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Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist.,We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.,The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16 485 patients with moderate COPD who had or were at high risk of CVD.,Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta2-agonist (vilanterol (VI) 25 µg; n=4118), corticosteroid (fluticasone furoate (FF) 100 µg; n=4135) and combination therapy (FF/VI; n=4121).,Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%).,The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93, 95% CI 0.75 to 1.14).,Outcomes were similar among all subgroups.,Adverse events, including palpitations and arrhythmias, did not differ by treatment.,In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.,NCT01313676. | Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily).,The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles.,This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.,Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks).,Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately.,In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure.,Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted).,The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]).,The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group.,Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium.,Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.,This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. | 1 |
To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.,This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland.,Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016.,For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline.,We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication.,Groups were compared via ANOVA.,Data of 305 patients (62±7 years, 66% men) were analysed.,In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline.,Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines.,Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively.,Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%).,The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups.,The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement. | Clinical care components for people with COPD are recommended in guidelines if high-level evidence exists.,However, there are gaps in their implementation, and factors which act as barriers or facilitators to their uptake are not well described.,The aim of this pilot study was to explore implementation of key high-evidence COPD guideline recommendations in patients admitted to hospital with a disease exacerbation, to inform the development of a larger observational study.,This study recruited consecutive COPD patients admitted to a tertiary hospital.,Patient demographic, disease and admission characteristics were recorded.,Information about implementation of target guideline recommendations (smoking cessation, pulmonary rehabilitation referral, influenza vaccination, medication use and long-term oxygen use if hypoxaemic) was gained from medical records and patient interviews.,Interviews with hospital-based doctors examined their perspectives on recommendation implementation.,Fifteen patients (aged 76(9) years, FEV1%pred 58(15), mean(SD)) and nine doctors participated.,Referral to pulmonary rehabilitation (5/15 patients) was underutilised by comparison with other high-evidence recommendations.,Low awareness of pulmonary rehabilitation was a key barrier for patients and doctors.,Other barriers for patients were access difficulties, low perceived health benefits, and co-morbidities.,Doctors reported they tended to refer patients with severe disease and frequent hospital attendance, a finding supported by the quantitative data.,This study provides justification for a larger observational study to test the hypothesis that pulmonary rehabilitation referral is low in suitable COPD patients, and closer investigation of the reasons for this evidence-practice gap. | 1 |
This study aimed to document the perspective of patients with chronic obstructive pulmonary disease (COPD) who underwent home-based pulmonary rehabilitation (HBPR) in a clinical trial.,In this qualitative study, open-ended questions explored participants’ views regarding HBPR.,Thirteen semi-structured interviews were analysed using a thematic analysis approach.,Major themes from interviews included the positive impact of HBPR on physical fitness, breathing and mood.,Participants valued the flexibility and convenience of the programme.,Participants also highlighted the importance of social support received, both from the physiotherapist over the phone and from family and friends who encouraged their participation.,Reported challenges were difficulties in initiating exercise, lack of variety in training and physical incapability.,While most participants supported the home setting, one participant would have preferred receiving supervised exercise training at the hospital.,Participants also reported that HBPR had helped establish an exercise routine and improved their disease management.,This study suggests that people with COPD valued the convenience of HBPR, experienced positive impacts on physical fitness and symptoms and felt supported by their community and programme staff.,This highly structured HBPR model may be acceptable to some people with COPD as an alternative to centre-based pulmonary rehabilitation. | The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR.,Randomised controlled feasibility trial.,Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes.,Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date.,103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)).,Participants had to be willing to participate in either arm of the trial, have internet access and be web literate.,Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material.,Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education).,Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected.,Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated.,A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0).,However, there were no significant differences between the groups in any outcome.,Dropout rates were higher in the web-based programme (57% vs 23%).,An interactive web-based PR programme is feasible and acceptable when compared with conventional PR.,Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care.,ISRCTN03142263; Results. | 1 |
Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.,To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.,3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.,An analysis of risk of COPD was carried out using ever smoking controls (n=4784).,Associations with %predicted FEV1 were tested in cases.,We followed-up signals of interest (p<10−5) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.,Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10−6, preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10−6).,In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10−6).,We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5.,No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10−7).,This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study. | Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung.,Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways.,Bacterial variety diminishes with increasing COPD severity.,Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections.,In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD.,In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial-viral infections and related immune response in COPD phenotypes need to be better clarified.,Our paper would address these points that we consider of great importance for the clinical management of COPD. | 1 |
The medico-economic impact of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) is poorly documented.,To estimate the effectiveness and cost-effectiveness of pulmonary rehabilitation in a hypothetical cohort of COPD patients.,We used a multi-state Markov model, adopting society’s perspective.,Simulated cohorts of French GOLD stage 2 to 4 COPD patients with and without pulmonary rehabilitation were compared in terms of life expectancy, quality-adjusted life years (QALY), disease-related costs, and the incremental cost-effectiveness ratio (ICER).,Sensitivity analyses included variations of key model parameters.,At the horizon of a COPD patient’s remaining lifetime, pulmonary rehabilitation would result in mean gain of 0.8 QALY, with an over disease-related costs of 14 102 € per patient.,The ICER was 17 583 €/QALY.,Sensitivity analysis showed that pulmonary rehabilitation was cost-effective in every scenario (ICER <50 000 €/QALY).,These results should provide a useful basis for COPD pulmonary rehabilitation programs. | Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent.,This analysis evaluated the incremental cost-effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective.,A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) was used.,Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council ≥2).,Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials).,Spanish utility values were derived from a published local observational study.,Unitary health care costs (€2015) were obtained from local sources.,A 3-year time horizon was selected, and 3% discount was applied to effects and costs.,Results were expressed as cost/quality-adjusted life years (QALYs).,Univariate and probabilistic sensitivity analysis (PSA) was performed.,UMEC/VI produced additional 0.03 QALY and €590 vs TIO, leading to an ICER of €21,475/QALY.,According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of €30,000/QALY.,UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective. | 1 |
Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. | 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. | 1 |
Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | 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 |
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. | Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | 1 |
Several differences have been reported in the clinical characteristics of chronic obstructive pulmonary disease (COPD) between men and women.,Differences have been found in the association between respiratory symptoms and lung function, and in the factors associated with dyspnea.,This raises the question of whether there are differences between the sexes in the relationship between fatigue, the second most prevalent symptom, and the variables of physical capacity and disease severity.,To examine the experience of fatigue and its relationship to physical capacity and disease severity in men and women with COPD.,In a cross-sectional study 121 patients with COPD (54 men and 67 women), the experience of fatigue (frequency, duration, and severity) and physical capacity (lung function, 6-minute walk distance [6MWD], grip strength, and timed-stand test) were assessed.,Disease severity was graded according to the Body mass index, airway Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Two multiple logistic regression models were tested, both of which were performed separately in men and women, to examine the association between the experience of fatigue and variables of physical capacity and the BODE index.,Eighty-nine (73.6%) patients experienced fatigue, with similar proportions in men and women.,The men with fatigue had worse physical capacity and more severe disease than did the men without fatigue: for men with and without fatigue, respectively, the percent of predicted forced expiratory volume in 1 second (FEV1) (mean [standard deviation]) was 47 (14) vs 64 (17); the 6MWD (mean [standard deviation]) was 398 (138) vs 539 (105) m; and the BODE index (median [quartile 1-3]) was 3 (2-5) vs 1 (0-1) (P<0.01).,In women, only higher leg fatigue post-6MWD was seen among those experiencing fatigue compared with women without fatigue: for women with and without fatigue, respectively, leg fatigue (median [quartile 1-3]) was 4 (3-5) vs 2 (0-3) (P<0.001).,The regression models showed that the 6MWD and the BODE index were associated with fatigue in both men and women, but in women, leg fatigue remained an independent associate in both models.,Exercise capacity and disease severity were associated with fatigue in both men and women.,In women, leg fatigue was strongly associated with fatigue, which warrants further investigation. | Many people with COPD report difficulties falling asleep or staying asleep, insufficient sleep duration, or nonrestorative sleep.,Cognitive behavioral therapy for insomnia (CBT-I) has proved effective not only in people with primary insomnia but also in people with insomnia comorbid with psychiatric and medical illness (eg, depression, cancer, and chronic pain).,However, CBT-I has rarely been tested in those with COPD who have disease-related features that interfere with sleep and may lessen the effectiveness of such therapies.,The purpose of this study was to determine the feasibility of applying a CBT-I intervention for people with COPD and to assess the impact of CBT-I on insomnia severity and sleep-related outcomes, fatigue, mood, and daytime functioning.,The study had two phases.,In Phase 1, a 6-weekly session CBT-I intervention protocol in participants with COPD was assessed to examine feasibility and acceptability.,Phase 2 was a small trial utilizing a prospective two-group pre- and post-test design with random assignment to the six-session CBT-I or a six-session wellness education (WE) program to determine the effects of each intervention, with both interventions being provided by a nurse behavioral sleep medicine specialist.,Fourteen participants (five in Phase 1 and nine in Phase 2) completed six sessions of CBT-I and nine participants completed six sessions of WE.,Participants indicated that both interventions were acceptable.,Significant positive treatment-related effects of the CBT-I intervention were noted for insomnia severity (P = 0.000), global sleep quality (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02), fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000).,Significant positive effects were noted for depressed mood after WE (P = 0.005).,Results suggest that using CBT-I in COPD is feasible and the outcomes compare favorably with those obtained in older adults with insomnia in the context of other chronic illnesses. | 1 |
Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD.,Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents.,Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent.,The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations.,Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes.,In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs.,Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results.,In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily).,Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments.,Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed.,Overall, the safety profiles of the FDCs were similar to placebo.,Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations. | Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 1 |
Cigarette smoke (CS) induces lung cellular senescence that plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,How aging influences cellular senescence and other molecular hallmarks, and increases the risk of CS-induced damage remains unknown.,We hypothesized that aging-associated changes in lungs worsen the COPD/emphysema by CS exposure.,Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls.,CS caused a decline in lung function and affected the lung structure of both groups of mice.,No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation.,Aging per se increased lung cellular senescence and significant changes in damage-associated molecular patterns marker S100A8.,Gene transcript analysis using the nanoString nCounter showed a significant upregulation of key pro-senescence targets by CS (Mmp12, Ccl2, Cdkn2a, Tert, Wrn, and Bub1b).,Aging independently influenced lung function and structure, as well as increased susceptibility to CS-induced inflammation in emphysema, but had a negligible effect on cellular senescence.,Thus, aging solely does not contribute to the induction of cellular senescence by CS in a mouse model of COPD/emphysema. | : To verify the accordance of functional and morphometric parameters during the development of emphysema.,: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days.,Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed.,To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma.,: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema.,However, only the mean linear intercept values remained increased until the 40th day.,The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day.,The number of macrophages increased beginning on the 1st day.,The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day.,However, 8-isoprostane expression was only increased on the 1st and 3rd days.,: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics.,Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process. | 1 |
Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD).,COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments.,The differential effects of TS, BS or their combined exposure have not been well characterized yet.,This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination.,Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS.,Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups.,TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01).,Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients.,CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01).,Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05).,There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures.,The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant. | Impaired renal function is often neglected in COPD patients.,Considering that COPD patients usually have an ongoing prothrombotic state and systemic inflammation status, we investigated the association among them and explored the predictive value of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), on concealed chronic renal failure (CRF) in COPD patients.,COPD patients were recruited from the First Affiliated Hospital of Sun Yat-Sen University between January 2015 and December 2016.,Control was selected from contemporaneous hospitalized patients without COPD and matched by age and gender at a ratio of 1:1.,Estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula, and all subjects were categorized as having normal renal function (eGFR ≥60 mL min−1 1.73 m−2) and having concealed CRF (normal serum creatinine while eGFR <60 mL min−1 1.73 m−2).,Independent correlates of concealed CRF were investigated by logistic regression analysis, and receiver operating characteristic (ROC) curves were used to determine the predictive value of ADAMTS-13.,In total, 106 COPD and 106 non-COPD patients were finally recruited, and the incidences of concealed CRF were 19.81% and 7.55%, respectively.,ADAMTS-13 (odds ratio [OR] =0.858, 95% CI =0.795-0.926), D-dimer (OR =1.095, 95% CI =1.027-1.169), and C-reactive protein (OR =1.252, 95% CI =1.058-1.480) were significantly associated with concealed CRF.,Sensitivity and specificity at an ADAMTS-13 cutoff of 318.72 ng/mL were 100% and 81.2%, respectively.,The area under the ROC curve was 0.959.,Prothrombotic state and systemic inflammation status might contribute to explaining the high incidence of concealed CRF in COPD, and plasma ADAMTS-13 levels may serve as a strong predictor. | 1 |
Patients with COPD often experience severe exacerbations involving hospitalization, which accelerate lung function decline and reduce quality of life.,This study aimed to develop and validate a predictive model to identify patients at risk of developing severe COPD exacerbations using administrative claims data, to facilitate appropriate disease management programs.,A predictive model was developed using a retrospective cohort of COPD patients aged 55-89 years identified between July 1, 2010 and June 30, 2013 using Humana’s claims data.,The baseline period was 12 months postdiagnosis, and the prediction period covered months 12-24.,Patients with and without severe exacerbations in the prediction period were compared to identify characteristics associated with severe COPD exacerbations.,Models were developed using stepwise logistic regression, and a final model was chosen to optimize sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).,Of 45,722 patients, 5,317 had severe exacerbations in the prediction period.,Patients with severe exacerbations had significantly higher comorbidity burden, use of respiratory medications, and tobacco-cessation counseling compared to those without severe exacerbations in the baseline period.,The predictive model included 29 variables that were significantly associated with severe exacerbations.,The strongest predictors were prior severe exacerbations and higher Deyo-Charlson comorbidity score (OR 1.50 and 1.47, respectively).,The best-performing predictive model had an area under the curve of 0.77.,A receiver operating characteristic cutoff of 0.4 was chosen to optimize PPV, and the model had sensitivity of 17%, specificity of 98%, PPV of 48%, and NPV of 90%.,This study found that of every two patients identified by the predictive model to be at risk of severe exacerbation, one patient may have a severe exacerbation.,Once at-risk patients are identified, appropriate maintenance medication, implementation of disease-management programs, and education may prevent future exacerbations. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation.,Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation.,With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD).,In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method.,We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method.,In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography.,Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE.,sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT.,The relationship remained statistically significant after adjusting for smoking history and comorbid conditions.,In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002).,Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity.,There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls.,sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction.,Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD. | We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene.,In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers.,25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992).,Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC) in all smokers.,Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression.,Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV1 respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV1/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent.,Interestingly, several of these associations were driven by male smokers not females.,This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers.,However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers.,PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
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. | Chronic obstructive pulmonary disease (COPD), a general airway disease, is featured by progressive and chronic immunoreaction in the lung.,Increasing evidences have showed that cigarette smoking is the main reason in the COPD progression, and human pulmonary microvascular endothelial cell (HPMEC) apoptosis often be observed in COPD, while its pathogenesis is not yet fully described.,Upregulation of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) was observed in COPD patients, but the specific mechanism of lncRNA MEG3 in COPD remains unknown.,The objective of this research was to explore the role of lncRNA MEG3 in cigarette smoke extract (CSE)-induced HPMECs.,HPMECs were induced by a series of concentrations of CSE (0%, 0.1%, 1%, and 10%).,Then cell apoptosis was analyzed by flow cytometry.,Cell apoptosis related proteins were tested using western blot assay.,Finally, we applied knockdown and over-expression system to explore the lncRNA MEG3 functions in CSE-induced HPMECs.,Our results indicated that various concentrations of CSE (0%, 0.1%, 1%, and 10%) significantly promoted cell apoptosis, augmented caspase-3 activity, upregulated Bax expression, decreased Bcl-2 expression, and enhanced lncRNA MEG3 level in HPMECs.,LncRNA MEG3-plasmid transfection resulted in the upregulation of lncRNA MEG3, more apoptotic HPMECs, and higher caspase-3 activity.,While lncRNA MEG3 knockdown presented the opposite effects.,Further investigation suggested that all the effects of CSE treatment on HPMECs were markedly reversed by lncRNA MEG3-shRNA (short hairpin RNA).,Our study illustrated a protective effect of lncRNA MEG3-shRNA on CSE-induced HPMECs, indicting lncRNA MEG3 can be a new therapeutic approach for COPD treatment. | 1 |
