerbations, diagnosis of lung cancer, and annual lung function decline.,The overall rate of death was 10.7 (95%CI: 8.7-12.7) per 1000 person-years.,In addition to male gender, age and comorbidity, FEV6 (hazard ratio [HR]: 0.981, 95%CI: 0.968-0.003) and FEV1/FEV6 quartiles (lowest quartile (<74% pred.): HR 3.558, 95%CI: 1.752-7.224; and second quartile (74-84% pred.): HR 2.599, 95%CI: 1.215-5.561; versus best quartile (>0.89% pred.)) were independently associated with mortality, whereas FEV1 was not retained in the model. 809 patients (30.9%) had at least one hospital admission due to COPD exacerbation.,In addition to sex, age, smoking and comorbidity, FEV1 and FEV1/FEV6 quartiles were independent risk factors of hospitalization.,FEV6 was the only spirometric parameter independently related with lung function annual decline, while the FEV6 and FEV1/FEV6 quartiles were independent risk factors for lung cancer.,In a general COPD outpatient population, airflow obstruction assessed by the FEV1/FEV6 is an independent risk factor for both death and hospitalization. | 1 |
Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue reparative properties, which may be beneficial in the treatment of inflammatory diseases such as COPD.,This study examined the mechanisms by which human MSCs protect against elastase induced emphysema.,Using a novel human relevant pre-clinical model of emphysema the efficacy of human MSC therapy and optimal cell dose were investigated.,Protective effects were examined in the lung through histological examination.,Further in vivo experiments examined the reparative abilities of MSCs after tissue damage was established and the role played by soluble factors secreted by MSCs.,The mechanism of MSC action was determined in using shRNA gene knockdown.,Human MSC therapy and MSC conditioned media exerted significant cytoprotective effects when administered early at the onset of the disease.,These protective effects were due to significant anti-inflammatory, anti-fibrotic and anti-apoptotic mechanisms, mediated in part through MSC production of hepatocyte growth factor (HGF).,When MSC administration was delayed, significant protection of the lung architecture was observed but this was less extensive.,MSC cell therapy was more effective than MSC conditioned medium in this emphysema model. | There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD).,Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD.,Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease.,To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice.,We also investigated the mechanisms of action of pioglitazone-pretreated ASCs.,Pioglitazone-pretreated ASCs had a more potent therapeutic effect than non-pretreated ASCs in the repair of both elastase-induced and smoke-induced emphysema models (mean linear intercept, 78.1±2.5 μm vs 83.2±2.6 μm in elastase models and 75.6±1.4 μm vs 80.5±3.2 μm in smoke models, P<0.05).,Furthermore, we showed that pioglitazone-pretreated ASCs increased vascular endothelial growth factor (VEGF) production both in vitro and in mouse lungs in the smoke-induced emphysema model.,Pioglitazone-pretreated ASCs may have more potent therapeutic effects than non-pretreated ASCs in emphysema mouse models. | 1 |
COPD patients have increased numbers of macrophages and neutrophils in the lungs.,Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3.,We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.,59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis.,Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.,COPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7).,COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts.,Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.,Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD.,Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.,The online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users. | Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated.,The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD.,Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue.,Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients.,Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA.,Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC).,LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors.,In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.,Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD.,Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.,In contrast, the number of intDC did not differ between study groups.,Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease.,In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A.,Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A.,This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis. | 1 |
The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.,A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar.,Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.,In total, 27 studies were included in the review.,LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS.,These effects were maintained over time.,Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected.,Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators.,Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators.,LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.,Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC.,So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes.,LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety. | Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems.,Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.,Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency.,Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database.,Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.,Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001).,The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs.,Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6).,Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.,Comorbidity burden determines elevated utilization for COPD patients.,Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease commonly encountered in primary care.,This study aimed to audit COPD care at primary care clinics of Hong Kong and to work out improvement strategies.,All COPD patients aged 40 or above who had been followed up at 13 public primary care clinics of Kowloon Central Cluster (KCC) under the Hospital Authority of Hong Kong (HAHK) were included in this clinic audit.,Evidence-based audit criteria and performance standards were established after thorough literature review.,Phase 1 was from 1st April 2016 to 31st March 2017, with deficiencies of care identified.,It was followed by a one-year implementation phase through which a series of improvement strategies were executed.,Outcome of the enhancement was reviewed during Phase 2 from 1st April 2018 to 31st March 2019.,Chi-square test and student’s t test were used to detect statistically significant changes between Phase 1 and Phase 2.,A total of 2358 COPD cases were identified in Phase 1 where 658 of them were smokers.,Of those smokers, 332 (50.5%) had been referred to Smoking Counselling and Cessation Service (SCCS) and 289 (43.9%) actually attended it. 991 cases (42%) received Seasonal Influenza Vaccine (SIV) and 938 cases (39.8%) received Pneumococcal Vaccine (PCV). 