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Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses.,In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up.,We analyzed dusty areas cohort comprising 272 patients with COPD.,The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline.,The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data.,The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups.,PCA revealed that six independent components accounted for 77.3% of variance.,Three distinct subgroups were identified through the cluster analysis.,Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up.,Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up.,Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization.,Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes.,These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.,The online version of this article (10.1186/s12890-017-0553-9) contains supplementary material, which is available to authorized users. | Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system.,Metabolic profiling of different high-resolution computed tomography (HRCT) phenotypes of COPD patients before and after treatment may identify discriminatory metabolites that can serve as biomarkers and therapeutic agents.,1H nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics was performed on a discovery set of plasma samples from 50 patients with stable COPD.,Patients were assigned into two groups on the basis of HRCT findings including phenotype E (n=22) and phenotype M (n=28).,After budesonide-formoterol treatment (160/4.5 µg ×2 inhalations twice daily for 3 months), clinical characteristics and metabolites were then compared between phenotype E pretreatment and posttreatment, phenotype M pretreatment and posttreatment, phenotype E pretreatment and phenotype M pretreatment, and phenotype E posttreatment and phenotype M posttreatment.,Inhaled budesonide-formoterol therapy for both phenotype E (emphysema without bronchial wall thickening) and phenotype M (emphysema with bronchial wall thickening) was effective.,However, phenotype E and phenotype M were different in response to therapy.,Patients with phenotype M in response to therapeutic effects were significantly greater compared with phenotype E.,Certain metabolites were identified, which were closely related to the treatment and phenotype.,Metabolic changes in phenotype E or phenotype M after treatment may be involved with adenosine diphosphate (ADP), guanosine, choline, malonate, tyrosine, glycine, proline, l-alanine, l-valine, l-threonine leucine, uridine, pyruvic acid, acetone and metabolism disturbance.,Metabolic differences between phenotype E and phenotype M in pretreatment and posttreatment covered glycine, d-glucose, pyruvic acid, succinate, lactate, proline, l-valine and leucine.,Bronchial wall thickening in COPD may be an indicator for predicting the better response to the treatment with bronchodilator and corticosteroid.,The identification of metabolic alterations provides new insights into different HRCT phenotypes and therapeutic assessment of COPD. | 1 |
Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5) has been associated with respiratory risk.,However, evidence on the risk of chronic obstructive pulmonary disease (COPD) exacerbations is still limited.,The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations.,After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model.,In addition, the population-attributable fractions (PAFs) were also calculated, and a subgroup analysis was conducted.,Heterogeneity was assessed by I2.,In total, 59 studies were included.,In the single-pollutant model, the risks of COPD were calculated by each 10 μg/m3 increase in pollutant concentrations, with the exception of CO (100 μg/m3).,There was a significant association between short-term exposure and COPD exacerbation risk for all the gaseous and particulate pollutants.,The associations were strongest at lag0 and lag3 for gaseous and particulate air pollutants, respectively.,The subgroup analysis not only further confirmed the overall adverse effects but also reduced the heterogeneities obviously.,When 100% exposure was assumed, PAFs ranged from 0.60% to 4.31%, depending on the pollutants.,The adverse health effects of SO2 and NO2 exposure were more significant in low-/middle-income countries than in high-income countries: SO2, relative risk: 1.012 (95% confidence interval: 1.001, 1.023); and NO2, relative risk: 1.019 (95% confidence interval: 1.014, 1.024).,Short-term exposure to air pollutants increases the burden of risk of COPD acute exacerbations significantly.,Controlling ambient air pollution would provide benefits to COPD patients. | Hospitalizations for COPD are associated with poor patient prognosis.,Length of stay (LOS) of COPD admissions in a large urban area and patient and hospital factors associated with it are described.,Retrospective longitudinal study.,All COPD patients registered with London general practitioners and admitted as an emergency with COPD (2006-2010), not having been admitted with COPD in the preceding 12 months were included.,Association of patient and hospital characteristics with mean LOS of COPD admissions was assessed.,Association between hospital and LOS was determined by negative binomial regression.,The total number of admissions was 38,504, from 22,462 patients.,The mean LOS for first admissions fell by 0.8 days (95% confidence interval [CI]: 0.7-1.5) from 8.2 to 7.0 days between 2006 and 2010.,Seventy-nine percent of first admissions were ≤10 days, with a mean LOS of 3.7 days (2009-2010).,The mean LOS of successive COPD admissions of the same patients was the same or less throughout the study period.,The interval between successive admissions fell from a mean of 357 days between the first and second admission to a mean of 19 days after eight admissions.,Age accounted for 2.3% of the variance in LOS.,Socioeconomic deprivation did not predict LOS.,Fewer discharges happened at the weekend (1,893/day) than on weekdays (5,218/day).,The mean LOS varied between hospitals, from 4.9 days (95% CI: 3.8-5.9) to 9.5 days (95% CI: 8.6-10.3) when adjusting for clustering, age, sex, and socioeconomic deprivation.,The fall in LOS of the first COPD admission between 2006 and 2010 reflects international trends.,The stability of LOS in successive admissions suggests that increasing severity of disease does not affect recovery time from an exacerbation.,Variations between hospitals of nearly 5 days in LOS for COPD admissions suggests that significant improvements in patient outcomes and in savings in health care utilization could be made in hospitals with longer LOS. | 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. | Two replicate, double-blind, placebo-controlled, 6-week crossover studies assessed the effect of the once-daily long-acting β2-agonist olodaterol 5 μg and 10 μg on constant work-rate cycle endurance in patients with moderate to very severe chronic obstructive pulmonary disease.,Patients received placebo, olodaterol 5 μg once daily (QD) and olodaterol 10 μg QD in a randomised order for 6 weeks each, with a 2-week washout period in between.,The primary end point was change in endurance time during constant work-rate cycle ergometry to symptom limitation at 75 % maximal work capacity after 6 weeks of treatment (2 h post-dose), based on log10-transformed data.,Key secondary end points were inspiratory capacity at isotime and intensity of breathing discomfort at isotime.,151 and 157 patients were randomised and treated in Studies 1222.37 and 1222.38, respectively, with 147 and 154 being included in the full analysis sets.,Mean endurance time at week 6 was increased compared to placebo by 14.0 % (Study 1222.37; p < 0.001) and 11.8 % (Study 1222.38; p < 0.01) with olodaterol 5 μg, and by 13.8 % (Study 1222.37; p < 0.001) and 10.5 % (Study 1222.38; p < 0.01) with olodaterol 10 μg.,Inspiratory capacity at isotime increased with olodaterol 5 μg (Study 1222.37, 0.182 L, p < 0.0001; Study 1222.38, 0.084 L, p < 0.05) and 10 μg (Study 1222.37, 0.174 L; Study 1222.38, 0.166 L; both studies, p < 0.0001), and breathing discomfort was significantly reduced in Study 1222.37 (olodaterol 5 μg, 0.77 Borg units, p < 0.001; olodaterol 10 μg, 0.63 Borg units, p < 0.01) but not Study 1222.38.,These studies provide further characterisation of the efficacy of olodaterol, showing that improvements in airflow (forced expiratory volume in 1 s) are associated with increases in inspiratory capacity and improvements in exercise endurance time.,NCT01040130 (1222.37) and NCT01040793 (1222.38).,The online version of this article (doi:10.1186/s12931-016-0389-5) contains supplementary material, which is available to authorized users. | 1 |
Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD).,Their coexistence implies that many COPD patients require anticoagulation therapy.,Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used.,VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway.,It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification.,No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease.,Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries.,Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival.,In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation.,We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease.,Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
Some COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.,To define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.,We analyzed baseline data from a multi-center observational study (SPIROMICS).,This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).,We defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire <5; 6-minute walking distance <250 m; St George’s Respiratory Questionnaire activity domain >60; COPD Assessment Test >20; fatigue (FACIT-F Trial Outcome Index) <50; SF-12 <20.,Using these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female).,Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%.,Compared with others, participants with disability had more emphysema (13.2 vs.,6.6%) and air-trapping (37.0 vs.,21.6%) on HRCT (P<0.0001).,Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point −1.0 reliably identified disability.,This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001).,Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.,Our novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers.,The disability score also proved to be an independent predictor of future exacerbations and death.,These findings validate disability as an important phenotype in the spectrum of COPD. | In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs.,The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand).,We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay.,Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD.,Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales.,The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES).,In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up.,Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD.,For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD).,The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD.,The SPPB can aid in clinical decision making and when prioritising healthcare resources. | 1 |
We aimed to characterise and quantify the incidence of common infectious agents in acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring ventilation, with a focus on respiratory viruses.,An epidemiological study conducted over 3 years.,A 12-bed intensive care unit (ICU).,ICU patients over 45 years of age with a primary diagnosis of COPD exacerbation requiring non-invasive ventilation (NIV) or ventilation via endotracheal tube (ETT).,Nasopharyngeal aspirates (NPA) and posterior pharyngeal swabs (PS) were tested for viruses with immunofluorescence assay (IFA), virus culture (VC) and polymerase chain reaction (PCR).,Paired virus and atypical pneumonia serology assays were taken.,Blood, sputum and endotracheal aspirates were cultured for bacteria.,107 episodes in 105 patients were recorded.,Twenty-three (21%) died within 28 days.,A probable infectious aetiology was found in 69 patient episodes (64%).,A virus was identified in 46 cases (43%), being the sole organism in 35 cases (33%) and part of a mixed infection in 11 cases (10%).,A probable bacterial aetiology was found in 25 cases (23%).,There was no statistically significant difference in clinical characteristics or outcomes between the group with virus infections and that without.,Forty-six (43%) of the patients with COPD exacerbation requiring mechanical ventilation had a probable viral pathogen.,Prodromal, clinical and outcome parameters did not distinguish virus from non-virus illness.,PCR was the most sensitive whilst virus culture was the least of virus assays.,The electronic reference of this article is http://dx.doi.org/10.1007/s00134-006-0202-x.,The online full-text version of this article includes electronic supplementary material.,This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article.,To cite or link to this article you can use the above reference. | Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | 1 |
Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.,Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.,Setting Tayside, Scotland (2001-2010),Population 5977 patients aged >50 years with a diagnosis of COPD.,Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.,Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective.,There was a 22% overall reduction in all cause mortality with β blocker use.,Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD.,Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker.,There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent,Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function. | Severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is a common reason for emergency room (ER) visit about which little has been documented from India.,Prospective study of the clinical presentation and predictors of outcome in 116 patients presenting with severe AE-COPD requiring admission to the medical intensive care unit between January 2000 and December 2004.,Their mean age was 62.1 ± 9.8 years.,There were 102 males.,Mean duration of COPD was 7.2 ± 5.8 years.,All males were smokers (22.3 ± 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis.,All women were exposed to domestic fuel.,Associated co-morbid illnesses were present in 81 patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28 (54.3%) had two or more co-morbid illnesses.,Evidence of past pulmonary tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II diabetes mellitus had active PTB.,Arterial blood gas analysis revealed respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%).,Invasive mechanical ventilation was required in 18 patients.,Sixteen (13.7%) patients died.,Stepwise multivariate logistic regression analysis revealed need for invasive ventilation (OR 45.809, 95%CI 607.46 to 3.009;p < 0.001); presence of co-morbid illness (OR 0.126, 95%CI 0.428 to 0.037;p < 0.01) and hypercapnia (OR 0.114, 95%CI 1.324 to 0.010;p < 0.05) were predictors of death.,Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD difficult and also contribute to mortality.,High prevalence of past PTB and active PTB in patients with AE-COPD suggests an intriguing relationship between smoking, PTB and COPD which merits further study. | 1 |
Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ ≥1, CAT ≥10, and mMRC scale ≥2 to indicate symptomatic patients.,The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George’s Respiratory Questionnaire (SGRQ) ≥25, as suggested by GOLD, following sensitivity and specificity analysis.,In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (≥25 and ≥20).,Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care.,Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires.,Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥25 were: study A, 0.99, 0.43, and 0.96 for CCQ ≥1, 0.92, 0.48, and 0.89 for CAT ≥10, and 0.68, 0.91, and 0.91 for mMRC ≥2; study B, 0.87, 0.77, and 0.9 for CCQ ≥1, 0.76, 0.73, and 0.82 for CAT ≥10, and 0.21, 1, and 0.81 for mMRC ≥2.,Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥20 were: study A, 0.99, 0.73, and 0.99 for CCQ ≥1, 0.91, 0.73, and 0.94 for CAT ≥10, and 0.66, 0.95, and 0.94 for mMRC ≥2; study B, 0.8, 0.89, and 0.89 for CCQ ≥1, 0.69, 0.78, and 0.8 for CAT ≥10, and 0.18, 1, and 0.81 for mMRC ≥2.,Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (≥25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels.,The correspondence with the mMRC scale seemed satisfactory, though not optimal.,The SGRQ threshold of ≥20 corresponded slightly better than SGRQ ≥25, recently suggested by GOLD 2015, with the established cutoff points for the CCQ, CAT, and mMRC scale. | 1 |
Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics.,The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence.,Current COPD guidelines were identified by a systematic literature search.,The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included.,Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised.,Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population.,A total of 19 COPD guidelines were included.,Systemic corticosteroids were often universally recommended to all patients with acute exacerbations.,Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms.,Objective diagnostic tests or clinical examination were only rarely recommended.,Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients.,Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment. | 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 |
Background: To validate the ‘Test of Adherence to Inhalers’ (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma.,Methods: A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study.,Patients with electronic adherence ≥80% were defined as adherents.,Construct validity, internal validity, and criterion validity were evaluated.,Self-reported adherence was compared with the Morisky-Green questionnaire.,Results: Factor analysis study demonstrated two factors, factor 1 was coincident with TAI patient domain (items 1 to 10) and factor 2 with TAI health-care professional domain (items 11 and 12).,The Cronbach's alpha was 0.860 and the test-retest reliability 0.883.,TAI scores correlated with electronic adherence (ρ=0.293, p=0.01).,According to the best cut-off for 10 items (score 50, area under the ROC curve 0.7), 569 (62.5%) patients were classified as non-adherents.,The non-adherence behavior pattern was: erratic 527 (57.9%), deliberate 375 (41.2%), and unwitting 242 (26.6%) patients.,As compared to Morisky-Green test, TAI showed better psychometric properties.,Conclusions: The TAI is a reliable and homogeneous questionnaire to identify easily non-adherence and to classify from a clinical perspective the barriers related to the use of inhalers in asthma and COPD. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
To evaluate outcomes of the Clinical Chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ) in patients with advanced COPD admitted for a post-acute pulmonary rehabilitation (PR) programme and to relate (change in) health status to lung function, degree of dyspnoea and (change in) functional capacity.,This is a prospective observational study in patients with advanced COPD admitted for a post-acute PR programme in a skilled nursing facility.,Health status (CCQ) and functional capacity were measured before and after rehabilitation.,Health status measured by the CCQ was severely impaired and showed significant and clinically relevant improvement during the post-acute PR programme.,Moderate to strong correlations were found between CCQ scores and functional capacity on admission and at discharge.,Moderate correlations were found between improvement in CCQ scores and improvement in functional capacity.,No correlation was found between CCQ scores and lung function (forced expiratory volume in 1 s % predicted).,Health status measured by the CCQ improves following a post-acute PR programme in patients with advanced COPD and correlates with improvement in functional capacity.,These results suggest that the CCQ is sensitive to change in response to PR in this specific group of patients. | Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally.,Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD.,Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality.,Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes.,In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels.,To date, only limited evidence exists to support the effectiveness of these interventions.,We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term. | 1 |
Bronchodilators are central in the symptomatic management of chronic obstructive pulmonary disease (COPD).,Long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are the main classes of long-acting bronchodilators.,To date, tiotropium is the only once-daily LAMA available for the treatment of COPD.,Glycopyrronium is a novel LAMA, currently in development for COPD.,Phase II studies have shown that glycopyrronium 50 μg once daily provides clinically significant 24-hour bronchodilation with a rapid onset of action, which is faster than that of tiotropium, and a favorable safety and tolerability profile.,The Phase III GLycopyrronium bromide in COPD airWays (GLOW) program has now confirmed the long-term efficacy and tolerability of glycopyrronium 50 μg once daily.,The three studies included in this program have further shown that the effect of glycopyrronium versus placebo is similar to that of tiotropium in reducing dyspnea and the risk of exacerbations, as well as improving lung function, exercise tolerance, and health status in patients with COPD.,The safety profile of glycopyrronium is also similar to that of tiotropium in terms of overall incidence of adverse events and muscarinic side effects.,Glycopyrronium could be an alternative choice to tiotropium, and like tiotropium, has the potential to be used as a monotherapy or combination therapy.,Phase II studies have shown that a fixed-dose combination of glycopyrronium and the 24-hour LABA indacaterol, produces rapid and sustained bronchodilation compared with indacaterol monotherapy in patients with COPD.,Phase III studies are currently ongoing to assess the long-term efficacy and safety of this combination. | Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD).,The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.,This study was performed as a systematic literature review.,Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action.,In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status.,Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance.,Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.,Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD. | 1 |
Smoking cessation is a key intervention for all smokers with chronic obstructive pulmonary disease (COPD).,Poor treatment adherence is a challenge in clinical practice that might contribute to the lower efficacy of medication (eg, oral drug).,However, it is unclear what factors will influence adherence among smokers with COPD.,This study was based on an open-label randomized controlled trial (RCT) of varenicline and bupropion for smoking cessation among patients with COPD in China.,The medication was given for 12 weeks, and visits and assessments were conducted at weeks 0, 1, 2, 4, 6, 9, 12, and 24.,We assessed whether the adherence to smoking cessation treatment affects the smoking cessation efficacy and evaluated predictors of adherence.,A total of 136 participants were recruited from February 2019 to June 2020, and analyzed using the intention-to-treat (ITT) method.,In this study, 48.5% (66/136) of the total participants had good adherence to smoking cessation, and good adherence significantly improved the efficacy of smoking cessation (OR=9.60, 95% CI 4.02-22.96, P < 0.001).,After adjusting for age, gender, nationality, education, and marital status, we found older age, higher education level, having more previous quitting attempts, stronger self-efficacy and preparation in quitting smoking, recognizing hazards of smoking, longer duration of COPD, and higher St.,George’s Respiratory Questionnaire (SGRQ) scores were relevant to good adherence (P < 0.05).,To our best knowledge, this is the first study to evaluate adherence to smoking cessation treatment among patients with COPD in China.,Our study found that good adherence to smoking cessation treatment significantly improved the smoking cessation efficacy, and predictors of adherence were evaluated.,We call on the medical community to pay attention to the adherence to smoking cessation among patients with COPD. | There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD).,It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation.,Patients were randomised to either singing classes or a film club for eight weeks.,Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist.,The singing group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline.,There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity.,In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group.,Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity.,Registration Current Controlled Trials - ISRCTN17544114 | 1 |