Patients with COPD who have higher eosinophil numbers in the airways and peripheral blood demonstrate a greater clinical response to inhaled corticosteroids (ICS) [1-3].,Furthermore, the effect of the oral phosphodiesterase-4 (PDE4) inhibitor roflumilast on exacerbations in severe COPD patients with chronic bronchitis, who are treated with ICS and long-acting bronchodilators, also appears to be greater at higher blood eosinophil counts [4].,The mechanisms responsible for these differential drug effects remain to be defined, but may relate to increased type-2 inflammation and/or decreased presence of colonising airway bacteria in COPD patients with more eosinophils [5, 6], leading to different responses to anti-inflammatory drugs.,An association between blood and sputum eosinophils has been observed in some, but not all studies [7-12].,Accurate sputum eosinophil count measurement requires good quality samples to make cytospins where eosinophils can be clearly counted; variable quality of sputum samples, particularly in multicentre studies, will affect the ability to show a relationship with blood eosinophil counts.,PDE4 inhibition reduces sputum eosinophils in those COPD patients with higher eosinophil counts.,This evidence supports an effect of PDE4 inhibitors on eosinophilic inflammation.https://bit.ly/3airXw7 | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 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. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
Metabolic syndrome (MetS) is frequent in both chronic obstructive pulmonary disease (COPD) and Obstructive sleep apnea (OSA).,The aim of this study was to assess the frequency of MetS and the status of systemic inflammation in overlap syndrome.,A total of 151 consecutive COPD patients were recruited in this cross‐sectional study.,Spirometry and polysomnography were done in all patients.,The MetS was defined according to the criteria of the International Diabetes Federation.,Anthropometry, metabolic parameters and inflammatory biomarkers: IL‐6, TNF‐α, leptin, resistin and adiponectin were recorded.,OSA was present in 19.2% COPD patients.,Subjects with overlap syndrome had higher neck and waist circumference compared to those with COPD alone.,Significant differences in levels of blood pressure, lipid metabolic and glucose metabolic were found between two groups with overlap and COPD, as well as inflammatory biomarkers.,Prevalence of MetS was increased in overlap group.,Multivariate logistic regression showed that BMI, systolic BP when fall asleep and recumbent angiotens levels as significant independent predictors of the presence of Mets in overlap syndrome.,This study shows that MetS is frequent in patients with overlap.,Overlap syndrome indicates a higher cardiometabolic risk and higher levels of systemic inflammatory. | Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases.,The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid.,An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid).,The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population.,Patients were deemed to have COPD if this diagnosis appeared on their clinical histories.,Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated.,Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%).,After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity.,Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs. | 1 |
Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD).,Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection.,Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation.,However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed.,We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD.,To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors.,Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors.,Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation.,Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects.,In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72-96 h post-infection.,Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response. | There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. | 1 |
Despite known benefits, a significant proportion of patients with COPD do not complete pulmonary rehabilitation (PR).,Little is known regarding which factors promote successful completion of PR.,We analyzed data from a prospectively maintained database of subjects with COPD who attended a PR program at the University of Alabama at Birmingham, from 1996 to 2013.,Subjects were categorized as either completers or non-completers, based on successful completion of at least 8 weeks of PR.,Demographics and comorbidities were recorded.,Short Form 36 Health Survey, Beck Depression Inventory-II, and San Diego Shortness of Breath Questionnaire were administered to all participants at baseline and on completion of PR to assess participants’ perception of their health status, severity of depression, and dyspnea with performance of activities of daily living.,Univariate and multivariable analyses were performed to identify predictors of successful completion of PR.,Four hundred and forty subjects were included, of whom 229 completed PR.,Forty-one percent were female, and 17% were African American.,Compared with non-completers, completers had greater Short Form 36 Health Survey pain score, lower forced expiratory volume in the first second, and lower Beck Depression Inventory score, and included a lower percentage of current smokers.,On multivariate analysis, cigarette smoking at enrollment was associated with lower likelihood of completion of PR (adjusted odds ratio 0.38, 95% confidence interval 0.16-0.90; P=0.02).,Cigarette smoking was the sole independent predictor of PR dropout, and smoking cessation may warrant greater emphasis prior to enrollment. | The aim of this study was to examine retrospective survival in elderly chronic obstructive pulmonary disease (COPD) patients receiving three different pulmonary rehabilitation (PR) programs.,193 patients [m / f 92 / 101, mean age 69.2 (standard deviation 8.6)] receiving PR were studied with lifetable and Cox regression analyses.,Forced expiratory volume in 1 second (FEV1) % pred. was significantly different in the in-patient (n = 72), out-patient (n = 72), and maintenance group (n = 49) [mean 54.5 (21.8), 52.2 (17.7), and 42.9 (15.0), respectively (p = 0.004)].,PR days were 30.3 (20.4), 18.9 (10.4) and 30.0 (20.3), respectively (p < 0.001).,Median survival rate was nine years in the in-patient, eight years in the out-patient and seven years in the maintenance group.,Hospital stays and days were significantly increased in the maintenance group compared with the other groups (p = 0.003 and 0.010, respectively).,The impact of evaluated variables on survival in the three PR groups was significant for age, FEV1 as well as the use of long-term oxygen therapy (LTOT) (HR 1.06, for five years, p < 0.001, HR 0.98, p = 0.01, and HR 2.18, p = 0.005, respectively).,The COPD patients in the maintenance group showed a worse survival, but after correction for gender, age and severity of obstruction, the difference was not statistically significant. | 1 |
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. | Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD) by office-based pulmonary specialists.,The aim of this study was to assess their outpatient management in relation to current guideline recommendations for COPD.,A nationwide prospective cross-sectional COPD questionnaire survey in the form of a multiple-choice questionnaire was sent to 1000 office-based respiratory specialists in Germany.,The product-neutral questions focused on routine COPD management and were based on current national and international COPD guideline recommendations being consistent in severity classification and treatment recommendations.,A total of 590 pulmonary specialists (59%) participated in the survey.,Body plethysmography was considered the standard for diagnosis (65.9%), followed by spirometry (32%).,Most respondents were able to cite the correct spirometric criteria for classifying moderate (87%) to very severe COPD (77%).,A quarter of the respondents equated the World Health Organization (WHO) definition of chronic bronchitis with COPD.,Notably, most participants preferred the updated national COPD guidelines (51.4%) to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (40.2%).,Improvement of functional exercise capacity and quality of life were considered the two most relevant treatment goals; whereas impact on mortality was secondary.,Treatment of COPD largely complied with the guidelines.,However, a significant percentage of the pulmonary specialists differed in their assessment of the benefits of various therapeutic measures from evidence-based results.,Referral for pulmonary rehabilitation was uncommon, regardless of the severity of COPD.,The findings of this large national survey suggest that most pulmonary specialists adhere to the current COPD guideline recommendations in daily practice.,However, physicians’ knowledge of guidelines is not sufficient as the sole benchmark when assessing their implementation in day-to-day practice.,Necessary changes in the health care system must include more effective ways to transfer knowledge to clinical practice and to give access to interventions of proven clinical benefit. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality.,We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.,Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death.,Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits.,Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.,In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.,COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.,The online version of this article (10.1186/s12890-018-0573-0) contains supplementary material, which is available to authorized users. | Excluding the tropics, exacerbations of chronic obstructive pulmonary disease (COPD) are more frequent in winter.,However, studies that directly relate hospitalizations for exacerbation of COPD to ambient temperature are lacking.,The aim of this study was to assess the influence of temperature on the number of hospitalizations for COPD.,This was a population-based study in a metropolitan area.,All hospital discharges for acute exacerbation of COPD during 2009 in Barcelona and its metropolitan area were analyzed.,The relationship between the number of hospitalizations for COPD and the mean, minimum, and maximum temperatures alongside comorbidity, humidity, influenza rate, and environmental pollution were studied.,A total of 9,804 hospitalization discharges coded with COPD exacerbation as a primary diagnosis were included; 75.4% of cases were male with a mean age of 74.9±10.5 years and an average length of stay of 6.5±6.1 days.,The highest number of admissions (3,644 [37.2%]) occurred during winter, followed by autumn with 2,367 (24.1%), spring with 2,347 (23.9%), and summer with 1,446 (14.7%; P<0.001).,The maximum, minimum, and mean temperatures were associated similarly with the number of hospitalizations.,On average, we found that for each degree Celsius decrease in mean weekly temperature, hospital admissions increased by 5.04% (r2=0.591; P<0.001).,After adjustment for humidity, comorbidity, air pollution, and influenza-like illness, only mean temperatures retained statistical significance, with a mean increase of 4.7% in weekly admissions for each degree Celsius of temperature (r2=0.599, P<0.001).,Mean temperatures are closely and independently related to the number of hospitalizations for COPD. | 1 |
Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms.,Characterizing the imaging manifestation of exacerbations could be useful for objective diagnosis of exacerbations in the clinic and clinical trials, as well as provide a mechanism for monitoring exacerbation treatment and recovery.,In this systematic review, we employed a comprehensive search across three databases (Medline, EMBASE, Web of Science) to identify studies that performed imaging of the thorax at COPD exacerbation.,We included 51 from a total of 5,047 articles which met all our inclusion criteria.,We used an adapted version of the Modified Newcastle-Ottawa Quality Assessment Scale for cohort studies to assess the quality of the included studies.,Conclusions were weighted towards higher-quality articles.,We identified a total of 36 thoracic imaging features studied at exacerbation of COPD.,Studies were generally heterogeneous in their measurements and focus.,Nevertheless, considering studies which performed consecutive imaging at stable state and exacerbation, which scored highest for quality, we identified salient imaging biomarkers of exacerbations.,An exacerbation is characterized by airway wall and airway calibre changes, hyperinflation, pulmonary vasoconstriction and imaging features suggestive of pulmonary arterial hypertension.,Most information was gained from CT studies.,We present the first ever composite imaging signature of COPD exacerbations.,While imaging during an exacerbation is comparatively new and not comprehensively studied, it may uncover important insights into the acute pathophysiologic changes in the cardiorespiratory system during exacerbations of COPD, providing objective confirmation of events and a biomarker of recovery and treatment response. | Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function and poor outcomes for patients.,However, there are limited data on the time course of changes in forced expiratory volume in 1 s (FEV1) preceding the first reported symptom and after the start of an exacerbation.,WISDOM was a multinational, randomized, double-blind, active-controlled, 52-week study in patients with severe-to-very severe COPD.,Patients received triple therapy (long-acting muscarinic antagonist and long-acting β2-agonist/inhaled corticosteroid [ICS]) for 6 weeks, and were randomized to continue triple therapy or stepwise withdrawal of the ICS (dual bronchodilator group).,After suitable training, patients performed daily spirometry at home using a portable, battery-operated spirometer.,In the present post hoc analysis, patients who continued to perform daily home spirometry and completed at least one measurement per week for a 56-day period before and after the start of a moderate or severe exacerbation were included.,Missing values were imputed by linear interpolation (intermittent), backfilling (beginning) or carry forward (end).,Exacerbation onset was the first day of a reported symptom of exacerbation.,Eight hundred and eighty-eight patients in the WISDOM study had a moderate/severe exacerbation after the complete ICS withdrawal visit; 360 of them contributed at least one FEV1 measure per week for the 8 weeks before and after the event and are included in this analysis.,Mean daily FEV1 began to decline from approximately 2 weeks before the onset of symptoms of an exacerbation, dropping from 0.907 L (mean Days − 56 to − 36 before the exacerbation) to 0.860 L on the first day of the exacerbation.,After the exacerbation, mean FEV1 improved but did not return to pre-exacerbation levels (mean Days 36-56 after the exacerbation, 0.875 L).,The pattern of FEV1 changes around exacerbations was similar in the triple therapy and dual bronchodilator groups, and a similar pattern was seen in moderate and severe exacerbations when analysed separately.,Mean lung function starts to decline prior to the first reported symptoms of an exacerbation, and does not recover to pre-exacerbation levels 8 weeks after the event.,WISDOM (ClinicalTrials.gov number, NCT00975195).,The online version of this article (10.1186/s12931-018-0944-3) contains supplementary material, which is available to authorized users. | 1 |
Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system.,Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity.,They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases.,However, the pathological mechanism of neutrophils remains complex and obscure.,The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD), pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed.,With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis) in diseases.,We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases. | Exhaled, endogenous particles are formed from the epithelial lining fluid in small airways, where surfactant protein A (SP-A) plays an important role in pulmonary host defense.,Based on the knowledge that chronic obstructive pulmonary disease (COPD) starts in the small airway epithelium, we hypothesized that chronic inflammation modulates peripheral exhaled particle SP-A and albumin levels.,The main objective of this explorative study was to compare the SP-A and albumin contents in exhaled particles from patients with COPD and healthy subjects and to determine exhaled particle number concentrations.,Patients with stable COPD ranging from moderate to very severe (n = 13), and healthy non-smoking subjects (n = 12) were studied.,Subjects performed repeated breath maneuvers allowing for airway closure and re-opening, and exhaled particles were optically counted and collected on a membrane using the novel PExA® instrument setup.,Immunoassays were used to quantify SP-A and albumin.,COPD patients exhibited significantly lower SP-A mass content of the exhaled particles (2.7 vs.,3.9 weight percent, p = 0.036) and lower particle number concentration (p<0.0001) than healthy subjects.,Albumin mass contents were similar for both groups.,Decreased levels of SP-A may lead to impaired host defense functions of surfactant in the airways, contributing to increased susceptibility to COPD exacerbations.,SP-A in exhaled particles from small airways may represent a promising non-invasive biomarker of disease in COPD patients. | 1 |
To explore the relationship between the blood eosinophil concentrations in the early stage and mortality in critically ill patients with acute exacerbation of chronic obstructive pulmonary disease.,Patient data were extracted from the MIMIC-III V1.4 database.,Only the acute exacerbation of chronic obstructive pulmonary disease patients with the first measurement time of blood eosinophil concentrations (%) between 24 hours before admission and 24 hours after admission was included.,The logistic regression model was used to analyze the association between eosinophil and outcomes.,1019 patients were included in the study.,Two multivariate regression models were built.,The adjusted odds ratio of in-hospital mortality, in-ICU mortality, hospital length of stay and ICU length of stay for initial blood eosinophil concentrations in model 1 (adjusted for SAPS Ⅱ, cardiac arrhythmias, solid tumor, metastatic cancer, liver disease, neutrophils) were 0.792 (95% CI: 0.643-0.976, p=0.028), 0.812 (95% CI: 0.645-1.022, p=0.076), 0.847 (95% CI: 0.772-0.930, p=0.001) and 0.914 (95% CI: 0.836-1.000, p=0.049) respectively.,Meanwhile, in model 2 (adjusted for SOFA score, age, cardiac arrhythmias, solid tumor, metastatic cancer, liver disease, neutrophils) ORs were 0.785 (95% CI: 0.636-0.968, p=0.024), 0.807 (95% CI: 0.641-1.016, p=0.068), 0.854 (95% CI: 0.778-0.939, p=0.001) and 0.917 (95% CI: 0.838-1.004, p=0.060) respectively.,The area under the ROC curve for eosinophil initial was 0.608 (95% CI: 0.559-0.657).,The discriminatory eosinophil thresholds were 0.35% (sensitivity=0.59, specificity=0.61) for in-hospital mortality.,Increased blood eosinophils were associated with decreased in-hospital mortality and shorten hospital length of stay in critically ill patients with acute exacerbation of chronic obstructive pulmonary disease.,A discriminatory eosinophil threshold of 0.35% for mortality was found, but further studies were needed to verify it. | Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | 1 |
Eosinophilia may guide response to inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease (COPD).,This study aimed to determine prevalence of eosinophilia and parasitic infestations in these patients.,We conducted a prospective cohort study between February 2019 and January 2020 and screened 107 stable COPD patients.,A total of 77 subjects (84.4% men) were included.,Age was 73.8 ± 8.9 years.,Forced expiratory volume in 1 s was 66.5 ± 25.5%.,Smoking history was 25.9 ± 18 pack-years.,Comorbidities included cardiovascular disease (57.1%).,Respiratory symptoms were assessed by modified Medical Research Council dyspnea score (1.6 ± 0.8), chronic obstructive pulmonary disease Assessment Test score (9.3 ± 4.9), and 6-min walking distance (317.2 ± 135.2 m).,Patients with blood eosinophil count at least 100 cells/μL were 79.2% and at least 300 cells/μL were 33.8%.,Intestinal parasites were not found.,Significant positive correlations were found between high blood eosinophilia and some post-bronchodilator lung function parameters.,In conclusion, eosinophilic COPD was not uncommon.,No intestinal parasite was found in this population.,This study suggests that stool parasite exam might be omitted for routine practice.,Clinicaltrials.in.th Number: TCTR20191129002. | Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization and is associated with considerable mortality, for which clinicians are seeking useful and easily obtained biomarkers for prognostic evaluation.,This study aimed to determine the potential role of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as prognostic makers for hospital mortality in patients with AECOPD.,We included 303 patients with AECOPD in this retrospective study.,Clinical characteristics, NLR, PLR, and serum levels of C-reactive protein (CRP) and other data were collected.,Relationships between NLR/PLR and CRP were evaluated by Pearson’s correlation test.,Receiver operating characteristics curve and the area under the curve (AUC) were used to assess the ability of NLR and PLR to predict hospital mortality in patients with AECOPD.,Mean levels of NLR and PLR of all patients with AECOPD were 7.92±8.79 and 207.21±148.47, respectively.,NLR levels correlated with serum CRP levels (r=0.281, P<0.05).,The overall hospital mortality rate was 12.21% (37/303).,Levels of NLR and PLR were signifi-cantly higher among non-survivors compared to survivors of AECOPD (both P<0.05).,At a cut-off value of 6.24, the sensitivity and specificity of the NLR in predicting hospital mortality were 81.08% and 69.17%, respectively, with an AUC of 0.803.,At a cut-off of 182.68, the corresponding sensitivity, specificity and AUC of PLR were 64.86%, 58.27%, and 0.639.,The combination of NLR, PLR, and CRP increased the prognostic sensitivity.,NLR and PLR levels were increased in non-survivor patients with AECOPD, and the NLR may be simple and useful prognostic marker for hospital mortality in patients with AECOPD.,More studies should be carried out to confirm our findings. | 1 |
While GOLD classification has been revised, its clinical impacts on outcomes of COPD patients have not been widely evaluated in real-world cohorts.,According to 2007, 2013, and 2017 GOLD classifications, distribution and clinical characteristics of group-shifted patients and the risk of acute exacerbation were analyzed in combined Korean COPD cohorts.,Future risk for annual moderate-to-severe exacerbation was estimated as incidence rate ratio (IRR) and compared by groups.,Among 1,880 COPD patients, in GOLD 2017 classification, groups B and A were increased to 61.2% and 22.2% of total population, while group C was shrunken to 2.2% and patients with higher risk were decreased (16.6% in GOLD 2017 vs 44.7% in GOLD 2013).,The kappa coefficient of agreement of both systems was 0.581 (agreement 71.7%).,Groups B and D showed higher IRR of moderate-to-severe exacerbation than group A (IRR 2.4 and 5.3 respectively, P<0.001), whereas group C was not different from group A.,When groups C and D were combined, the IRR for acute exacerbation for each group showed good linear trends (2.5 [1.6-3.7] for group B and 4.8 [3.0-7.7] for combined group [C+D], P<0.001).,In the revised GOLD 2017 system, COPD patients with higher risk were much decreased in Korean cohorts, and group C was negligible in size and clinical impacts on expecting future exacerbation.,Serial increase in the risk for exacerbation was more concrete and predictable when group C was combined with group D. | Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency.,We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations.,We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD.,Exacerbation frequency was observed for the previous year and for the following year.,Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1-4).,Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year.,The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54-6.97).,COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50-9.93).,However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75-5.82).,Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients.,Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year. | 1 |
Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA® dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo.,Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast.,A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler.,Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only).,Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6-136.9 L/min), pressure drops (1.2-13.8 kPa), and inhaled volumes through the inhaler (0.7-4.2L).,DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed.,Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy.,Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy.,Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency. | Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD).,However, their bronchodilating effect has not yet been compared in the central and distal airways.,Functional imaging using computational fluid dynamics offers the possibility of making such a comparison.,The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.,Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments.,Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging.,Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.,Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product.,On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways.,Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient.,Salbutamol was more effective in the other patients.,This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics. | 1 |
Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies.,The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses.,FULFIL co-primary endpoint data have been previously reported.,FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β2-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations.,A subset participated for 52 weeks.,Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD™ (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.,FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period.,FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR.,At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).,These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR.,The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.,ClinicalTrials.gov number: NCT02345161.,GSK.,The online version of this article (10.1007/s12325-017-0650-4) contains supplementary material, which is available to authorized users. | Even with the dissemination of several clinical guidelines, chronic obstructive pulmonary disease (COPD) remains underdiagnosed and mismanaged by many primary care physicians (PCPs).,The objective of this study was to elucidate barriers to consistent implementation of COPD guidelines.,A cross-sectional study implemented in July 2008 was designed to assess attitudes and barriers to COPD guideline usage.,Five hundred US PCPs (309 family medicine physicians, 191 internists) were included in the analysis.,Overall, 23.6% of the surveyed PCPs reported adherence to spirometry guidelines over 90% of the time; 25.8% reported adherence to guidelines related to long-acting bronchodilator (LABD) use in COPD patients.,In general, physicians were only somewhat familiar with COPD guidelines, and internal medicine physicians were significantly more familiar than family physicians (P < 0.05).,In a multivariate model controlling for demographics and barriers to guideline adherence, we found significant associations with two tested guideline components.,Adherence to spirometry guidelines was associated with agreement with guidelines, confidence in interpreting data, ambivalence to outcome expectancy, and ability to incorporate spirometry into patient flow.,Adherence to LABD therapy guidelines was associated with agreement with guidelines and confidence in gauging pharmacologic response.,Adherence to guideline recommendations of spirometry use was predicted by agreement with the recommendations, self-efficacy, perceived outcome expectancy if recommendations were adhered to, and resource availability.,Adherence to recommendations of LABD use was predicted by agreement with guideline recommendations and self-efficacy.,Increasing guideline familiarity alone may have limited patient outcomes, as other barriers, such as low confidence and outcome expectancy, are more likely to impact guideline adherence. | 1 |
COPD is a disease associated with significant economic burden.,It was reported that Global initiative for chronic Obstructive Lung Disease (GOLD) guideline-oriented pharmacotherapy improves airflow limitation and reduces health care costs.,However, several studies showed a significant dissociation between international recommendations and clinicians’ practices.,The consequent reduced diagnostic and therapeutic inappropriateness has proved to be associated with an increase in costs and a waste of economic resources in the health sector.,The aim of the study was to evaluate COPD management in the Puglia region.,The study was performed in collaboration with the pulmonology centers and the Regional Health Agency (AReS Puglia).,An IT platform allowed the pulmonologists to enter data via the Internet.,All COPD patients who visited a pneumological outpatient clinic for the first time or for regular follow-ups or were admitted to a pneumological department for an exacerbation were considered eligible for the study.,COPD’s diagnosis was confirmed by a pulmonologist at the moment of the visit.,The project lasted 18 months and involved 17 centers located in the Puglia region.,Six hundred ninety-three patients were enrolled, evenly distributed throughout the region.,The mean age was 71±9 years, and 85% of them were males.,Approximately 23% were current smokers, 63% former smokers and 13.5% never smokers.,The mean post-bronchodilator forced expiratory volume in 1 second was 59%±20% predicted.,The platform allowed the classification of patients according to the GOLD guidelines (Group A: 20.6%, Group B: 32.3%, Group C: 5.9% and Group D: 39.2%), assessed the presence and severity of exacerbations (20% of the patients had an exacerbation defined as mild [13%], moderate [37%] and severe [49%]) and evaluated the appropriateness of inhalation therapy at the time of the visit.,Forty-nine percent of Group A patients were following inappropriate therapy; in Group B, 45.8% were following a therapy in contrast with the guidelines.,Among Group C patients, 41.46% resulted in triple combination therapy, whilê14% of Group D patients did not have a therapy or were following an inappropriate therapy.,In conclusion, 30% of all patients evaluated had been following an inadequate therapy.,Subsequently, an online survey was developed to inquire about the reasons for the results obtained.,In particular, we investigated the reasons why 30% of our population did not follow the therapy suggested by the GOLD guidelines: 1) why was there an excessive use of inhaled corticosteroids, 2) why a significantly high percentage was inappropriately treated with triple therapy and 3) why a consistent percentage (11%) of Group D patients were not treated at all.,The data provides an overview on the management of COPD in the region of Puglia (Italy) and represents a resource in order to improve appropriateness and reduce the waste of health resources. | In Tunisia, there is a paucity of population-based data on Chronic Obstructive Pulmonary Disease (COPD) prevalence.,To address this problem, we estimated the prevalence of COPD following the Burden of Lung Disease Initiative.,We surveyed 807 adults aged 40+ years and have collected information on respiratory history and symptoms, risk factors for COPD and quality of life.,Post-bronchodilator spirometry was performed and COPD and its stages were defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,Six hundred and sixty one (661) subjects were included in the final analysis.,The prevalence of GOLD Stage I and II or higher COPD were 7.8% and 4.2%, respectively (Lower Limit of Normal modified stage I and II or higher COPD prevalence were 5.3% and 3.8%, respectively).,COPD was more common in subjects aged 70+ years and in those with a BMI < 20 kg/m2.,Prevalence of stage I+ COPD was 2.3% in <10 pack years smoked and 16.1% in 20+ pack years smoked.,Only 3.5% of participants reported doctor-diagnosed COPD.,In this Tunisian population, the prevalence of COPD is higher than reported before and higher than self-reported doctor-diagnosed COPD.,In subjects with COPD, age is a much more powerful predictor of lung function than smoking. | 1 |
Whereas nutrition deficits are recognized as an expression of systemic inflammation in the elderly with diagnosed chronic obstructive pulmonary disease (COPD), if they occur in symptomatic elderly smokers, unfulfilled COPD criteria are not confirmed.,Respiratory function, anthropometry assessment, and diet intake evaluation of 13 COPD patients (COPD group), ten symptomatic elderly smokers (SYSM group), and 27 healthy volunteers (control group) were compared.,All were 70 years old or older.,The SYSM group had lower body weight, body mass index, percentage ideal body weight, body fat percentage, arm muscle circumference, tricep skin fold thickness, serum albumin, prealbumin, and transferrin than the control group and were similar to the COPD group (P < 0.05 each and nonsignificant each).,Resting energy expenditure was no different among the groups.,Intake of energy, vitamins (A, B1, B2, and C), calcium, iron, fiber, and sodium was also lower in the SYSM group than in the control group (P < 0.05 all) and was similar to the COPD group.,Elderly smokers who are symptomatic but who do not fulfill the COPD diagnostic criteria have nutritional deficits related to insufficient energy intake that are similar to those seen in COPD patients. | Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease.,However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD).,This is a post-hoc analysis of a study which enrolled a population of adults aged 35-79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000.,In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels.,We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia.,To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures.,In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs.,49.2 (SD 9.1); p < 0.0001].,Among patients with COPD (n = 495) the PF scores (39.9 vs.,45.4) and the PCS (41.9 vs.,45.9) were significantly lower in individuals with anemia compared to those without.,In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003).,There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD.,In patients with moderate to very severe COPD anemia may be associated with worse HRQL.,However, co-morbidities may explain part or all of this association in these patients. | 1 |
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders.,Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality.,Systemic inflammation appears to be a major factor linking COPD to metabolic alterations.,Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as “adipokines”, involved in various processes such as metabolism, immunity and inflammation.,There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology.,Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease.,Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium.,This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders. | Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking.,Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress.,Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD.,There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients.,Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema.,Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung.,Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema.,In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed.,The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema. | 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. | A decrease in bone mineral density (BMD) is a systemic consequence of chronic obstructive pulmonary disease (COPD).,Past reports have rarely examined any correlation between sarcopenia and BMD.,We investigated the relationship cross-sectionally between the presence of sarcopenia and BMD reduction in COPD patients.,COPD patients aged 50 or older with qualifying spirometry and dual-energy X-ray absorptiometry data were from participants in the Korean National Health and Nutrition Examination Surveys IV and V (2008-2011).,There were 286 (33.3%) subjects in the sarcopenia group and 572 (66.7%) in the non-sarcopenia group.,The sarcopenia group had lower T-scores than the non-sarcopenia group (femur: -0.73±0.88 vs. -0.18±0.97, p < 0.001; femur neck: -1.44±0.98 vs. -0.99±1.06, p < 0.001; lumbar: -1.38±1.36 vs. -0.84±1.38, p < 0.001).,The prevalences of osteopenia and osteoporosis were 60.8% and 22.0%, respectively, in the sarcopenia group and 45.6% and 13.3% in the non-sarcopenia group (both p < 0.001).,After adjusting for multiple variables, the presence of sarcopenia associated with increased the risk of osteopenia, osteoporosis, and a low BMD (OR = 3.227, 95% CI = 2.125-4.899, p < 0.001, OR = 6.952, 95% CI = 3.418-14.139, p < 0.001, and OR = 3.495, 95% CI = 2.315-5.278, p < 0.001, respectively).,In a subgroup analysis, similar OR changes were confirmed in the high-body-weight group (n = 493) (OR = 2.248, 95% CI = 1.084-4.665, p = 0.030, OR = 4.621, 95% CI = 1.167-18.291, p = 0.029, and OR = 2.376, 95% CI = 1.158-4.877, p = 0.018, respectively).,The presence of sarcopenia was associated with increased the risk for decreased BMD in COPD. | 1 |
This study was conducted in order to investigate the differences in the respiratory physiology of patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), and asthma with airflow limitation (asthma FL+).,The medical records for a series of all stable patients with persistent airflow limitation due to COPD, ACOS, or asthma were retrospectively reviewed and divided into the COPD group (n=118), the ACOS group (n=32), and the asthma FL+ group (n=27).,All the patients underwent chest high-resolution computed tomography (HRCT) and pulmonary function tests, including respiratory impedance.,The low attenuation area score on chest HRCT was significantly higher in the COPD group than in the ACOS group (9.52±0.76 vs 5.09±1.16, P<0.01).,The prevalence of bronchial wall thickening on chest HRCT was significantly higher in the asthma FL+ group than in the COPD group (55.6% vs 25.0%, P<0.01).,In pulmonary function, forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate were significantly higher in the asthma FL+ group than in the ACOS group (76.28%±2.54% predicted vs 63.43%±3.22% predicted, P<0.05 and 74.40%±3.16% predicted vs 61.08%±3.54% predicted, P<0.05, respectively).,Although residual volume was significantly lower in the asthma FL+ group than in the COPD group (112.05%±4.34% predicted vs 137.38%±3.43% predicted, P<0.01) and the ACOS group (112.05%±4.34% predicted vs148.46%±6.25% predicted, P<0.01), there were no significant differences in functional residual capacity or total lung capacity.,The increase in FEV1 in response to short-acting β2-agonists was significantly greater in the ACOS group than in the COPD group (229±29 mL vs 72±10 mL, P<0.01) and the asthma FL+ group (229±29 mL vs 153±21 mL, P<0.05).,Regarding respiratory impedance, resistance at 5 Hz and resistance at 20 Hz, which are oscillatory parameters of respiratory resistance, were significantly higher in the asthma FL+ group than in the COPD group at the whole-breath (4.29±0.30 cmH2O/L/s vs 3.41±0.14 cmH2O/L/s, P<0.01 and 3.50±0.24 cmH2O/L/s vs 2.68±0.10 cmH2O/L/s, P<0.01, respectively), expiratory, and inspiratory phases.,Although persistent airflow limitation occurs in patients with COPD, ACOS, and asthma FL+, they may have distinct characteristics of the respiratory physiology and different responsiveness to bronchodilators. | Objectives: To understand the key characteristics of Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS) and to identify evidence gaps relating to the identification, treatment and management of ACOS patients.,Methods: A structured literature review and 1-hour telephone interviews with specialist respiratory physicians were conducted (n=10; China, France, Germany, Japan and the USA).,Results: All 10 physicians used the term ACOS in clinical practice.,ACOS was not clearly defined in the literature.,Prevalence of ACOS among adult patients with COPD or asthma ranged from 12-55%.,ACOS patients had severe disease, with increased exacerbations and hospitalisations compared to some asthma and COPD patients.,ACOS represented a clinical challenge due to a lack of evidence-based guidelines distinguishing between asthma, COPD and ACOS.,Published data quantifying ACOS costs were limited.,Conclusions: There is a need for consensus evidence-based guidance to facilitate earlier diagnosis and to optimise the management of ACOS patients. | 1 |
CD8+ T-lymphocytes, natural killer T-like cells (NKT-like cells, CD56+CD3+) and natural killer cells (NK cells, CD56+CD3−) are the three main classes of human killer cells and they are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Activation of these cells can initiate immune responses by virtue of their production of inflammatory cytokines and chemokines that cause lung tissue damage, mucus hypersecretion and emphysema.,The objective of the current study was to investigate the activation levels of human killer cells in healthy non-smokers, healthy smokers, ex-smokers with COPD and current smokers with COPD, in both peripheral blood and induced sputum.,After informed consent, 124 participants were recruited into the study and peripheral blood or induced sputum was taken.,The activation states and receptor expression of killer cells were measured by flow cytometry.,In peripheral blood, current smokers, regardless of disease state, have the highest proportion of activated CD8+ T-lymphocytes, NKT-like cells and NK cells compared with ex-smokers with COPD and healthy non-smokers.,Furthermore, CD8+ T-lymphocyte and NK cell activation is positively correlated with the number of cigarettes currently smoked.,Conversely, in induced sputum, the proportion of activated killer cells was related to disease state rather than current smoking status, with current and ex-smokers with COPD having significantly higher rates of activation than healthy smokers and healthy non-smokers.,A differential effect in systemic and lung activation of killer cells in COPD is evident.,Systemic activation appears to be related to current smoking whereas lung activation is related to the presence or absence of COPD, irrespective of current smoking status.,These findings suggest that modulating killer cell activation may be a new target for the treatment of COPD. | Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies.,In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.,An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls.,Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique.,By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.,By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera.,The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values.,By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.,The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features.,The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD. | 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. | To determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers.,Of the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival.,Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system.,Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of −950 HU or less) (LAA-950).,Median duration of follow-up was 7.4 years.,Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1).,Observer agreement in visual scoring was good (weighted κ values, 0.71-0.80).,There were 519 deaths in the study cohort.,Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001).,This increased mortality generally persisted after adjusting for LAA-950.,The visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema.,Online supplemental material is available for this article. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are natural events in the progression of the disease, and are characterised by acute worsening of symptoms, especially dyspnoea.,These heterogeneous events follow increased airway inflammation, often due to infection, and lead to decreased airflow and increased lung hyperinflation relative to stable COPD.,Although exacerbation frequency generally increases as COPD progresses, some patients experience frequent exacerbations (≥2 per year) independently of disease severity.,Exacerbations, especially frequent exacerbations, are associated with impaired health-related quality of life, reduced physical activity and poor disease prognosis.,The cornerstone of pharmacotherapy for stable COPD is long-acting bronchodilators, including the long-acting β2-agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs) alone or combined with inhaled corticosteroids (ICS).,While ICS treatment can potentially reduce the risk of exacerbations, clinical studies have demonstrated the efficacy of LABAs and LAMAs in reducing COPD symptoms, primarily by reducing lung hyperinflation secondary to reduced airway resistance.,Sustained reduction in lung hyperinflation may in turn lessen dyspnoea during an exacerbation.,Indeed, recent studies suggest that bronchodilators may also reduce the incidence of, or prevent, exacerbations.,Using data from recent studies, this review explores the evidence and possible mechanisms through which bronchodilators may prevent exacerbations. | 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 |
Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).,To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.,In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg).,Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.,In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD.,Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients.,In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals −46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD.,However, FRI endpoints remained unchanged.,We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group.,We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD. | Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response.,Wnt/β‐catenin and AMP‐activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury.,However, it remains elusive whether Wnt/β‐catenin and AMPK modulate nuclear factor erythroid‐2 related factor‐2 (Nrf2)‐mediated protective responses during the development of emphysema.,Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase‐induced airspace enlargement and cigarette smoke extract (CSE)‐induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway.,Interestingly, these effects of LiCl were not observed in Nrf2−/− mice exposed to elastase.,In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up‐regulated, whereas Wnt3a knockdown further down‐regulated the levels of Nrf2 and its target proteins heme oxygenase‐1 (HO‐1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment.,In contrast, Nrf2 deficiency did not have any effects on Wnt/β‐catenin pathway in mouse lungs and NHBE cells.,Both elastase and CSE exposures reduced AMPK phosphorylation.,A specific AMPK activator metformin increased Wnt3a, β‐catenin, Nrf2 phosphorylation and activation but reduced the levels of IL‐6 and IL‐8 in NHBE cells and mouse lungs exposed to CSE.,Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE‐induced increase in IL‐6 and IL‐8 in NHBE cells.,In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β‐catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema.,These findings provide potential therapeutic targets for the intervention of COPD/emphysema. | 1 |
Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.,The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation.,A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007.,Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication.,Multivariable negative binomial regression was performed with adjustment for potential confounding factors.,The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.,We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications.,COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group.,In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81-0.92).,Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD. | Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | 1 |
Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial.,Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD.,We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD.,Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies.,Publication bias was assessed using a funnel plot.,Our search identified nine retrospective cohort studies that met the study inclusion criteria.,The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%).,The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality.,Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded.,The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials. | The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades.,However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.,We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies.,Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD.,In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.,22 studies comprising 21,150 participants were included in this analysis.,Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality.,We further performed a baseline risk-adjusted analysis and obtained statistically similar results.,Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality.,However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies. | 1 |
Pulmonary rehabilitation is a highly effective treatment for people with chronic lung disease but remains underused across the world.,Recent years have seen the emergence of new program models that aim to improve access and uptake, including telerehabilitation and low-cost, home-based models.,This workshop was convened to achieve consensus on the essential components of pulmonary rehabilitation and to identify requirements for successful implementation of emerging program models.,A Delphi process involving experts from across the world identified 13 essential components of pulmonary rehabilitation that must be delivered in any program model, encompassing patient assessment, program content, method of delivery, and quality assurance, as well as 27 desirable components.,Only those models of pulmonary rehabilitation that have been tested in clinical trials are currently considered as ready for implementation.,The characteristics of patients most likely to succeed in each program model are not yet known, and research is needed in this area.,Health professionals should use clinical judgment to determine those patients who are best served by a center-based, multidisciplinary rehabilitation program.,A comprehensive patient assessment is critical for personalization of pulmonary rehabilitation and for effectively addressing individual patient goals.,Robust quality-assurance processes are important to ensure that any pulmonary rehabilitation service delivers optimal outcomes for patients and health services.,Workforce capacity-building and training should consider the skills necessary for emerging models, many of which are delivered remotely.,The success of all pulmonary rehabilitation models will be judged on whether the essential components are delivered and on whether the expected patient outcomes, including improved exercise capacity, reduced dyspnea, enhanced health-related quality of life, and reduced hospital admissions, are achieved. | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