698 patients (29.6%) had spirometry done before and 423 patients (17.9%) had been admitted to hospital due to acute exacerbation of COPD (AECOPD).,With the concerted effort taken during the implementation phase, Phase 2 data showed significant improvement in nearly all criteria.,There was a marked increase in the SIV and PCV uptake rate, spirometry performance rate and most importantly, a significant reduction in AECOPD rate leading to hospital admission (13.5%, P = 0.000043).,However, the referral rate and attendance rate of SCCS among smokers remained stagnant (P > 0.05).,Via a systematic team approach, COPD care at primary care clinics of KCC under HAHK had been significantly improved for most of the audit criteria, which in turn reduced the burden of the healthcare system. | Chronic obstructive pulmonary disease (COPD) is a public health problem.,Interprofessional collaboration and health promotion interventions such as exercise training, education, and behaviour change are cost effective, have a good effect on health status, and are recommended in COPD treatment guidelines.,There is a gap between the guidelines and the healthcare available to people with COPD.,The aim of this study was to increase the understanding of what shapes the provision of primary care services to people with COPD and what healthcare is offered to them from the perspective of healthcare professionals and managers.,The study was conducted in primary care in a Swedish county council during January to June 2015.,A qualitatively driven mixed methods design was applied.,Qualitative and quantitative findings were merged into a joint analysis.,Interviews for the qualitative component were performed with healthcare professionals (n = 14) from two primary care centres and analysed with qualitative content analysis.,Two questionnaires were used for the quantitative component; one was answered by senior managers or COPD nurses at primary care centres (n = 26) in the county council and the other was answered by healthcare professionals (n = 18) at two primary care centres.,The questionnaire data were analysed with descriptive statistics.,The analysis gave rise to the overarching theme building COPD care on shaky ground.,This represents professionals driven to build a supportive COPD care on ‘shaky’ organisational ground in a fragmented and non-compliant healthcare organisation.,The shaky ground is further represented by uninformed patients with a complex disease, which is surrounded with shame.,The professionals are autonomous and pragmatic, used to taking responsibility for their work, and with limited involvement of the management.,They wish to provide high quality COPD care with interprofessional collaboration, but they lack competence and are hindered by inadequate routines and lack of resources.,There is a gap between COPD treatment guidelines and the healthcare that is provided in primary care.,To facilitate implementation of the guidelines several actions are needed, such as further training for professionals, additional resources, and improved organisational structure for interprofessional collaboration and patient education.,The online version of this article (doi:10.1186/s12913-017-2393-y) contains supplementary material, which is available to authorized users. | 1 |
The respiratory diaphragm is the most important muscle for breathing.,It contributes to various processes such as expectoration, vomiting, swallowing, urination, and defecation.,It facilitates the venous and lymphatic return and helps viscera located above and below the diaphragm to work properly.,Its activity is fundamental in the maintenance of posture and body position changes.,It can affect the pain perception and emotional state.,Many authors reported on diaphragmatic training by using special instruments, whereas only a few studies focused on manual therapy approaches.,To the knowledge of the authors, the existing scientific literature does not exhaustively examines the manual evaluation of the diaphragm in its different portions.,A complete evaluation of the diaphragm is mandatory for several professional subjects, such as physiotherapists, osteopaths, and chiropractors not only to elaborate a treatment strategy but also to obtain information on the validity of the training performed on the patient.,This article aims to describe a strategy of manual evaluation of the diaphragm, with particular attention to anatomical fundamentals, in order to stimulate further research on this less explored field. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis.,Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection.,The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages.,The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.,A causal association has not yet been proven, but it is biologically plausible that COPD, and particularly the infective and exacerbator COPD phenotypes, could be the cause of bronchiectasis without any other known etiology, beyond any mere association or comorbidity.,The study of the relationship between COPD and bronchiectasis could have important clinical implications, since both diseases have different and complementary therapeutic approaches.,Longitudinal studies are needed to investigate the development of bronchiectasis in COPD, and clinical trials with treatments aimed at reducing bacterial loads should be conducted to investigate their impact on the reduction of exacerbations and improvements in the long-term evolution of the disease. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by ongoing inflammatory and remodeling processes of the airways and lung tissue.,Inflammation can be targeted by corticosteroids.,However, airway inflammation is generally less responsive to steroids in COPD than in asthma.,The underlying mechanisms are yet unclear.,This study aimed to assess whether skin corticosteroid insensitivity is associated with COPD and COPD severity using the corticosteroid skin blanching test.,COPD patients GOLD stage I-IV (n = 27, 24, 22, and 16 respectively) and healthy never-smokers and smokers (n = 28 and 56 respectively) were included.,Corticosteroid sensitivity was assessed by the corticosteroid skin blanching test.,Budesonide was applied in 8 logarithmically increasing concentrations (0-100 μg/ml) on subject's forearm.,Assessment of blanching was performed after 7 hours using a 7-point scale (normal skin to intense blanching).,All subjects performed spirometry and body plethysmography.,Both GOLD III and GOLD IV COPD patients showed significantly lower skin blanching responses than healthy never-smokers and smokers, GOLD I, and GOLD II patients.,Their area under the dose-response curve values of the skin blanching response were 586 and 243 vs. 1560, 1154, 1380, and 1309 respectively, p<0.05.,Lower FEV1 levels and higher RV/TLC ratios were significantly associated with lower skin blanching responses (p = 0.001 and p = 0.004 respectively).,GOLD stage I, II, III and IV patients had similar age and packyears.,In this study, severe and very severe COPD patients had lower skin corticosteroid sensitivity than mild and moderate COPD patients and non-COPD controls with comparable age and packyears.,Our findings together suggest that the reduced skin blanching response fits with a subgroup of COPD patients that has an early-onset COPD phenotype. | 1 |
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