The aim of this study was to explore to what extent a combined counselling and pulmonary rehabilitation program (PR) influences the perception of physical activity (PA) and motivation for behavioral change in PA in individuals with COPD.,The results of previous quantitative trial that investigated the effect of this combined treatment on daily PA were inconclusive.,It is conjectured that a more targeted tailoring of the counselling and PR intervention could improve its effectiveness.,Eighteen individuals with COPD (median age 69, 8 females) who had participated in the PneumoReha program were interviewed twice (following PR and at three-month follow-up).,These interviews were transcribed and analyzed thematically.,Based on the codes thus identified, three categories ‘perception of PA intensity’, ‘quality of motivation to perform PA’, and ‘strategies to cope with barriers’ were used to differentiate ‘types’ of participants.,Four different types of COPD individuals were distinguished.,Study findings indicate that those individuals who participated in the PR program combined with embedded counselling tended to be more active and intrinsically motivated.,A typology of four types of people with COPD was developed, characterized by their perception of activity, individual motivation and strategies for managing barriers.,The patients’ physical activity level might be influenced by their concept of physical activity and the quality of motivation.,Recognizing patients’ different activity behaviors is important for improving the quality of outpatient PR programs and developing tailored (according to each type) counselling interventions embedded in outpatient PR programs.,The study was registered on the website of https://www.clinicaltrials.gov/ with the identifier NCT02455206 (27/05/2015), as well as on the Swiss National Trails Portal SNCTP000001426 (05/21/2015). | Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis.,Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD.,COPD-associated osteoporosis is however extremely undertreated.,Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients.,Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described.,It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks.,Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. | 1 |
The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity. | The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD).,Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV1) over 5 years, baseline FEV1, serum protein levels, cardiovascular disease, and interactions with smoking.,The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV1 (P = 0.049), and was found to have a significant interaction (P = 0.004) with mean number of cigarettes smoked per day.,There was also a significant interaction of IFNG rs2069727 with smoking on prebronchodilator (P = 0.008) and postbronchodilator (P =0.01) FEV1.,The IL6 polymorphism was also associated with cardiovascular disease in heterozygous individuals (P = 0.044), and was found to have a significant interaction with smoking (P = 0.024).,None of the genetic variants were associated with their respective serum protein levels.,The results suggest interactions of IL6 rs2069825 and IFNG rs2069727 single nucleotide polymorphisms with cigarette smoking on measures of lung function.,The IL6 rs2069825 single nucleotide polymorphism also interacted with smoking to affect the risk of cardiovascular disease in COPD patients. | 1 |
A multidimensional approach in the risk assessment of chronic obstructive pulmonary disease (COPD) is preferable.,The aim of this study is to compare the prognostic ability for mortality by different COPD assessment systems; spirometric staging, classification by GOLD 2011, GOLD 2017, the age, dyspnea, obstruction (ADO) and the dyspnea, obstruction, smoking, exacerbation (DOSE) indices.,A total of 490 patients diagnosed with COPD were recruited from primary and secondary care in central Sweden in 2005.,The cohort was followed until 2017.,Data for categorization using the different assessment systems were obtained through questionnaire data from 2005 and medical record reviews between 2000 and 2003.,Kaplan-Meier survival analyses and Cox proportional hazard models were used to assess mortality risk.,Receiver operating characteristic curves estimated areas under the curve (AUC) to evaluate each assessment systems´ ability to predict mortality.,By the end of follow-up, 49% of the patients were deceased.,The mortality rate was higher for patients categorized as stage 3-4, GOLD D in both GOLD classifications and those with a DOSE score above 4 and ADO score above 8.,The ADO index was most accurate for predicting mortality, AUC 0.79 (95% CI 0.75-0.83) for all-cause mortality and 0.80 (95% CI 0.75-0.85) for respiratory mortality.,The AUC values for stages 1-4, GOLD 2011, GOLD 2017 and DOSE index were 0.73, 0.66, 0.63 and 0.69, respectively, for all-cause mortality.,All of the risk assessment systems predict mortality.,The ADO index was in this study the best predictor and could be a helpful tool in COPD risk assessment. | Chronic obstructive pulmonary disease (COPD) is the third leading cause of death by disease worldwide and has a 30-day readmission rate of 22.6%.,In 2015, COPD was added to the Medicare Hospital Readmission Reductions Program.,The objective of this paper was to survey the current medical technologies for remote patient monitoring (RPM) tools that forecast COPD exacerbations in order to reduce COPD readmissions.,We searched literature and digital health news to find commercially available RPM devices focused on predicting COPD exacerbations.,These technologies were reviewed and compared according to four criteria: forecasting ability, cost, ease of use, and appearance.,A rating system was developed to facilitate the evaluation process.,As of June 2019, a list of handheld and hands-free devices was compiled.,We compared features and found substantial variations.,Devices that ranked higher on all criteria tended to have a high or unlisted price.,Commonly mass-marketed devices like the pulse oximeter and spirometer surprisingly fulfilled the least criteria.,The COPD RPM technologies with most technological promise and compatibility with daily living appear to have high or unlisted prices.,Consumers and providers need better access to product information to make informed decisions. | 1 |
It remains unclear whether eosinophilia is useful for in guiding inhaled corticosteroid (ICS) therapy in chronic obstructive pulmonary disease (COPD) patients.,The goal of this study is to evaluate the risk of acute exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality with various levels of eosinophil counts among COPD patients using ICS.,A cohort study was conducted using the UK Clinical Practice Research Datalink.,Patients were aged 40+ and had COPD (n = 32 693).,Current users of ICS were stratified by relative and absolute eosinophil counts to determine the risk of outcomes with blood eosiniphilia using Cox regression analysis.,Among COPD patients, current use of ICS was not associated with a reduced risk of acute COPD exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality.,Stratification of ICS use by absolute or relative eosinophil counts did not result in significant differences in risk of COPD exacerbations or hospitalisations/accident and emergency visits.,However, all‐cause mortality was reduced by 12% to 24% among patients with eosinophilia.,COPD‐related acute exacerbations or hospitalisations/accident and emergency visits were not reduced with eosinophilia among users of ICS with COPD.,However, all‐cause mortality was reduced by 12% to 24%.,These findings are potentially important and require further evaluation in prospective studies. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality.,Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin.,A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included.,All patients underwent coronary angiography within 72 hours after hospitalization.,Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed.,Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention.,Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history.,Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01).,Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups.,Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin.,In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,The prevalence of COPD among cigarette smokers in the Middle East is not well studied.,A prospective descriptive study was performed in the north of Jordan.,Male cigarette smokers (≥10 pack-year) aged 35 years and older were recruited from the community.,They completed a questionnaire and a postbronchodilator spirometry.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (postbronchodilator forced expiratory volume in 1 second <70%) was used to define COPD.,A total of 512 subjects completed the study protocol.,According to the GOLD criteria, 42 subjects (8.2%) had COPD.,Of those, 27 subjects (64.3%) had symptomatic COPD.,Using the GOLD criteria, eight subjects (19%) with COPD had mild disease, 24 (57.1%) had moderate disease, eight (19%) had severe disease, and two (4.8%) had very severe disease.,Only 10.6% were aware of COPD as a smoking-related respiratory illness, and 6.4% had received counseling about risk for COPD by a physician.,Chronic bronchitis (cough for 3 months in 2 consecutive years) was reported by 15% of the subjects, wheezes by 44.1%, and dyspnea by 65.2%.,Subjects with COPD reported having more chronic bronchitis 18/42 (42.9%) and wheezing 28/42 (66.7%) than subjects without COPD.,The prevalence of COPD increased with increased number of pack-years smoked.,In conclusion, COPD prevalence among cigarette-smoking men in Jordan is lower than in the developed world.,COPD was largely underdiagnosed, despite the majority of participants being symptomatic and having moderate to severe disease. | 1 |
Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations.,Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.,Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.,Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies.,Time to ACM was prespecified.,Additional vital status data collection and subsequent analyses were performed post hoc.,Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI.,For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI.,Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient’s COPD.,Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations. | Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | 1 |
There is growing evidence that many diseases develop, progress, and respond to therapy differently in men and women.,This variability may manifest as a result of sex-specific structures in gene regulatory networks that influence how those networks operate.,However, there are few methods to identify and characterize differences in network structure, slowing progress in understanding mechanisms driving sexual dimorphism.,Here we apply an integrative network inference method, PANDA (Passing Attributes between Networks for Data Assimilation), to model sex-specific networks in blood and sputum samples from subjects with Chronic Obstructive Pulmonary Disease (COPD).,We used a jack-knifing approach to build an ensemble of likely networks for each sex.,By adapting statistical methods to compare these network ensembles, we were able to identify strong differential-targeting patterns associated with functionally-related sets of genes, including those involved in mitochondrial function and energy metabolism.,Network analysis also identified several potential sex- and disease-specific transcriptional regulators of these pathways.,Network analysis yielded insight into potential mechanisms driving sexual dimorphism in COPD that were not evident from gene expression analysis alone.,We believe our ensemble approach to network analysis provides a principled way to capture sex-specific regulatory relationships and could be applied to identify differences in gene regulatory patterns in a wide variety of diseases and contexts.,The online version of this article (doi:10.1186/s12918-014-0118-y) contains supplementary material, which is available to authorized users. | Individuals with COPD have systemic inflammation that can be assessed by measuring C-reactive protein (CRP).,In this paper we evaluated whether CRP is related to COPD, lung function and rate of lung function decline.,We included 1237 randomly selected subjects (mean age 42, range 28-56 years) from three centers in the European Community Respiratory Health Survey: Reykjavik, Uppsala and Tartu.,CRP was measured at the end of the follow-up (mean 8.3 years) and the values were divided into 4 quartiles.,Fifty-three non-asthmatic subjects fulfilled spirometric criteria for COPD (FEV1/FVC < 70%).,COPD occurred more often in the 4th CRP quartile (OR (95% CI) 3.21 (1.13-9.08)) after adjustment for age, gender, body weight and smoking.,High CRP levels were related to lower FEV1 values in both men (−437 (−596, −279) mL) and women (−144 (−243, −44) mL).,The negative association between CRP and FEV1 was significantly larger in men than women (p = 0.04).,The decline in FEV1 was larger (16 (5, 27) mL) in men with high CRP levels whereas no significant association between CRP and FEV1 decline was found in women.,Higher CRP values are significantly associated with COPD and lower lung function in men and women.,In men higher CRP values are related to a larger decline in FEV1. | 1 |
Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | 1 |
The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear.,We aimed to determine TGF-β pathway protein expression in patients with stable COPD.,The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis.,TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium, with TGF-β1 also decreased in alveolar macrophages, in patients with stable COPD compared with control smokers with normal lung function.,TGF-β3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and smokers with mild/moderate stable COPD compared with control nonsmokers and correlated significantly with pack-years of smoking.,However, TGF-β3+ cells decreased in patients with severe/very severe COPD compared with control smokers.,Latent TGF-β binding protein 1 expression was increased in the bronchial lamina propria in subjects with stable COPD of all severities compared with control smokers with normal lung function.,Bone morphogenetic protein and activin membrane-bound inhibitor expression (BAMBI) in the bronchial mucosa was significantly increased in patients with stable COPD of all severities compared with control subjects.,No other significant differences were observed between groups for all the other molecules studied in the bronchial mucosa and peripheral lung.,Expression of TGF-βs and their regulatory proteins is distinct within different lower airway compartments in stable COPD.,Selective reduction in TGF-β1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD. | Adenosine receptor stress agents for myocardial perfusion imaging (MPI) may cause A2B and/or A3 receptor-mediated bronchoconstriction, of particular concern to physicians testing patients with asthma or chronic obstructive pulmonary disease (COPD).,A Phase 4, randomized, double-blind study (NCT00862641) assessed the safety of the selective A2A receptor agonist, regadenoson, compared with placebo in subjects with asthma or COPD who represented likely candidates for MPI.,Overall, 356 and 176 subjects with asthma and 316 and 151 subjects with COPD received regadenoson and placebo, respectively.,The percentage of subjects experiencing a >15% decrease in FEV1 from baseline to any assessment up to 24 hours post-baseline was not statistically significantly different between the regadenoson and the placebo groups in the asthma or COPD stratum.,Dyspnea, the most frequent respiratory adverse event, occurred with higher incidence (P < .0001) in the regadenoson group than the placebo group in the asthma (10.7% vs 1.1%) and COPD (18.0% vs 2.6%) strata.,No subjects experienced severe bronchoconstriction, although the occurrence of such reactions with adenosine receptor agonists cannot be ruled out, such that caution is advised.,This information may be helpful to physicians selecting a pharmacologic stress agent for MPI in patients with asthma or COPD. | 1 |
This study was conducted in order to investigate the diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative computed tomography (CT) in patients with COPD.,Medical records of 174 stable COPD patients were retrospectively reviewed to obtain the patients’ clinical data, including the pulmonary function and imaging data.,According to the software-based quantification of the degree of emphysema and airway wall thickness, the patients were classified into the “normal by CT” phenotype, the airway-dominant phenotype, the emphysema-dominant phenotype, and the mixed phenotype.,The pulmonary function, including the respiratory impedance evaluated by using the forced oscillation technique (FOT) and the reversibility of airway obstruction in response to inhaled short-acting β2-agonists, was then compared among the four phenotypes.,The respiratory system resistance at 5 and 20 Hz (R5 and R20) was significantly higher, and the respiratory system reactance at 5 Hz (X5) was significantly more negative in the airway-dominant and mixed phenotypes than in the other phenotypes.,The within-breath changes of X5 (ΔX5) were significantly greater in the mixed phenotype than in the “normal by CT” and emphysema-dominant phenotypes.,The FOT parameters (R5, R20, and X5) were significantly correlated with indices of the degree of airway wall thickness and significantly but weakly correlated with the reversibility of airway obstruction.,There was no significant correlation between the FOT parameters (R5, R20, and X5) and the degree of emphysema.,There is a diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative CT in patients with COPD.,The FOT measurements may reflect the degree of airway disease and aid in detecting airway remodeling in patients with COPD. | Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD).,It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD).,However, little is known about which phenotypes of COPD are associated with increased EAT.,One hundred and eighty smokers who were referred to the clinic were consecutively enrolled.,A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT.,These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively.,The same measurements were made on 225 Vietnamese COPD patients to replicate the results.,Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70.,The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients.,The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001).,These results were replicated in the Vietnamese population.,The EAT area is independently associated with airway wall thickness.,Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. | 1 |
COPD is characterized by persistent respiratory symptoms and airflow limitation, caused by a mixture of small airway disease and pulmonary emphysema.,Programmed cell death has drawn the attention of COPD researchers because emphysema is thought to result from epithelial cell death caused by smoking.,Although apoptosis has long been thought to be the sole form of programmed cell death, recent studies have reported the existence of a genetically programmed and regulated form of necrosis called necroptosis.,Autophagy was also previously considered a form of programmed cell death, but this has been reconsidered.,However, recent studies have revealed that autophagy can regulate programmed cell death, including apoptosis and necroptosis.,It is also becoming clear that autophagy can selectively degrade specific proteins, organelles, and invading bacteria by a process termed “selective autophagy” and that this process is related to the pathogenesis of human diseases.,In this review, we outline the most recent studies implicating autophagy, selective autophagy, and necroptosis in COPD.,Strategies targeting these pathways may yield novel therapies for COPD. | Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users. | Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD).,This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.,This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2).,A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation.,Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy.,Adverse events (AEs) were also assessed.,Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818).,Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001).,Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population.,No significant reduction in risk of a SGRQ CID was observed.,AE incidence was similar between treatment groups.,Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations.,Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.,GlaxoSmithKline (study number: 202067).,Plain language summary available for this article.,The online version of this article (10.1007/s12325-018-0771-4) contains supplementary material, which is available to authorized users. | 1 |
Comorbidities are associated with the severity of coronavirus disease 2019 (COVID‐19).,This meta‐analysis aimed to explore the risk of severe COVID‐19 in patients with pre‐existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history.,A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases.,The languages of literature included English and Chinese.,The point prevalence of severe COVID‐19 in patients with pre‐existing COPD and those with ongoing smoking was evaluated with this meta‐analysis.,Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study.,The pooled OR of COPD and the development of severe COVID‐19 was 4.38 (fixed‐effects model; 95% CI: 2.34‐8.20), while the OR of ongoing smoking was 1.98 (fixed‐effects model; 95% CI: 1.29‐3.05).,There was no publication bias as examined by the funnel plot and Egger's test (P = not significant).,The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID‐19.,COPD and ongoing smoking history attribute to the worse progression and outcome of COVID‐19. | Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | 1 |
Previous studies have demonstrated significant variability in the processes of care and outcomes of chronic obstructive pulmonary disease (COPD) exacerbations.,The AUDIPOC is a Spanish nationwide clinical audit that identified large between‐hospital variations in care and clinical outcomes.,Here, we test the hypothesis that these variations can be attributed to either patient characteristics, hospital characteristics and/or the so‐called hospital‐clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted.,A clinical audit of 5178 COPD patients consecutively admitted to 129 Spanish public hospitals was performed, with a 90‐day follow‐up.,Multilevel regression analysis was conducted to model the probability of patients experiencing adverse outcomes.,For each outcome, an empty model (with no independent variables) was fitted to assess the clustering effect, followed by a model adjusted for the patient‐ and hospital‐level covariables.,The hospital‐clustering effect was estimated using the intracluster correlation coefficient (ICC); the cluster heterogeneity was estimated with the median odds ratio (MOR), and the coefficients of predictors were estimated with the odds ratio (OR).,In the empty models, the ICC (MOR) for inpatient mortality and the follow‐up mortality and readmission were 0.10 (1.80), 0.08 (1.65) and 0.01 (1.24), respectively.,In the adjusted models, the variables that most represented the patients’ clinical conditions and interventions were identified as outcome predictors and further reduced the hospital variations.,By contrast, the resource factors were primarily unrelated with outcomes.,This study demonstrates a noteworthy reduction in the observed crude between‐hospital variation in outcomes after accounting for the hospital‐cluster effect and the variables representing patient's clinical conditions.,This emphasises the predictor importance of the patients’ clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality.,Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance.,However, none of these studies were designed with physical activity as primary outcome.,This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.,In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods).,Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70.,The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure.,Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day.,Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.,A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study.,Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264).,IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days.,The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.,In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels.,This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.,ClinicalTrials.gov number: NCT01996319.,The online version of this article (doi:10.1186/s12890-016-0256-7) contains supplementary material, which is available to authorized users. | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