COPD affects over 13 million Americans, and accounts for over half a million hospitalizations annually.,The Hospital Readmission Reduction Program, established by the Affordable Care Act requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals with excess readmissions for COPD as of 2015.,This study sought to develop a predictive readmission scale to identify COPD patients at higher readmission risk.,Demographic and clinical data on 339,389 patients from New York and California (derivation cohort) and 258,113 patients from Washington and Florida (validation cohort) were abstracted from the State Inpatient Database (2006-2011), and the Readmission After COPD Exacerbation (RACE) Scale was developed to predict 30-day readmission risk.,Thirty-day COPD readmission rates were 7.54% for the derivation cohort and 6.70% for the validation cohort.,Factors including age 40-65 years (odds ratio [OR] 1.17; 95% CI, 1.12-1.21), male gender (OR 1.16; 95% CI, 1.13-1.19), African American (OR 1.11; 95% CI, 1.06-1.16), 1st income quartile (OR 1.10; 95% CI, 1.06-1.15), 2nd income quartile (OR 1.06; 95% CI, 1.02-1.10), Medicaid insured (OR 1.83; 95% CI, 1.73-1.93), Medicare insured (OR 1.45; 95% CI, 1.38-1.52), anemia (OR 1.05; 95% CI, 1.02-1.09), congestive heart failure (OR 1.06; 95% CI, 1.02-1.09), depression (OR 1.18; 95% CI, 1.14-1.23), drug abuse (OR 1.17; 95% CI, 1.09-1.25), and psychoses (OR 1.19; 95% CI, 1.13-1.25) were independently associated with increased readmission rates, P<0.01.,When the devised RACE scale was applied to both cohorts together, it explained 92.3% of readmission variability.,The RACE Scale reliably predicts an individual patient’s 30-day COPD readmission risk based on specific factors present at initial admission.,By identifying these patients at high risk of readmission with the RACE Scale, patient-specific readmission-reduction strategies can be implemented to improve patient care as well as reduce readmissions and health care expenditures. | Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED).,Such information could help stratify these patients and guide medical decision-making.,The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit.,This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals.,Recruitment started in June 2008 and ended in September 2010.,Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up.,Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit.,Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample.,The score was compared with other published prediction rules for patients with stable COPD.,In total, 2,487 patients were included in the study.,Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85).,Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model.,The same variables were predictors of death at 1 month (AUC = 0.85).,Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better.,Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process. | 1 |
Nuclear factor E2-related factor 2 (Nrf2) is involved in oxidative stress and lung inflammation and regulates the etiology of chronic obstructive pulmonary disease (COPD).,Ferroptosis is characterized by the accumulation of lipid reactive oxygen species (ROS) via ferrous ion-dependent Fenton reactions and is involved in COPD.,However, the role of Nrf2 in ferroptosis and its epigenetic regulation in the pathogenesis of COPD remain unclear.,Ferroptosis was detected by 4-HNE, MDA, C11BODIPY, DCFH-DA, Peals’ staining and CCK-8 assays. qPCR and Western blotting were performed to examine the Nrf2 levels in peripheral lung tissues, primary epithelial cells collected from patients with COPD and subjects with normal pulmonary function (never-smoker [control-NS]; smoker [control-S]), and cigarette smoke extract (CSE)-treated human bronchial epithelial (HBE) cells.,ELISA was used to quantify IL-8 and IL-1β levels.,Methylation of the Nrf2 promoter was analyzed by bisulfite sequencing and pyrosequencing.,Ferroptosis was involved in COPD and glutathione peroxidase 4 (GPX4) expression was downregulated in the COPD group.,Reactive oxygen species (ROS), lipid peroxides and MDA were increased, but GPX4 and SOD were exhausted in CSE-treated HBE cells.,The production of IL-1β and IL-8 was promoted in HBE cells in response to CSE but could be reversed by the ferroptosis inhibitor fer-1.,The Nrf2 level was significantly decreased in the COPD group compared with the control-S and control-NS groups.,Increased Nrf2 expression enhanced GPX4 and SOD levels and inhibited ferroptosis and proinflammatory cytokines in the supernatant.,Inhibition of GPX4 reversed the effect of Nrf2 overexpression and promoted ferroptosis.,Two specific CpG sites within the Nrf2 promoter were hypermethylated in the COPD group.,Similarly, CSE-treated HBE cells exhibited hypermethylation of the Nrf2 gene.,Nrf2 expression was downregulated in the lungs of COPD patients due to hypermethylation of the Nrf2 promoter, inhibiting Nrf2/GPX4 and ferroptosis, which is related to the initiation and progression of COPD.,Targeting Nrf2/GPX4 may inhibit ferroptosis, which could provide strategies to delay or treat COPD. | Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic particles, such as coal fly ash (CFA), diesel-exhaust particle (DEP), and cigarette smoke (CS), leading to chronic bronchitis, mucus production, and a subsequent lung dysfunction.,This study, using a mouse model of COPD, aimed to evaluate the effect of herbal combinational medication of Glycyrrhiza glabra (GG), Agastache rugosa (AR) containing glycyrrhizic acid (GA), and tilianin (TN) as active ingredients.,GA, a major active component of GG, possesses a range of pharmacological and biological activities including anti-inflammatory, anti-allergic, anti-oxidative.,TN is a major flavonoid that is present in AR.,It has been reported to have anti-inflammatory effects of potential utility as an anti-COPD agent.,The COPD in the mice model was induced by a challenge with CFA and DEP.,BALB/c mice received CFA and DEP alternately three times for 2 weeks to induce COPD.,The herbal mixture of GG, AR, and TN significantly decreased the number of neutrophils in the lungs and bronchoalveolar lavage (BAL) fluid.,It also significantly reduced the production of C-X-C motif chemokine ligand 2 (CXCL-2), IL-17A, CXCL-1, TNF-α, symmetric dimethylarginine (SDMA) in BALF and CXCL-2, IL-17A, CXCL-1, MUC5AC, transient receptor potential vanilloid-1 (TRPV1), IL-6, COX-2, NOS-II, and TNF-α mRNA expression in the lung tissue.,Notably, a combination of GG and AR was more effective at regulating such therapeutic targets than GG or AR alone.,The histolopathological lung injury was alleviated by treatment with the herbal mixture and their active ingredients (especially TN).,In this study, the herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway.,Therefore, a herbal mixture of GG and AR may be a potential therapeutic agent to treat COPD. | 1 |
Ensifentrine is an inhaled dual inhibitor of phosphodiesterase (PDE) 3 and 4 that has shown bronchodilatory effects and symptom improvement in clinical studies in patients with chronic obstructive pulmonary disease (COPD), and anti-inflammatory effects in healthy volunteers in a model of COPD-like inflammation.,This manuscript reports on the results of the clinical study examining if ensifentrine provides meaningful improvements in lung function when added on to tiotropium over 4 weeks in patients with COPD who have impaired lung function and symptoms despite treatment with tiotropium.,This randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study recruited patients with moderate-to-severe COPD.,Patients were randomized to open-label tiotropium once daily (QD) plus (+) blinded escalating doses of ensifentrine or placebo twice daily (BID).,Effects on lung function, symptoms and quality of life (QoL) were assessed over 4 weeks.,A total of 416 COPD patients were randomized and 413 received at least one dose of blinded study medication + tiotropium.,All ensifentrine doses produced a significant and dose-dependent increase in peak forced expiratory volume in 1 second (FEV1) from baseline to Week 4, with placebo-corrected differences of 77.5 mL when added to tiotropium (0.375 mg; 95% CI: 4.8, 150.1 mL; p=0.037) to 124.2 mL (3 mg; 95% CI: 51.0, 196.8 mL; p<0.001).,A significant increase in average FEV1 (0-12h) was shown at Week 4 with the 3 mg dose (87.3 mL; 95% CI: 20.0, 154.5 mL; p=0.011).,Clinically meaningful and statistically significant improvements in the St.,George’s Respiratory Questionnaire - COPD (SGRQ-C) additive to tiotropium were observed at Week 4, exceeding the minimally clinically important difference of 4 units with the 1.5 and 3 mg doses.,Adverse events were similar in frequency between the ensifentrine and placebo arms.,This clinical study demonstrated that nebulized ensifentrine added on to tiotropium produced clinically important improvements in lung function and QoL over 4 weeks in COPD patients receiving tiotropium who demonstrated symptoms and lung function impairment, with a safety profile similar to placebo. | We investigated the short-term bronchodilator effects of RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined with other bronchodilators in chronic obstructive pulmonary disease patients with reversibility (>150 mL to short-acting bronchodilators).,Study 1 was a six-way, placebo-controlled crossover study (n=36) with single doses of RPL554 (6 mg), salbutamol (200 µg), ipratropium (40 µg), RPL554 (6 mg)+salbutamol (200 µg), RPL554 (6 mg)+ipratropium (40 µg) or placebo.,Study 2 was a three-way crossover study (n=30) of tiotropium (18 µg) combined with RPL554 (1.5 or 6 mg) or placebo for 3 days.,Forced expiratory volume in 1 s (FEV1), lung volumes and specific airway conductance (sGaw) were measured.,In study 1, peak FEV1 change compared with placebo was similar with RPL554, ipratropium and salbutamol (mean 223, 199 and 187 mL, respectively).,The peak FEV1 was higher for RPL554+ipratropium versus ipratropium (mean difference 94 mL; p<0.0001) and RPL554+salbutamol versus salbutamol (mean difference 108 mL; p<0.0001).,In study 2 (day 3), both RPL554 doses caused greater peak FEV1 effects than placebo.,The average FEV1(0-12 h) increase was greater with RPL554 6 mg only versus placebo (mean difference 65 mL; p=0.0009).,In both studies, lung volumes and sGaw showed greater RPL554 combination treatment effects versus monotherapy.,RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.,The dual PDE3 and PDE4 inhibitor RPL554 causes additional bronchodilation when combined with commonly used short- or long-acting bronchodilatorshttp://ow.ly/CUYi30lDcYW | 1 |
Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations.,Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations.,Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status.,ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone.,The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma-COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.,Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed.,Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness.,The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids.,The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity.,ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used.,In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms.,Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment. | The fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).,This 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD.,The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin −50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84.,Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St.,George’s Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.,Trough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) −29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND.,The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference −23 mL; 95 % CI −54 to 8 mL).,The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores.,The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.,UMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.,ClinicalTrials.gov study ID NCT02257385; GSK study no.,116961.,The online version of this article (doi:10.1007/s40268-016-0131-2) contains supplementary material, which is available to authorized users. | 1 |
Targeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD).,In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.,Enzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles.,Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles.,MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets.,Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.,The tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings.,Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge.,No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur.,However, further confirmatory studies are required to conclusively establish this observation.,Coupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI. | 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. | 1 |
Supplemental Digital Content is available in the text,Presently, there is no recommendation on how to assess functional status of chronic obstructive pulmonary disease (COPD) patients.,This study aimed to summarize and systematically evaluate these measures.,Studies on measures of COPD patients’ functional status published before the end of January 2015 were included using a search filters in PubMed and Web of Science, screening reference lists of all included studies, and cross-checking against some relevant reviews.,After title, abstract, and main text screening, the remaining was appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) 4-point checklist.,All measures from these studies were rated according to best-evidence synthesis and the best-rated measures were selected.,A total of 6447 records were found and 102 studies were reviewed, suggesting 44 performance-based measures and 14 patient-reported measures.,The majority of the studies focused on internal consistency, reliability, and hypothesis testing, but only 21% of them employed good or excellent methodology.,Their common weaknesses include lack of checks for unidimensionality, inadequate sample sizes, no prior hypotheses, and improper methods.,On average, patient-reported measures perform better than performance-based measures.,The best-rated patient-reported measures are functional performance inventory (FPI), functional performance inventory short form (FPI-SF), living with COPD questionnaire (LCOPD), COPD activity rating scale (CARS), University of Cincinnati dyspnea questionnaire (UCDQ), shortness of breath with daily activities (SOBDA), and short-form pulmonary functional status scale (PFSS-11), and the best-rated performance-based measures are exercise testing: 6-minute walk test (6MWT), endurance treadmill test, and usual 4-meter gait speed (usual 4MGS).,Further research is needed to evaluate the reliability and validity of performance-based measures since present studies failed to provide convincing evidence.,FPI, FPI-SF, LCOPD, CARS, UCDQ, SOBDA, PFSS-11, 6MWT, endurance treadmill test, and usual 4MGS performed well and are preferable to assess functional status of COPD patients. | Muscle dysfunction represents a pathophysiological feature of chronic obstructive pulmonary disease (COPD).,Muscle impairment contributes to decreased effort capacity in these patients at least in the same proportion as pulmonary function limitation.,Maximal inspiratory pressure (MIP) is a reliable, noninvasive parameter for assessing the respiratory muscle capacity.,The aim of the present study was to determine the role of MIP in effort capacity decrease in COPD patients.,MIP was measured in 121 COPD patients without hyperinflation (RV < 150%) together with the following investigations: body plethysmography, body impedance analysis, dynamometry, 6-minute walking test (6MWT), determination of SaO2 and serum levels of highly sensitive C-reactive protein (hsCRP).,MIP (kPa) was significantly decreased in moderate-severe stages (6.19 ± 2.42, COPD II; 5.35 ± 2.49, COPD III; 4.56 ± 1.98, COPD IV vs 7.90 ± 2.61 in controls, P < 0.001), whereas the muscle force assessed by dynamometry was decreased only in advanced stages of disease (0.47 ± 0.12, COPD III; 0.41 ± 0.07, COPD IV vs 0.71 ± 0.16 in controls, P < 0.001).,The values of MIP correlated (r = 0.53, P = 0.0003) with the distance walked in 6MWT.,MIP may provide additive information concerning the general profile of muscle dysfunction in COPD patients. | 1 |
Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results.,Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.,Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years.,Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.,Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB−) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB+).,CB+ subjects were older, more frequently current smokers and had more pack-years than CB− subjects.,During a median 6.5 years of follow-up, CB+ subjects had greater decline in lung function (−38 mL·year−1, 95% CI −61.7-−14.6; p=0.024).,CB+ subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001).,In females, survival was significantly worse in CB+ subjects compared to CB− subjects.,Regarding cause-specific mortality, CB+ subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).,COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.,Chronic bronchitis increases the risk of exacerbations and mortality among patients with COPDhttp://ow.ly/o1fq30bFf9Q | Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality.,Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone.,To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach.,Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database.,Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used.,169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2).,20.1% died; mean survival was 115.4 months.,Age (HR = 1.098, 95% Cl = 1.04-1.252) and emphysema score (HR = 1.034, 95% CI = 1.007-1.07) were the only independent predictors of mortality.,Pulmonary artery dimensions were not associated with survival.,An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals.,Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied.,This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted).,This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094-10.412) than either individual component alone.,Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone. | 1 |
Although COPD exacerbations are known to occur more frequently in winter, there is little information on hospitalizations and cause-specific mortality.,This study aimed to examine seasonal variations in mortality and exacerbations in patients with COPD during the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial.,TIOSPIR was a large-scale, multicenter trial, which assessed the safety and efficacy of tiotropium delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ (2.5 or 5 μg once daily) inhaler in patients with COPD.,Patients were aged ≥40 years, with a smoking history ≥10 pack-years, and post-bronchodilator forced expiratory volume in 1 second ≤70% and forced expiratory volume in 1 second/forced vital capacity ≤0.70.,COPD exacerbations and deaths were monitored throughout the trial.,The data were pooled to examine seasonal patterns.,Southern hemisphere data were shifted by 6 months to align with northern hemisphere seasons.,TIOSPIR was conducted in 43 northern (n=15,968) and 7 southern (n=1,148) hemisphere (n=1,148) countries.,The median duration of treatment was 835 days, with a mean follow-up of 2.3 years.,Among 19,494 exacerbations, there were clear seasonal differences (winter, 6,646 [34.1%]; spring, 4,515 [23.2%]; summer, 3,198 [16.4%]; autumn, 5,135 [26.3%]).,Exacerbations peaked in early winter (December in the northern hemisphere and June in the southern hemisphere), respiratory hospitalizations in midwinter, and respiratory deaths in early spring.,Although winter poses a 2-fold hazard for COPD exacerbations vs summer, respiratory deaths peak in early spring.,These data suggest that seasonal intensification of preventive treatments may impact COPD morbidity and mortality.,NCT01126437. | 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 |
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. | Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems.,Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.,Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency.,Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database.,Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.,Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001).,The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs.,Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6).,Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.,Comorbidity burden determines elevated utilization for COPD patients.,Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients. | 1 |
Chronic obstructive pulmonary disease (COPD) progresses very slowly and the majority of patients are therefore elderly.,COPD is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli and there are increasing evidences for a close relationship between premature aging and chronic inflammatory diseases.,Thus, COPD is considered to be a disease of an accelerating aging.,In this review, we collected the evidence for roles of aging on pathogenesis of COPD and considered future therapeutic strategy for COPD based on this senescence hypothesis.,Since calorie restriction has been proved to extend lifespan, many efforts were made to clarify the molecular mechanism of aging.,Aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death due to impaired DNA repair after damage by oxidative stress or telomere shortening as a result of repeated cell division.,During aging, pulmonary function progressively deteriorates; innate immunity is impaired and pulmonary inflammation increases, accompanied by structural changes, such as an enlargement of airspaces.,Noxious environmental gases, such as cigarette smoke, may worsen these aging-related events in the lung or accelerate aging of the lung due to reduction in anti-aging molecules and/or stimulation of aging molecules.,Aging signaling are complex but conserved in divert species, such as worm, fruit fry, rodent and humans.,Especially the insulin like growth factor (IGF-1) signaling was well documented.,Geroprotectors are therapeutics that affect the root cause of aging and age-related diseases, and thus prolong the life-span of animals.,Most of geroprotectors such as melatonin, metformin, rapamycin and resveratrol are anti-oxidant or anti-aging molecule regulators.,Therefore, geroprotection for the lung might be an attractive approach for the treatment of COPD by preventing premature aging of lung. | COPD is characterized by progressive airflow obstruction which does not fully reverse to inhaled or oral pharmacotherapy.,The management of patients with COPD has taken a totally new direction over the past 20 years, thank to the use of novel therapies aimed to improve and modify the natural history of COPD.,Long-acting bronchodilators, including long-acting β2-agonists (LABAs), were introduced several years ago in order to enhance improvements in lung function, health status related quality of life, and reduce the rate of exacerbations.,These effects can be boosted by the combination of LABAs with long-acting anticholinergic, and/or with inhaled corticosteroids.,Inhaled LABAs are commonly well tolerated although adverse effects such as tremor and palpitations are occasionally troublesome. | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | The assessment of symptoms of chronic obstructive pulmonary disease (COPD) is important for monitoring and managing the disease and for evaluating outcomes of interventions.,COPD patients experience symptoms during the day and night, and symptoms experienced at night often disturb sleep.,The aim of this paper is to describe methods used to develop a patient-reported outcome (PRO) instrument for evaluating nighttime symptoms of COPD, and to document evidence for the content validity of the instrument.,Literature review and clinician interviews were conducted to inform discussion guides to explore patients’ nighttime COPD symptom experience.,Data from focus groups with COPD patients was used to develop a conceptual framework and the content of a new PRO instrument.,Patient understanding of the new instrument was assessed via cognitive interviews with COPD patients.,The literature review confirmed that there is no instrument with evidence of content validity currently available to assess nighttime symptoms of COPD.,Additionally, the literature review and clinician interviews suggested the need to understand patients’ experience of specific symptoms in order to evaluate nighttime symptoms of COPD.,Analyses of patient focus group data (N = 27) supported saturation of concepts and aided in development of a conceptual framework.,Items were generated using patients’ terminology to collect data on concepts in the framework including the occurrence and severity of COPD symptoms, use of rescue medication at night, and nocturnal awakening.,Response options were chosen to reflect concepts that were salient to patients.,Subsequent cognitive interviewing with ten COPD patients demonstrated that the items, response options, recall period, and instructions were understandable, relevant, and interpreted as intended.,A new PRO instrument, the Nighttime Symptoms of COPD Instrument (NiSCI), was developed with documented evidence of content validity.,The NiSCI is ready for empirical testing, including item reduction and evaluation of psychometric properties. | 1 |