A loss of physical functioning (i.e., a low physical capacity and/or a low physical activity) is a common feature in patients with chronic obstructive pulmonary disease (COPD).,To date, the primary care physiotherapy and specialized pulmonary rehabilitation are clearly underused, and limited to patients with a moderate to very severe degree of airflow limitation (GOLD stage 2 or higher).,However, improved referral rates are a necessity to lower the burden for patients with COPD and for society.,Therefore, a multidisciplinary group of healthcare professionals and scientists proposes a new model for referral of patients with COPD to the right type of exercise-based care, irrespective of the degree of airflow limitation.,Indeed, disease instability (recent hospitalization, yes/no), the burden of disease (no/low, mild/moderate or high), physical capacity (low or preserved) and physical activity (low or preserved) need to be used to allocate patients to one of the six distinct patient profiles.,Patients with profile 1 or 2 will not be referred for physiotherapy; patients with profiles 3-5 will be referred for primary care physiotherapy; and patients with profile 6 will be referred for screening for specialized pulmonary rehabilitation.,The proposed Dutch model has the intention to get the right patient with COPD allocated to the right type of exercise-based care and at the right moment. | Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time.,Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year.,Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics.,Four subtypes were identified.,Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity.,Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C.,Subtype D had higher rates of hospitalization the previous year, and comorbidities.,After 1 year, all clusters remained stable.,Generally, patients continued in the same subtype but 28% migrated to another cluster.,Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to.,Chronic obstructive pulmonary disease clusters remained stable over 1 year.,Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes. | 1 |
Health-related quality of life (HRQL) is an important patient-reported outcome for chronic obstructive pulmonary disease (COPD).,We developed models predicting chronic respiratory questionnaire (CRQ) dyspnoea, fatigue, emotional function, mastery and overall HRQL at 6 and 24 months using predictors easily available in primary care.,We used the “least absolute shrinkage and selection operator” (lasso) method to build the models and assessed their predictive performance.,Results were displayed using nomograms.,For each domain-specific CRQ outcome, the corresponding score at baseline was the best predictor.,Depending on the domain, these predictions could be improved by adding one to six other predictors, such as the other domain-specific CRQ scores, health status and depression score.,To predict overall HRQL, fatigue and dyspnoea scores were the best predictors.,Predicted and observed values were on average the same, indicating good calibration.,Explained variance ranged from 0.23 to 0.58, indicating good discrimination.,To predict COPD-specific HRQL in primary care COPD patients, previous HRQL was the best predictor in our models.,Asking patients explicitly about dyspnoea, fatigue, depression and how they cope with COPD provides additional important information about future HRQL whereas FEV1 or other commonly used predictors add little to the prediction of HRQL. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
The economic burden of COPD has not been well studied in China.,This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.,A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011.,The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation).,Logistic regression model was used to explore factors related to high total costs on COPD.,The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively.,The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China.,Hospitalization accounted for 56.7% of the total costs.,High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.,COPD posed a heavy economic burden in China.,Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care. | Randomized controlled trials, evidence-based medicine, clinical guidelines, and total quality management are some of the approaches used to render science-based health care services.,The clinical pathway for hospitalized patients suffering from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly established, although a clinical pathway is an integral part of total quality management.,To evaluate the outcomes of patients hospitalized with AECOPD in Japan, treated with a clinical pathway following published guidelines.,Prospective data were collected for patients with AECOPD admitted to a general hospital over a 5-year period since 2003.,The clinical pathway was designed to establish general rules for the entire treatment protocol.,The clinical pathway indicates which treatments and interventions should be performed, and when.,In this study, health care providers were required to check the clinical pathway sheets to determine the next step of treatment.,This study analyzed 276 hospitalizations in 165 patients.,The clinical pathway was interrupted and defined as a dropout in 45 cases (16.3%).,Nine patients died during hospitalization (3.3%).,Oxygen was administered in 232 hospitalizations (84.1%).,Noninvasive positive pressure ventilation (NPPV) treatment was administered in 110 hospitalizations (39.9%).,The rate of intubation in those cases where NPPV treatment had been administered was 8.2% (9 cases out of 110).,The average length of stay (LOS) was 20.3 days, and the median value was 15 days.,The LOS was longer than 30 days in 34 admissions (12.3%), mainly due to complications.,AECOPD can be managed using a clinical pathway.,This clinical pathway could fill the gap between guidelines and clinical practice. | 1 |
Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases.,The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of smokers or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis.,Computational analyses of omics technologies are expected as one of the solutions to resolve such complexities.,We obtained transcriptomic data by in vitro testing with exposures of human bronchial epithelial cells to the inducers for early events of COPD to identify the potential descriptive marker genes.,With the identified genes, the machine learning technique was employed with the publicly available transcriptome data obtained from the lung specimens of COPD and non-COPD patients to develop the model that can reflect the risk continuum across smoking and COPD.,The expression levels of 15 genes were commonly altered among in vitro tissues exposed to known inducible factors for earlier events of COPD (exposure to cigarette smoke, DNA damage, oxidative stress, and inflammation), and 10 of these genes and their corresponding proteins have not previously reported as COPD biomarkers.,Although these genes were able to predict each group with 65% accuracy, the accuracy with which they were able to discriminate COPD subjects from smokers was only 29%.,Furthermore, logistic regression enabled the conversion of gene expression levels to a numerical index, which we named the “potential risk factor (PRF)” index.,The highest significant index value was recorded in COPD subjects (0.56 at the median), followed by smokers (0.30) and non-smokers (0.02).,In vitro tissues exposed to cigarette smoke displayed dose-dependent increases of PRF, suggesting its utility for prospective risk estimation of tobacco products.,Our experimental-based transcriptomic analysis identified novel genes associated with COPD, and the 15 genes could distinguish smokers and COPD subjects from non-smokers via machine-learning classification with remarkable accuracy.,We also suggested a PRF index that can quantitatively reflect the risk continuum across smoking and COPD pathogenesis, and we believe it will provide an improved understanding of smoking effects and new insights into COPD. | COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | 1 |
Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 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. | Chronic obstructive pulmonary disease (COPD) is among the most important causes of death.,Signaling systems that are relevant for tissue repair and detoxification of reactive oxygen species or xenobiotics are thought to be impaired in lungs of patients suffering from this disease.,Here, we developed a simple cigarette smoke induced Drosophila model of COPD based on chronic cigarette smoke exposure that recapitulates major pathological hallmarks of the disease and thus can be used to investigate new therapeutic strategies.,Chronic cigarette smoke exposure led to premature death of the animals and induced a set of phenotypes reminiscent of those seen in COPD patients, including reduced physical activity, reduced body fat, increased metabolic rate and a substantial reduction of the respiratory surface.,A detailed transcriptomic analysis revealed that especially the TGF-β, Nrf2 and the JAK/STAT signaling pathways are altered by chronic cigarette smoke exposure.,Based on these results, we focused on Nrf2 signaling.,A pharmacological intervention study performed with oltipraz, an activator of Nrf2 signaling, increased survival of cigarette smoke exposed animals significantly.,Thus, the Drosophila COPD model recapitulates many major hallmarks of COPD and it is highly useful to evaluate the potential of alternative therapeutic strategies. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is characterised by complex inflammatory, neuronal and fibrotic changes.,Brain-derived Neurotrophic Factor (BDNF) is a key regulator of neuronal plasticity, whereas Transforming Growth Factor-β1 (TGF-β1) plays a crucial role in tissue repair and emphysema pathogenesis.,Both mediators are stored in platelets and released from platelets in inflammatory conditions and during serum preparation.,In patients with asthma, it was previously shown that elevated serum BDNF concentrations correlate with disease severity, whereas TGF-β1 concentrations were normal.,In the present study, 63 patients with stable COPD (spirometric GOLD stages 2-4) and 17 age- and comorbidity-matched controls were studied.,Lung function, smoking history, medication, platelet concentrations in peripheral blood and serum concentrations of BDNF, TGF-β1 and Serotonin (5-HT) were assessed in all participants.,Serum levels of both BDNF and TGF-β1 (but not concentrations of platelets in peripheral blood) were significantly elevated in all stages of COPD as compared to controls.,Highest BDNF concentrations were found in spirometric GOLD stage 3, whereas highest TGF-β1 serum levels were found in spirometric GOLD stage 4.,There were specific, stage-dependent correlations of these mediators with lung function parameters of the patients.,Taken together, we show that, in contrast to asthma, COPD is characterised by elevated concentrations of both BDNF and TGF-β1 in serum.,The stage-dependent association with lung function supports the hypothesis that these platelet mediators may play a role in the pathogenesis of COPD. | Airway remodeling in COPD includes reorganization of the extracellular matrix.,Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix.,Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis.,The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts.,Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations.,This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production.,Proliferation, proteoglycan production and the response to TGF-β1 were examined in vitro in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects.,Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma.,Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p < 0.01).,In addition, perlecan production was lower in centrally derived fibroblasts from COPD patients than from control subjects (p < 0.01).,TGF-β1 triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects.,In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-β1 than those from control subjects.,The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development.,Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil.,In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD. | 1 |
Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD.,While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with - according to Belgian market research data - up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting β2-adrenoreceptor agonist.,Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD.,However, historical habits appear difficult to change even in the light of recent scientific evidence.,We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | Genome-wide association studies identified several genomic regions associated with the risk of chronic obstructive pulmonary disease (COPD), including the 4q22 and 15q25 regions.,These regions contain the FAM13A and IREB2 genes, which have been associated with COPD but data are lacking for Chinese patients.,The objective of the study was to identify new genetic variants in the FAM13A and IREB2 associated with COPD in Northwestern China.,This was a case-control study performed in the Ningxia Hui Autonomous Region between January 2014 and December 2016.,Patients were grouped as COPD and controls based on FEV1/FVC<70%.,Seven tag single-nucleotide polymorphisms (SNPs) in the FAM13A and IREB2 genes were genotyped using the Agena MassARRAY platform.,Logistic regression was used to determine the association between SNPs and COPD risk.,rs17014601 in FAM13A was significantly associated with COPD in the additive (odds ratio [OR]=1.36, 95% confidence interval [CI]: 1.11-1.67, P=0.003), heterozygote (OR=1.76, 95% CI: 1.33-2.32, P=0.0001), and dominant (OR=1.67, 95% CI: 1.28-2.18, P=0.0001) models.,Stratified analyses indicated that the risk was higher in never smokers. rs16969858 in IREB2 was significantly associated with COPD but in the univariate analysis only, and the multivariate analysis did not show any association.,The results suggest that the new variant rs17014601 in the FAM13A gene was significantly associated with COPD risk in a Chinese rural population.,Additional studies are required to confirm the role of this variant in COPD development and progression. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | This review summarizes the long-term clinical outcomes associated with β-agonist and anticholinergic bronchodilator use in patients with chronic obstructive pulmonary disease (COPD).,Pooled data from randomized placebo-controlled trials of at least three months duration were used to evaluate the risk for COPD hospitalizations, respiratory mortality, and total mortality.,The results show that anticholinergic use is associated with a 30% reduction in COPD hospitalizations, a 70% reduction in respiratory mortality, and without a significant effect on total mortality.,In contrast, β-agonist use had no effect on COPD hospitalizations and was associated with a two-fold increased risk for respiratory death compared with placebo.,When the two bronchodilators were directly compared with each other, β-agonists were associated with a two-fold increased risk for COPD hospitalization and a five-fold increased risk for total mortality compared with anticholinergics.,When β-agonists were added to either anticholinergic use or inhaled corticosteroid use alone, there was no significant improvement in any long-term clinical outcome.,These results indicate that anticholinergics should be the bronchodilator of choice in COPD, while β-agonists may be associated with poorer disease control. | 1 |
Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa.,The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined.,To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients.,A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year.,High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients.,P. aeruginosa isolates were genotyped by PFGE.,Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis.,P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%).,Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization.,In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation.,Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75).,In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients.,The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics.,Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis. | Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems.,Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity.,To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses.,Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings.,We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation.,Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality.,We pooled the results using fixed effects models where statistically significant heterogeneity (p ≤ 0.1) was absent.,We identified six trials including 230 patients.,Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and mortality (0.45 [0.22-0.91]).,Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain, 1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery.,Weighted mean differences for the St.,Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7).,In all trials, rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115).,Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation.,Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD. | 1 |
Individuals with chronic obstructive pulmonary disease (COPD) commonly experience exacerbations, which may require hospital admission.,Early detection of exacerbations, and therefore early treatment, could be crucial in preventing admission and improving outcomes.,Our previous research has demonstrated that the pattern analysis of peripheral oxygen saturation (SpO2) fluctuations provides novel insights into the engagement of the respiratory control system in response to physiological stress (hypoxia).,Therefore, this pilot study tested the hypothesis that the pattern of SpO2 variations in overnight recordings of individuals with COPD would distinguish between stable and exacerbation phases of the disease.,Overnight pulse oximetry data from 11 individuals with COPD, who exhibited exacerbation after a period of stable disease, were examined.,Stable phase recordings were conducted overnight and one night prior to exacerbation recordings were also analyzed.,Pattern analysis of SpO2 variations was carried examined using sample entropy (for assessment of irregularity), the multiscale entropy (complexity), and detrended fluctuation analysis (self‐similarity).,SpO2 variations displayed a complex pattern in both stable and exacerbation phases of COPD.,During an exacerbation, SpO2 entropy increased (p = 0.029) and long‐term fractal‐like exponent (α2) decreased (p = 0.002) while the mean and standard deviation of SpO2 time series remained unchanged.,Through ROC analyses, SpO2 entropy and α2 were both able to classify the COPD phases into either stable or exacerbation phase.,With the best positive predictor value (PPV) for sample entropy (PPV = 70%) and a cut‐off value of 0.454.,While the best negative predictor value (NPV) was α2 (NPV = 78%) with a cut‐off value of 1.00.,Alterations in SpO2 entropy and the fractal‐like exponent have the potential to detect exacerbations in COPD.,Further research is warranted to examine if SpO2 variability analysis could be used as a novel objective method of detecting exacerbations.,This report provides evidence that the pattern of peripheral oxygen saturation (SpO2) fluctuations detects exacerbations in individuals with COPD.,The entropy of SpO2 signal increases a day prior to clinical diagnosis of exacerbation in COPD while mean and total variability of SpO2 signals remain unchanged.,This finding has potential for development of a non‐invasive method for early detection of exacerbations in COPD. | Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed, but the most effective approach for identifying these patients is unknown.,The aim of this study was to summarise and compare the effectiveness of different case finding approaches for undiagnosed COPD in primary care.,A systematic review of primary studies of any design evaluating case finding strategies for COPD in primary care among individuals aged ⩾35 years with no prior diagnosis was conducted.,Medline, Embase and other bibliographic databases were searched from 1997 to 2013, and methodological quality was assessed using standard tools.,Results were described and meta-analysis of the uptake and yield from different approaches was performed where there was sufficient homogeneity.,Three randomised controlled trials (RCTs), 1 controlled trial and 35 uncontrolled studies were identified that assessed the identification of new cases of COPD through systematic case finding.,A range of approaches were used including pre-screening with questionnaires (n=13) or handheld flow meters (n=5) or direct invitation to diagnostic spirometry (n=30).,Overall, any approach identified more undiagnosed COPD compared with usual care.,Targeting those at higher risk (e.g., smokers) and pre-screening (e.g., using questionnaires) is likely to increase the yield.,However, studies were heterogeneous and were limited by a lack of comparison groups, inadequate reporting and diversity in the definition of COPD, which limited our ability to draw firm conclusions.,There is extensive heterogeneity among studies evaluating case finding strategies for COPD, with few RCTs.,Well-conducted RCTs comparing case finding approaches are needed to identify the most effective target population, recruitment strategy and screening tests, using a clinical definition of COPD, and addressing the limitations highlighted in this review.,There is also a need to evaluate the impact of case finding on clinical care and patient outcomes. | 1 |