The prevalence of chronic obstructive pulmonary disease (COPD) in Anhui Province of eastern China remain uncertain.,The present study provides the first estimate of the prevalence and risk factors of COPD in Anhui.,A population-based survey was conducted in a representative sample of population aged 40 years or older in 2015.,COPD was diagnosed based on 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,A total of 2770 participants had reliable post-bronchodilator results and were included in the final analysis.,The overall prevalence of COPD was 9.8% (95% CI: 8.2, 11.7).,Prevalence was higher in men (14.8, 95% CI: 12.6, 17.2) than it was in women (5.2, 95% CI: 3.1, 8.7).,Among adults with COPD, 45.0% (95% CI: 39.1, 51.0) had moderate or severe disease (GOLD stage II-IV), 0.7% (95% CI: 0.2, 2.9) reported that they had a previous pulmonary function test, and only 0.4% (95% CI: 0.1, 2.6) knew their diagnosis of COPD.,Risk factors for COPD included older age (OR 1.06, 95% CI: 1.04, 1.08), male sex (OR 2.01, 95% CI: 1.22, 3.33), current smoking status (OR 2.63, 95% CI: 1.86, 3.73), primary school or lower education (OR 1.61, 95% CI: 1.12, 2.31), family history of lung disease (OR 1.50, 95% CI: 1.17, 1.93), and indoor exposure to coal for cooking or heating (OR 1.55, 95% CI: 1.11, 2.15).,In addition, people in north region has a significantly higher risk for developing COPD than people in south region of Anhui (OR 1.98, 95% CI:1.44, 2.71).,COPD is prevalent in Anhui and the prevalence is highest in north region.,Strategies aiming at prevention, early detection and treatment of COPD are urgently needed to reduce COPD-related burden.,The online version of this article (10.1186/s12890-019-0864-0) contains supplementary material, which is available to authorized users. | COPD is a globally significant public health problem and is the second leading cause of mortality.,This study presents the health burden of COPD in Nepal using the Global Burden of Disease (GBD) study 2016 dataset.,This study used the data from the GBD repository presenting morbidity and mortality attributed to COPD, by sex and age.,In GBD 2016, due to a lack of the primary source of data in Nepal, estimations on morbidity and mortality of COPD were based on its predictive covariates.,Years of life lost (YLLs) were calculated based on the cause of death estimations, applying GBD’s Cause of Death Ensemble modeling.,Likewise, years lived with disability (YLDs) were calculated by multiplying the prevalence of each sequela by the disability weight.,Disability-adjusted life years (DALYs) were derived as the sum of YLLs and YLDs.,Between 1990 and 2016, the estimated age-standardized mortality rate due to COPD was decreasing for both genders, but the decline was much higher among males.,Unlike the high rate of incidence among males, the age-standardized DALYs were found to be high among females (2,274.9 [95% UI: 1,702.0-2,881.5] per 100,000).,YLLs contributed around 80% of DALYs due to COPD in 2016.,Age-standardized YLLs rate was higher among females, with a value of 1,860 (95% uncertainty interval (UI): 1,282.8-2,472.8) vs 1,547.6 (95% UI: 992.1-2,018.5) among the males per 100,000 population.,The prevalence and incidence of COPD remained almost stationary over the years, but still very high.,Though the incidence and prevalence of disease were high among males, the death rate and DALYs were more significant among females throughout the years.,If the current situation prevails, the burden of COPD will continue to increase in the country.,Hence, comprehensive social, environmental, and behavioral approaches to curtail the risk factors along with early identification, treatment, and management of COPD is of utmost importance. | 1 |
We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors.,Few gene studies of the Chinese population have focused on COPD.,We investigated candidate genes associated with susceptibility to COPD in the Chinese Han population.,A total of 331 COPD patients and 213 control subjects were recruited for this study.,Nighty-seven single-nucleotide polymorphisms (SNPs) of 46 genes were selected for genotyping.,Genotypes were determined using multiplex polymerase chain reaction (PCR).,Significant differences between patients and healthy controls were observed in the allele frequencies of seven SNPs: rs1205 C, rs2353397 C, rs20541 T, rs2070600 G, rs10947233 G, rs1800629 G, and rs2241712 A.,After Bonferroni correction, rs2353397 C was most strongly associated with susceptibility to COPD.,Haplotype analysis showed that the frequencies of the GC, GT haplotypes of rs2241718 (TGF-β1 gene), and rs6957 (CDC97 gene) were significantly higher in the control group than in the COPD case group (p=1.88×10-9); the frequencies of the TT haplotype of rs1205 and rs2808630 (CRP gene) were significantly higher in the control group (p=0.0377).,Our study suggests some genetic variants associated with the susceptibility of COPD in the Chinese Han population. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD).,Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients.,However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied.,Primary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5).,PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation.,ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air.,Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression.,DE alone induced an increase in markers of oxidative stress (HMOX1, 50-100-fold) and of the integrated stress response (CHOP, 1.5-2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls.,Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold).,Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP.,Our findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls.,Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response.,DE reduced the NTHi-induced expression of S100A7.,These data suggest that DE exposure may cause adverse health effects in part by decreasing host defense against infection and by modulating stress responses.,The online version of this article (doi:10.1186/s12931-017-0510-4) contains supplementary material, which is available to authorized users. | Impaired immune function contributes to the development of chronic obstructive pulmonary disease (COPD).,Disease progression is further exacerbated by pathogen infections due to impaired immune responses.,Elimination of infected cells is achieved by cytotoxic CD8+ T cells that are activated by MHC I-mediated presentation of pathogen-derived antigenic peptides.,The immunoproteasome, a specialized form of the proteasome, improves generation of antigenic peptides for MHC I presentation thereby facilitating anti-viral immune responses.,However, immunoproteasome function in the lung has not been investigated in detail yet.,In this study, we comprehensively characterized the function of immunoproteasomes in the human and murine lung.,Parenchymal cells of the lung express low constitutive levels of immunoproteasomes, while they are highly and specifically expressed in alveolar macrophages.,Immunoproteasome expression is not altered in whole lung tissue of COPD patients.,Novel activity-based probes and native gel analysis revealed that immunoproteasome activities are specifically and rapidly induced by IFNγ treatment in respiratory cells in vitro and by virus infection of the lung in mice.,Our results suggest that the lung is potentially capable of mounting an immunoproteasome-mediated efficient adaptive immune response to intracellular infections. | 1 |
An association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use.,Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear.,We selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB.,Among 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected.,Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205-2.762]) were independent risk factors for TB.,Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists.,Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB.,The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios.,Keeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications.,Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice. | Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide.,COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions.,COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality.,All individuals ≥40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987-2003 were identified in the Swedish Inpatient Register (n = 115,867).,Records were linked to the Swedish Tuberculosis Register 1989-2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression.,The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB.,COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB.,In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1).,This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population.,The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB.,The underlying contributory factors need to be disentangled in further studies. | 1 |
The prevalence of chronic obstructive pulmonary disease (COPD) in females appears to be increasing.,Recent studies have revealed that the percentage of women with COPD in Greece is approximately 12.5%.,To evaluate the burden of COPD among males and females in Greece through a nationwide cross-sectional survey and to explore sex differences regarding functional characteristics and exacerbation frequency.,Data collection was completed in a 6-month period.,The present study followed a nationwide sampling approach of respiratory medicine physicians.,The sampling approach included three steps: 1) estimation of expected incidence and prevalence of COPD cases in each prefecture of Greece and in total; 2) estimation of expected incidence of COPD cases per physician in each prefecture; and 3) creation of a frame of three different sampling zones.,Following this sampling, data were provided by 199 respiratory physicians.,The participating physicians provided data from 6,125 COPD patients.,Female patients represented 28.7% of the study participants.,Female COPD patients were, on average, 5 years younger than male COPD patients.,Never smokers accounted for 9.4% within female patients, compared to 2.7% of males (P<0.001).,Female patients were characterized by milder forms of the disease.,Comorbidities were more prevalent in men, with the exception of gastroesophageal reflux (14.6% versus 17.1% for men and women, respectively, P=0.013).,Female COPD patients had a higher expected number of outpatient visits per year (by 8.9%) than males (P<0.001), although hospital admissions did not differ significantly between sexes (P=0.116).,Females had fewer absences from work due to COPD per year, by 19.0% (P<0.001), compared to males.,The differences observed between male and female COPD patients provide valuable information which could aid the prevention and management of COPD in Greece. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users. | 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. | 1 |
Biomass smoke is the leading cause of COPD in developing countries such as Turkey.,In rural areas of Turkey, females are more exposed to biomass smoke because of traditional lifestyles.,The aim of this study was to determine the adverse effects of biomass smoke on pulmonary functions and define the relationship between duration in years and an index (cumulative exposure index) with altered pulmonary function test results.,A total of 115 females who lived in the village of Kağizman (a borough of Kars located in the eastern part of Turkey) and were exposed to biomass smoke were included in the study.,The control group was generated with 73 individuals living in the same area who were never exposed to biomass smoke.,Twenty-seven (23.8%) females in the study group and four (5.5%) in the control group had small airway disease (P=0.038).,Twenty-two (19.1%) females in the study group and ten (13.7%) in the control group had obstruction (P=0.223).,Twenty (17.3%) females in the study group who were exposed to biomass smoke had restriction compared with ten (13%) in the control group (P=0.189).,The duration needed for the existence of small airway disease was 16 years, for obstructive airway disease was 17 years, and for restrictive airway disease was 17 years.,The intensity of biomass smoke was defined in terms of cumulative exposure index; it was calculated by multiplying hours per day, weeks per month, and total years of smoke exposure and dividing the result by three.,Exposure to biomass smoke is a serious public health problem, especially in rural areas of developing countries, because of its negative effects on pulmonary functions.,As the duration and the intensity of exposure increase, the probability of having altered pulmonary function test results is higher. | Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | 1 |
COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. | Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | 1 |
We previously reported a progressive decline in absolute responses of FEV1 and FVC to a near-maximal dose of 2 different short-acting bronchodilators over 4 years.,Since varying host factors and the method of expressing the response may impact the time trend of acute bronchodilator responses, we now examined the potential influence of salient host characteristics on changes in bronchodilator responses over time expressed in different ways.,As part of the 4-year, placebo-controlled Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial, pre- and post-bronchodilator spirometry was performed at baseline and 1 month and every 6 months thereafter.,Post-bronchodilator values for FEV1 and FVC were analyzed for subjects completing at least the 1 year visit (Placebo - N = 2463; Tiotropium - N = 2579), stratified by GOLD stage, age, gender and smoking status and expressed as absolute, relative (%) and % predicted changes from pre-bronchodilator values.,Annual changes in bronchodilator response were estimated using linear mixed effects models.,For all subjects analyzed, FEV1 and FVC bronchodilator responses showed progressive and highly significant (p < 0.0001) declines over 4 years.,Declines were generally larger in patients with severe/very severe than mild/moderate airflow obstruction, in older patients (≥65 yrs) and in former than continuing smokers.,Acute FEV1 and FVC responses to bronchodilators decline significantly over time in COPD patients, whether expressed as absolute, relative or % predicted changes, potentially impacting on the clinical responses to bronchodilator therapy as well as on the annual rate of decline in post-bronchodilator lung function.,NCT00144339,The online version of this article (doi:10.1186/s12931-014-0102-5) contains supplementary material, which is available to authorized users. | This study was conducted to determine COPD severity at the time of diagnosis as confirmed by spirometry in patients treated in a US managed care setting.,All patients with one or more inpatient stays, one or more emergency department visits, or two or more outpatient visits with diagnosis codes for COPD during 1994-2006 were identified from the Lovelace Patient Database.,From this group, a subset of continuously enrolled patients with evidence in claims of a first available pulmonary function test or pulmonary clinic visit and a confirmatory claim for a COPD diagnosis was selected.,Medical chart abstraction was undertaken for this subset to gather information for diagnosis and severity staging of each patient based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD.,Of the 12,491 patients with a primary or secondary COPD diagnosis between 1994 and 2006, there were 1520 continuously enrolled patients who comprised the study cohort.,Among the 648 eligible records from patients with evidence of a pulmonary function test, 366 were identified by spirometry as having COPD of GOLD stage I or higher (average percentage of predicted forced expiratory volume in 1 second: 60%): 19% were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III or IV, respectively).,The majority of patients in these groups were not receiving maintenance treatment.,The results demonstrate a very low incidence of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a large US sample and support calls for increased screening for COPD and treatment upon diagnosis. | 1 |
The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | 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 |
Understanding the breadth of patients’ support needs is important for the delivery of person-centered care, particularly in progressive long-term conditions such as chronic obstructive pulmonary disease (COPD).,Existing reviews identify important aspects of managing life with COPD with which patients may need support (support needs); however, none of these comprehensively outlines the full range of support needs that patients can experience.,We therefore sought to systematically determine the full range of support needs for patients with COPD to inform development of an evidence-based tool to enable person-centered care.,We conducted a systematic search and narrative review of the literature.,Medline (Ovid), EMBASE, PsycINFO, Cochrane Library, and CINAHL were systematically searched for papers which included data addressing key aspects of support need, as identified by patients with COPD.,Relevant data were extracted, and a narrative analysis was conducted.,Thirty-one papers were included in the review, and the following 13 domains (broad areas) of support need were identified: 1) understanding COPD, 2) managing symptoms and medication, 3) healthy lifestyle, 4) managing feelings and worries, 5) living positively with COPD, 6) thinking about the future, 7) anxiety and depression, 8) practical support, 9) finance work and housing, 10) families and close relationships, 11) social and recreational life, 12) independence, and 13) navigating services.,These 13 domains of support need were mapped to three of the four overarching categories of need commonly used in relevant national strategy documents (ie, physical, psychological, and social); however, support needs related to the fourth category (spiritual) were notably absent.,This review systematically identifies the comprehensive set of domains of support need for patients with COPD.,The findings provide the evidence base for a tool to help patients identify and express their support needs, which underpins a proposed intervention to enable the delivery of person-centered care: the Support Needs Approach for Patients (SNAP). | The purpose of this study was to identify four non-cancer populations that might benefit from a palliative approach; and describe and compare the prevalence and patterns of dignity related distress across these diverse clinical populations.,A prospective, multi-site approach was used.,Outpatient clinics, inpatient facilities or personal care homes, located in Winnipeg, Manitoba and Edmonton, Alberta, Canada.,Patients with advanced Amyotrophic Lateral Sclerosis (ALS), Chronic Obstructive Pulmonary Disease (COPD), End Stage Renal Disease (ESRD); and the institutionalized alert frail elderly.,In addition to standardized measures of physical, psychological and spiritual aspects of patient experience, the Patient Dignity Inventory (PDI).,Between February 2009 and December 2012, 404 participants were recruited (ALS, 101; COPD, 100; ESRD, 101; and frail elderly, 102).,Depending on group designation, 35% to 58% died within one year of taking part in the study.,While moderate to severe loss of sense of dignity did not differ significantly across the four study populations (4-11%), the number of PDI items reported as problematic was significantly different i.e.,ALS 6.2 (5.2), COPD 5.6 (5.9), frail elderly 3.0 (4.4) and ESRD 2.3 (3.9) [p < .0001].,Each of the study populations also revealed unique and distinct patterns of physical, psychological and existential distress.,People with ALS, COPD, ESRD and the frail elderly face unique challenges as they move towards the end of life.,Knowing the intricacies of distress and how they differ across these groups broadens our understanding of end-of-life experience within non-cancer populations and how best to meet their palliative care needs. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) carries a considerable economic burden, both for individuals and societies.,This study aimed to assess direct and indirect costs associated with COPD, and how costs vary across disease severity.,This was a nationwide, population-based cohort study utilizing Danish health registries.,Patients; ≥40 years of age, with an in- and/or outpatient diagnosis of COPD (ICD-10 J44) in 2008-2016, were identified in the nationwide Danish COPD Registry.,Included patients were matched 1:4 to a population-based non-COPD reference population of 196,623 individuals by sex, year of birth, co-habitation status, and municipality.,Patients were grouped by disease severity according to different characteristics including GOLD groups A-D, based on moderate (short-term oral corticosteroid use), presence of severe exacerbations (emergency visit or hospitalization) and symptom score.,Index was the date of the first outpatient visit with a symptom score registration.,The costs were calculated during a 12 months post-index follow-up.,In all, 49,826 patients with COPD (mean age 69.2 years, 52% females) were included.,Total annual costs, including direct costs, costs for elderly care, and costs for retirement home, were higher for patients with COPD (€28,969) compared with the reference population (€10,6913).,In GOLD groups A-D, the total direct costs were A: €8,766, B: €13,060, C: €11,113, and D: €17,749, respectively.,A major driver of direct costs was severe exacerbations.,The mean costs per moderate and severe exacerbation were €888 and €7,091, respectively, during 28 days of follow-up.,The costs for non-COPD-related Health Care Resource Utilization were higher than the COPD-related costs in GOLD groups A-C, but not in GOLD group D.,In this nationwide real-world study, total direct costs were three-fold higher among patients with COPD compared with the reference population.,Severe exacerbations were a major driver of the direct costs.,The costs increased with increasing disease severity. | Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide.,Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected.,This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute.,The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available.,A systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters.,Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables.,In total, the systematic search yielded 151 publications.,After title and abstract screening, 38 publications were included into the systematic assessment.,In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits.,Only four out of 38 studies used methods other than ICD coding.,In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided.,Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies.,Only five studies used spirometry, two used surgery and one used oxygen therapy.,A variety of different criteria is used for the identification of COPD from routine data.,The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data.,Further health services research should focus on the application of more systematic internal and/or external validation approaches. | 1 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | Many patients with chronic obstructive pulmonary disease (COPD) receive inhaled corticosteroids (ICSs) without a clear indication, and thus, the impact of ICS withdrawal on disease control is of great interest.,DACCORD is a prospective, noninterventional 2-year study in the primary and secondary care throughout Germany.,A subgroup of patients were taking ICS prior to entry - 1,022 patients continued to receive ICS for 2 years; physicians withdrew ICS on entry in 236 patients.,Data from these two subgroups were analyzed to evaluate the impact of ICS withdrawal.,Patients aged ≥40 years with COPD, initiating or changing COPD maintenance medication were recruited, excluding patients with asthma.,Demographic and disease characteristics, prescribed COPD medication, COPD Assessment Test, exacerbations, and lung function were recorded.,There were few differences in baseline characteristics; ICS withdrawn patients had shorter disease duration and better lung function, with 74.2% of ICS withdrawn patients not exacerbating, compared with 70.7% ICS-continued patients.,During Year 1, exacerbation rates were 0.414 in the withdrawn group and 0.433 in the continued group.,COPD Assessment Test total score improved from baseline in both groups.,These data suggest that ICS withdrawal is possible with no increased risk of exacerbations in patients with COPD managed in the primary and secondary care. | 1 |
Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD).,We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.,Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD.,Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1-5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009.,Stepwise multivariate logistic regression estimated independent associations with dyspnoea.,Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.,The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded.,Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC≥3).,Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction.,Other factors associated with increased dyspnoea grade included female gender, older age (≥70 years), obesity (BMI ≥30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner.,Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.,Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care.,Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up. | Background: Chronic obstructive pulmonary disease (COPD) is a disease of increasing significance in terms of economic and social burden due to its increasing prevalence and high costs.,Direct costs of COPD are mostly associated with hospitalization expenditures.,In this study, our objective was to investigate the costs of hospitalization and factors affecting these costs in patients hospitalized due to acute exacerbation of COPD (AECOPD).,Methods: A total of 284 patients hospitalized AECOPD were included in the study.,Data were examined retrospectively using the electronic hospital charts.,Results: Mean duration of hospitalization was 11.38 ± 6.94 days among study patients.,Rates of admission to the intensive care unit, initiation of non-invasive mechanical ventilation (NIMV) and invasive mechanical ventilation (MIV) were 37.3% (n=106), 44.4% (n=126) and 18.3% (n=52) respectively.,The rate of mortality was 14.8% (n=42).,Mean cost of a single patient hospitalized for an AECOPD was calculated as $1765 ± 2139.,Mean cost of admission was $889 ± 533 in standard ward, and $2508 ± 2857 in intensive care unit (ICU).,The duration of hospitalization, a FEV1% predicted value below 30%, having smoked 40 package-years or more, the number of co-morbidities, NIMV, IMV, ICU, exitus and the number of hospitalizations in the past year were among the factors that increased costs significantly.,Hospital acquired pneumonia, chronic renal failure and anemia also increased the costs of COPD significantly.,Conclusion: The costs of treatment increase with the severity of COPD or with progression to a higher stage.,Efforts and expenditures aimed at preventing COPD exacerbations might decrease the costs in COPD. | 1 |
The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD).,However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown.,In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF.,Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity.,The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets.,There was a significant target overlap between the herbal constituents of BJF.,These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them.,The integrated target-disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases.,The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others.,Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo.,This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD. | Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years.,This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients.,A four-center, open-label randomized controlled method was conducted.,A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine).,The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up.,A total of 306 patients completed the study fully.,The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306.,After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire.,There were no differences between the trial and control group in FVC, FEV1% and adverse events.,Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events.,This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406. | 1 |
COPD exacerbations accelerate disease progression.,To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration.,403 COPD patients, GOLD stage II-IV, aged 44-76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years.,Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO2<8 kPa), cough, use of inhaled steroids, and the inflammatory markers leucocytes, C-reactive protein (CRP), neutrophil gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor 1 (sTNF-R1), and osteoprotegrin (OPG).,Negative binomial models with random effects were fitted to estimate the annual incidence rate ratios (IRR).,For analysis of AECOPD duration, a generalized estimation equation logistic regression model was fitted, also adjusting for season, time since inclusion and AECOPD severity.,After multivariate adjustment, significant predictors of AECOPD were: female sex [IRR 1.45 (1.14-1.84)], age per 10 year increase [1.23 (1.03-1.47)], >1 AECOPD last year before baseline [1.65 (1.24-2.21)], GOLD III [1.36 (1.07-1.74)], GOLD IV [2.90 (1.98-4.25)], chronic cough [1.64 (1.30-2.06)] and use of inhaled steroids [1.57 (1.21-2.05)].,For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39-0.92)], years since inclusion [1.19 (1.03-1.37)], AECOPD severity; moderate [OR 1.58 (1.14-2.18)] and severe [2.34 (1.58-3.49)], season; winter [1.51 (1.08-2.12)], spring [1.45 (1.02-2.05)] and sTNF-R1 per SD increase [1.16 (1.00-1.35)].,Several COPD characteristics were independent predictors of both AECOPD frequency and duration. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
To ascertain the stakeholders' views and devise recommendations for further stages of the Wearable Sensing and Smart Cloud Computing for Integrated Care to Chronic Obstructive Pulmonary Disease (COPD) Patients with Co-morbidities (WELCOME) system development.,This system aims to create a wearable vest to monitor physiological signals for patients concerned incorporating an inhaler adherence monitoring, weight, temperature, blood pressure and glucose metres, and a mobile health application for communication with healthcare professionals (HCPs).,A study of qualitative data derived from focus groups and semistructured interviews.,4 participating clinical sites in Greece, the UK, Ireland and the Netherlands.,Purposive sampling was used to recruit 32 patients with COPD with heart failure, diabetes, anxiety or depression, 27 informal carers and 23 HCPs from 4 European Union (EU) countries for focus groups and interviews.,Most patients and HCPs described the WELCOME system as ‘brilliant and creative’ and felt it gave a sense of safety.,Both users and HCPs agreed that the duration and frequency of vest wear should be individualised as should the mobile application functions.,The parameters and frequency of monitoring should be personalised using a multidisciplinary approach.,A ‘traffic light’ alert system was proposed by HCPs for abnormal results.,Patients were happy to take actions in response.,WELCOME stakeholders provided valuable views on the development of the system, which should take into account patient's individual comorbidities, circumstances and concerns.,This will enable the development of the individualised system in each member state concerned. | Chronic obstructive pulmonary disease (COPD) is a growing economic burden worldwide.,Smoking cessation is thought to be the single most effective way of reducing the economic burden of COPD.,The impact of other strategies such as interventions that predict risk of disease, reduce progression of disease, or reduce exacerbations has not been systematically studied.,We estimated the economic and clinical burden of COPD over the next 25 years in Canada and the impact of three potential interventions (screening test for predisposition to COPD, new drugs to avoid progression into more severe disease stages, and predictive test for exacerbations) on COPD burden.,Using a dynamic simulation model, we projected the total burden of COPD (cost, morbidity, and mortality) from 2011 to 2035 using the population of Canada as a case study.,The model stratified population based on sex, age, smoking status, respiratory symptoms, and their COPD stage.,The cost and quality adjusted life years (QALYs) associated with each intervention were estimated.,The model indicates that annual societal cost of COPD is $4.52 billion (B) Canadian dollars in 2011 and will reach $3.61B ($7.33B undiscounted) per year in 2035.,Over the next 25 years, COPD will be responsible for approximately $101.4B in societal costs ($147.5B undiscounted) and 12.9 million QALYs lost (19.0 million undiscounted).,Our results suggested that the best strategy to reduce the financial burden of COPD is by reducing exacerbations.,Smoking cessation, while it is the cornerstone of COPD prevention, has only a modest effect in attenuating the financial burden of COPD over the next 25 years in Western countries such as Canada.,Our data suggest that any intervention that can reduce the number of exacerbations has a substantial impact on morbidity and costs of COPD and should be considered in conjunction with the ongoing efforts to reduce smoking rates. | 1 |
Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations.,In addition, a reducing effect on mortality has been shown by this treatment.,However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not.,Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects.,Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial.,We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest.,We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579).,ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64-0.83) and improved the QOL score and trough FEV1 compared to LAMA/LABA.,In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18-0.48) and mortality (odds ratio 0.66, 95% CI 0.50-0.87).,However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16-2.00).,In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV1 than LAMA/LABA.,Concerning the trough FEV1, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference.,Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV1 and better QOL score.,In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score.,However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations.,Clinical Trial Registration: PROSPERO; CRD42020191978.,The online version contains supplementary material available at 10.1186/s12931-021-01777-x. | Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | 1 |
Readmission after hospital discharge is common in patients with acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD).,Although frailty predicts hospital readmission in patients with chronic nonpulmonary diseases, no multidimensional frailty measures have been validated to stratify the risk for patients with COPD.,The aim of this study was to explore multidimensional frailty as a potential risk factor for readmission due to a new exacerbation episode during the 90 days after hospitalization for AE-COPD and to test whether frailty could improve the identification of patients at high risk of readmission.,We hypothesized that patients with moderate-to-severe frailty would be at greater risk for readmission within that period of follow up.,A secondary aim was to test whether frailty could improve the accuracy with which to discriminate patients with a high risk of readmission.,Our investigation was part of a wider study protocol with additional aims on the same study population.,Frailty, demographics, and disease-related factors were measured prospectively in 102 patients during hospitalization for AE-COPD.,Some of the baseline data reported were collected as part of a previously study.,Readmission data were obtained on the basis of the discharge summary from patients’ electronic files by a researcher blinded to the measurements made in the previous hospitalization.,The association between frailty and readmission was assessed using bivariate analyses and multivariate logistic regression models.,Whether frailty better identifies patients at high risk for readmission was evaluated by area under the receiver operator curve (AUC).,Severely frail patients were much more likely to be readmitted than nonfrail patients (45% versus 18%).,After adjusting for age and relevant disease-related factors in a final multivariate model, severe frailty remained an independent risk factor for 90-day readmission (odds ratio = 5.19; 95% confidence interval: 1.26-21.50).,Age, number of hospitalizations for exacerbations in the previous year and length of stay were also significant in this model.,Additionally, frailty improved the predictive accuracy of readmission by improving the AUC.,Multidimensional frailty predicts the risk of early hospital readmission in patients hospitalized for AE-COPD.,Frailty improved the accuracy of discriminating patients at high risk for readmission.,Identifying patients with frailty for targeted interventions may reduce early readmission rates. | Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life.,Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays.,The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients.,We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations.,78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George’s Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test.,Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time.,Correlations between the CAT and other measurements were examined.,After 7 days’ therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001).,Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001).,The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05).,The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = -0.101, P > 0.05).,No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).,The CAT is associate with the changes of systemic inflammation following COPD exacerbations.,Moreover, the CAT is responsive to the treatments, similar to other measures such as SGRQ, mMRC dyspnea scale and pulmonary function.,Therefore, the CAT is a potentially useful instrument to assess the efficacy of treatments following COPD exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD).,We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls.,This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.,To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.,Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable.,The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects.,Rbm fragmentation correlated with smoking history in COPD but not with age.,There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05).,The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004).,In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).,Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall.,Rbm fragmentation was also present to as great an extent in ex-smokers with COPD.,These characteristics may have potential physiological consequences. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are a burden to patients and impose a major cost on health services.,Long-term antibiotic therapy may prevent exacerbations, but at present it is not recommended by management guidelines.,To identify the type and prevalence of long-term oral antibiotic treatments prescribed to patients with COPD and to assess the patient characteristics associated with long-term antibiotic use.,A retrospective cohort using all eligible practices in The Health Improvement Network (THIN) UK primary care database between 2000 and 2009 was studied.,We identified patients with COPD and then those who received a course of long-term antibiotics.,Long-term courses were defined as ≥6 months in duration with <50% concomitant oral corticosteroid treatment.,We identified 92,576 patients with COPD, but only 567 patients (0.61%) who received 998 long-term antibiotic courses.,Mean follow-up time was 3 years and 10 months.,The median long-term antibiotic course length was 280 days (interquartile range 224, 394) and 58 patients (0.06%) were continuously prescribed antibiotics for >2 years.,The most commonly used long-term antibiotics were oxytetracycline, doxycycline, and penicillin.,Azithromycin, erythromycin, and clarithromycin were less frequently used.,There was little evidence of the use of rotating courses of antibiotics.,Men, people aged 50-79 years, non-smokers, and patients with poorer lung function were more likely to receive long-term antibiotic treatment.,Relatively few COPD patients are currently prescribed long-term antibiotics.,Further clinical trials are required to determine the efficacy of this therapy.,If beneficial, the use of such treatments should be incorporated into clinical guidelines. | Randomised trials comparing different drugs head-to-head are extremely valuable for clinical decision-making.,However, it is scientifically and ethically sensible to demand strong evidence that a drug is effective by showing superiority over a placebo before embarking on head-to-head comparisons of potentially ineffective drugs.,Our aim was to study the evolvement of evidence from placebo-controlled and head-to-head trials on the effects of antibiotics for the treatment of mild to moderate exacerbations of chronic obstructive pulmonary disease.,We conducted a historical systematic review.,Through electronic databases and hand-searches, we identified placebo-controlled and head-to-head antibiotic trials for the treatment of mild to moderate chronic obstructive pulmonary disease exacerbations.,We compared the numbers of patients recruited in placebo-controlled and head-to-head trials between 1957 and 2005.,Using cumulative meta-analysis of placebo-controlled trials, we determined when, if ever, placebo-controlled trials had shown convincing evidence that antibiotics are effective in preventing treatment failure in patients with mild to moderate chronic obstructive pulmonary disease exacerbations.,The first head-to-head trial was published in 1963.,It was followed by another 100 trials comparing different antibiotics in a total of 34,029 patients with mild to moderate chronic obstructive pulmonary disease exacerbations.,Over time, the cumulative odds ratio in placebo-controlled trials remained inconclusive throughout with odds ratios ranging from 0.39 (95% confidence intervals 0.04-4.22) to the most recent estimate (1995) of 0.81 (95% confidence intervals 0.52-1.28, P = 0.37).,Placebo-controlled trials do not support the use of antibiotics in chronic obstructive pulmonary disease patients with mild to moderate exacerbations.,Conducting head-to-head trials is, therefore, scientifically and ethically questionable.,This underscores the requirement to perform or study systematic reviews of placebo-controlled trials before conducting head-to-head trials. | 1 |
Supplemental Digital Content is available in the text,Nowadays, there is growing recognition that chronic obstructive pulmonary disease (COPD) may have influence on lung cancer.,However, coexisted COPD related to prognosis of lung cancer is still elusive.,We conducted this meta-analysis to examine the association between COPD and 5-year overall survival (OS) and postoperative pulmonary complications of patients with lung cancer.,A comprehensive computer-based online search was conducted using PubMed, Embase, Medline, and the Cochrane Library for articles published before September 30, 2017.,We identified 29 eligible studies, which included 70,111 patients in the related literature.,Twenty-two of the 29 studies provided hazard ratio for OS (1.18, 95% confidence interval: 1.11-1.25; P < .001), it suggested that the presence of COPD indicated poor survival for the patients with lung cancer.,In subgroup analysis, the relationship between COPD and OS occurrence remained statistically prominent in the subgroups stratified by study designs, COPD diagnosis timing, lung cancer surgery, cancer stage, and origins of patients.,The presence of COPD increased the risk of bronchopleural fistula, pneumonia, prolonged air leakage, and prolonged mechanical ventilation.,The present meta-analysis suggested that coexisting COPD is associated with poor survival outcomes in patients with lung cancer and higher rates of postoperative pulmonary complications. | COPD is an important comorbidity of lung cancer, but the impact of COPD on the outcomes of lung cancer remains uncertain.,Because both COPD and lung cancer are heterogeneous diseases, we evaluated the link between COPD phenotypes and the prognosis of different histological subtypes of lung cancer.,In this retrospective study, subjects with a newly and pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery.,All participants underwent pulmonary function test (PFT).,The diagnosis of COPD was based on GOLD criteria.,Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT.,The HRs were estimated by Cox regression analysis.,Among 2,222 lung cancer patients, 32.6% coexisted with COPD.,After adjustment for age, sex, body mass index (BMI), smoking status, and therapy method, COPD was significantly associated with the decreased overall survival (OS) of lung cancer (HR 1.28, 95% CI 1.05-1.57).,With the increased severity of COPD, the OS of lung cancer was gradually worsened (HR 1.23, 95% CI 1.08-1.39).,But surgical treatment and high BMI were independent prognostic protective factors (HR 0.46, 95% CI 0.37-0.56; HR 0.96, 95% CI 0.94-0.99).,Moreover, in terms of disease heterogeneity, emphysema-predominant phenotype of COPD was an independent prognostic risk factor for squamous carcinoma (HR 2.53, 95% CI 1.49-4.30).,No significant relationship between COPD phenotype and lung cancer prognosis was observed among adenocarcinoma, small cell lung cancer, large cell lung cancer, and other subtype patients.,These findings suggest that COPD, especially emphysema-predominant phenotype, is an independent prognostic risk factor for squamous carcinoma only. | 1 |
Diaphragmatic breathing (DB) is widely used in pulmonary rehabilitation (PR) of patients with chronic obstructive pulmonary disease (COPD), however it has been little studied in the scientific literature.,The Pilates breathing (PB) method has also been used in the rehabilitation area and has been little studied in the scientific literature and in COPD.,To compare ventilatory parameters during DB and PB in COPD patients and healthy adults.,Fifteen COPD patients (COPD group) and fifteen healthy patients (healthy group) performed three types of respiration: natural breathing (NB), DB, and PB, with the respiratory pattern being analyzed by respiratory inductive plethysmography.,The parameters of time, volume, and thoracoabdominal coordination were evaluated.,After the Shapiro-Wilk normality test, ANOVA was applied followed by Tukey's test (intragroup analysis) and Student's t-test (intergroup analysis; p<0.05).,DB promoted increase in respiratory volumes, times, and SpO2 as well as decrease in respiratory rate in both groups.,PB increased respiratory volumes in healthy group, with no additional benefits of respiratory pattern in the COPD group.,With respect to thoracoabdominal coordination, both groups presented higher asynchrony during DB, with a greater increase in the healthy group.,DB showed positive effects such as increase in lung volumes, respiratory motion, and SpO2 and reduction in respiratory rate.,Although there were no changes in volume and time measurements during PB in COPD, this breathing pattern increased volumes in the healthy subjects and increased oxygenation in both groups.,In this context, the acute benefits of DB are emphasized as a supporting treatment in respiratory rehabilitation programs. | Detection of smoking effects is of utmost importance in the prevention of cigarette‐induced chronic airway obstruction.,The forced oscillation technique offers a simple and detailed approach to investigate the mechanical properties of the respiratory system.,However, there have been no data concerning the use of the forced oscillation technique to evaluate respiratory mechanics in groups with different degrees of tobacco consumption.,(1) to evaluate the ability of the forced oscillation technique to detect smoking‐induced respiratory alterations, with special emphasis on early alterations; and (2) to compare the diagnostic accuracy of the forced oscillation technique and spirometric parameters.,One hundred and seventy subjects were divided into five groups according to the number of pack-years smoked: four groups of smokers classified as <20, 20-39, 40-59, and >60 pack-years and a control group.,The four groups of smokers were compared with the control group using receiver operating characteristic (ROC) curves.,The early adverse effects of smoking in the group with <20 pack-years were adequately detected by forced oscillation technique parameters.,In this group, the comparisons of the ROC curves showed significantly better diagnostic accuracy (p<0.01) for forced oscillation technique parameters.,On the other hand, in groups of 20-39, 40-59, and >60 pack-years, the diagnostic performance of the forced oscillation technique was similar to that observed with spirometry.,This study revealed that forced oscillation technique parameters were able to detect early smoking‐induced respiratory involvement when pathologic changes are still potentially reversible.,These findings support the use of the forced oscillation technique as a versatile clinical diagnostic tool in helping with chronic obstructive lung disease prevention, diagnosis, and treatment. | 1 |