Wood smoke exposure is a risk factor for COPD.,For a given degree of airway obstruction, the reduction in DLCO is smaller in individuals with wood smoke-related COPD than in those with smoking-related COPD, suggesting that there is less emphysema in the former.,The objective of this study was to compare HRCT findings between women with wood smoke-related COPD and women with smoking-related COPD.,Twenty-two women with severe COPD (FEV1/FVC ratio < 70% and FEV1 < 50%) were divided into two groups: those with wood smoke-related COPD (n = 12) and those with smoking-related COPD (n = 10).,The two groups were compared regarding emphysema scores and airway involvement (as determined by HRCT); and functional abnormalities-spirometry results, DLCO, alveolar volume (VA), the DLCO/VA ratio, lung volumes, and specific airway resistance (sRaw).,There were no significant differences between the two groups in terms of FEV1, sRaw, or lung hyperinflation.,Decreases in DLCO and in the DLCO/VA ratio were greater in the smoking-related COPD group subjects, who also had higher emphysema scores, in comparison with the wood smoke-related COPD group subjects.,In the wood smoke-related COPD group, HRCT scans showed no significant emphysema, the main findings being peribronchial thickening, bronchial dilation, and subsegmental atelectasis.,Female patients with severe wood smoke-related COPD do not appear to develop emphysema, although they do show severe airway involvement.,The reduction in DLCO and VA, with a normal DLCO/VA ratio, is probably due to severe bronchial obstruction and incomplete mixing of inspired gas during the determination of single-breath DLCO. | Socioeconomic status is likely an independent risk factor for Chronic Obstructive Pulmonary Disease (COPD), but little research has been done in China to study this association in a nationwide sample.,We used data from the 2007 China Chronic Disease Risk Factor Surveillance of 49,363 Chinese men and women aged 15-69 years to examine the association between the prevalence of self-reported physician diagnosed COPD and socioeconomic status defined by both educational level and annual household income.,Multivariable logistic regression modelling was performed with adjustement for potential confounders.,Both low educational attainment and low household income were independently associated with higher risk of physician-diagnosed COPD.,Compared to subjects with high educational level, subjects with low educational level had a significantly increased risk of COPD (OR 1.67, 95%CI 1.32-2.13, p for trend< 0.001 for urban, OR 1.76, 95%CI 1.34-2.30, p for trend < 0.001 for rural) after adjusting for age, sex, smoking status, passive smoking and geographic regions.,Similarly increased risk was observed for household income and COPD in urban (OR 1.64, 95%CI 1.28-2.09, P for trend< 0.001) but not rural areas.,Among never smokers, low educational level and household income were still associated with a significant higher prevalence of COPD (OR 1.77, 95%CI 1.40-2.25, OR 1.31, 95%CI 1.05-1.62).,Removal of those with asthma diagnosis did not alter the observed associations.,Socioeconomic status is a risk factor for self-reported physician-diagnosed COPD independently of current or passive smoking.,Prospective studies are needed in China to better understand the association between socioeconomic status and COPD. | 1 |
Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease.,An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly.,We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry.,We also studied 10 healthy never smokers (not exposed to smoking) as controls.,Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection) might be different in man and women, we stratified participant recruitment by sex.,Differentially expressed genes were validated by q-PCR.,Ontology enrichment was evaluated and interaction networks inferred.,Principal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking.,In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature) or smokers with normal spirometry (Smoking related signature), their ontologies and interaction networks.,The use of an experimental intervention (smoking exposure) to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females. | Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease, primarily affecting the airways.,Stable biomarkers characterizing the inflammatory phenotype of the disease, relevant for disease activity and suited to predict disease progression are needed to monitor the efficacy and safety of drug interventions.,We therefore analyzed a large panel of markers in bronchoalveolar lavage, bronchial biopsies, serum and induced sputum of 23 healthy smokers and 24 smoking COPD patients (GOLD II) matched for age and gender.,Sample collection was performed twice within a period of 6 weeks.,Assays for over 100 different markers were validated for the respective matrices prior to analysis.,In our study, we found 51 markers with a sufficient repeatability (intraclass correlation coefficient >0.6), most of these in serum.,Differences between groups were observed for markers from all compartments, which extends (von-Willebrand-factor) and confirms (e.g.,C-reactive-protein, interleukin-6) previous findings.,No correlations between lung and serum markers were observed, including A1AT.,Airway inflammation defined by sputum neutrophils showed only a moderate repeatability.,This could be improved, when a combination of neutrophils and four sputum fluid phase markers was used to define the inflammatory phenotype.In summary, our study provides comprehensive information on the repeatability and interrelationship of pulmonary and systemic COPD-related markers.,These results are relevant for ongoing large clinical trials and future COPD research.,While serum markers can discriminate between smokers with and without COPD, they do not seem to sufficiently reflect the disease-associated inflammatory processes within the airways. | 1 |
Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity.,Potential biomarkers need to be readily available in real-life clinical practice.,Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).,In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up.,Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.,178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods.,Median BNC was 5200cells/μL (IQR 4000-7000cells/μL).,Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL).,People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs.,5%, P < 0.001) in the following year.,Eosinophil counts were much less predictive of these outcomes.,In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.,High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients. | There is some evidence that quality of life measured by long disease-specific questionnaires may predict exacerbations in asthma and COPD, however brief quality of life tools, such as the Airways Questionnaire 20 (AQ20) or the Clinical COPD Questionnaire (CCQ), have not yet been evaluated as predictors of hospital exacerbations.,To determine the ability of brief specific health-related quality of life (HRQoL) questionnaires (AQ20 and CCQ) to predict emergency department visits (ED) and hospitalizations in patients with asthma and COPD, and to compare them to longer disease-specific questionnaires, such as the St George´s Respiratory Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ) and the Asthma Quality of Life Questionnaire (AQLQ).,We conducted a two-year prospective cohort study of 208 adult patients (108 asthma, 100 COPD).,Baseline sociodemographic, clinical, functional and psychological variables were assessed.,All patients completed the AQ20 and the SGRQ.,COPD patients also completed the CCQ and the CRQ, while asthmatic patients completed the AQLQ.,We registered all exacerbations that required ED or hospitalizations in the follow-up period.,Differences between groups (zero ED visits or hospitalizations versus ≥ 1 ED visits or hospitalizations) were tested with Pearson´s X2 or Fisher´s exact test for categorical variables, ANOVA for normally distributed continuous variables, and Mann-Whitney U test for non-normally distributed variables.,Logistic regression analyses were performed to estimate the predictive ability of each HRQoL questionnaire.,In the first year of follow-up, the AQ20 scores predicted both ED visits (OR: 1.19; p = .004; AUC 0.723) and hospitalizations (OR: 1.21; p = .04; AUC 0.759) for asthma patients, and the CCQ emerged as independent predictor of ED visits in COPD patients (OR: 1.06; p = .036; AUC 0.651), after adjusting for sociodemographic, clinical, and psychological variables.,Among the longer disease-specific questionnaires, only the AQLQ emerged as predictor of ED visits in asthma patients (OR: 0.9; p = .002; AUC 0.727).,In the second year of follow-up, none of HRQoL questionnaires predicted exacerbations.,AQ20 predicts exacerbations in asthma and CCQ predicts ED visits in COPD in the first year of follow-up.,Their predictive ability is similar to or even higher than that of longer disease-specific questionnaires. | 1 |
Ultrasound (US) evaluation of diaphragmatic dysfunction (DD) has proved to be a reliable technique in critical care.,In this single-center prospective study, we investigated the impact of US-assessed DD on noninvasive ventilation (NIV) failure in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and its correlation with the transdiaphragmatic pressure assessed using the invasive sniff maneuver (Pdi sniff).,A population of 75 consecutive patients with AECOPD with hypercapnic acidosis admitted to our respiratory intensive care unit (RICU) were enrolled.,Change in diaphragm thickness (ΔTdi) < 20% during tidal volume was the predefined cutoff for identifying DD+/− status.,Correlations between ΔTdi < 20% NIV failure and other clinical outcomes were investigated.,Correlation between ΔTdi and Pdi sniff values was analyzed in a subset of ten patients.,DD+ patients had a higher risk for NIV failure than DD− patients (risk ratio, 4.4; p < 0.001), and this finding was significantly associated with higher RICU, in-hospital, and 90-day mortality rates; longer mechanical ventilation duration; higher tracheostomy rate; and longer RICU stay.,Huge increases in NIV failure (HR, 6.2; p < 0.0001) and 90-day mortality (HR, 4.7; p = 0.008) in DD+ patients were found by Kaplan-Meier analysis.,ΔTdi highly correlated with Pdi sniff (Pearson’s r = 0.81; p = 0.004).,ΔTdi < 20% showed better accuracy in predicting NIV failure than baseline pH value and early change in both arterial blood pH and partial pressure of carbon dioxide following NIV start (AUCs 0.84 to DTdi < 20%, 0.51 to pH value at baseline, 0.56 to early change in arterial blood pH following NIV start, and 0.54 to early change in partical pressure of carbon dioxide following NIV start, respectively; p < 0.0001).,Early and noninvasive US assessment of DD during severe AECOPD is reliable and accurate in identifying patients at major risk for NIV failure and worse prognosis. | Many patients with chronic obstructive pulmonary disease (COPD) suffer from exercise intolerance.,In about 40% of the patients exercise capacity is limited by alterations in skeletal muscle rather than pulmonary problems.,Indeed, COPD is often associated with muscle wasting and a slow-to-fast shift in fiber type composition resulting in weakness and an earlier onset of muscle fatigue, respectively.,Clearly, limiting muscle wasting during COPD benefits the patient by improving the quality of life and also the chance of survival.,To successfully combat muscle wasting and remodeling during COPD a clear understanding of the causes and mechanisms is needed.,Disuse, hypoxemia, malnutrition, oxidative stress and systemic inflammation may all cause muscle atrophy.,Particularly when systemic inflammation is elevated muscle wasting becomes a serious complication.,The muscle wasting may at least partly be due to an increased activity of the ubiquitin proteasome pathway and apoptosis.,However, it might well be that an impaired regenerative potential of the muscle rather than the increased protein degradation is the crucial factor in the loss of muscle mass during COPD with a high degree of systemic inflammation.,Finally, we briefly discuss the various treatments and rehabilitation strategies available to control muscle wasting and fatigue in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264. | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | 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 |
Chronic obstructive pulmonary disease (COPD) is a very prevalent and invalidating disease.,The aim of this study was to analyze the burden borne by informal caregivers of patients with COPD.,We used the Survey on Disabilities, Personal Autonomy, and Dependency Situations (Encuesta sobre Discapacidad, Autonomía personal y Situaciones de Dependencia [EDAD]-2008) to obtain information on the characteristics of disabled individuals with COPD and their caregivers in Spain.,Additionally, statistical multivariate analyses were performed to analyze the impact that an increase in dependence would have on the problems for which caregivers provide support, in terms of health, professional, and leisure/social dimensions.,A total of 461,884 individuals with one or more disabilities and with COPD were identified, and 220,892 informal caregivers were estimated.,Results showed that 35% of informal caregivers had health-related problems due to the caregiving provided; 83% had leisure/social-related problems; and among caregivers of working age, 38% recognized having profession-related problems.,The probability of a problem arising was significantly associated with the degree of dependence of the patient receiving care.,Caregivers of patients with great dependence showed a 39% higher probability of presenting health-related problems, 27% more professional problems, and 23% more leisure problems compared with those with nondependent patients.,The results show the large impact on society in terms of the welfare of informal caregivers of patients with COPD.,A higher level of dependence was associated with more severe problems in caregivers, in all dimensions. | The human cost of advanced chronic obstructive pulmonary disease (COPD) for informal caregivers in Canada is mostly unknown.,Formal care is episodic, and informal caregivers provide the bulk of care between exacerbations.,While patients fear becoming burdensome to family, we lack relevant data against which to assess the validity of this fear.,The purpose of our qualitative study was to better understand the extent and nature of ‘burden’ experienced by informal caregivers in advanced COPD.,The analysis of 14 informal caregivers interviews yielded the global theme ‘a day at a time,’ reflecting caregivers’ approach to the process of adjusting/coping.,Subthemes were: loss of intimate relationship/identity, disease-related demands, and coping-related factors.,Caregivers experiencing most distress described greater negative impact on relational dynamics and identity, effects they associated with increasing illness demands especially care recipients’ difficult, emotionally controlling attitudes/behaviors.,Our findings reflect substantial caregiver vulnerability in terms of an imbalance between burden and coping capacity.,Informal caregivers provide necessary, cost-effective care for those living with COPD and/or other chronic illness.,Improved understanding of the physical, emotional, spiritual, and relational factors contributing to their vulnerability can inform new chronic care models better able to support their efforts. | 1 |
The Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once‐daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records.,The objective of this study was to describe and discuss the safety monitoring methodology and the challenges associated with ensuring patient safety in the SLS.,Refinements to safety monitoring processes and infrastructure are also discussed.,The study results are outside the remit of this paper.,The results of the COPD study were published recently and a more in‐depth exploration of the safety results will be the subject of future publications.,The SLS used a linked database system to capture relevant data from primary care practices in Salford and South Manchester, two university hospitals and other national databases.,Patient data were collated and analysed to create daily summaries that were used to alert a specialist safety team to potential safety events.,Clinical research teams at participating general practitioner sites and pharmacies also captured safety events during routine consultations.,Confidence in the safety monitoring processes over time allowed the methodology to be refined and streamlined without compromising patient safety or the timely collection of data.,The information technology infrastructure also allowed additional details of safety information to be collected.,Integration of multiple data sources in the SLS may provide more comprehensive safety information than usually collected in standard randomised controlled trials.,Application of the principles of safety monitoring methodology from the SLS could facilitate safety monitoring processes for future pragmatic randomised controlled trials and yield important complementary safety and effectiveness data.,© 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. | New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy.,Patients with chronic obstructive pulmonary disease (COPD), ≥40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 μg/vilanterol 25 μg in a novel dry-powder inhaler versus continuing their existing therapy.,The primary endpoint is the mean annual rate of COPD exacerbations; an electronic medical record allows real-time collection and monitoring of endpoint and safety data.,The Salford Lung Study is the world’s first pragmatic randomised controlled trial of a pre-licensed medication in COPD.,Clinicaltrials.gov identifier NCT01551758. | 1 |
Patients with COPD present a major recruitment of the inspiratory muscles, predisposing to chest incoordination, increasing the degree of dyspnea and impairing their exercise capacity.,Stretching techniques could decrease the respiratory muscle activity and improve their contractile capacity; however, the systemic effects of stretching remain unknown.,The aim of this study was to evaluate the effects of aerobic training combined with respiratory muscle stretching on functional exercise capacity and thoracoabdominal kinematics in patients with COPD.,This study was a randomized and controlled trial.,A total of 30 patients were allocated to a treatment group (TG) or a control group (CG; n=15, each group).,The TG was engaged in respiratory muscle stretching and the CG in upper and lower limb muscle stretching.,Both groups performed 24 sessions (twice a week, 12 weeks) of aerobic training.,Functional exercise capacity (6-minute walk test), thoracoabdominal kinematics (optoelectronic plethysmography), and respiratory muscle activity (surface electromyography) were evaluated during exercise.,Analysis of covariance was used to compare the groups at a significance level of 5%.,After the intervention, the TG showed improved abdominal (ABD) contribution, compartmental volume, mobility, and functional exercise capacity with decreased dyspnea when compared with the CG (P<0.01).,The TG also showed a decreased respiratory muscle effort required to obtain the same pulmonary volume compared to the CG (P<0.001).,Our results suggest that aerobic training combined with respiratory muscle stretching increases the functional exercise capacity with decreased dyspnea in patients with COPD.,These effects are associated with an increased efficacy of the respiratory muscles and participation of the ABD compartment. | Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease.,Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life.,The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.,Five databases were searched with no dates or language limits.,The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords.,The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014.,The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale.,Studies supplied by the database search strategy were assessed independently by two blinded researchers.,A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords.,Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome.,Thus, only 14 studies had postural control as their primary outcome.,Our study examiners found only seven studies that had a PEDro score higher than five points.,The examiners’ interrater agreement was 76.4%.,Six of those studies were accomplished with a control group and one study used their patients as their own controls.,The studies were published between 2004 and 2013.,Patients with COPD present postural control impairment when compared with age-matched healthy controls.,Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility. | 1 |
In the phase III, 52-week ETHOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF), at two inhaled corticosteroid dose levels, resulted in significantly lower moderate/severe exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) and budesonide/formoterol fumarate (BFF).,Here, we report results from the ETHOS pulmonary function test (PFT) sub-study, which assessed lung function in a subset of ETHOS patients.,ETHOS (NCT02465567) was a randomized, double-blind, multi-center, parallel-group study in patients with moderate to very severe COPD who had experienced ⩾1 moderate/severe exacerbation in the previous year.,Patients received BGF 320/18/9.6 µg, BGF 160/18/9.6 μg, GFF 18/9.6 µg, or BFF 320/9.6 µg twice daily via a single metered dose Aerosphere inhaler for 52 weeks.,A subset of patients participated in the 4-hour PFT sub-study; primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in one second (FEV1) versus GFF and FEV1 area under the curve from 0 to 4 hours (AUC0-4) versus BFF at week 24.,The PFT modified intent-to-treat population included 3088 patients (mean age 64.4 years; mean reversibility post-albuterol 16.7%; mean post-albuterol FEV1% predicted 42.8).,BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved morning pre-dose trough FEV1 at week 24 versus GFF (p ⩽ 0.0035 for both).,Improvements in trough FEV1 were also observed at week 52 for BGF 320/18/9.6 µg and 160/18/9.6 µg versus GFF (p ⩽ 0.0005 for both).,For FEV1 AUC0-4 at week 24, BGF 320/18/9.6 µg and 160/18/9.6 µg showed significant improvements versus BFF (p < 0.0001 for both).,Improvements were maintained at week 52 (p < 0.0001).,BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved trough FEV1 versus GFF and FEV1 AUC0-4 versus BFF at week 24.,The lung function benefits with both doses of BGF were maintained following 52 weeks of treatment.,The reviews of this paper are available via the supplemental material section. | In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended.,A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD.,Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks.,This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS.,A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD.,The methodologic quality and risk of bias of included studies were assessed.,Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks.,Meta-regression and sensitivity analyses were used to assess heterogeneity across studies.,Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network.,LAMA/LABA dual combinations were combined as a single treatment group to create a connected network.,Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks.,Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA.,In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD.,The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.,The online version contains supplementary material available at 10.1007/s12325-021-01703-z. | 1 |