To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.,This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland.,Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016.,For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline.,We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication.,Groups were compared via ANOVA.,Data of 305 patients (62±7 years, 66% men) were analysed.,In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline.,Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines.,Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively.,Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%).,The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups.,The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement. | This study aimed to assess the adherence rate of pharmacological treatment to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline published in 2011 and the prevalence of comorbidities among patients with COPD in Hong Kong (HK).,Patients were recruited from five tertiary respiratory centers and followed up for 12 months.,Data on baseline physiological, spirometric parameters, use of COPD medications and coexisting comorbidities were collected.,The relationship between guideline adherence rate and subsequent COPD exacerbations was assessed.,Altogether, 450 patients were recruited.,The mean age was 73.7±8.5 years, and 92.2% of them were males.,Approximately 95% of them were ever-smokers, and the mean post-bronchodilator (BD) forced expiratory volume in 1 second was 50.8%±21.7% predicted.,The mean COPD Assessment Test and modified Medical Research Council Dyspnea Scale were 13.2±8.1 and 2.1±1.0, respectively.,In all, five (1.1%), 164 (36.4%), eight (1.8%) and 273 (60.7%) patients belonged to COPD groups A, B, C and D, respectively.,The guideline adherence rate for pharmacological treatment ranged from 47.7% to 58.1% in the three clinic visits over 12 months, with overprescription of inhaled corticosteroids (ICS) and underutilization of long-acting BDs in group B COPD patients.,Guideline nonadherence was not associated with increased risk of exacerbation after adjustment of confounding variables.,However, this study was not powered to assess a difference in exacerbations.,In all, 80.9% of patients had at least one comorbidity.,A suboptimal adherence to GOLD guideline 2011, with overprescription of ICS, was identified.,The commonly found comorbidities also aligned with the trend observed in other observational cohorts. | 1 |
A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination.,Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations.,This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period.,Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations.,Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks.,Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period.,The primary end point is time to first occurrence of an acute exacerbation during the treatment period.,Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen).,Analyses will be performed on an intent-to-treat basis.,The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres.,Study findings will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals.,NCT02587351; Pre-results. | Objectives To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use.,Design Population based cohort study in England.,Setting UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11.,Participants Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record.,Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London.,Main outcome measure Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct.,Results Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years).,Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001).,Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers.,With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02).,Conclusions The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD.,Registration NCT01335672. | 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. | Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.,The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation.,A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007.,Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication.,Multivariable negative binomial regression was performed with adjustment for potential confounding factors.,The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.,We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications.,COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group.,In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81-0.92).,Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD. | 1 |
Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.,A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed.,Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples.,Levels in patients colonized by H. influenzae and non-colonized patients were compared.,Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test).,Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test).,Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).,Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients.,Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases. | Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD).,We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD.,Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients.,Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models.,Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells.,None of the TLR4 SNPs was associated with FEV1 level.,Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time.,This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD. | 1 |
Objective: This study aimed to investigate the quantitative effects of outdoor air pollution, represented by 10 µg/m3 increment of PM10, on chronic obstructive pulmonary disease in China, United States and European Union through systematic review and meta-analysis.,Methods: Publications in English and Chinese from PubMed and EMBASE were selected.,The Cochrane Review Handbook of Generic Inverse Variance was used to synthesize the pooled effects on incidence, prevalence, mortality and hospital admission.,Results: Outdoor air pollution contributed to higher incidence and prevalence of COPD.,Short-term exposure was associated with COPD mortality increased by 6%, 1% and 1% in the European Union, the United States and China, respectively (p < 0.05).,Chronic PM exposure produced a 10% increase in mortality.,In a short-term exposure to 10 µg/m3 PM10 increment COPD mortality was elevated by 1% in China (p < 0.05) and hospital admission enrollment was increased by 1% in China, 2% in United States and 1% in European Union (p < 0.05).,Conclusions: Outdoor air pollution contributes to the increasing burdens of COPD.10 µg/m3 increase of PM10 produced significant condition of COPD death and exacerbation in China, United States and European Union.,Controlling air pollution will have substantial benefit to COPD morbidity and mortality. | Acute exacerbations of COPD can complicate the course of the disease in patients with severe airway obstruction.,Reduction of exacerbations is an important clinical outcome in evaluating new therapies in COPD.,Combination therapies with long-acting β-agonists and inhaled corticosteroids have now been approved for use.,Three 1-year randomized clinical trials, which studied the effect of combining a long-acting β2-agonist with an inhaled corticosteroid in COPD, documented that exacerbation frequency was lower with therapy than placebo.,Combination therapy had a similar effect to its monocomponents in the trial evaluating salmeterol/fluticasone combination.,However, when patients with more severe COPD were studied using a combination of budesonide and formoterol, a clear improvement was seen in the overall exacerbation rates compared with the use of a long-acting β2-agonist alone. | 1 |