Limited information is available regarding medication use in COPD patients from Latin America.,This study evaluated the type of medication used and the adherence to different inhaled treatments in stable COPD patients from the Latin American region.,This was an observational, cross-sectional, multinational, and multicenter study in COPD patients attended by specialist doctors from seven Latin American countries.,Adherence to inhaled therapy was assessed using the Test of Adherence to Inhalers (TAI) questionnaire.,The type of medication was assessed as: short-acting β-agonist (SABA) or short-acting muscarinic antagonist (SAMA) only, long-acting muscarinic antagonist (LAMA), long-acting β-agonist (LABA), LABA/LAMA, inhaled corticosteroid (ICS), ICS/LABA, ICS/LAMA/LABA, or other.,In total, 795 patients were included (59.6% male), with a mean age of 69.5±8.7 years and post-bronchodilator FEV1 of 50.0%±18.6%.,The ICS/LAMA/LABA (32.9%) and ICS/LABA (27.7%) combinations were the most common medications used, followed by LABA/LAMA (11.3%), SABA or SAMA (7.9%), LABA (6.4%), LAMA (5.8%), and ICS (4.3%).,The types of medication most commonly used in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 category were ICS/LABA (A: 32.7%; B: 19.8%; C: 25.7%; D: 28.2%) and ICS/LAMA/LABA (A: 17.3%; B: 30.2%; C: 33%; D: 41.1%).,The use of long-acting bronchodilators showed the highest adherence (good or high adherence >50%) according to the TAI questionnaire.,COPD management in specialist practice in Latin America does not follow the current guideline recommendations and there is an overuse of ICSs in patients with COPD from this region.,Treatment regimens including the use of long-acting bronchodilators are associated with the highest adherence. | It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol.,Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD.,Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol.,All patients were recruited from the Taiwan National Health Insurance database.,The outcomes including severe exacerbations, pneumonia, and pneumonia requiring mechanical ventilation (MV) were measured.,During the study period, 11,519 COPD patients receiving fluticasone/salmeterol and 7,437 patients receiving budesonide/formoterol were enrolled in the study.,Pairwise matching (1:1) of fluticasone/salmeterol and budesonide/formoterol populations resulted in to two similar subgroups comprising each 7,295 patients.,Patients receiving fluticasone/salmeterol had higher annual rate and higher risk of severe exacerbation than patients receiving budesonide/formoterol (1.2219/year vs 1.1237/year, adjusted rate ratio, 1.08; 95% CI, 1.07-1.10).,In addition, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia than patients receiving budesonide/formoterol (12.11 per 100 person-years vs 10.65 per 100 person-years, adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.20).,Finally, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia requiring MV than patients receiving budesonide/formoterol (3.94 per 100 person-years vs 3.47 per 100 person-years, aHR, 1.14; 95% CI, 1.05-1.24).,A similar trend was seen before and after propensity score matching analysis, intention-to-treat, and as-treated analysis with and without competing risk.,Based on this retrospective observational study, long-term treatment with fixed combination budesonide/formoterol was associated with fewer severe exacerbations, pneumonia, and pneumonia requiring MV than fluticasone/salmeterol in COPD patients. | 1 |
The ongoing pandemic of the novel Corona Virus Disease 2019 (COVID-19) is an unprecedented challenge to global health, never experienced before.,This study aims to describe the clinical characteristics and outcomes of patients with COVID-19 admitted to Mercy Hospitals.,Retrospective, observational cohort study designed to include every COVID-19 subject aged 18 years or older admitted to Mercy Saint (St) Vincent, Mercy St Charles, and Mercy St Anne’s hospital in Toledo, Ohio from January 1, 2020 through June 15th, 2020.,Primary Outcome Measure was mortality in the emergency department or as an in-patient.,470 subjects including 224 males and 246 females met the inclusion criteria for the study.,Subjects with the following characteristics had higher odds (OR) of death: Older age [OR 8.3 (95% CI 1.1-63.1, p = 0.04)] for subjects age 70 or more compared to subjects age 18-29); Hypertension [OR 3.6 (95% CI 1.6-7.8, p = 0.001)]; Diabetes [OR 3.1 (95% CI 1.7-5.6, p<0.001)]; COPD [OR 3.4 (95% CI 1.8-6.3, p<0.001)] and CKD stage 2 or greater [OR 2.5 (95% CI 1.3-4.9, p = 0.006)].,Combining all age groups, subjects with hypertension had significantly greater odds of the following adverse outcomes: requiring hospital admission (OR 2.2, 95% CI 1.4-3.4, p<0.001); needing respiratory support in 24 hours (OR 2.5, 95% CI: 1.7-3.7, p<0.001); ICU admission (OR 2.7, 95% CI 1.7-4.4, p<0.001); and death (OR 3.6, 95% CI 1.6-7.8, p = 0.001).,Hypertension was not associated with needing vent in 24 hours (p = 0.07).,Age and hypertension were associated with significant comorbidity and mortality in Covid-19 Positive patients.,Furthermore, people who were older than 70, and had hypertension, diabetes, COPD, or CKD had higher odds of dying from the disease as compared to patients who hadn’t.,Subjects with hypertension also had significantly greater odds of other adverse outcomes. | The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population.,This is a retrospective, multicentre, cohort study.,Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history.,First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients.,Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed.,A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively.,Compared with the first and second generations, third-generation patients were older (61.3 vs.,48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs.,36.1% and 27.3%, p 0.013).,At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs.,0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs.,17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs.,412.5 and 549 μg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs.,53.0% and 34.1%, p < 0.001).,The proportions of third-generation patients developing severe illness (72.7% vs.,32.5% and 27.3%, p < 0.001), critical illness (38.6% vs.,10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs.,3.6% and 2.3%, p 0.002) were higher than in the other two groups.,Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients. | 1 |
This study aims to investigate the disease knowledge and self-management behavior of patients with chronic obstructive pulmonary disease (COPD) in the respiratory ward of a tertiary hospital in China, and analyze the relationship between these.,A total of 360 COPD patients were surveyed using the internationally validated COPD Questionnaire (COPD-Q), the COPD Patients’ Self-Management Behavior Scale and a general sociodemographic questionnaire, and 346 valid responses were obtained.,The results revealed that the surveyed COPD patients scored an average of 4.90 ± 2.50 points (maximal of 13 points) on the COPD-Q and 117.23 ± 20.56 points on the COPD Self-Management Behavior Scale, in which 86.1% of COPD patients were classified as having low to medium levels of self-management behavior.,Pearson correlation analysis revealed that the total points on the COPD Self-Management Behavior Scale, symptom management, daily life management, emotional management and information management were all positively correlated to the disease knowledge of COPD (P < .01).,In addition to COPD knowledge, the multiple regression analysis revealed that age, marital status and place of residence could also affect self-management behavior.,The level of disease knowledge and self-management behaviors of patients with COPD is rather low in China.,COPD knowledge level was found to correlate with the level of self-management behavior.,Health education that enhances the disease knowledge of COPD patients might thereby be necessary to help improve self-management behavior. | Evidence from longitudinal studies on the impact of exacerbation symptoms on physical activity in chronic obstructive pulmonary disease (COPD) is lacking.,The aim of this first exploratory study was to assess the association between exacerbation symptoms and physical activity, and to quantify the relative influence of specific symptoms.,We recruited COPD patients at high risk for exacerbations from 2 pulmonary rehabilitation clinics and 1 acute care clinic in Switzerland.,For 3 months after discharge, patients completed a daily symptom diary on a smartphone application, the EXAcerbations of Chronic pulmonary disease Tool (EXACT), and wore a pedometer to measure daily steps.,We used mixed-effects models to determine the association of daily steps with exacerbation symptoms.,A total of 21 patients (Global Initiative for Chronic Obstructive Lung Disease grades 2-4) were enrolled for a mean of 94.4 days (standard deviation 4.2).,The baseline median number of daily steps was 3,264.6 (interquartile range [IQR]: 1,851.3-4,784.1) and EXACT score was 37.0 (IQR: 30.9-41.4).,A 12-point increase in EXACT score (indicating the start of an exacerbation) was statistically significantly associated with a decrease in daily steps of 653.3 (95% CI 969.7-336.9).,Chest symptoms (tightness, discomfort and congestion) were more strongly associated with change in steps than breathlessness, and cough and sputum (z-value −4.5 vs −2.9 and −3.0).,This is the first study to show that, in a small cohort of COPD patients, increases in exacerbation symptoms were associated with a statistically and clinically significant reduction in daily physical activity.,These results underscore the importance for symptom control and exacerbation prevention in COPD patients. | 1 |
Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are burdened by the potential risk of inducing cardiovascular serious adverse events (SAEs) in COPD patients.,Since the risk of combining a LABA with a LAMA could be greater, we have carried out a quantitative synthesis to investigate the cardiovascular safety profile of LABA/LAMA fixed-dose combinations (FDCs).,A pair-wise and network meta-analysis was performed by using the data of the repository database ClinicalTrials.gov concerning the impact of approved LABA/LAMA FDCs versus monocomponents and/or placebo on cardiovascular SAEs in COPD.,Overall, LABA/LAMA FDCs did not significantly (P>0.05) modulate the risk of cardiovascular SAEs versus monocomponents.,However, the network meta-analysis indicated that aclidinium/formoterol 400/12 µg and tiotropium/olodaterol 5/5 µg were the safest FDCs, followed by umeclidinium/vilanterol 62.5/25 µg which was as safe as placebo, whereas glycopyrronium/formoterol 14.9/9.6, glycopyrronium/indacaterol 15.6/27.5 µg, and glycopyrronium/indacaterol 50/110 µg were the least safe FDCs.,No impact on mortality was detected for each specific FDC.,This meta-analysis indicates that LABA/LAMA FDC therapy is characterized by an excellent cardiovascular safety profile in COPD patients.,However, the findings of this quantitative synthesis have been obtained from populations that participated in randomized clinical trials, and were devoid of major cardiovascular diseases.,Thus, post-marketing surveillance and observational studies may help to better define the real impact of specific FDCs with regard to the cardiovascular risk. | 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 |
Tobacco smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), a debilitating respiratory condition with high mortality and morbidity (1,2).,However, an estimated 24% of adults with COPD have never smoked (3,4).,Among these persons, 26%-53% of COPD can be attributed to workplace exposures, including dust, fumes, gases, vapors, and secondhand smoke exposure (4-6).,To assess industry-specific and occupation-specific COPD prevalence among adults aged ≥18 years who have never smoked and who were employed any time during the past 12 months, CDC analyzed 2013-2017 National Health Interview Survey (NHIS) data.,Among an estimated 106 million workers who had never smoked, 2.2% (2.4 million) have COPD.,Highest prevalences were among workers aged ≥65 years (4.6%), women (3.0%), and those reporting fair/poor health (6.7%).,Among industries and occupations, the highest COPD prevalences were among workers in the information industry (3.3%) and office and administrative support occupations (3.3%).,Among women, the highest prevalences were among those employed in the information industry (5.1%) and in the transportation and material moving occupation (4.5%), and among men, among those employed in the agriculture, forestry, fishing, and hunting industry (2.3%) and the administrative and support, waste management, and remediation services industry (2.3%).,High COPD prevalences in certain industries and occupations among persons who have never smoked underscore the importance of continued surveillance, early identification of COPD, and reduction or elimination of COPD-associated risk factors, such as the reduction of workplace exposures to dust, vapors, fumes, chemicals, and exposure to indoor and outdoor air pollutants. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting.,Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014.,Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed.,A total of 17,479 patients with COPD and 84,514 reference controls were analyzed.,During 2013, direct costs were considerably higher among the COPD patient population (€13,179) versus the reference population (€2,716), largely due to hospital nights unrelated to COPD.,Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights.,Indirect costs (~€28,000 per patient) were the largest economic burden in COPD patients of working age during 2013.,As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease. | To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD. | 1 |
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. | COPD is uniquely situated as a chronic disease at the beginning of the 21st century; it is not only an established major cause of mortality and morbidity but is increasing in prevalence despite current medical interventions.,In addition COPD is not a stable disease but its natural history is punctuated by periods of acute deterioration or exacerbations.,Exacerbations generate considerable additional morbidity and mortality, and directly affect patients’ quality of life.,However, despite significant advances in understanding and treating this disease, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs.,This review will consider the current management of COPD exacerbations and how new clinical strategies may improve outcome of these important clinical events. | 1 |
Frailty is a state of increased vulnerability that has a significant risk of unfavorable outcomes such as increased dependency and/or death, but little is known about frailty in people with chronic obstructive pulmonary disease (COPD).,We aimed to determine the prevalence of frailty in COPD patients and to identify the associated risk factors.,Two hundred fifty-seven COPD patients enrolled from primary care in Greece between 2015 and 2016.,Physicians used structured interviews to collect cross-sectional data including demographics, medical history, symptoms and COPD Assessment Tool (CAT) or modified Medical Research Council Dyspnea scale (mMRC) score.,Patients were classified into severity groups according to GOLD 2017 guidelines.,Participants completed the The Frail Non-Disabled (FiND) questionnaire, exploring the frailty and disability domains.,In the present analyses, frail patients with and without mobility disability were pooled and were compared to non-frail patients.,Factors associated with frailty were analyzed using univariate and multivariate logistic regression.,Mean (SD) age was 65 (12.3) with 79% males.,The majority of patients suffered with frailty (82%) of which 76.8% had mobility disability.,84.2% were married/with partner and 55.4% retired.,55.6% were current smokers.,Uncontrolled disease (≥10 CAT score) was reported in 91.1% and 37.2% of patients had ≥2 exacerbations in the past year.,Dyspnea (38%) and cough (53.4%) were the main symptoms.,Main comorbidities were hypertension (72.9%), hyperlipidaemia (24.6%) and diabetes (11%).,Risk of frailty was significantly increased with age (OR; 95%CI: 1.05; 1.02-1.08), hypertension (2.25; 1.14-4.45), uncontrolled disease (≥10 CAT score 4.65; 1.86-11.63, ≥2 mMRC score 5.75 (2.79-11.85) or ≥ 2 exacerbations 1.73; 1.07-2.78), smoking cessation (ex compared to current smokers: 2.37; 1.10-5.28) and GOLD status (B&D compared to A&C groups: CAT-based 4.65; 1.86-11.63; mMRC-based: 5.75; 2.79-11.85).,In multivariate regression smoking cessation and GOLD status remained significant.,Gender, body mass index, occupational or marital status, symptoms and other comorbidities were not significant.,Frailty with mobility disability is common in COPD patients and severity of disease increases the risk.,It is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease.,Routine assessment of frailty in addition to COPD control may allow early interventions for preventing or delaying progression of frailty and improvement in COPD disease. | Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | 1 |
Common colds are associated with acute respiratory symptom exacerbations in COPD patients.,To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds.,Global initiative for chronic Obstructive Lung Disease stage I-IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009.,Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway.,A composite daily symptom score was derived for each subject from diarized symptom data.,The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models.,Daily diary transmission compliance of >97% enabled detection of all possible exacerbations.,Among 262 exacerbations meeting Anthonisen criteria, 218 (83%) had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%).,Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P<0.001) greater with colds present.,Compared to cold- and virus-negative exacerbations (n=57), the mean increase in composite symptom score in those cold and virus positive (n=79) was 0.93 (95% CI: 0.61, 1.25; P<0.001), cold-positive and virus-negative exacerbations (n=100) 0.51 (95% CI: 0.21, 0.81; P<0.001), cold-negative and virus-positive exacerbations (n=26) 0.58 (95% CI: 0.23, 0.94; P<0.001).,This study emphasizes the importance of colds in COPD exacerbation risk and severity, even in the absence of virus detection.,COPD patients should act promptly when cold symptoms appear to facilitate early intervention for exacerbation prevention or management. | ICAM-1 is a major receptor for ~60% of human rhinoviruses, and non-typeable Haemophilus influenzae, two major pathogens in COPD.,Increased cell-surface expression of ICAM-1 in response to tobacco smoke exposure has been suggested.,We have investigated epithelial ICAM-1 expression in both the large and small airways, and lung parenchyma in smoking-related chronic airflow limitation (CAL) patients.,We evaluated epithelial ICAM-1 expression in resected lung tissue: 8 smokers with normal spirometry (NLFS); 29 CAL patients (10 small-airway disease; 9 COPD-smokers; 10 COPD ex-smokers); Controls (NC): 15 normal airway/lung tissues.,Immunostaining with anti-ICAM-1 monoclonal antibody was quantified with computerized image analysis.,The percent and type of cells expressing ICAM-1 in large and small airway epithelium and parenchyma were enumerated, plus percentage of epithelial goblet and submucosal glands positive for ICAM- 1.,A major increase in ICAM-1 expression in epithelial cells was found in both large (p < 0.006) and small airways (p < 0.004) of CAL subjects compared to NC, with NLFS being intermediate.,In the CAL group, both basal and luminal areas stained heavily for ICAM-1, so did goblet cells and sub-mucosal glands, however in either NC or NLFS subjects, only epithelial cell luminal surfaces stained.,ICAM-1 expression on alveolar pneumocytes (mainly type II) was slightly increased in CAL and NLFS (p < 0.01).,Pack-years of smoking correlated with ICAM-1 expression (r = 0.49; p < 0.03).,Airway ICAM-1 expression is markedly upregulated in CAL group, which could be crucial in rhinoviral and NTHi infections.,The parenchymal ICAM-1 is affected by smoking, with no further enhancement in CAL subjects.,The online version of this article (doi:10.1186/s12931-016-0483-8) contains supplementary material, which is available to authorized users. | 1 |
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. | Our objective was to assess the 5-year cost effectiveness of bronchodilator therapy with tiotropium, salmeterol or ipratropium for chronic obstructive pulmonary disease (COPD) from the perspective of the Spanish National Health System (NHS).,A probabilistic Markov model was designed wherein patients moved between moderate, severe or very severe COPD and had the risk of exacerbation and death.,Probabilities were derived from clinical trials.,Spanish healthcare utilisation, costs and utilities were estimated for each COPD and exacerbation state.,Outcomes were exacerbations, exacerbation-free months, quality-adjusted life years (QALYs), and cost(-effectiveness).,The mean (SE) 5-year number of exacerbations was 3.50 (0.14) for tiotropium, 4.16 (0.40) for salmeterol and 4.71 (0.54) for ipratropium.,The mean (SE) number of QALYs was 3.15 (0.08), 3.02 (0.15) and 3.00 (0.20), respectively.,Mean (SE) 5-year costs were €6,424 (€305) for tiotropium, €5,869 (€505) for salmeterol, and €5,181 (€682) for ipratropium (2005 values).,Ipratropium and tiotropium formed the cost-effectiveness frontier, with tiotropium being preferred when willingness to pay (WTP) exceeded €639 per exacerbation-free month and €8,157 per QALY.,In Spain, tiotropium demonstrated the highest expected net benefit for ratios of the willingness to pay per QALY, well within accepted limits. | 1 |
Chronic obstructive pulmonary disease (COPD) is the most prevalent obstructive lung disease worldwide characterized by decline in lung function.,It is associated with airway obstruction, oxidative stress, chronic inflammation, mucus hypersecretion, and enhanced autophagy and cellular senescence.,Cigarette smoke being the major risk factor, other secondary risk factors such as the exposure to air pollutants, occupational exposure to gases and fumes in developing countries, also contribute to the pathogenesis of COPD.,Conventional therapeutic strategies of COPD are based on anti-oxidant and anti-inflammatory drugs.,However, traditional anti-oxidant pharmacological therapies are commonly used to alleviate the impact of COPD as they have many associated repercussions such as low diffusion rate and inappropriate drug pharmacokinetics.,Recent advances in nanotechnology and stem cell research have shed new light on the current treatment of chronic airway disease.,This review is focused on some of the anti-oxidant therapies currently used in the treatment and management of COPD with more emphasis on the recent advances in nanotechnology-based therapeutics including stem cell and gene therapy approaches for the treatment of chronic airway disease such as COPD and asthma. | Recently, the therapeutic potential of immune-modulation during the progression of chronic obstructive pulmonary disease (COPD) has been attracting increasing interest.,However, chronic inflammatory response has been over-simplified in descriptions of the mechanism of COPD progression.,As a form of first-line airway defense, epithelial cells exhibit phenotypic alteration, and participate in epithelial layer disorganization, mucus hypersecretion, and extracellular matrix deposition.,Dendritic cells (DCs) exhibit attenuated antigen-presenting capacity in patients with advanced COPD.,Immature DCs migrate into small airways, where they promote a pro-inflammatory microenvironment and bacterial colonization.,In response to damage-associated molecular patterns (DAMPs) in lung tissue affected by COPD, neutrophils are excessively recruited and activated, where they promote a proteolytic microenvironment and fibrotic repair in small airways.,Macrophages exhibit decreased phagocytosis in the large airways, while they demonstrate high pro-inflammatory potential in the small airways, and mediate alveolar destruction and chronic airway inflammation.,Natural killer T (NKT) cells, eosinophils, and mast cells also play supplementary roles in COPD progression; however, their cellular activities are not yet entirely clear.,Overall, during COPD progression, “exhausted” innate immune responses can be observed in the large airways.,On the other hand, the innate immune response is enhanced in the small airways.,Approaches that inhibit the inflammatory cascade, chemotaxis, or the activation of inflammatory cells could possibly delay the progression of airway remodeling in COPD, and may thus have potential clinical significance. | 1 |
Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.,Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity.,In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling.,The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.,Patients scheduled for lung resection were prospectively recruited.,Demographic, clinical data and pulmonary function tests results were recorded.,Emphysema was visually scored and histological remodeling features were noted.,Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.,We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding.,In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.,13 COPD and 7 non COPD patients were included.,The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03] respectively).,Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD, p = 0.04).,The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs 12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]).,Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively).,Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels.,Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).,Our results showed an abnormal bronchial epithelial wound closure process in severe COPD.,Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.,The online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users. | T cells and B cells participate in the pathogenesis of COPD.,Currently, NK cells and NKT cells have gained increasing attention.,In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS) were recruited, and their pulmonary function was assessed.,The frequencies of CD3+ T, CD4+ T, CD8+ T, B, NK, and NKT-like cells were determined using flow cytometry.,The frequencies of spontaneous and inducible IFN-γ + or CD107a+ NK and NKT-like cells as well as activating or inhibitory receptors were also detected.,The potential association of lymphocyte subsets with disease severity was further analyzed.,Significantly decreased numbers of CD3+ and CD4+ T cells, and the CD4+/CD8+ ratio, but increased numbers of CD3−CD56+ NK and CD3+CD56+ NKT-like cells were observed in COPD patients compared to HNS.,The frequencies of inducible IFN-γ-secreting NK and NKT-like cells were less in COPD patients.,The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater.,The frequency of CD158b+ NK cells was negatively correlated with FEV1% prediction and FEV1/FVC.,Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD. | 1 |
Chronic obstructive pulmonary disease is associated with significant morbidity and mortality.,Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations, while patients are much more concerned about symptoms and health status.,Our aim was to investigate the effects of tiotropium + olodaterol on patient-reported health outcomes, breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease, compared to placebo, tiotropium or olodaterol monotherapy.,Two pairs of replicate, phase III studies of 12 (OTEMTO 1 + 2) and 52 weeks’ (TONADO 1 + 2) duration were evaluated, in which patients received either tiotropium + olodaterol 2.5/5 or 5/5 μg, tiotropium 2.5 or 5 μg, olodaterol 5 μg or placebo, all delivered once daily via Respimat inhaler.,Patient-reported outcomes included breathlessness assessed by transition dyspnoea index focal score, health status assessed by St George’s Respiratory Questionnaire total score and night-time rescue medication use at 12 or 24 weeks.,Outcomes from the pooled study data are reported.,Overall, 1621 and 5162 patients were treated in the OTEMTO and TONADO trials, respectively.,Significantly larger improvements in St George’s Respiratory Questionnaire and transition dyspnoea index focal scores were observed and a greater proportion of patients were responders to therapy (based on minimum clinically important differences in St George’s Respiratory Questionnaire and transition dyspnoea index) with tiotropium + olodaterol compared to either monotherapy or to placebo.,Tiotropium + olodaterol 5/5 µg significantly reduced night-time rescue medication usage.,Results from four in-depth studies show that a combined inhaler is very effective for treatment of moderate to severe chronic lung disease.,Alleviating the symptoms of chronic obstructive pulmonary disease (COPD), particularly sleep disturbance, is crucial to enhancing patients’ quality of life.,Gary Ferguson at the Pulmonary Research Institute of Southeast Michigan, together with other scientists across the USA and Germany, analysed data from four large-scale studies to evaluate the efficacy of STIOLTO Respimat, a combination of two bronchodilators-tiotropium, and olodaterol, which tackle airway obstruction and breathlessness, improving long-term lung function.,They found that the new drug combination triggered significant improvements in patients’ quality of life and levels of breathlessness.,Use of night-time rescue medication in patients on STIOLTO Respimat was considerably reduced.,A greater number of patients responded positively to the combined inhaler than to monotherapy. | Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | 1 |
Based on blood and sputum samples, up to 40% of patients with COPD have eosinophilic inflammation; however, there is little epidemiology data characterizing the health care burden within this sub-population.,Given that COPD-attributable medical costs in the USA are predicted to approach $50 billion by 2020, we analyzed the effect of blood eosinophil counts and exacerbations on health care resource utilization and costs.,This cross-sectional study used electronic medical records and insurance claims data from the Reliant Medical Group (January 2011-December 2015).,Eligible patients were ≥40 years of age, continuously enrolled during the year of interest (2012, 2013, 2014, or 2015), had ≥1 COPD-related code in the preceding year, and documented maintenance therapy use.,Patients with ≥1 blood eosinophil count recorded were stratified into 2 cohorts: <150 cells/µL and ≥150 cells/µL.,Endpoints included demographics, clinical characteristics, health care resource utilization, and costs.,The impact of blood eosinophil count and exacerbation patterns on health care resource utilization and costs was assessed with multivariate analyses.,On average, 2,832 eligible patients were enrolled annually, of whom ~28% had ≥1 eosinophil count recorded during the year.,The ≥150 cells/µL cohort had numerically higher all-cause and COPD-related health care resource utilization and cost each year compared with the <150 cells/µL cohort, but varied by service and year.,Among patients with exacerbations, the ≥150 cells/µL cohort exhibited significantly higher COPD-related costs compared with the <150 cells/µL cohort.,Blood eosinophil counts may be a useful biomarker for burden of disease in a subgroup of patients with COPD. | Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | 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 lung is composed of airways and lung parenchyma, and the extracellular matrix (ECM) contains the main building blocks of both components.,The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure.,More recent research has provided novel insights revealing that the ECM is also a bioactive environment that orchestrates the cellular responses in its environs.,Changes in the ECM in the airway or parenchymal tissues are now recognized in the pathological profiles of many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF).,Only recently have we begun to investigate whether these ECM changes result from the disease process, or whether they constitute a driving factor that orchestrates the pathological outcomes.,This review summarizes our current knowledge of the alterations in the ECM in asthma, COPD, and IPF, and the contributions of these alterations to the pathologies.,Emerging data suggest that alterations in the composition, folding or rigidity of ECM proteins may alter the functional responses of cells within their environs, and in so doing change the pathological outcomes.,These characteristics highlight potential avenues for targeting lung pathologies in the future.,This may ultimately contribute to a better understanding of chronic lung diseases, and novel approaches for finding therapeutic solutions.,© 2016 The Authors.,The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is defined as a disease characterized by persistent, progressive airflow limitation.,Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation.,In COPD fractional exhaled Nitric Oxide (FeNO) levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters.,Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones.,In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression.,FeNO measurements may be useful in clinical setting to identify the level of airway inflammation, per se and in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment.,Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD.,In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development. | Rhinovirus (RV) is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations, and primarily infects bronchial epithelial cells.,Immune responses from BECs to RV infection are critical in limiting viral replication, and remain unclear in COPD.,The objective of this study is to investigate innate immune responses to RV infection in COPD primary BECs (pBECs) in comparison to healthy controls.,Primary bronchial epithelial cells (pBECs) from subjects with COPD and healthy controls were infected with RV-1B.,Cells and cell supernatant were collected and analysed using gene expression microarray, qPCR, ELISA, flow cytometry and titration assay for viral replication.,COPD pBECs responded to RV-1B infection with an increased expression of antiviral and pro-inflammatory genes compared to healthy pBECs, including cytokines, chemokines, RNA helicases, and interferons (IFNs).,Similar levels of viral replication were observed in both disease groups; however COPD pBECs were highly susceptible to apoptosis.,COPD pBECs differed at baseline in the expression of 9 genes, including calgranulins S100A8/A9, and 22 genes after RV-1B infection including the signalling proteins pellino-1 and interleukin-1 receptor associated kinase 2.,In COPD, IFN-β/λ1 pre-treatment did not change MDA-5/RIG-I and IFN-β expression, but resulted in higher levels IFN-λ1, CXCL-10 and CCL-5.,This led to reduced viral replication, but did not increase pro-inflammatory cytokines.,COPD pBECs elicit an exaggerated pro-inflammatory and antiviral response to RV-1B infection, without changing viral replication.,IFN pre-treatment reduced viral replication.,This study identified novel genes and pathways involved in potentiating the inflammatory response to RV in COPD. | 1 |
Thrombocytosis has been associated with COPD prevalence and increased all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but whether it is associated with morbidity in stable COPD is unknown.,This study aims to determine the association of thrombocytosis with COPD morbidity including reported AECOPD, respiratory symptoms and exercise capacity.,Participants with COPD were included from two multi-center observational studies (SPIROMICS and COPDGene).,Cross-sectional associations of thrombocytosis (platelet count ≥350 × 109/L) with AECOPD during prior year (none vs. any), exertional dyspnea (modified Medical Research Council (mMRC) score ≥ 2), COPD Assessment Test (CAT) score ≥ 10, six-minute-walk distance (6MWD), and St.,George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic or linear regression.,A pooled effect estimate for thrombocytosis was produced using meta-analysis of data from both studies.,Thrombocytosis was present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene participants.,In meta-analysis thrombocytosis was associated with any AECOPD (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0), severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC ≥ 2 aOR 1.4; 95% CI: 1.0-1.9), respiratory symptoms (CAT ≥ 10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ score (β 2.7; 95% CI: 0.5, 5).,Thrombocytosis was also associated with classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D (aOR 1.7 95% CI: 1.2-2.4).,Thrombocytosis was associated with higher likelihood of prior exacerbation and worse symptoms.,Platelet count, a commonly measured clinical assay, may be a biomarker for moderate-severe COPD symptoms, guide disease classification and intensity of treatment.,Future longitudinal studies investigating the role of platelets in COPD progression may be warranted.,ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
To identify differentially methylated probes (DMPs) and regions (DMRs) in relation to chronic obstructive pulmonary disease (COPD) and lung function traits.,We performed an epigenome-wide association study of COPD and spirometric parameters, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC, in blood DNA using the Infinium HumanMethylation450 (n = 100, a Korean COPD cohort).,We found one significant DMP (cg03559389, DIP2C) and 104 significant DMRs after multiple-testing correction.,Of these, 34 DMRs mapped to genes differential expressed with respect to the same trait.,Five of the genes were associated with more than two traits: CTU2, USP36, ZNF516, KLK10 and CPT1B.,We identified novel differential methylation loci related to COPD and lung function in blood DNA in Koreans and confirmed previous findings in non-Asians.,Epigenetic modification could contribute to the etiology of these phenotypes. | Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease.,Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD.,However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD.,miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR.,Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry.,Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR.,Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1.,We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p < 0.01).,We also observed a down-regulation of miR-181c in HBECs and a mouse model after cigarette smoke (CS) exposure.,Functional assays demonstrated that miR-181c over-expression decreased the inflammatory response, neutrophil infiltration, reactive oxygen species (ROS) generation, and inflammatory cytokines induced by CS, while its down-regulation produced the opposite effects.,Subsequent investigation found that CCN1 was a direct target of miR-181c.,CCN1 expression was increased in lung tissues of COPD patients, and was negatively correlated with miR-181c expression in human COPD samples (p < 0.01).,Taken together, our data suggest the critical roles of miR-181c and its target CCN1 in COPD development, and provide potential therapeutic targets for COPD treatment. | 1 |
The importance of the underlying local and systemic oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD) has long been established.,In view of the lack of therapy that might inhibit the progress of the disease, there is an urgent need for a successful therapeutic approach that, through affecting the pathological processes, will influence the subsequent issues in COPD management such as lung function, airway clearance, dyspnoea, exacerbation, and quality of life.,N-acetylcysteine (NAC) is a mucolytic and antioxidant drug that may also influence several inflammatory pathways.,It provides the sulfhydryl groups and acts both as a precursor of reduced glutathione and as a direct reactive oxygen species (ROS) scavenger, hence regulating the redox status in the cells.,The changed redox status may, in turn, influence the inflammation-controlling pathways.,Moreover, as a mucolytic drug, it may, by means of decreasing viscosity of the sputum, clean the bronchi leading to a decrease in dyspnoea and improved lung function.,Nevertheless, as successful as it is in the in vitro studies and in vivo studies with high dosage, its actions at the dosages used in COPD management are debatable.,It seems to influence exacerbation rate and limit the number of hospitalization days, however, with little or no influence on the lung function parameters.,Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives with their multiple molecular modes of action remain promising medication once doses and route of administration are optimized. | Prescription of mucoactive drugs for chronic obstructive pulmonary disease (COPD) is increasing.,This development in clinical practice arises, at least in part, from a growing understanding of the important role that exacerbation frequency, systemic inflammation and oxidative stress play in the pathogenesis of respiratory disease.,S-carboxymethylcysteine (carbocisteine) is the most frequently prescribed mucoactive agent for long-term COPD use in the UK.,In addition to its mucoregulatory activity, carbocisteine exhibits free-radical scavenging and anti-inflammatory properties.,These characteristics have stimulated interest in the potential that this and other mucoactive drugs may offer for modification of the disease processes present in COPD.,This article reviews the pharmacology, in vivo and in vitro properties, and clinical trial evidence for carbocisteine in the context of guidelines for its use and the current understanding of the pathogenic processes that underlie COPD. | 1 |
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. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult.,Incorporation of patient preferences is widely encouraged.,To summarize original research articles determining patient preference in moderate-to-severe disease.,Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma.,The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease.,We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences.,Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion.,Data were tabulated and analyzed descriptively.,About 478 articles identified, 448 were rejected and 30 analyzed.,There were 25 on COPD and five on asthma.,Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient-physician relationship, quality-of-life impairments, and information availability.,Patients strongly preferred sponsors’ inhalers.,At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention.,While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience.,Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler.,Few studies have examined patient preference in these diseases.,More research is needed to fill in knowledge gaps. | NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | 1 |
Introduction: Inhaled corticosteroids (ICS) (in fixed combinations with long-acting β2-agonists [LABAs]) are frequently prescribed for patients with chronic obstructive pulmonary disease (COPD), outside their labeled indications and recommended treatment strategies and guidelines, despite having the potential to cause significant side effects.,Areas covered: Although the existence of asthma in patients with asthma-COPD overlap syndrome (ACOS) clearly supports the use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS monotherapy is usually not indicated for COPD), the current level of ICS/LABA use is not consistent with the prevalence of ACOS in the COPD population.,Data have recently become available showing the comparative efficacy of fixed bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with ICS/LABA combinations).,Additionally, new information has emerged on ICS withdrawal without increased risk of exacerbations, under cover of effective bronchodilation.,Expert opinion: For patients with COPD who do not have ACOS, a LAMA/LABA combination may be an appropriate starting therapy, apart from those with mild disease who can be managed with a single long-acting bronchodilator.,Patients who remain symptomatic or present with exacerbations despite effectively delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or phosphodiesterase-4 inhibitors.,When prescribing an ICS/LABA, the risk:benefit ratio should be considered in individual patients. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
It is known that biomarkers of systemic inflammation are raised in COPD caused by tobacco (T-COPD) compared with healthy controls, but there is less information on the inflammatory status of subjects with COPD caused by biomass smoke (B-COPD).,In addition, the possible (if any) differences in inflammation between both types of the disease are still not well known.,The aim of this study was to assess the inflammatory profile in B-COPD and T-COPD.,A total of 20 subjects (15 men and five women) with T-COPD were matched one to one for sex, age and forced expiratory volume in 1 s (FEV1) to 20 B-COPD patients.,In all, 20 sex-matched healthy subjects with normal lung function without smoking history or biomass exposure were included as controls.,The following biomarkers were measured: exhaled nitric oxide, serum IL-6, IL-8, IL-5, IL-13, periostin, surfactant protein-P, TNF-α, IgE, erythrocyte sedimentation rate, C-reactive protein and fibrinogen.,Complete blood count was also obtained.,The age of the subjects was 70.2±7.9 years and FEV1% was 56.2%±14.6%.,Most inflammatory biomarkers were higher in both types of COPD than in healthy controls.,IL-6, IL-8 and IL-5 were significantly higher in T-COPD than in B-COPD, without other significant differences.,Both types of COPD are associated with high levels of systemic inflammation biomarkers.,T-COPD patients have a higher systemic inflammatory status than the patients with B-COPD. | Objectives.,A detailed understanding of the intricate relationships between different acute phase reactants (APRs) in chronic obstructive pulmonary disease (COPD) can shed new light on its clinical course.,In this case-control study, we sought to identify the interaction networks of a number of plasma APRs in COPD, with a special focus on their association with disease severity.,Methods.,COPD cases and healthy smoking controls (3:1 ratio) were recruited in our outpatient pulmonary clinic.,Cardiopulmonary exercise testing was used to rule out the presence of ischemic heart disease.,All subjects were males as per protocol.,Multiple plasma APRs - including α-2-macroglobulin, C-reactive protein (CRP), ferritin, fibrinogen, haptoglobin, procalcitonin (PCT), serum amyloid A (SAA), serum amyloid P, and tissue plasminogen activator (tPA) - were measured using commercial Acute Phase Bio-Plex Pro Assays and analyzed on the Bio-Plex manager software.,Correlations between different APRs were investigated using a heat map.,Network visualization and analyses were performed with the Cytoscape software platform.,Results.,A total of 96 COPD cases and 33 controls were included in the study.,Plasma A2M, CRP, and SAP levels were higher in COPD patients than in controls.,Circulating concentrations of haptoglobin and tPA were found to increase in parallel with the severity of the disease.,Increasing disease severity was associated with distinct intricate networks of APRs, which were especially evident in advanced stages.,Conclusions.,We identified different networks of APRs in COPD, which were significantly associated with disease severity. | 1 |