To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017.,Systematic analysis.,The Global Burden of Diseases, Injuries, and Risk Factors Study 2017.,Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool.,The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution.,Mortality and DALYs were stratified according to the Socio-demographic index.,The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation.,Risk factors for chronic respiratory diseases were analysed from exposure data.,Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017.,The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually.,During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased.,Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased.,Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries.,Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma.,Regions with a low Socio-demographic index had the highest mortality and DALYs.,Smoking remained the major risk factor for mortality due to COPD and asthma.,Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index.,Since 2013, a high body mass index has become the principal risk factor for asthma.,Regions with a low Socio-demographic index had the greatest burden of disease.,The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them. | Hospitalization brings considerable economic pressure on COPD patients in China.,A clear understanding of hospitalization costs for patients with COPD is warranted to improve treatment strategies and to control costs.,Currently, investigation on factors contributing to hospitalization costs for patients with COPD in China is limited.,This study aimed to measure the hospitalization costs of COPD and to determine the contributing factors.,Medical record data from the First Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2016 were used for a retrospective analysis.,Patients who were hospitalized with a diagnosis of COPD were included.,Patient characteristics, medical treatment, and hospitalization costs were analyzed by descriptive statistics and multivariable regression.,Among the 1,943 patients included in this study, 87.85% patients were male; the mean (SD) age was 71.15 (9.79) years; 94.49% patients had comorbidities; and 82.30% patients had health insurance.,Regarding medical treatment, the mean (SD) length of stay was 9.38 (7.65) days; 11.12% patients underwent surgery; 87.91% used antibiotics; and 4.53% underwent emergency treatment.,For hospitalization costs, the mean (SD) of the total costs per COPD patient per admission was 24,372.75 (44,173.87) CNY (3,669.33 [6,650.38] USD), in which Western medicine fee was the biggest contributor (45.53%) followed by diagnosis fee (27.00%) and comprehensive medical fee (12.04%).,Regression found that reimbursement (−0.032; 95% CI −0.046 to 0.007), length of stay (0.738; 95% CI 0.832-0.892), comorbidity (0.044; 95% CI 0.029-0.093), surgery (0.145; 95% CI 0.120-0.170), antibiotic use (0.086; 95% CI 0.060-0.107), and emergency treatment (0.121; 95% CI 0.147-0.219) were significantly (P<0.01) associated with total hospitalization costs.,To control hospitalization costs for COPD patients in China, the significance of comorbidity, length of stay, antibiotic use, surgery, and emergency treatment suggests the importance of controlling the COPD progression and following clinical guidelines for inpatients.,Interventions such as examination of pulmonary function for early detection, quality control of medical treatment, and patient education warrant further investigation. | 1 |
A core feature of chronic obstructive pulmonary disorder (COPD) and chronic heart failure (CHF) is that symptoms may change rapidly because of illness progression.,Thus, these chronic conditions are associated with high rehospitalisation rates.,Person-centred care (PCC) has been shown to have several benefits for patients with COPD or CHF (or both disorders) but it has not yet been investigated through e-health services.,The project aims to evaluate the effects of PCC by a combined digital platform and structured telephone support for people with COPD and/or CHF.,A randomised controlled trial with open, parallel groups which employs a participatory design process will be used.,This project will also include process and health economic evaluation of the intervention.,Ethical approval has been secured from the Regional Ethical Review Board in Gothenburg, Sweden (Dnr 063-17 and T063-18).,Results will be presented at conferences and to healthcare professionals, participants and patient organisations.,Findings will also be submitted for publication in peer-reviewed journals.,NCT03183817 | Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) seem to have several symptoms in common that impact health.,However, methodological differences make this difficult to compare.,Comparisons of symptoms, impact of symptoms on function and health between patients with COPD and CHF in primary health care (PHC).,The study is cross sectional, including patients with COPD (n=437) and CHF (n=388), registered in the patient administrative systems of PHC.,The patients received specific questionnaires - the Memorial Symptom Assessment Scale, the Medical Research Council dyspnea scale, and the Fatigue Impact Scale - by mail and additional questions about psychological and physical health.,The mean age was 70±10 years and 78±10 years for patients with COPD and CHF respectively (P=0.001).,Patients with COPD (n=273) experienced more symptoms (11±7.5) than the CHF patients (n=211) (10±7.6).,The most prevalent symptoms for patients with COPD were dyspnea, cough, and lack of energy.,For patients with CHF, the most prevalent symptoms were dyspnea, lack of energy, and difficulty sleeping.,Experience of dyspnea, cough, dry mouth, feeling irritable, worrying, and problems with sexual interest or activity were more common in patients with COPD while the experience of swelling of arms or legs was more common among patients with CHF.,When controlling for background characteristics, there were no differences regarding feeling irritable, worrying, and sexual problems.,There were no differences in impact of symptoms or health.,Patients with COPD and CHF seem to experience similar symptoms.,There were no differences in how the patients perceived their functioning according to their cardinal symptoms; dyspnea and fatigue, and health.,An intervention for both groups of patients to optimize the management of symptoms and improve function is probably more relevant in PHC than focusing on separate diagnosis groups. | 1 |
Currently, the majority of genetic association studies on chronic obstructive pulmonary disease (COPD) risk focused on identifying the individual effects of single nucleotide polymorphisms (SNPs) as well as their interaction effects on the disease.,However, conventional genetic studies often use binary disease status as the primary phenotype, but for COPD, many quantitative traits have the potential correlation with the disease status and closely reflect pathological changes.,Here, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms.,Based on the 310 patients and the whole samples of 513 subjects, the best gene-gene interactions models were detected for four lung-function-related quantitative traits.,For the forced expiratory volume in 1 s (FEV1), the best interaction was seen from EPHX1, SERPINE2, and GSTP1.,For FEV1%pre, the forced vital capacity (FVC), and FEV1/FVC, the best interactions were seen from SERPINE2 and TGFB1.,The results of this study provide further evidence for the genotype combinations at risk of developing COPD in Chinese Han population and improve the understanding on the genetic etiology of COPD and COPD-related quantitative traits.,The online version of this article (doi:10.1186/s40246-016-0076-0) contains supplementary material, which is available to authorized users. | Diet and nutrition may be important modifiable risk factors for the development, progression and management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).,This review examines the relationship between dietary patterns, nutrient intake and weight status in obstructive lung diseases, at different life stages, from in-utero influences through childhood and into adulthood.,In vitro and animal studies suggest important roles for various nutrients, some of which are supported by epidemiological studies.,However, few well-designed human intervention trials are available to definitively assess the efficacy of different approaches to nutritional management of respiratory diseases.,Evidence for the impact of higher intakes of fruit and vegetables is amongst the strongest, yet other dietary nutrients and dietary patterns require evidence from human clinical studies before conclusions can be made about their effectiveness. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy.,Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo.,Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire.,Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment.,Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol.,Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo.,Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo.,St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo.,No safety signals were identified from adverse-event or other safety data.,Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile. | 1 |
The aim of this study was to determine the incidence of exacerbations due to Streptococcus pneumoniae in chronic obstructive pulmonary disease (COPD) patients during stable state.,We conducted a prospective, observational, cohort study including stable COPD patients, who were evaluated at least every 4 months over a 24-month period at the Respiratory Unit of the IRCCS Policlinico Hospital in Milan, Italy, from 2012 to 2015.,Sputum samples were collected at enrollment during stable state to evaluate the frequency of S. pneumoniae colonization and in case of an acute exacerbation to evaluate the incidence of pneumococcal infection.,A total of 79 stable patients with moderate to very severe COPD were enrolled.,A total of 217 samples were collected, and 27% (n = 59) of those were positive for S. pneumoniae.,A total of four exacerbations due to S. pneumoniae occurred during follow up (0.31 per 100 person/month).,Among positive samples of S. pneumoniae, 109 serotypes were identified.,The most frequent serotypes in moderate-to-severe COPD patients during both stable state and exacerbation were 19F (12%), 18 (10%), 19A and 9V (9%) and 35 F (7%).,Only 32% of COPD patients were effectively vaccinated for S. pneumoniae with PPV23 vaccine.,The most frequent S. pneumoniae serotypes in COPD patients are 19F, 18, 19A, 9V and 35 F, and that almost 50% of S. pneumoniae strains could be covered by PCV13 in adult COPD patients. | Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung disease that affects a large number of patients and has significant impact.,One hallmark of the disease is the presence of bacteria in the lower airways.,Objective: The aim of this study was to analyze the detailed structure of microbial communities found in the lungs of healthy individuals and patients with COPD.,Nine COPD patients as compared and 9 healthy individuals underwent flexible bronchoscopy and BAL was performed.,Bacterial nucleic acids were subjected to terminal restriction fragment (TRF) length polymorphism and clone library analysis.,Overall, we identified 326 T-RFLP band, 159 in patients and 167 in healthy controls.,The results of the TRF analysis correlated partly with the data obtained from clone sequencing.,Although the results of the sequencing showed high diversity, the genera Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus constituted the major part of the core microbiome found in both groups.,A TRF band possibly representing Pseudomonas sp. monoinfection was associated with a reduction of the microbial diversity.,Non-cultural methods reveal the complexity of the pulmonary microbiome in healthy individuals and in patients with COPD.,Alterations of the microbiome in pulmonary diseases are correlated with disease. | 1 |
Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema.,The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects.,Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways.,20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks.,Bronchoalveolar lavage (BAL) was performed at baseline and after treatment.,Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites.,The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed.,Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens.,Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid.,Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40.,AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects.,NCT02557958. | Statins have immunomodulatory properties that may provide beneficial effects in the treatment of COPD.,We investigated whether a statin improves the IL-17/IL-10 imbalance in patients with COPD, as has previously been demonstrated in patients with asthma.,Thirty patients with stable COPD were recruited to a double-blind, randomized, controlled, crossover trial comparing the effect of simvastatin, 20 mg po daily, with that of a matched placebo on sputum inflammatory markers and airway inflammation.,Each treatment was administered for 4 weeks separated by a 4-week washout period.,The primary outcome was the presence of T-helper 17 cytokines and indoleamine 2,3-dioxygenase (IDO) in induced sputum.,Secondary outcomes included sputum inflammatory cells, FEV1, and symptoms using the COPD Assessment Test (CAT).,At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, −16.4 pg/mL, P = .01; −48.6 pg/mL, P < .001; −45.3 pg/mL, P = .002; and −190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively).,The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced after simvastatin compared with placebo (mean difference, −0.16 × 106, P = .004; −14.1%, P < .001; and −3.2, P = .02, respectively).,Values for other clinical outcomes were similar between the simvastatin and placebo treatments.,Simvastatin reversed the IL-17A/IL-10 imbalance in the airways and reduced sputum macrophage but not neutrophil counts in patients with COPD.,ClinicalTrials.gov; No.: NCT01944176; www.clinicaltrials.gov | 1 |
To evaluate the disease and treatment information provided to patients with chronic obstructive pulmonary disease at hospital discharge.,This was a cross-sectional study including hospitalized patients with chronic obstructive pulmonary disease at three tertiary hospitals.,The study was based on seven items of the Global Initiative for Obstructive Lung Disease (GOLD) discharge guidelines.,Two hospitals in this study had a Medical Residency Program in Pulmonology, and one did not have the program.,Fifty-four patients were evaluated.,Large amounts of information were provided concerning effective pharmacological maintenance (item 1), blood gas evaluation/measurement of oxygen saturation (item 2), assessment of inhalation technique (item 4), and maintenance therapy (item 5).,Less information was provided regarding comorbidity management planning (item 3), the completion of antibiotic/corticosteroid therapy (item 6) and follow-up with the attending physician or specialist (item 7) had less information.,We observed significant differences between hospitals for items 1, 4 and 7, and better performance in hospitals with medical residency in pulmonology.,Hospitalized patients with chronic obstructive pulmonary disease received little to no information about the seven items addressed by GOLD discharge guidelines.,This finding suggests that these guidelines should be used more often by clinicians in hospital with or without medical residency in pulmonology.,The lack of specialized care resulted in insufficient amount of information for patients with chronic obstructive pulmonary disease at discharge.,Avaliar informações sobre a doença e o tratamento fornecidos a pacientes com doença pulmonar obstrutiva crônica no momento da alta hospitalar.,Estudo transversal incluindo pacientes internados com doença pulmonar obstrutiva crônica de três hospitais terciários.,O estudo baseou-se em sete itens das diretrizes de alta hospitalar da Global Initiative for Obstructive Lung Disease (GOLD).,Dois hospitais participantes deste estudo tinham um Programa de Residência Médica em Pneumologia, e o terceiro não tinha.,Foram avaliados 54 pacientes.,Muitas informações foram fornecidas em relação à manutenção farmacológica efetiva (item 1), avaliação de gasometria/medida da saturação de oxigênio (item 2), avaliação da técnica de inalação (item 4) e terapia de manutenção (item 5).,Foram fornecidas menos informações em relação ao planejamento do manejo de comorbidade (item 3), a realização de antibioticoterapia/corticoterapia (item 6) e seguimento com o médico assistente ou especialista (item 7).,Observaram-se diferenças significativas entre os hospitais para os itens 1, 4 e 7, e melhor desempenho nos hospitais com Programa de Residência Médica em Pneumologia.,Pacientes hospitalizados com doença pulmonar obstrutiva crônica receberam pouca ou nenhuma informação relacionada aos sete itens abordados pelas diretrizes da GOLD para alta.,Esses achados sugerem que essas diretrizes deveriam ser utilizadas com maior frequência por clínicos em hospitais com ou sem Programa Residência Médica em Pneumologia.,A falta de atendimento especializado resultou em informação insuficiente para pacientes com doença pulmonar obstrutiva crônica na alta hospitalar. | Exacerbations of chronic obstructive pulmonary disease (COPD) are the third largest cause of emergency hospital admissions in the UK.,This systematic literature review explored the relationship between the hospitalization rates and the COPD comorbidities, anxiety, and depression.,The Centre for Research Dissemination’s framework for systematic reviews was followed using search terms relating to COPD, anxiety, depression, and hospital admission.,Papers identified were assessed for relevance and quality, using a suitable Critical Appraisal Skills Programme tool and Mixed Methods Assessment Tool.,Twenty quantitative studies indicated that anxiety and depression led to a statistically significant increase in the likelihood of COPD patients being hospitalized.,These comorbidities also led to an increased length of stay and a greater risk of mortality postdischarge.,Other significant factors included lower Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise scores, female gender, lower socioeconomic status, poorer patient perceived quality of life, increased severity of lung function, and less improvement in dyspnea from admission to discharge.,It was also highlighted that only 27%-33% of those with depression were being treated for it.,Four qualitative studies revealed that patients saw anxiety and depression as a major factor that affected their ability to cope with and self-manage their condition.,Findings from the systematic review have highlighted a need for better recognition and treatment of anxiety and depression amongst individuals with COPD.,Ongoing research will develop and test strategies for promoting better management and self-management as a means of reducing hospital admissions. | 1 |
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD).,In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new.,In combination, these variants strongly predict COPD in independent patient populations.,Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups.,We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants.,This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD. | New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences.,There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema).,The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD). | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with a high global prevalence.,The main scientific societies dedicated to the management of this disease have published clinical practice guidelines for quality practice.,However, at present, there are important weaknesses in COPD diagnosis criteria that often lead to underdiagnosis or misdiagnosis.,We sought to develop a new support system for COPD diagnosis.,The system was designed to overcome the weaknesses detected in current guidelines with the goals of enabling early diagnosis, and improving the diagnostic accuracy and quality of care provided.,We first analyzed the main clinical guidelines for COPD to detect weaknesses that exist in the current diagnostic process, and then proposed a redesign based on a business process management (BPM) strategy for its optimization.,The BPM system acts as a backbone throughout the process of COPD diagnosis in this proposed approach.,The newly developed support system was integrated into a health information system for validation of its use in a hospital environment.,The system was qualitatively evaluated by experts (n=12) and patients (n=36).,Among the 12 experts, 10 (83%) positively evaluated our system with respect to increasing the speed for making the diagnosis, helping in interpreting results, and encouraging opportunistic diagnosis.,With an overall rating of 4.29 on a 5-point scale, 27/36 (75%) of patients considered that the system was very useful in providing a warning about possible cases of COPD.,The overall assessment of the system was 4.53 on a 5-point Likert scale with agreement to extend its use to all primary care centers.,The proposed system provides a functional method to overcome the weaknesses detected in the current diagnostic process for COPD, which can help foster early diagnosis, while improving the diagnostic accuracy and quality of care provided. | Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use.,The objective was to report and summarise the current evidence supporting the use of nutritional supplementation to improve outcomes during PR in stable COPD patients.,A systematic search was conducted up to 7 August 2019 (registration number CRD42018089142).,The preferred reporting items for systematic reviews and meta-analyses guidelines were used.,Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online, Allied and Complementary Medicine Database, the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE, Cumulative Index of Nursing and Allied Health Literature and Web of Science.,This systematic search generated 580 initial matches, of which 22 studies (917 COPD participants) met the pre-specified criteria and were included.,Sixteen of 19 studies that used nutritional supplements in addition to PR did not show additional benefit compared to PR alone when measuring exercise capacity.,Nutritional supplements significantly increased body weight in 7 of 11 studies.,Body mass index increased significantly in two of six studies.,Handgrip strength did not improve, while quadriceps muscle strength significantly improved in 3 of 11 studies.,Four of eight studies showed a significant improvement in inspiratory muscle function.,Only 2 of 14 studies demonstrated a significant improvement in quality of life with supplementation in addition to PR.,There remains insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD due to heterogeneity in supplements, outcome measures and PR programmes.,Therefore, controversy remains and further research is needed. | 1 |
Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naïve chronic obstructive pulmonary disease (COPD).,We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naïve COPD patients.,A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted.,Eighty Japanese patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks.,Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment.,Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment.,There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups.,Changes in FEV1 (mean±standard error, 242.8±28.8 mL) and transient dyspnea index (TDI) (2.4±0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1±31.9 mL, p<0.01 and 1.5±0.3, p=0.02, respectively).,Changes in the duration of physical activity with 1.0-1.5 metabolic equivalents (METs) estimated in the sedentary position following tiotropium/olodaterol treatment (−38.7±14.7 min) tended to be reduced more than with tiotropium treatment (−4.6±10.6 min) (p=0.06), although those with ≥2.0 METs numerically increased with both treatments (+10.8±7.6 min for tiotropium/olodaterol vs +8.3±7.6 min for tiotropium, p=0.82).,Tiotropium/olodaterol treatment reduced the duration of physical activity with 1.0-1.5 METs (regression coefficient, −43.6 [95% CI −84.1, −3.1], p=0.04) in a multiple regression model adjusted for cofounding factors such as age, FEV1, total CAT scores, 6MWD, and TDI.,This is the first study to report the impact of dual bronchodilator on physical activity in treatment-naïve COPD patients of Japanese with low BMI. | This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD.,A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa.,The primary endpoint was inspiratory capacity (IC) at peak post-dose.,Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001).,Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001).,Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254).,In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337).,Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients.,A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress.,Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation.,However, no data on the possible relationship between COPD and ox-LDL are available.,This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress.,Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits.,Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62 ± 7.56 versus 12.57 ± 5.90 mU/L, P < 0.05).,Serum levels of CRP and ROS were also significantly higher in COPD patients.,Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r = −0.347, P = 0.016), while they correlated positively with CRP and ROS levels.,These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD.,Future studies are needed to determine whether and how ox-LDL plays a role in COPD. | Statins have anti-inflammatory and immunomodulating properties which could possibly influence inflammatory airways disease.,We assessed evidence for disease modifying effects of statin treatment in patients with chronic obstructive pulmonary disease (COPD).,A systematic review was conducted of studies which reported effects of statin treatment in COPD.,Data sources searched included MEDLINE, EMBASE and reference lists.,Eight papers reporting nine original studies met the selection criteria.,One was a randomized controlled trial (RCT), one a retrospective nested case-control study, five were retrospective cohort studies of which one was linked with a case-control study, and one was a retrospective population-based analysis.,Outcomes associated with treatment with statins included decreased all-cause mortality in three out of four studies (OR/HR 0.48-0.67 in three studies, OR 0.99 in one study), decreased COPD-related mortality (OR 0.19-0.29), reduction in incidence of respiratory-related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary function.,The RCT reported improvement in exercise capacity and dyspnea after exercise associated with decreased levels of C-reactive protein and Interleukin-6 in statin users, but no improvement of lung function.,There is evidence from observational studies and one RCT that statins may reduce morbidity and/or mortality in COPD patients.,Further interventional studies are required to confirm these findings. | 1 |