The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 μg twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD.,Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair™/Pressair® dry powder inhaler for 8 weeks.,From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals).,The primary end point was trough functional residual capacity (FRC) at Week 4.,Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI).,Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise.,After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690).,However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P<0.0001).,AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 (P<0.01 and P<0.0001, respectively) and Week 8 (P<0.05 and P<0.0001, respectively).,AB/FF achieved higher step counts (P<0.01) with fewer inactive patients (P<0.0001) at Week 4 versus placebo.,Following BI, AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo.,AB/FF 400/12 μg demonstrated improvements in lung hyperinflation, exercise capacity, and physical activity versus placebo that were maintained following the addition of BI.,A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF. | Patients with COPD show a significant reduction of the lobar hyperinflation at the functional residual capacity level in the patients who improved >120 mL in forced expiratory volume in 1 second (FEV1) after 6 months of treatment with roflumilast in addition to inhaled corticosteroids (ICSs)/long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs).,Functional respiratory imaging was used to quantify lobar hyperinflation, blood vessel density, ventilation, aerosol deposition, and bronchodilation.,To investigate the exact mode of action of roflumilast, correlations between lobar and global measures have been tested using a mixed-model approach with nested random factors and Pearson correlation, respectively.,The reduction in lobar hyperinflation appears to be associated with a larger blood vessel density in the respective lobes (t=−2.154, P=0.040); lobes with a higher percentage of blood vessels reduce more in hyperinflation in the responder group.,Subsequently, it can be observed that lobes that reduce in hyperinflation after treatment are better ventilated (t=−5.368, P<0.001).,Functional respiratory imaging (FRI)-based aerosol deposition showed that enhanced ventilation leads to more peripheral particle deposition of ICS/LABA/LAMA in the better-ventilated areas (t=2.407, P=0.024).,Finally, the study showed that areas receiving more particles have increased FRI-based bronchodilation (t=2.564, P=0.017), leading to an increase in FEV1 (R=0.348, P=0.029).,The study demonstrated that orally administered roflumilast supports the reduction of regional hyperinflation in areas previously undertreated by inhalation medication.,The local reduction in hyperinflation induces a redistribution of ventilation and aerosol deposition, leading to enhanced efficacy of the concomitant ICS/LABA/LAMA therapy.,FRI appears to be a sensitive tool to describe the mode of action of novel compounds in chronic obstructive pulmonary disease.,Future studies need to confirm the enhanced sensitivity and the potential of FRI parameters to act as surrogates for clinically relevant, but more difficult to measure, end points such as exacerbations. | 1 |
Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity.,However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking.,A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted.,Patients with a diagnosis of COPD aged ≥40 years were followed up for 5 years from January 1, 2010.,CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time.,In addition, baseline factors predicting future risk of CAP and hospital admission with CAP were identified.,A total of 14,513 COPD patients were identified: 13.4% (n=1,938) had ≥1 CAP episode, of whom 18.8% suffered from recurrent (≥2) CAP.,Highest rates of both CAP and exacerbations were seen in winter.,A greater proportion of frequent, compared to infrequent, exacerbators experienced recurrent CAP (5.1% versus 2.0%, respectively, P<0.001); 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations.,Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission with CAP.,Other independent predictors of future CAP included lower body mass index, inhaled corticosteroid use, prior frequent exacerbations and comorbidities, including ischemic heart disease and diabetes.,CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission with CAP.,Highlighting this burden of COPD-associated CAP during the winter period informs us of the likely triggers and the need for more effective preventive strategies. | Development of adult respiratory disease is influenced by events in childhood.,The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined.,We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.,COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included.,Childhood pneumonia was defined by self-report of pneumonia at <16 years.,Subjects with lung disease other than COPD or asthma were excluded.,Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.,Of 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood.,Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs.,77.1 % predicted), FVC (82.7 vs.,87.4 % predicted), FEV1/FVC ratio (0.63 vs.,0.67; p < 0.001 for all comparisons).,Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema.,Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).,Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function.,This association is supported by airway changes on chest CT scans.,Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.,ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).,The online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users. | 1 |
Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed.,We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park).,We aimed to validate the trails’ design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults.,On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces.,We measured physiological response and energy expenditure using a gas analyzer.,We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression.,In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak V˙O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trend<0.01) in low, moderate and high intensity trails, respectively.,In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces.,We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails’ intensity and did not change across trails of the same intensity in different public space.,Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community. | There is a wide variability in measurement methodology of physical activity.,This study investigated the effect of different analysis techniques on the statistical power of physical activity outcomes after pulmonary rehabilitation.,Physical activity was measured with an activity monitor armband in 57 patients with COPD (mean ± SD age, 66 ± 7 years; FEV1, 46 ± 17% predicted) before and after 3 months of pulmonary rehabilitation.,The choice of the outcome (daily number of steps [STEPS], time spent in at least moderate physical activity [TMA], mean metabolic equivalents of task level [METS], and activity time [ACT]), impact of weekends, number of days of assessment, postprocessing techniques, and influence of duration of daylight time (DT) on the sample size to achieve a power of 0.8 were investigated.,The STEPS and ACT (1.6-2.3 metabolic equivalents of task) were the most sensitive outcomes.,Excluding weekends decreased the sample size for STEPS (83 vs 56), TMA (160 vs 148), and METS (251 vs 207).,Using 4 weekdays (STEPS and TMA) or 5 weekdays (METS) rendered the lowest sample size.,Excluding days with < 8 h wearing time reduced the sample size for STEPS (56 vs 51).,Differences in DT were an important confounder.,Changes in physical activity following pulmonary rehabilitation are best measured for 4 weekdays, including only days with at least 8 h of wearing time (during waking hours) and considering the difference in DT as a covariate in the analysis.,ClinicalTrials.gov; No.: NCT00948623; URL: www.clinicaltrials.gov | 1 |
Recruitment and retention are two significant barriers in research, particularly for historically underrepresented groups, including racial and ethnic minorities, patients who are low-income, or people with substance use or mental health issues.,Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and disproportionately affects many underrepresented groups.,The lack of representation of these groups in research limits the generalizability and applicability of clinical research and results.,In this paper we describe our experience and rates of recruitment and retention of underrepresented groups for the Aides in Respiration (AIR) COPD Health Coaching Study.,A priori design strategies included minimizing exclusion criteria, including patients in the study process, establishing partnerships with the community clinics, and ensuring that the health coaching intervention was flexible enough to accommodate patient needs.,Challenges to recruitment included lack of spirometric data in patient records, space constraints at the clinic sites, barriers to patient access to clinic sites, lack of current patient contact information and poor patient health.,Of 282 patients identified as eligible, 192 (68%) were enrolled in the study and 158 (82%) completed the study.,Race, gender, educational attainment, severity of disease, health literacy, and clinic site were not associated with recruitment or retention.,However, older patients were less likely to enroll in the study and patients who used home oxygen or had more than one hospitalization during the study period were less likely to complete the study.,Three key strategies to maximize recruitment and retention were identified during the study: incorporating the patient perspective, partnering with the community clinics, and building patient rapport.,While the AIR study included design features to maximize the recruitment and retention of patients from underrepresented groups, additional challenges were encountered and responded to during the study.,We also identified three key strategies recommended for future studies of COPD and similar conditions.,Incorporating the approaches described into future studies may increase participation rates from underrepresented groups, providing results that can be more accurately applied to patients who carry a disparate burden of disease.,This trial was registered at ClinicalTrial.gov at identifier NCT02234284 on August 12, 2014.,Descriptor number: 2.9 Racial, ethnic, or social disparities in lung disease and treatment. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | 1 |
Triple combination therapy involving long-acting muscarinic antagonists long-acting β2 agonists, and inhaled corticosteroids has recently become an option for maintenance treatment of COPD.,Some add-on clinical trials have reported the benefits of these combinations.,However, the process to step up to triple therapy varies for individual cases.,Keio University and affiliated hospitals conducted an observational COPD cohort study, recruiting patients diagnosed as having COPD by pulmonary physicians and those referred for investigation of possible COPD.,Their prescription history and clinical course were retrospectively analyzed based on the physicians’ medical records and patient questionnaires.,This study was registered with UMIN (UMIN000003470, April 10, 2010).,A total of 95 of the 445 COPD patients (21%) were treated with inhaled corticosteroids/long-acting β2 agonists/long-acting muscarinic antagonists as maintenance therapy, including 12 in COPD Grade I, 31 in Grade II, 38 in Grade III, and 14 in Grade IV, based on the Global Initiative for Chronic Obstructive Lung Disease spirometric grading.,For more than half of the patients on triple therapy, the treatment had been intensified due to unsatisfactory improvement of symptoms, and 32% were treated with triple therapy due to comorbid asthma.,In contrast, there were COPD patients whose therapy was maintained after starting with triple therapy because of their serious conditions or concurrent exacerbation at diagnosis (8%).,Triple therapy was often prescribed in the real-life management of COPD, even in patients whose airflow limitation was not severe.,To better control symptoms was the major reason for choosing triple therapy, regardless of the severity of COPD, in Japan. | Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD).,We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom.,We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006.,Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI).,The association with FSC or ICS exposure was modeled using conditional logistic regression.,Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date.,Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents.,We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191).,FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders.,We observed a lack of a dose response in all analyses, where low dose was the reference group.,The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7).,The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8).,FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom. | 1 |
Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear.,Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis.,MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization.,NMT patients had received short-acting bronchodilators or no treatment.,Outcomes included forced expiratory volume over 1 s (FEV1), clinically important deterioration (CID), rescue medication use, and safety.,GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV1 treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001).,GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts.,Safety profiles for all cohorts were consistent with each other and the parent studies.,NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk.,Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment. | 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 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.