The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear.,Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults.,A cross-sectional study was conducted in southern China.,Seven clusters were randomly selected from four cities across Guangdong province.,Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry.,COPD was defined as a post-bronchodilator FEV1/FVC less than 70%.,Atmosphere PM sampling was conducted across the clusters along with our survey.,Of the subjects initially recruited, 84.4% (n=5993) were included for analysis.,COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters.,COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1.,A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV1, a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV1/FVC ratio.,The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker.,Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function.,ChiCTR-OO-14004264; Post-results. | Smoking prevalence is frequently estimated on the basis of self-reported smoking status.,That can lead to an underestimation of smoking rates.,The aim of this study was to evaluate the difference between self-reported smoking status and that determined through the use of objective measures of smoking at a pulmonary outpatient clinic.,This was a cross-sectional study involving 144 individuals: 51 asthma patients, 53 COPD patients, 20 current smokers, and 20 never-smokers.,Smoking status was determined on the basis of self-reports obtained in interviews, as well as through tests of exhaled carbon monoxide (eCO) and urinary cotinine.,All of the asthma patients and COPD patients declared they were not current smokers.,In the COPD and asthma patients, the median urinary cotinine concentration was 167 ng/mL (range, 2-5,348 ng/mL) and 47 ng/mL (range, 5-2,735 ng/mL), respectively (p < 0.0001), whereas the median eCO level was 8 ppm (range, 0-31 ppm) and 5 ppm (range, 2-45 ppm), respectively (p < 0.05).,In 40 (38%) of the patients with asthma or COPD (n = 104), there was disagreement between the self-reported smoking status and that determined on the basis of the urinary cotinine concentration, a concentration > 200 ng/mL being considered indicative of current smoking.,In 48 (46%) of those 104 patients, the self-reported non-smoking status was refuted by an eCO level > 6 ppm, which is also considered indicative of current smoking.,In 30 (29%) of the patients with asthma or COPD, the urinary cotinine concentration and the eCO level both belied the patient claims of not being current smokers.,Our findings suggest that high proportions of smoking pulmonary patients with lung disease falsely declare themselves to be nonsmokers.,The accurate classification of smoking status is pivotal to the treatment of lung diseases.,Objective measures of smoking could be helpful in improving clinical management and counseling. | 1 |
Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance.,The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments.,There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations.,A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff)/formoterol fumarate (6 µg/puff)/glycopyrronium bromide (12.5 µg/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler.,Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation.,This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. | Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD.,The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used.,Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS.,The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose.,To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used.,14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS.,On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS.,Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size.,These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk. | 1 |
Thrombocytosis has been associated with COPD prevalence and increased all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but whether it is associated with morbidity in stable COPD is unknown.,This study aims to determine the association of thrombocytosis with COPD morbidity including reported AECOPD, respiratory symptoms and exercise capacity.,Participants with COPD were included from two multi-center observational studies (SPIROMICS and COPDGene).,Cross-sectional associations of thrombocytosis (platelet count ≥350 × 109/L) with AECOPD during prior year (none vs. any), exertional dyspnea (modified Medical Research Council (mMRC) score ≥ 2), COPD Assessment Test (CAT) score ≥ 10, six-minute-walk distance (6MWD), and St.,George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic or linear regression.,A pooled effect estimate for thrombocytosis was produced using meta-analysis of data from both studies.,Thrombocytosis was present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene participants.,In meta-analysis thrombocytosis was associated with any AECOPD (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0), severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC ≥ 2 aOR 1.4; 95% CI: 1.0-1.9), respiratory symptoms (CAT ≥ 10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ score (β 2.7; 95% CI: 0.5, 5).,Thrombocytosis was also associated with classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D (aOR 1.7 95% CI: 1.2-2.4).,Thrombocytosis was associated with higher likelihood of prior exacerbation and worse symptoms.,Platelet count, a commonly measured clinical assay, may be a biomarker for moderate-severe COPD symptoms, guide disease classification and intensity of treatment.,Future longitudinal studies investigating the role of platelets in COPD progression may be warranted.,ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). | The alveolar compartment, the fundamental gas exchange unit in the lung, is critical for tissue oxygenation and viability.,We explored hepatocyte growth factor (HGF), a pleiotrophic cytokine that promotes epithelial proliferation, morphogenesis, migration, and resistance to apoptosis, as a candidate mediator of alveolar formation and regeneration.,Mice deficient in the expression of the HGF receptor Met in lung epithelial cells demonstrated impaired airspace formation marked by a reduction in alveolar epithelial cell abundance and survival, truncation of the pulmonary vascular bed, and enhanced oxidative stress.,Administration of recombinant HGF to tight-skin mice, an established genetic emphysema model, attenuated airspace enlargement and reduced oxidative stress.,Repair in the TSK/+ mouse was punctuated by enhanced akt and stat3 activation.,HGF treatment of an alveolar epithelial cell line not only induced proliferation and scattering of the cells but also conferred protection against staurosporine-induced apoptosis, properties critical for alveolar septation.,HGF promoted cell survival was attenuated by akt inhibition.,Primary alveolar epithelial cells treated with HGF showed improved survival and enhanced antioxidant production.,In conclusion, using both loss-of-function and gain-of-function maneuvers, we show that HGF signaling is necessary for alveolar homeostasis in the developing lung and that augmentation of HGF signaling can improve airspace morphology in murine emphysema.,Our studies converge on prosurvival signaling and antioxidant protection as critical pathways in HGF-mediated airspace maintenance or repair.,These findings support the exploration of HGF signaling enhancement for diseases of the airspace. | 1 |
Oxidative stress is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Evidence suggests that leukocytes mitochondria DNA (mtDNA) is susceptible to undergo mutations, insertions, or depletion in response to reactive oxidative stress (ROS).,We hypothesize that mtDNA copy number is associated with the development of COPD.,Relative mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral leukocytes.,MtDNA copy number of peripheral leukocytes in the COPD group (n = 86) is significantly decreased compared with non-smoker group (n = 77) (250.3± 21.5 VS.,464.2± 49.9, P<0.001).,MtDNA copy number in the COPD group was less than that in the healthy smoking group, but P value nearly achieved significance (250.3± 21.5 VS.,404.0± 76.7, P = 0.08) MtDNA copy number has no significance with age, gender, body mass index, current smoking, and pack-years in COPD group, healthy smoker group and no smoker group, respectively.,Serum glutathione level in the COPD group is significantly decreased compared with healthy smoker and non-smoker groups (4.5± 1.3 VS.,6.2± 1.9 and 4.5± 1.3 VS.,7.1±1.1 mU/mL; P<0.001 respectively).,Pearson correlation test shows a significant liner correlation between mtDNA copy number and serum glutathione level (R = 0.2, P = 0.009).,COPD is associated with decreased leukocyte mtDNA copy number and serum glutathione.,COPD is a regulatory disorder of leukocytes mitochondria.,However, further studies are needed to determine the real mechanisms about the gene and the function of mitochondria. | Rtp801, a stress - related protein triggered by adverse environmental conditions, inhibits mTOR and enhances oxidative stress - dependent cell death.,We postulated that Rtp801 acts as potential amplifying switch in the development of cigarette smoke - induced lung injury, leading to emphysema.,Rtp801 was overexpressed in human emphysematous lungs and in lungs of mice exposed to cigarette smoke.,The upregulation of Rtp801 expression by cigarette smoke in the lung relied on oxidative stress - dependent activation of the CCAAT response element.,Rtp801 was necessary and sufficient for NF - κ B activation in cultured cells and, when forcefully expressed in mouse lungs, it promoted NF - kB activation, alveolar inflammation, oxidative stress, and apoptosis of alveolar septal cells.,On the other hand, Rtp801 − / − mice were markedly protected against acute cigarette smoke - induced lung injury, partly via increased mTOR signaling, and, when exposed chronically, against emphysema.,Our data support the notion that Rtp801 may represent an important molecular sensor and mediator of lung injury to cigarette smoke. | 1 |
To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009.,A total of 45,837 male residents were observed for a median period of 19.1 years.,Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019.,During follow-up, 268 participants died from COPD.,The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41-0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59-0.68).,These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years.,Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality. | Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients.,However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index.,For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.,In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation.,The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months.,The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index.,Mortality was assessed using Kaplan-Meier survival and Cox Regression.,Performance of models was compared using C-statistics.,Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively.,Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function.,The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.,Cachexia is associated with increased mortality among COPD patients.,Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.,The online version of this article (10.1186/s12931-019-1073-3) contains supplementary material, which is available to authorized users. | 1 |
COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL).,However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care.,We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD.,We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression.,We report no difference in HRQoL at final follow-up (St George’s Respiratory Questionnaire total score −0.29; 95%CI −2.09, 1.51; I2 0%), nor any difference in anxiety or depression.,In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective.,Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.,Further work is needed to ensure that self-management of chronic lung disease in primary care settings actively improves patients’ quality of life.,While self-management is beneficial to patients in secondary care with severe chronic obstructive pulmonary disease (COPD), few studies have examined self-management effectiveness in primary care patients with milder COPD.,Kate Jolly at the University of Birmingham, UK, and co-workers identified only 12 studies out of over 12,500 that specifically examined self-management in primary care.,Of these, seven were suitable for metanalysis.,The team found that community-based interventions to support self-management did not make a significant difference to patients’ perceived quality of life, or in reducing anxiety and depression.,They call for further research to identify specific support that will help patients with mild to moderate COPD cope and adapt to the progressive condition. | 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 |
Inhaled bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) play a central role in the treatment of stable chronic obstructive pulmonary disease (COPD).,However, it is still unclear whether LABA or LAMA should be used for the initial treatment.,Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LABA versus LAMA in patients with stable COPD.,We searched relevant randomized control trials (RCTs) with a period of treatment of at least 12 weeks and analyzed the exacerbations, quality of life, dyspnea score, lung function and adverse events as the outcomes of interest.,We carefully excluded unblinded data and identified a total of 19 RCTs (N = 28,211).,LAMA significantly decreased the exacerbations compared to LABA (OR 0.85, 95% CI 0.74 to 0.98; P = 0.02).,In St George’s Respiratory Questionnaire and transitional dyspnoea index score, there were no differences between LABA and LAMA treatment.,Compared to LABA, there was a small but significant increase in the trough FEV1 after LAMA treatment (Mean difference 0.02, 95% CI 0.01 to 0.03, P = 0.0006).,In the safety components, there was no difference in the serious adverse events between LABA and LAMA.,However, LAMA showed a significantly lower incidence of total adverse events compared to LABA (OR 0.92, 95% CI 0.86 to 0.98; P = 0.02).,Treatment with LAMA in stable COPD provided a significantly lower incidence of exacerbation and non-serious adverse events, and a higher trough FEV1 compared to LABA.,(PROSPERO: CRD42019144764) | Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | 1 |
Neuromuscular electrical stimulation (NMES) has been shown to produce benefits in the muscle function of chronic obstructive pulmonary disease (COPD) patients.,The definite effectiveness of NMES, applied in isolation or concurrently with conventional pulmonary rehabilitation (PR) or exercise training, remains unclear.,This review was to determine the effects of NMES on exercise capacity, functional performance, symptoms, and health-related quality of life (HRQoL) in COPD patients.,Electronic databases (PubMed, Embase, Web of Science, the Cochrane Library) were searched for relevant randomized controlled trials (RCTs).,Two investigators independently screened the eligible studies up to February 2020 that used NMES as the intervention group.,The outcome measures were 6-min walking distance (6MWD), peak rate of oxygen uptake (VO2 peak), St George’s Respiratory Questionnaire (SGRQ), and symptoms of dyspnoea and fatigue.,Data were extracted using a predefined table and papers were appraised using Downs and Black tool.,We analyzed 13 RCTs with 447 COPD patients.,In the analysis of 6MWD, pooled estimates showed a significant increase in the NMES group, compared with the control group (mean difference (MD) = 27.05, 95% confidence interval (CI): 8.46-45.63, P<0.001).,There were also improvements in symptoms of dyspnea or leg fatigue, and reduction in London Chest Activity of Daily Living (LCADL) scores.,No statistically significant difference was observed in VO2 peak, peak power, and SGRQ.,NMES could improve exercise capacity and reduce perceived sensation of dyspnea during exercise in patients with COPD, but not to be recommended as an effective alternative training modality in the rehabilitation of stable COPD patients. | Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings.,Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests.,The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV.,To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease.,The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality.,Both tests were also significantly associated with health-related quality of life but not with exacerbations.,The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62).,The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings.,The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settingshttp://ow.ly/mxrPx | 1 |
COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend limiting the use of inhaled corticosteroids (ICS) to patients with more severe disease and/or increased exacerbation risk.,However, there are discrepancies between guidelines and real-life practice, as ICS are being overprescribed.,In light of the increasing concerns about the clinical benefit and long-term risks associated with ICS use, therapy needs to be carefully weighed on a case-by-case basis, including in patients already on ICS.,Several studies sought out to determine the effects of withdrawing ICS in patients with COPD.,Early studies have deterred clinicians from reducing ICS in patients with COPD as they reported that an abrupt withdrawal of ICS precipitates exacerbations, and results in a deterioration in lung function and symptoms.,However, these studies were fraught with numerous methodological limitations.,Recently, two randomized controlled trials and a real-life prospective study revealed that ICS can be safely withdrawn in certain patients.,Of these, the WISDOM (Withdrawal of Inhaled Steroids During Optimized Bronchodilator Management) trial was the largest and first to examine stepwise withdrawal of ICS in patients with COPD receiving maintenance therapy of long-acting bronchodilators (ie, tiotropium and salmeterol).,Even with therapy being in line with the current guidelines, the findings of the WISDOM trial indicate that not all patients benefit from including ICS in their treatment regimen.,Indeed, only certain COPD phenotypes seem to benefit from ICS therapy, and validated markers that predict ICS response are urgently warranted in clinical practice.,Furthermore, we are now better equipped with a larger armamentarium of novel and more effective long-acting β2-agonist/long-acting muscarinic antagonist combinations that can be considered by clinicians to optimize bronchodilation and allow for safer ICS withdrawal.,In addition to providing a review of the aforementioned, this perspective article proposes an algorithm for the stepwise withdrawal of ICS in real-life clinical practice. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis.,Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD.,COPD-associated osteoporosis is however extremely undertreated.,Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients.,Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described.,It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks.,Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. | Recent studies described association between chronic obstructive pulmonary disease (COPD) and increased risk of cardiovascular diseases (CVD).,In their analysis none of these studies accounted for sociodemographic factors, health behaviors, and patient comorbidities simultaneously.,To study whether COPD diagnosis is an independent risk factor for CVD.,Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002 National Health Interview Survey (NHIS) were included in the analysis.,Chi-squared tests and odds ratios (OR) were utilized to compare the data.,Multiple logistic regression was employed to analyze the association between COPD and CVD with simultaneous control for sociodemographic factors (age, gender, race, marital status, education, income), health behaviors (tobacco use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension, high cholesterol, and obesity).,The analysis employed NHIS sampling weights to generate data representative of the entire US population.,The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P < 0.0001).,Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having coronary heart disease (OR = 2.0, 95% CI: 1.5-2.5), angina (OR = 2.1, 95% CI: 1.6-2.7), myocardial infarction (OR = 2.2, 95% CI: 1.7-2.8), stroke (OR = 1.5, 95% CI: 1.1-2.1), congestive heart failure (OR = 3.9, 95% CI: 2.8-5.5), poor circulation in lower extremities (OR = 2.5, 95% CI: 2.0-3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0-2.8).,Overall, the presence of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3-3.2).,These findings support the conclusion that COPD is an independent risk factor for CVD. | 1 |
COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes.,Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies.,As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes.,The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites.,Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions.,However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies.,Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis.,This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms.,It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors.,Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid illness and new therapeutic strategies for both the diseases.,However, further research is needed to clarify factors that may be directly causal as opposed to confounding relationships. | Many epidemiological studies have found a positive association between periodontal disease (PD) and risk of chronic obstructive pulmonary disease (COPD), but this association is varied and even contradictory among studies.,We performed a meta-analysis to ascertain the relationship between PD and COPD.,PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD.,Data from the studies selected were extracted and analyzed independently by two authors.,The meta-analysis was performed using the Comprehensive Meta-Analysis software.,Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional) involving 3,988 COPD patients were yielded.,Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001), with sensitivity analysis showing that the result was robust.,Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association.,Publication bias was detected.,Based on current evidence, PD is a significant and independent risk factor of COPD.,However, whether a causal relationships exists remains unclear.,Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression. | 1 |
Statins by their anti-inflammatory and endothelial stabilizing effect can be beneficial in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH).,The present study was done to evaluate the effect of rosuvastatin on pulmonary functions and quality of life (QOL) in patients with concomitant COPD and PH.,It was a prospective, randomized, double-blind, placebo-controlled, study conducted in patients with COPD and PH.,A total of sixty patients were assigned to receive either rosuvastatin 10 mg or placebo once a day in addition to their conventional treatment for 12 weeks.,Routine blood investigations, pulmonary functions, echocardiogram, exercise capacity, and QOL using a questionnaire were assessed at the baseline and after 12 weeks.,In patients of rosuvastatin group, there was a statistically significant increase in peak expiratory flow rate (PEFR) (P = 0.04) but no significant change in other pulmonary functions: Forced vital capacity (FVC), forced expiratory volume at 1 s (FVC, FEV1, FEV1/FVC), and echocardiogram parameters.,There was a significant increase in 6-min walk test (6-min walk distance) (P = 0.03) at the end of 12 weeks.,On comparing with placebo, rosuvastatin showed a significant reduction (P = 0.045) in COPD exacerbations while adverse effects did not differ.,Statins have a favorable effect on patients with COPD and PH regarding the improvement in PEFR, COPD exacerbations, and exercise capacity.,Such effects can be beneficial in these patients and more so in patients with concomitant coronary artery disease or hyperlipidemia where long-term benefits of statins have been established. | There are limited data on the risk of pulmonary disease in patients with diabetes.,The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.,We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California.,Age and sex data were available for all cohort members (n = 1,811,228).,Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.,Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort.,No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes.,These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03-1.12], COPD HR 1.22 [1.15-1.28], pulmonary fibrosis HR 1.54 [1.31-1.81], and pneumonia HR 1.92 [1.84-1.99]).,The risk of pneumonia and COPD increased significantly with increasing A1C.,Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer.,This increased risk may be a consequence of declining lung function in patients with diabetes. | 1 |