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | Patients with COPD have an increased risk of cardiovascular disease.,Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated.,We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.,Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment.,In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined.,These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.,On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar.,The IL-6 was also increased (p < 0.05).,Twenty-two patients completed study assessments.,In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01).,Total cholesterol and ISWT also improved (p < 0.05).,On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.,Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD. | 1 |
Cigarette smoking is the leading modifiable risk factor for disease and death worldwide.,Previous studies quantifying gene-level expression have documented the effect of smoking on mRNA levels.,Using RNA sequencing, it is possible to analyze the impact of smoking on complex regulatory phenomena (e.g. alternative splicing, differential isoform usage) leading to a more detailed understanding of the biology underlying smoking-related disease.,We used whole-blood RNA sequencing to describe gene and exon-level expression differences between 229 current and 286 former smokers in the COPDGene study.,We performed differential gene expression and differential exon usage analyses using the voom/limma and DEXseq R packages.,Samples from current and former smokers were compared while controlling for age, gender, race, lifetime smoke exposure, cell counts, and technical covariates.,At an adjusted p-value <0.05, 171 genes were differentially expressed between current and former smokers.,Differentially expressed genes included 7 long non-coding RNAs that have not been previously associated with smoking: LINC00599, LINC01362, LINC00824, LINC01624, RP11-563D10.1, RP11-98G13.1, AC004791.2.,Secondary analysis of acute smoking (having smoked within 2-h) revealed 5 of the 171 smoking genes demonstrated an acute response above the baseline effect of chronic smoking.,Exon-level analyses identified 9 exons from 8 genes with significant differential usage by smoking status, suggesting smoking-induced changes in isoform expression.,Transcriptomic changes at the gene and exon levels from whole blood can refine our understanding of the molecular mechanisms underlying the response to smoking.,The online version of this article (10.1186/s12920-017-0295-9) contains supplementary material, which is available to authorized users. | Genome Wide Association Studies (GWAS) and expression quantitative trait locus (eQTL) analyses have identified genetic associations with a wide range of human phenotypes.,However, many of these variants have weak effects and understanding their combined effect remains a challenge.,One hypothesis is that multiple SNPs interact in complex networks to influence functional processes that ultimately lead to complex phenotypes, including disease states.,Here we present CONDOR, a method that represents both cis- and trans-acting SNPs and the genes with which they are associated as a bipartite graph and then uses the modular structure of that graph to place SNPs into a functional context.,In applying CONDOR to eQTLs in chronic obstructive pulmonary disease (COPD), we found the global network “hub” SNPs were devoid of disease associations through GWAS.,However, the network was organized into 52 communities of SNPs and genes, many of which were enriched for genes in specific functional classes.,We identified local hubs within each community (“core SNPs”) and these were enriched for GWAS SNPs for COPD and many other diseases.,These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions.,These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits. | 1 |
Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients. | In patients with acute hypercapnic respiratory failure (AHRF) during exacerbations of COPD, mortality can be high despite noninvasive ventilation (NIV).,For some, AHRF is terminal and NIV is inappropriate.,However there is no definitive method of identifying patients who are unlikely to survive.,The aim of this study was to identify factors associated with inpatient mortality from AHRF with respiratory acidosis due to COPD.,COPD patients presenting with AHRF and who were treated with NIV were studied prospectively.,The forced expiratory volume in 1 second (FEV1), World Health Organization performance status (WHO-PS), clinical observations, a composite physiological score (Early Warning Score), routine hematology and biochemistry, and arterial blood gases prior to commencing NIV, were recorded.,In total, 65 patients were included for study, 29 males and 36 females, with a mean age of 71 ± 10.5 years.,Inpatient mortality in the group was 33.8%.,Mortality at 30 days and 12 months after admission were 38.5% and 58.5%, respectively.,On univariate analysis, the variables associated with inpatient death were: WHO-PS ≥ 3, long-term oxygen therapy, anemia, diastolic blood pressure < 70 mmHg, Early Warning Score ≥ 3, severe acidosis (pH < 7.20), and serum albumin < 35 g/L.,On multivariate analysis, only anemia and WHO-PS ≥ 3 were significant.,The presence of both predicted 68% of inpatient deaths, with a specificity of 98%.,WHO-PS ≥ 3 and anemia are prognostic factors in AHRF with respiratory acidosis due to COPD.,A combination of the two provides a simple method of identifying patients unlikely to benefit from NIV. | 1 |
Chronic obstructive pulmonary disease (COPD) constitutes a growing health care problem worldwide.,Integrated disease management (IDM) of mild to moderate COPD patients has been demonstrated to improve exercise capacity and health status after one year, but long-term results are currently lacking in primary care.,Long-term data from the Bocholtz study, a controlled clinical trial comparing the effects of IDM versus usual care on health status in 106 primary care COPD patients during 24 months of follow-up, were analyzed using the Clinical COPD Questionnaire (CCQ).,In addition, the Kroonluchter IDM implementation program has treated 216 primary care patients with mild to moderate COPD since 2006.,Longitudinal six-minute walking distance (6MWD) results for patients reaching 24 months of follow-up were analyzed using paired-sample t-tests.,In prespecified subgroup analyses, the differential effects of baseline CCQ score, Medical Research Council (MRC) dyspnea score, and 6MWD were investigated.,In the Bocholtz study, subjects were of mean age 64 years, with an average postbronchodilator forced expiratory volume in one second (FEV1) of 63% predicted and an FEV1/forced vital capacity (FVC) ratio of 0.56.,No significant differences existed between groups at baseline.,CCQ improved significantly and in a clinically relevant manner by 0.4 points over 24 months; effect sizes were doubled in patients with CCQ > 1 at baseline and tripled in patients with MRC dyspnea score >2.,In the Kroonluchter cohort, 56 subjects completed follow-up, were of mean age 69 years, with an FEV1/FVC ratio of 0.59, while their postbronchodilator FEV1 of 65% predicted was somewhat lower than in the total group.,6MWD improved significantly and in a clinically relevant manner up to 93 m at 12 months and was sustained at 83 m over 24 months; this effect occurred faster in patients with MRC dyspnea score >2.,In patients with baseline 6MWD < 400 m the improvement remained >100 m at 24 months.,In this study, IDM improved and sustained health status and exercise capacity in primary care COPD patients during two years of follow-up.,Improvements in health status are consistently higher in patients with CCQ > 1 at baseline, being strongest in patients with baseline MRC dyspnea score >2.,Improvements in exercise capacity remain highest in patients with 6MWD < 400 m at baseline and seem to occur earlier in patients with MRC dyspnea score >2. | Patient-reported outcomes (PRO) questionnaires are being increasingly used in COPD clinical studies.,The challenge facing investigators is to determine what change is significant, ie what is the minimal clinically important difference (MCID).,This study aimed to identify the MCID for the clinical COPD questionnaire (CCQ) in terms of patient referencing, criterion referencing, and by the standard error of measurement (SEM).,Patients were ≥40 years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and were participating in a randomized, controlled clinical trial comparing intravenous and oral prednisolone in patients admitted with an acute exacerbation of COPD.,The CCQ was completed on Days 1-7 and 42.,A Global Rating of Change (GRC) assessment was taken to establish the MCID by patient referencing.,For criterion referencing, health events during a period of 1 year after Day 42 were included in this analysis.,210 patients were recruited, 168 completed the CCQ questionnaire on Day42.,The MCID of the CCQ total score, as indicated by patient referencing in terms of the GRC, was 0.44.,The MCID of the CCQ in terms of criterion referencing for the major outcomes was 0.39, and calculation of the SEM resulted in a value of 0.21.,This investigation, which is the first to determine the MCID of a PRO questionnaire via more than one approach, indicates that the MCID of the CCQ total score is 0.4. | 1 |
Ipratropium bromide/albuterol Respimat inhaler (CVT-R) was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI), which uses a chlorofluorocarbon propellant.,The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I) and albuterol HFA (A) metered-dose inhalers as dual monotherapies (I + A).,This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470) comparing CVT-R to CVT-MDI and to I + A.,Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD), and current or exsmokers.,Patients were randomized to receive: (1) CVT-R, one inhalation four times daily (QID); or (2) CVT-MDI, two inhalations QID; or (3) I + A two inhalations of each inhaler QID.,Patient Satisfaction and Preference Questionnaire (PASAPQ) performance score (primary endpoint) and adverse events.,PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001) when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar.,Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22).,Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT-MDI and I + A groups (CVT-R versus CVT-MDI, P = 0.09; CVT-R versus I + A, P = 0.005).,The percentage of patients reporting adverse events and serious adverse events was similar across all three treatment groups.,CVT-R is an effective, environmentally friendly inhaler that provides patients with a high level of user satisfaction and may positively impact clinical outcomes while having no adverse impacts on patients using the device. | Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy.,Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices.,The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs.,This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy.,In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI.,In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases.,Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD. | 1 |
Cognitive behavioral therapy (CBT) is increasingly recommended in the management of people living with chronic obstructive pulmonary disease (COPD).,This rapid review presents the evidence base for CBT for people with COPD and describes 1) the nature of CBT interventions and comparators in controlled trials (high or low resource intensity); and 2) factors influencing intervention effects on health outcomes (anxiety, depression, breathlessness, quality of life and exercise capacity).,Primary studies reporting CBT interventions in adults with COPD were identified with data extracted by a single reviewer (20% of studies checked for data accuracy).,Studies were synthesized descriptively with meta-analyses (random effects models) of controlled trials undertaken to report mean standardized effect sizes (95% CI) for health outcomes.,Random effects meta-regression models explored whether CBT target, intervention dosage, intensity, facilitator profession, delivery mode, clinically significant anxiety/depression, trial design/quality and sample size predicted effect size.,The search identified 33 primary studies published between 1996 and 2019 (controlled trials n=24, single group cohort n=6, case exemplars n=2, phenomenological n=1).,Controlled trials frequently compared high-intensity CBT interventions against enhanced/usual care (n=12) or high-intensity CBT interventions against high-intensity comparators (n=11).,When all controlled studies were included, small, significant improvements favoring CBT were evident across all health outcomes (SMD ranged from −0.27 to 0.35, p<0.05).,When intensity dyads were considered, significant improvements were evident only when high-intensity CBT interventions were compared to enhanced usual care/usual care (SMDs ranged from −0.45 to 0.54, p <0.05).,No other variable consistently predicted intervention effect sizes across all health outcomes.,Overall, the evidence base supports the use of CBT for a range of health outcomes in people with COPD.,Consistent benefits were evident when high-resource-intensive CBT interventions were compared to usual care.,Low-resource-intensity CBT warrants further investigation in settings where cost of comprehensive care is prohibitive. | 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 |
Background and objective: Viruses are important aetiological agents of acute exacerbation of COPD (AECOPD).,Their reported prevalence varies from region to region.,This systematic review calculated the prevalence of respiratory viral infections in AECOPD.,Methods: A systematic search was performed using Medline, and references of relevant articles and conference proceedings were hand searched.,Articles for review were selected based on the following criteria: (i) prospective or cross‐sectional study, (ii) original research, (iii) viral detection used the highly sensitive techniques of PCR and/or Reverse Transcriptase PCR (RT‐PCR), (iv) viral prevalence in AECOPD defined, and (v) full paper available in English.,We assessed the study quality and extracted data independently and in duplicate using a pre‐defined data extraction form.,Weighted mean prevalence (WMP) was calculated and a forest plot was constructed to show the dispersion.,Results: Eight studies met the inclusion criteria.,The WMP of respiratory viral infection in AECOPD was 34.1% (95% CI: 23.9-44.4). picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2-27.3), followed by influenza; 7.4% (95% CI: 2.9-12.0), respiratory syncytial virus; 5.3% (95% CI: 1.6-9.0), corona viruses; 3.1% (95% CI: 0.4-5.8), parainfluenza; 2.6% (95% CI: 0.4-4.8), adenovirus; 1.1% (95% CI: −1.1 to 3.3), and human metapneumovirus; 0.7% (95% CI: −0.3 to 1.8).,Maximum WMP was observed in studies from Europe followed by the USA, Australia and Asia.,Picorna was the most common virus detected in Western countries whereas influenza was most common in Asia.,Conclusions: This systematic review demonstrated that viruses are strongly associated with AECOPD, with the highest detection rates of viruses being in Europe.,The geographical epidemiology of viruses may have important therapeutic implications for management of AECOPD.,Viruses are an important cause of acute exacerbation of COPD (AECOPD).,This systematic review calculated the weighted mean prevalence (WMP) of respiratory viruses detected in patients with AECOPD.,The overall WMP was 34.1% (95% CI: 23.9‐44.4), and picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2‐27.3). | Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD).,However, little is known about viral etiology related to AECOPD in Asia.,We aimed to study the viral etiology of AECOPD in Hong Kong.,Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005.,Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture.,Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge.,There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 ± 7.7 years [± SD]; 160 men).,Mean FEV1 was 39.6 ± 18.9% of predicted normal, and FEV1/FVC ratio was 58.0 ± 15.2%.,Fifty-eight episodes (22.1%) yielded positive viral PCR results.,The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%).,The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture.,The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV1 ≥ 50%, ≥ 30 to 50%, and < 30% of predicted normal.,Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year,Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong.,These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | The aim of this study was to investigate the predicting value of miR-146a/b for acute exacerbation chronic obstructive pulmonary disease (AECOPD) and COPD, and to explore their associations with inflammatory cytokines in AECOPD and stable COPD patients.,One hundred six AECOPD, 122 stable COPD patients, and 110 health volunteers with age and sex matched to total COPD patients (AECOPD and stable COPD) were enrolled.,Blood samples were collected from all participants.,Relative expression of miR-146a/b was determined by real-time polymerase chain reaction.,Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), leukotriene B4 (LTB-4) expression in serum from AECOPD and stable COPD patients were assessed using commercial ELISA kit.,Serum levels of miR-146a and miR-146b were down regulated in AECOPD patients compared with stable COPD patients and HCs. miR-146a and miR-146b are of good values for predicting the risk of AECOPD in HCs with AUC of 0.702 and 0.715.,Additionally, miR-146a and miR-146b could distinguish AECOPD from stable COPD patients with AUC of 0.670 and 0.643.,In AECOPD patients, levels of miR-146a in AECOPD patients were negatively associated with TNF-α, IL-6, IL-8, and LTE-4 expression.,In stable COPD patients, miR-146a expressions were negatively correlated with TNF-α, IL-1β, IL-6, IL-8, and LTE-4 levels.,And, the expressions of miR-146b in AECOPD patients were negatively associated with IL-1β and LTB-4 expression.,While in stable COPD patients, miR-146b expressions were only negatively correlated with TNF-α level.,In conclusion, miR-146a and miR-146b were negatively correlated with inflammatory cytokines, and could be promising biomarkers for predicting the risk of AECOPD in stable COPD patients and healthy individuals. | 1 |
The role of statins as anti-inflammatory drugs in chronic obstructive pulmonary disease (COPD) is controversial.,This study aimed to determine the efficacy of statins used with or without corticosteroids in COPD patients.,This was a retrospective cohort study and used the two million outpatients and inpatients in Taiwan’s Longitudinal Health Insurance Database covering 2000 to 2015.,A total of 92,460 patients were identified in this study.,We divided COPD patients into four groups by auditing each patient’s medication (statins used or not; corticosteroids used or not) and used Cox regression to analyze and compare the effects of statins in COPD patients with or without corticosteroids.,In terms of all COPD patients, our findings were consistent with previous studies showing that statins decreased COPD-related hospitalization and mortality rates.,However, the beneficial effects were only observed in younger patients or those not taking corticosteroids in further analysis.,Statins significantly decreased hospitalization and mortality rates in the non-corticosteroids groups.,The hazard ratios increased with age and were not statistically significant for patients > 70 years old.,Statins did not significantly decrease ED visits, hospitalization, and mortality in corticosteroids groups.,Statins decreased hospitalization and mortality rates in COPD patients not taking corticosteroids but were not efficacious in patients on corticosteroids therapy.,Furthermore, the beneficial effects of statins gradually decreased with patient age.,Based on the findings, statins used in COPD patients may need to consider the patient age and corticosteroids used or not. | The objective of this study is to assess whether statin use is associated with beneficial effects on COPD outcomes.,We conducted a systematic review and meta-analysis of all available studies describing the association between statin use and COPD mortality, exacerbations and cardiovascular events.,Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched, with no restrictions.,The hazard ratio (HR) with 95% confidence interval (CI) was estimated.,Fifteen studies with a total of 238,459 patients were included.,Nine articles provided data on all-cause mortality (124,543 participants), and they gave a HR of 0.62 (95% CI 0.52 to 0.73).,Three studies provided data on cancer mortality (90,077 participants), HR 0.83 (0.65 to 1.08); four studies on COPD mortality (88,767 participants), HR 0.48 (0.23 to 0.99); and three studies on cardiovascular mortality (90,041 participants), HR 0.93 (0.50 to 1.72).,Six articles provided data on COPD exacerbation with or without hospitalization (129,796 participants), HR 0.64 (0.55 to 0.75).,Additionally, the use of statins was associated with a significant reduction risk of myocardial infarction, but not for stroke.,Our systematic review showed a clear benefit of statins in patients with COPD. | 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. | The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries.,Using data from this survey we evaluated the economic impact of COPD.,This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology.,Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications.,Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale.,Combined direct and indirect costs estimated the total societal costs per patient.,The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs.,The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%.,Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.,The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities.,Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of the disease that require hospitalization.,Current guidelines offer little guidance for identifying patients whose clinical situation is appropriate for admission to the hospital, and properly developed and validated severity scores for COPD exacerbations are lacking.,To address these important gaps in clinical care, we created the IRYSS-COPD Appropriateness Study.,The RAND/UCLA Appropriateness Methodology was used to identify appropriate and inappropriate scenarios for hospital admission for patients experiencing COPD exacerbations.,These scenarios were then applied to a prospective cohort of patients attending the emergency departments (ED) of 16 participating hospitals.,Information was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up after admission or discharge home.,While complete data were generally available at the time of ED admission, data were often missing at the time of decision making.,Predefined assumptions were used to impute much of the missing data.,The IRYSS-COPD Appropriateness Study will validate the appropriateness criteria developed by the RAND/UCLA Appropriateness Methodology and thus better delineate the requirements for admission or discharge of patients experiencing exacerbations of COPD.,The study will also provide a better understanding of the determinants of outcomes of COPD exacerbations, and evaluate the equity and variability in access and outcomes in these patients. | Chronic obstructive lung disease (COPD) exacerbations are a significant cause of morbidity and mortality.,Data regarding factors which causes or prevents exacerbations is very limited.,The aim of this systematic review is to summarize the results from available studies to identify potential risk factors for hospital admission and/or re-admission among patients experiencing COPD exacerbations.,We undertook a systematic review of the literature.,Potential studies were identified by searching the electronic databases: PubMed, EMBASE, BIOSIS, CINAHL, PsycINFO, Cochrane library, reference lists in trial reports, and other relevant articles.,Seventeen articles that met the predefined inclusion criteria were identified.,Heterogeneity of study designs, risk factors and outcomes restrict the result to only a systematic review and precluded a formal meta-analysis.,In this review, three predictive factors: previous hospital admission, dyspnea and oral corticosteroids were all found to be significant risk factors of readmissions and variables including using long term oxygen therapy, having low health status or poor health related quality of life and not having routine physical activity were all associated with an increased risk of both admission and readmission to hospital.,There are a number of potential modifiable factors that are independently associated with a higher risk of COPD exacerbation requiring admission/readmission to the hospital.,Identifying these factors and the development of targeted interventions could potentially reduce the number and severity of such exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema.,Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development.,Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS).,Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression.,ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death.,Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal.,In this review, we summarize the main findings regarding the biological role of ROS, which may contribute to COPD development, and cytoprotective mechanisms against this disease progression. | Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible.,In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease.,Development of hyperinflation during the course of COPD is insidious.,Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation.,Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease.,Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD.,The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD.,We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. | 1 |