Asthma-COPD overlap syndrome (ACOS) prevalence varies depending on the studied population and definition criteria.,The prevalence and clinical characteristics of ACOS in an at-risk COPD primary care population from Latin America was assessed.,Patients ≥40 years, current/ex-smokers and/or exposed to biomass, attending routine primary care visits completed a questionnaire and performed spirometry.,COPD was defined as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) < 0.70; asthma was defined as either prior asthma diagnosis or wheezing in the last 12 months plus reversibility (increase in post-bronchodilator FEV1 or FVC ≥200 mL and ≥12%); ACOS was defined using a combination of COPD with the two asthma definitions.,Exacerbations in the past year among the subgroups were evaluated.,One thousand seven hundred forty three individuals completed the questionnaire, 1540 performed acceptable spirometry, 309 had COPD, 231 had prior asthma diagnosis, and 78 asthma by wheezing + reversibility.,ACOS prevalence in the total population (by post-bronchodilator FEV1/FVC < 0.70 plus asthma diagnosis) was 5.3 and 2.3% by post-bronchodilator FEV1/FVC < 0.70 plus wheezing + reversibility.,In the obstructive population (asthma or COPD), prevalence rises to 17.9 and 9.9% by each definition, and to 26.5 and 11.3% in the COPD population.,ACOS patients defined by post-bronchodilator FEV1/FVC < 0.7 plus wheezing + reversibility had the lowest lung function measurements.,Exacerbations for ACOS showed a prevalence ratio of 2.68 and 2.20 (crude and adjusted, p < 0.05, respectively) (reference COPD).,ACOS prevalence in primary care varied according to definition used.,ACOS by post-bronchodilator FEV1/FVC < 0.7 plus wheezing + reversibility represents a clinical phenotype with more frequent exacerbations, which is probably associated with a different management approach.,The online version of this article (doi:10.1186/s12890-017-0414-6) contains supplementary material, which is available to authorized users. | Overlap syndrome shares features of both asthma and chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate characteristics of overlap syndrome and their effect on self-rated health (SRH).,We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey of 2007-2009.,Subjects with acceptable spirometry and available wheezing history were included.,Subjects were classified into four groups based on forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) results and the presence or absence of self-reported wheezing for the previous 12 months: 1) COPD group, defined as having FEV1/FVC <0.7 without self-reported wheezing history; 2) asthma group, defined as having self-reported wheezing history without FEV1/FVC <0.7; 3) overlap syndrome group, having both FEV1/FVC <0.7 and wheezing history; and 4) non-obstructive disease (NOD) group, having neither FEV1/FVC <0.7 nor self-reported wheezing.,SRH was categorized as better or lower based on responses to a questionnaire.,From a total 9,104 subjects, 700 were assigned to the COPD group, 560 to the asthma group, 210 to the overlap syndrome group, and 7,634 to the NOD group.,Compared to the other groups, subjects in the overlap syndrome group were more likely to have low lung function, a high proportion of smokers, low socioeconomic status, short education duration, lower SRH, and past diagnosis of pulmonary tuberculosis or bronchiectasis.,Multiple logistic regression analysis revealed that both overlap syndrome and asthma groups were independently associated with lower SRH after adjustment for age, sex, socioeconomic status, education level, smoking status, comorbidities, and lung function.,Female, old age, low education level, low economic status, smoker and other comorbidities were also associated with lower SRH.,Overlap syndrome was accompanied by high morbidity and was associated with lower SRH, which needs more appropriate care. | 1 |
The extracellular matrix (ECM) of the lung plays several important roles in lung function, as it offers a low resistant pathway that allows the exchange of gases, provides compressive strength and elasticity that supports the fragile alveolar-capillary intersection, controls the binding of cells with growth factors and cell surface receptors and acts as a buffer against retention of water.,COPD is a chronic inflammatory respiratory condition, characterised by various conditions that result in progressive airflow limitation.,At any stage in the course of the disease, acute exacerbations of COPD may occur and lead to accelerated deterioration of pulmonary function.,A key factor of COPD is airway remodelling, which refers to the serious alterations of the ECM affecting airway wall thickness, resistance and elasticity.,Various studies have shown that serum biomarkers of ECM turnover are significantly associated with disease severity in patients with COPD and may serve as potential targets to control airway inflammation and remodelling in COPD.,Unravelling the complete molecular composition of the ECM in the diseased lungs will help to identify novel biomarkers for disease progression and therapy.,Airway remodelling in COPD refers to alterations of the lung ECM that affect airway wall thickness, resistance and elasticity.,Unravelling such molecular modifications will help us to identify novel biomarkers for disease progression and therapy.https://bit.ly/2LObAga | The role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established.,More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has been realised.,These studies position ABCA1 as a potential therapeutic target in a diverse range of diseases where inflammation is an underlying cause.,Chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) are driven by inflammation, and as such, there is now a growing recognition that we need a greater understanding of the signaling pathways responsible for regulation of ABCA1 expression in this clinical context.,While the signaling pathways responsible for cholesterol-mediated ABCA1 expression have been clearly delineated through decades of studies in the atherosclerosis field, and thus far appear to be translatable to the respiratory field, less is known about the cholesterol-independent signaling pathways that can modulate ABCA1 expression in inflammatory lung disease.,This review will identify the various signaling pathways and ligands that are associated with the regulation of ABCA1 expression and may be exploited in future as therapeutic targets in the setting of chronic inflammatory lung diseases. | 1 |
Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users. | 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 |
Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity.,This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD.,The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 μg, once-daily umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks.,Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk.,A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates.,At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206).,Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores.,By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: − 0.56 [p < 0.001]; low: − 0.10 [p = 0.132]).,Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol.,Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day.,In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation.,SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome.,GlaxoSmithKline (study number 201749 [NCT03034915]). | As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users. | 1 |
Lung macrophage subpopulations have been identified based on size.,We investigated characteristics of small and large macrophages in the alveolar spaces and lung interstitium of COPD patients and controls.,Alveolar and interstitial cells were isolated from lung resection tissue from 88 patients.,Macrophage subpopulation cell-surface expression of immunological markers and phagocytic ability were assessed by flow cytometry.,Inflammatory related gene expression was measured.,Alveolar and interstitial macrophages had subpopulations of small and large macrophages based on size and granularity.,Alveolar macrophages had similar numbers of small and large cells; interstitial macrophages were mainly small.,Small macrophages expressed significantly higher cell surface HLA-DR, CD14, CD38 and CD36 and lower CD206 compared to large macrophages.,Large alveolar macrophages showed lower marker expression in COPD current compared to ex-smokers.,Small interstitial macrophages had the highest pro-inflammatory gene expression levels, while large alveolar macrophages had the lowest.,Small alveolar macrophages had the highest phagocytic ability.,Small alveolar macrophage CD206 expression was lower in COPD patients compared to smokers.,COPD lung macrophages include distinct subpopulations; Small interstitial and small alveolar macrophages with more pro-inflammatory and phagocytic function respectively, and large alveolar macrophages with low pro-inflammatory and phagocytic ability. | Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality.,Patients with advanced disease often have a poor quality of life, such that guidelines recommend providing palliative care in their last year of life.,Uptake and use of palliative care in advanced COPD is low; difficulty in predicting 1-year mortality is thought to be a major contributing factor.,We identified two primary care COPD cohorts using UK electronic healthcare records (Clinical Practice Research Datalink).,The first cohort was randomised equally into training and test sets.,An external dataset was drawn from a second cohort.,A risk model to predict mortality within 12 months was derived from the training set using backwards elimination Cox regression.,The model was given the acronym BARC based on putative prognostic factors including body mass index and blood results (B), age (A), respiratory variables (airflow obstruction, exacerbations, smoking) (R) and comorbidities (C).,The BARC index predictive performance was validated in the test set and external dataset by assessing calibration and discrimination.,The observed and expected probabilities of death were assessed for increasing quartiles of mortality risk (very low risk, low risk, moderate risk, high risk).,The BARC index was compared to the established index scores body mass index, obstructive, dyspnoea and exacerbations (BODEx), dyspnoea, obstruction, smoking and exacerbations (DOSE) and age, dyspnoea and obstruction (ADO).,Fifty-four thousand nine hundred ninety patients were eligible from the first cohort and 4931 from the second cohort.,Eighteen variables were included in the BARC, including age, airflow obstruction, body mass index, smoking, exacerbations and comorbidities.,The risk model had acceptable predictive performance (test set: C-index = 0.79, 95% CI 0.78-0.81, D-statistic = 1.87, 95% CI 1.77-1.96, calibration slope = 0.95, 95% CI 0.9-0.99; external dataset: C-index = 0.67, 95% CI 0.65-0.7, D-statistic = 0.98, 95% CI 0.8-1.2, calibration slope = 0.54, 95% CI 0.45-0.64) and acceptable accuracy predicting the probability of death (probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27).,The BARC compared favourably to existing index scores that can also be applied without specialist respiratory variables (area under the curve: BARC = 0.78, 95% CI 0.76-0.79; BODEx = 0.48, 95% CI 0.45-0.51; DOSE = 0.60, 95% CI 0.57-0.61; ADO = 0.68, 95% CI 0.66-0.69, external dataset: BARC = 0.70, 95% CI 0.67-0.72; BODEx = 0.41, 95% CI 0.38-0.45; DOSE = 0.52, 95% CI 0.49-0.55; ADO = 0.57, 95% CI 0.54-0.60).,The BARC index performed better than existing tools in predicting 1-year mortality.,Critically, the risk score only requires routinely collected non-specialist information which, therefore, could help identify patients seen in primary care that may benefit from palliative care.,The online version of this article (10.1186/s12916-019-1310-0) contains supplementary material, which is available to authorized users. | The aim of this study was to analyse mortality and associated risk factors, with special emphasis on health status, medications and co-morbidity, in patients with chronic obstructive pulmonary disease (COPD) that had been hospitalized for acute exacerbation.,This prospective study included 416 patients from each of the five Nordic countries that were followed for 24 months.,The St.,George's Respiratory Questionnaire (SGRQ) was administered.,Information on treatment and co-morbidity was obtained.,During the follow-up 122 (29.3%) of the 416 patients died.,Patients with diabetes had an increased mortality rate [HR = 2.25 (1.28-3.95)].,Other risk factors were advanced age, low FEV1 and lower health status.,Patients treated with inhaled corticosteroids and/or long-acting beta-2-agonists had a lower risk of death than patients using neither of these types of treatment.,Mortality was high after COPD admission, with older age, decreased lung function, lower health status and diabetes the most important risk factors.,Treatment with inhaled corticosteroids and long-acting bronchodilators may be associated with lower mortality in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality.,The most important pathophysiological change of COPD is airway obstruction.,Airway obstruction can cause airflow restriction and obstructive ventilation dysfunction.,Currently, many studies have shown that there is EMT phenomenon in the process of airway remodeling of COPD.,Cullin4A (CUL4A) is an E3 ubiquitin ligase that interacts with other factors to form the E3 complex.,Studies have shown that CLU4A is associated with EMT in non-small cell lung cancer and other cancers.,However, its relationship with EMT in COPD has not been reported systematically.,In this study, we detected the expression of CUL4A in lung epithelium of COPD patients.,In addition, the regulatory effect and mechanism of CUL4A on EMT in COPD were clarified in small airway epithelial cells.,The expression of CUL4A was assessed by immunohistochemistry in lung epithelium specimens from smokers, non-smokers and patients with chronic obstructive pulmonary disease.,The role of CUL4A on cigarette smoke extract (CSE)-induced epithelial-mesenchymal transition (EMT) in human small airway epithelial cells (HSAEpiCs) was assessed by silencing or overexpression CUL4A in vitro.,Cigarette smoke is recognized as a high-risk factor in the induction of COPD, and its damage to the airway involves airway damage, airway inflammation and airway remodeling.,The results shown that CUL4A expression in small airway epithelium was significantly increased in patients with COPD.,We also observed a significant negative association between CUL4A and FEV1%, a useful clinical marker for the diagnosis and evaluation of COPD severity, in small airway epithelial cells.,In vitro, CSE-induced EMT is associated with high expression of CUL4A, and targeted silencing of CUL4A with shRNA inhibits CSE-induced EMT in human small airway epithelial cells.,Our results showed that CUL4A was overexpressed in lung epithelium of COPD patients, and CUL4A could regulate EMT of human small airway epithelium, which revealed a new mechanism of remodeling of small airway epithelium of COPD patients.,The online version of this article (10.1186/s12931-019-1048-4) contains supplementary material, which is available to authorized users. | 1 |
There is increasing evidence that structural lung changes may be present before the occurrence of airflow limitation as assessed by spirometry.,This study investigated the prevalence of computed tomography (CT) quantified emphysema, airway wall thickening and gas trapping according to classification of airflow limitation (FEV1/FVC <70% and/or < the lower limit of normal (LLN)) in (heavy) smokers.,A total number of 1,140 male former and current smokers participating in a lung cancer screenings trial (NELSON) were included and underwent chest CT scanning and spirometry.,Emphysema was quantified by the 15th percentile, air way wall thickening by the square root of wall area for a theoretical airway with 10mm lumen perimeter (Pi10) and gas trapping by the mean lung density expiratory/inspiratory (E/I)-ratio.,Participants were classified by entry FEV1/FVC: group 1>70%; group 2<70% but >LLN; and group 3<LLN. 32 restricted subjects, i.e.,FEV1/FVC >70% but FEV1 <80% predicted, were excluded.,Multivariate regression analysis correcting for covariates was used to asses the extent of emphysema, airway wall thickening and gas trapping according to three groups of airflow limitation.,Mean (standard deviation) age was 62.5 (5.2) years and packyears smoked was 41.0 (18.0).,Group 2 subjects when compared to group 1 had a significantly lower 15th percentile, −920.6 HU versus −912.2 HU; a higher Pi10, 2.87 mm versus 2.57 mm; and a higher E/I-ratio, 88.6% versus 85.6% (all p<0.001).,Subjects with an FEV1/FVC<70%, but above the LLN, have a significant greater degree of structural lung changes on CT compared to subjects without airflow limitation. | The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events.,The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease.,This definition is pragmatic and compromises the different approaches for exacerbation.,However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication") in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiologal process which characterizes exacerbations.,It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition.,In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism) that can masquerade as exacerbations but they should not be considered as causes of them.,The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition.,Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung fuction.,These fundamental aspects should be accounted in diagnosis/definition of exacerbations.,This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events.,The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations.,However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward in the management of COPD. | 1 |
Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics.,The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence.,Current COPD guidelines were identified by a systematic literature search.,The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included.,Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised.,Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population.,A total of 19 COPD guidelines were included.,Systemic corticosteroids were often universally recommended to all patients with acute exacerbations.,Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms.,Objective diagnostic tests or clinical examination were only rarely recommended.,Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients.,Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment. | To investigate the incidence of asthma and chronic obstructive pulmonary disease (COPD) exacerbations in primary care during one year and to identify risk factors for such events.,The study was carried out at seven general practice offices in Norway.,Patients aged 40 years or more registered with a diagnosis of asthma and/or COPD the previous 5 years were included.,After a baseline examination, the participants consulted their GP during exacerbations for the following 12 months.,A questionnaire on exacerbations during the follow-up year was distributed to all.,Univariable and multivariable logistic regression was performed to determine predictors of future exacerbations.,Three hundred and eighty patients attended the baseline examination and complete follow-up data were retrieved from 340 patients.,COPD as defined by forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC) < 0.7, was found in 132 (38.8%) patients.,One hundred and fifty-nine patients (46.8%) experienced one exacerbation or more and 101 (29.7%) two exacerbations or more.,Patients who had an exacerbation treated with antibiotics or systemic corticosteroids or leading to hospitalization the year before baseline (N = 88) had the highest risk of getting an exacerbation during the subsequent year (odds ratio 9.2), whether the FEV1/FVC was below 0.7 or not.,Increased risk of future exacerbations was also related to age ≥ 65 years and limitations in social activities, but not to the FEV1.,The study confirms that previous exacerbations strongly predict future exacerbations in patients with COPD or asthma.,Identification and a closer follow-up of patients at risk of such events could promote earlier treatment when necessary and prevent a rapid deterioration of their condition. | 1 |
Current studies of asthma history on coronavirus disease 2019 (COVID-19) outcomes are limited and lack consideration of disease status.,To conduct a population-based study to assess asthma disease status and chronic obstructive pulmonary disease (COPD) in relation to COVID-19 severity.,Patients diagnosed with COVID-19 (n = 61,338) in a large, diverse integrated health care system were identified.,Asthma/COPD history, medication use, and covariates were extracted from electronic medical records.,Asthma patients were categorized into those with and without clinical visits for asthma 12 or fewer months prior to COVID-19 diagnosis and labeled as active and inactive asthma, respectively.,Primary outcomes included COVID-19-related hospitalizations, intensive respiratory support (IRS), and intensive care unit admissions within 30 days, and mortality within 60 days after COVID-19 diagnosis.,Logistic and Cox regression were used to relate COVID-19 outcomes to asthma/COPD history.,The cohort was 53.9% female and 66% Hispanic and had a mean age of 43.9 years.,Patients with active asthma had increased odds of hospitalization, IRS, and intensive care unit admission (odds ratio 1.47-1.66; P < .05) compared with patients without asthma or COPD.,No increased risks were observed for patients with inactive asthma.,Chronic obstructive pulmonary disease was associated with increased risks of hospitalization, IRS, and mortality (odds ratio and hazard ratio 1.27-1.67; P < .05).,Among active asthma patients, those using asthma medications had greater than 25% lower odds for COVID-19 outcomes than those without medication.,Patients with asthma who required clinical care 12 or fewer months prior to COVID-19 or individuals with COPD history are at increased risk for severe COVID-19 outcomes.,Proper medication treatment for asthma may lower this risk. | Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19).,We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19.,Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system.,CRD was diagnosed based on International Classification of Diseases-10 codes.,The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization.,The secondary endpoint was death within 30 days after hospitalization.,We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020.,Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively.,Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%).,COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%).,After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization.,Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without.,Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without.,CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19. | 1 |
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD. | Eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with more frequent exacerbations, lower lung function, and corticosteroid responsiveness.,We hypothesized increased eosinophils are associated with a severe COPD phenotype, including exacerbation frequency, and tested whether blood eosinophils reliably predict sputum eosinophils.,Comprehensive baseline data on SPIROMICS subjects, recruited for a range of COPD severity for smokers with ≥20 pack year history, included demographics, questionnaires, clinical assessments, quantitative computed tomography (QCT), blood and induced sputum.,Significantly, stratification by mean sputum eosinophils ≥1·25% (N=827) was associated with reduced FEV1 % predicted (differences: 10% pre-bronchodilator, 4·7% post-bronchodilator), QCT density measures for emphysema and air trapping, and exacerbations treated with corticosteroids (p=0·002).,In contrast, stratification by mean blood eosinophils ≥200/µL (N=2499) showed that FEV1 % predicted was significant between low and high blood subgroups, but less than observed between sputum subgroups (blood eosinophil group differences: 4·2% pre-bronchodilator, 2·7% post-bronchodilator), slightly increased airway wall thickness (0·02 mm, p=0·032), greater symptoms (p=0·037), and wheezing (p=0·018), but no evidence of association with COPD exacerbations or other indices of severity.,Blood eosinophils showed weak although significant association with sputum eosinophils (ROC AUC=0·64, p<0·001), but with a high false discovery rate (72%).,Elevated sputum eosinophils, with or without blood eosinophils, were associated with lower lung function.,Elevated blood eosinophils only in combination with elevated sputum eosinophils were associated with COPD exacerbations.,Stratification of SPIROMICS subjects by blood eosinophils alone showed minimal clinical differences and no association with exacerbations, whereas stratification by sputum eosinophils was associated with larger phenotypic differences and COPD exacerbations.,Importantly, increased blood eosinophils did not reliably predict airway eosinophils in induced sputum. | 1 |
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