The functional work capacity of chronic obstructive pulmonary disease (COPD) patients is usually assessed with walk tests such as the 6-minute walk test (6MWT) or the shuttle test.,Because these exercise modalities require a controlled environment which limits their use by pulmonologists and severely restricts their use among general practitioners, different modalities of a short (1 minute or less) sit-to-stand test were recently proposed.,In this study, we evaluated a new modality of a semipaced 3-minute chair rise test (3CRT) in 40 patients with COPD, and compared the reproducibility of physiological responses and symptoms during the 3CRT and their interchangeability with the 6MWT.,The results demonstrate that physiological variables, heart rate, pulse oxygen saturation, work done, and symptoms (Borg dyspnea and fatigue scores), during the 3CRT were highly reproducible, and that the physiological responses and symptoms obtained during the 3CRT and the 6MWT were interchangeable for most patients.,Moreover, these preliminary data suggest that patients able to perform more than 50 rises during 3 minutes had no significant disability.,The simplicity and ease of execution of the 3CRT will facilitate the assessment of exercise symptoms and disability in COPD patients during routine consultations with pulmonologists and general practitioners, and will thus contribute to the improved management of COPD patients. | Chronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation.,We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD.,Ninety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).,Mean 6MWD was 403 (± 113) meters.,All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%.,Stroke volume decreased while heart rate increased with COPD severity and hyperinflation.,In 66% of patients, some degree of diastolic dysfunction was present.,Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance.,Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation.,Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2 = .511) compared well to a model with lung function parameters alone (adjusted r2 = .475).,LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables.,Among subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality.,Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI.,We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function.,Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD) by office-based pulmonary specialists.,The aim of this study was to assess their outpatient management in relation to current guideline recommendations for COPD.,A nationwide prospective cross-sectional COPD questionnaire survey in the form of a multiple-choice questionnaire was sent to 1000 office-based respiratory specialists in Germany.,The product-neutral questions focused on routine COPD management and were based on current national and international COPD guideline recommendations being consistent in severity classification and treatment recommendations.,A total of 590 pulmonary specialists (59%) participated in the survey.,Body plethysmography was considered the standard for diagnosis (65.9%), followed by spirometry (32%).,Most respondents were able to cite the correct spirometric criteria for classifying moderate (87%) to very severe COPD (77%).,A quarter of the respondents equated the World Health Organization (WHO) definition of chronic bronchitis with COPD.,Notably, most participants preferred the updated national COPD guidelines (51.4%) to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (40.2%).,Improvement of functional exercise capacity and quality of life were considered the two most relevant treatment goals; whereas impact on mortality was secondary.,Treatment of COPD largely complied with the guidelines.,However, a significant percentage of the pulmonary specialists differed in their assessment of the benefits of various therapeutic measures from evidence-based results.,Referral for pulmonary rehabilitation was uncommon, regardless of the severity of COPD.,The findings of this large national survey suggest that most pulmonary specialists adhere to the current COPD guideline recommendations in daily practice.,However, physicians’ knowledge of guidelines is not sufficient as the sole benchmark when assessing their implementation in day-to-day practice.,Necessary changes in the health care system must include more effective ways to transfer knowledge to clinical practice and to give access to interventions of proven clinical benefit. | 1 |
COPD is often associated with cardiovascular comorbidity.,Treatment guidelines recommend therapy with bronchodilators as first choice.,We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.,In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD.,Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score.,Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout.,All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators.,Consensus decisions were taken on every value and parameter.,The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.,Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol.,Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time.,The cardiac frequency was also significantly reduced in indacaterol-treated patients.,Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea.,These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency. | 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 |
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264. | 1 |
Anxiety and depression are highly prevalent in patients with COPD and their informal carers, and associated with numerous risk factors.,However, few studies have investigated these in primary care or the link between patient and carer anxiety and depression.,We aimed to determine this association and factors associated with anxiety and depression in patients, carers, and both (dyads), in a population-based sample.,This was a prospective, cross-sectional study of 119 advanced COPD patients and their carers.,Patient and carer scores ≥8 on the Hospital Anxiety and Depression Scale defined symptoms of anxiety and depression, χ2 tests determined associations between patient and carer symptoms of anxiety/depression, and χ2 and independent t-tests for normally distributed variables (otherwise Mann-Whitney U tests) were used to identify other variables significantly associated with these symptoms in the patient or carer.,Patient-carer dyads were categorized into four groups relating to the presence of anxious/depressive symptoms in: both patient and carer, patient only, carer only, and neither.,Factors associated with dyad symptoms of anxiety/depression were determined with χ2 tests and one-way analysis of variance for normally distributed variables (otherwise Kruskal-Wallis tests).,Prevalence of symptoms of anxiety and depression was 46.4% (n=52) and 42.9% (n=48) in patients, and 46% (n=52) and 23% (n=26) in carers, respectively.,Patient and carer symptoms of anxiety/depression were significantly associated.,Anxious and depressive symptoms in the patient were also significantly associated with more physical comorbidities, more exacerbations, greater dyspnea, greater fatigue, poor mastery, and depressive symptoms with younger age.,Symptoms of carer anxiety were significantly associated with being female and separated/divorced/widowed, and depressive symptoms with younger age, higher educational level, and more physical comorbidities, and symptoms of carer anxiety and depression with more unmet support needs, greater subjective caring burden, and poor patient mastery.,Dyad symptoms of anxiety/depression were significantly associated with greater patient fatigue.,Symptoms of anxiety and depression in COPD patients and carers are significantly associated.,Given their high prevalence, considerable impact on mortality, impact on quality of life and health care use, and associations with each other, screening for and addressing patient and carer anxiety and depression in advanced COPD is recommended. | Several clinical studies suggest common underlying pathogenetic mechanisms of COPD and depressive/anxiety disorders.,We aim to evaluate psychopathological and physical effects of aerobic exercise, proposed in the context of pulmonary rehabilitation, in a sample of COPD patients, through the correlation of some psychopathological variables and physical/pneumological parameters.,Fifty-two consecutive subjects were enrolled.,At baseline, the sample was divided into two subgroups consisting of 38 depression-positive and 14 depression-negative subjects according to the Hamilton Depression Rating Scale (HAM-D).,After the rehabilitation treatment, we compared psychometric and physical examinations between the two groups.,The differences after the rehabilitation program in all assessed parameters demonstrated a significant improvement in psychiatric and pneumological conditions.,The reduction of BMI was significantly correlated with fat mass but only in the depression-positive patients.,Our results suggest that pulmonary rehabilitation improves depressive and anxiety symptoms in COPD.,This improvement is significantly related to the reduction of fat mass and BMI only in depressed COPD patients, in whom these parameters were related at baseline.,These findings suggest that depressed COPD patients could benefit from a rehabilitation program in the context of a multidisciplinary approach. | 1 |
Little is known about patients who frequently visit the emergency department (ED) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,We aimed to quantify the proportion and characteristics of patients with frequent ED visits for AECOPD and associated healthcare utilization.,We conducted a retrospective cohort study of adults aged ≥40 years with at least one ED visit for AECOPD between 2010 and 2011, derived from population-based all-payer data of State ED and Inpatient Databases for two large and diverse states: California and Florida.,Outcome measures were frequency of ED visits for AECOPD, 30-day ED revisits, subsequent hospitalizations, near-fatal events (AECOPD involving mechanical ventilation), and charges for both ED and inpatient services (available only for Florida) during the year after the first ED visit.,The analytic cohort comprised 98,280 unique patients with 154,736 ED visits for AECOPD.,During the 1-year period, 29.4% (95% CI, 29.1%-29.7%) of the patients had two or more (frequent) visits, accounting for 55.2% (95% CI, 54.9%-55.4%) of all ED visits for AECOPD.,In the multivariable model, significant predictors of frequent ED visits were age 55-74 years (vs. 40-54 years), male sex, non-Hispanic white or black race, Medicaid insurance (vs. private), and lower median household income (all P < 0.001).,At the visit-level, 12.3% of ED visits for AECOPD were 30-day revisit events (95% CI, 12.1%-12.4%).,Additionally, 62.8% of ED visits for AECOPD (95% CI, 62.6%-63.0%) resulted in a hospitalization; patients with frequent ED visits comprised 55.5% (95% CI, 55.2%-55.8%) of all hospitalizations.,Furthermore, 7.3% (95% CI, 7.3%-7.5%) of ED visits for AECOPD led to a near-fatal event; patients with frequent ED visits accounted for 64.4% (95% CI, 63.5%-65.3%) of all near-fatal events.,Total charges for AECOPD were $1.94 billion (95% CI, $1.90-1.97 billion) in Florida; patients with frequent ED visits accounted for $1.07 billion (95% CI, $1.04-1.09 billion).,In this large cohort study, we found that 29% had frequent ED visits for AECOPD and that lower socioeconomic status was significantly associated with a higher frequency of ED visits.,Individuals with frequent ED visits for AECOPD accounted for a substantial amount of healthcare utilization and financial burden. | Chronic Obstructive Pulmonary Disease (COPD) accounts for around 4% of all public hospital annual admissions in Hong Kong.,By year 2020, COPD will be ranked fifth among the conditions with the highest burden to the society.,This study identifies admission and unplanned readmission of COPD patients, factors affecting unplanned readmission, and estimates its cost burden on the public healthcare system in Hong Kong.,This is a retrospective study analyzing COPD admissions to all public hospitals in Hong Kong.,All admission episodes to acute medical wards with the principal diagnosis of COPD (ICD-9:490-492, 494-496) from January 2006 to December 2007 were captured.,Unplanned readmission was defined as an admission which followed a previous admission within 30 days.,In 2006 and 2007, 65497 (8.0%) of episodes from medical wards were identified as COPD admissions, and among these, 15882 (24.2%) were unplanned readmissions.,The mean age of COPD patients was 76.81 ± 9.59 years and 77% were male.,Unplanned readmission was significantly associated with male gender, receiving public assistance and living in nursing homes while no association was found with the Charlson comorbidity index.,Patients who were readmitted unplanned had a significant longer acute length of stay (β = 0.3894, P < 0.001) after adjustment for other covariates.,Unplanned readmission of COPD patients has a huge impact on the public healthcare system.,A systematic approach in programme provision and a good discharge planning process targeting on COPD patients who are at high risk of unplanned readmission are essential. | 1 |
One of the aims of the COPD Assessment Test (CAT) is to aid communication between the physician and patient about the burden of chronic obstructive pulmonary disease (COPD) on the patient's life.,To investigate the impact of the CAT on the quality of primary care consultations in COPD patients.,Primary care physicians across Europe conducted six consultations with standardised COPD patients (played by trained actors).,Physicians were randomised to see the patient with the completed CAT (CAT+ arm) or without (no CAT arm) during the consultation.,These were videoed and independent assessors scored the physicians on their ability to identify and address patient-specific issues such as depression (sub-score A); review standard COPD issues such as breathlessness (sub-score B); their understanding of the case (understanding score); and their overall performance.,The primary endpoint was the global score (sub-scores A+B; scale range 0-40).,A total of 165 physicians enrolled in the study and carried out six consultations each; 882 consultations were deemed suitable for analysis.,No difference was seen between the arms in the global score (no CAT arm 20.3; CAT+ arm 20.7; 95% CI −1.0 to 1.8; p=0.606) or on sub-score A (p=0.255).,A statistically significant difference, though of limited clinical relevance, was observed in mean sub-score B (no CAT arm 8.8; CAT+ arm 9.6; 95% CI 0.0 to 1.6; p=0.045).,There was no difference in understanding score (p=0.824) or overall performance (p=0.655).,The CAT is a disease-specific instrument that aids physician assessment of COPD.,It does not appear to improve detection of non-COPD symptoms and co-morbidities. | Chronic obstructive pulmonary disease (COPD) is a leading cause of disability in all its stages, and death in patients with moderate or severe obstruction.,At present, COPD is suboptimally managed; current health is often not measured properly and hardly taken into account in management plans, and the future risk for patients with regard to health status and quality of life is not being evaluated.,This review addresses the effect of COPD on the lives of patients and examines ways in which existing assessment tools meet physicians’ needs for a standardized, simple method to measure consistently the full impact of COPD on patients in routine clinical practice.,Current assessment of COPD severity tends to focus on airflow limitation, but this does not capture the full impact of the disease and is not well correlated with patient perception of symptoms and health-related quality of life.,Qualitative studies have demonstrated that patients usually consider COPD impact in terms of frequency and severity of symptoms, and physical and emotional wellbeing.,However, patients often have difficulty expressing their disease burden and physicians generally have insufficient time to collect this information.,Therefore, it is important that methods are implemented to help generate a more complete understanding of the impact of COPD.,This can be achieved most efficiently using a quick, reliable, and standardized measure of disease impact, such as a short questionnaire that can be applied in daily clinical practice.,Questionnaires are precision instruments that contribute sensitive and specific information, and can potentially help physicians provide optimal care for patients with COPD.,Two short, easy-to-use, specific measures, ie, the COPD Assessment Test and the Clinical COPD Questionnaire, enable physicians to assess patients’ health status accurately and improve disease management.,Such questionnaires provide important measurements that can assist primary care physicians to capture the impact of COPD on patients’ daily lives and wellbeing, and improve long-term COPD management. | 1 |
In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society.,Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE).,In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis.,We searched the terms “chronic obstructive pulmonary disease,” “pulmonary embolism,” “exacerbations,” and “thromboembolic” in PubMed database and collected the results up to April 2018.,The language was limited to English.,We thoroughly examined the titles and abstracts of all studies that met our search strategy.,The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review.,The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria.,Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department.,PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms.,However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation.,Obesity and lower limb asymmetry were described as independent predictors for PE.,Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation.,According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay.,Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated. | 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 |
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. | The air pollution in China is a severe problem.,The aim of our study was to investigate the impact of air pollutants on acute respiratory outcomes in outpatients.,Outpatient data from 2 December 2013 to 1 December 2014 were collected, as well as air pollutant data including ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and particulate matter (PM2.5 and PM10).,We screened six categories of acute respiratory outcomes and analyzed their associations with different air pollutant exposures, including upper respiratory tract infection (URTI), acute bronchitis (AB), community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), acute exacerbation of asthma (AE-asthma), and acute exacerbation of bronchiectasis (AEBX).,A case-crossover design with a bidirectional control sampling approach was used for statistical analysis.,A total of 57,144 patients were enrolled for analysis.,PM2.5, PM10, NO2, SO2, and CO exposures were positively associated with outpatient visits for URTI, AB, CAP, and AEBX.,PM10, SO2, and CO exposures were positively associated with outpatient visits for AECOPD.,Exposure to O3 was positively associated with outpatient visits for AE-asthma, but negatively associated with outpatient visits for URTI, CAP, and AEBX.,In conclusion, air pollutants had acute effects on outpatient visits for acute respiratory outcomes, with specific outcomes associated with specific pollutants. | 1 |
The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations.,The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations.,However, the clinical characteristics and outcomes in these patients are not well documented.,In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry.,All patients with stable COPD were classified into the four groups defined by GOLD 2017.,The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.,Four hundred and one patients with stable COPD were identified.,There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D.,Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A.,Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period.,Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B).,Mortality was not different between the high-risk and low-risk groups.,The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality. | This study was designed to evaluate errors in inhaler technique in COPD vs asthma patients and to investigate the association of poor inhaler technique with patient demographics and clinical variables.,A total of 509 adult patients with COPD (n=328) or asthma (n=181) who were currently using an inhaler device were included in this study.,Data on patient demographics, duration of disease, type and duration of inhaler therapy, and assessment of inhaler technique were recorded.,Metered dose inhaler (MDI) was the most common type of inhaler used by a similarly high percentage of patients in both COPD (83.2%) and asthma (77.3%) groups.,Failure to exhale before inhaling through device (75.8% and 68.5% for MDIs; 73.2% and 71.8% for Aerolizer®/Handihaler®; 53.1% and 66.7% for Turbuhaler®) was the most common error in inhaler technique, in both COPD and asthma groups.,Device-specific errors in inhaler techniques were more common in asthma patients as compared with COPD patients, particularly for MDIs (P-values ranged from 0.046 to 0.0005), as associated with female gender (failure to press the buttons on both sides of Aerolizer®/Handihaler®, P=0.006), shorter duration of disease (failure to hold MDI or head in a vertical position, P<0.001, and to keep Turbuhaler® upright, P=0.005), and shorter duration of inhaler usage (failure to hold head in a vertical position during MDI usage, P=0.006, and to keep Turbuhaler® upright, P=0.012).,In conclusion, our findings revealed that errors in inhaler technique in terms of inhalation maneuvers and device handling were similarly common in COPD and asthma patients.,Errors in certain device handling maneuvers, particularly with MDIs, were more common among asthma patients than among COPD patients and associated with female gender and shorter durations of disease and inhaler therapy. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by an irreversible proliferation arrest associated with secretion of inflammatory mediators.,ROS production, known to induce senescence, is increased in COPD fibroblasts and mitochondria dysfunction participates in this process.,Among the battery of cellular responses against oxidative stress damage, heme oxygenase (HO)‐1 plays a critical role in defending the lung against oxidative stress and inflammation.,Therefore, we investigated whether pharmacological induction of HO‐1 by chronic hemin treatment attenuates senescence and improves dysfunctional mitochondria in COPD fibroblasts.,Fibroblasts from smoker controls (S‐C) and COPD patients were isolated from lung biopsies.,Fibroblasts were long‐term cultured in the presence or absence of hemin, and/or ZnPP or QC‐15 (HO‐1 inhibitors).,Lung fibroblasts from smokers and COPD patients displayed in long‐term culture a senescent phenotype, characterized by a reduced replicative capacity, an increased senescence and inflammatory profile.,These parameters were significantly higher in senescent COPD fibroblasts which also exhibited decreased mitochondrial activity (respiration, glycolysis, and ATP levels) which led to an increased production of ROS, and mitochondria biogenesis and impaired mitophagy process.,Exposure to hemin increased the gene and protein expression level of HO‐1 in fibroblasts and diminished ROS levels, senescence, the inflammatory profile and simultaneously rescued mitochondria dysfunction by restoring mitophagy in COPD cells.,The effects of hemin were abolished by a cotreatment with ZnPP or QC‐15.,We conclude that HO‐1 attenuates senescence in COPD fibroblasts by protecting, at least in part, against mitochondria dysfunction and restoring mitophagy. | 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 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
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