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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 | In adult Chinese men, smoking prevalence is high, but little is known about its association with chronic respiratory disease, which is still poorly diagnosed and managed.,A nationwide study recruited 0.5 million men and women aged 30-79 years during 2004-2008 from ten geographically diverse areas across the Mainland China.,Information was collected from each participant regarding smoking and self-reported physician diagnosis of chronic bronchitis/emphysema (CB/E), along with measurement of lung function indices.,Logistic regression was used to yield sex-specific odds ratios (ORs) relating smoking to airflow obstruction (AFO), defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.7 and CB/E, adjusting for age, areas, education, and income.,Overall 74% of men were ever regular smokers; among them, 7.2% had AFO compared with 5.4% in never-smokers, yielding an OR of 1.42 (95% confidence interval [CI]: 1.34-1.50).,The risk was strongly associated with amount smoked and starting to smoke at a younger age.,Among ex-smokers, the OR was more extreme for those who had quit due to illness (OR: 1.86, 95% CI: 1.77-1.96) than those who had quit by choice (OR:1.08, 95% CI: 1.01-1.16).,CB/E prevalence was also significantly elevated in ex-smokers who had quit because of ill health (OR:2.79, 95% CI: 2.64-2.95), but not in regular smokers (OR:1.04, 95% CI: 0.96-1.11).,Female smokers was rare (3%), but carried an excess risk for AFO (OR:1.53, 95% CI: 1.43-1.65) and, to a lesser extent, for CB/E (OR:1.28, 95% CI: 1.15-1.42).,In Mainland China, adult smokers, particularly ex-smokers who had quit because of illness, had significantly higher prevalence of chronic respiratory disease.,AFO appeared to be more strongly associated with smoking than self-reported chronic respiratory disease. | 1 |
The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | The prescription of physical activity for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can be complicated by the presence of comorbidities.,The current research aimed to synthesize the relevant literature on the benefits of exercise for people with multimorbidities who experience an AECOPD, and ask: What are the parameters and outcomes of exercise in AECOPD and in conditions that are common comorbidities as reported by systematic reviews (SRs)?,An SR was performed using the Cochrane Collaboration protocol.,Nine electronic databases were searched up to July 2011.,Articles were included if they (1) described participants with AECOPD, chronic obstructive pulmonary disease (COPD), or one of eleven common comorbidities, (2) were an SR, (3) examined aerobic training (AT), resistance training (RT), balance training (BT), or a combination thereof, (4) included at least one outcome of fitness, and (5) compared exercise training versus control/sham.,This synthesis examined 58 SRs of exercise training in people with AECOPD, COPD, or eleven chronic conditions commonly associated with COPD.,Meta-analyses of endurance (aerobic or exercise capacity, 6-minute walk distance - 6MWD) were shown to significantly improve in most conditions (except osteoarthritis, osteoporosis, and depression), whereas strength was shown to improve in five of the 13 conditions searched: COPD, older adults, heart failure, ischemic heart disease, and diabetes.,Several studies of different conditions also reported improvements in quality of life, function, and control or prevention outcomes.,Meta-analyses also demonstrate that exercise training decreases the risk of mortality in older adults, and those with COPD or ischemic heart disease.,The most common types of training were AT and RT.,BT and functional training were commonly applied in older adults.,The quality of the SRs for most conditions was moderate to excellent (>65%) as evaluated by AMSTAR scores.,In summary, this synthesis showed evidence of significant benefits from exercise training in AECOPD, COPD, and conditions that are common comorbidities.,A broader approach to exercise and activity prescription in pulmonary rehabilitation may induce therapeutic benefits to ameliorate clinical sequelae associated with AECOPD and comorbidities such as the inclusion of BT and functional training. | 1 |
Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of 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 |
Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality.,It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient.,Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases.,Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model.,604 patients were included (mean±sd age 61.9±9.7 years; forced expiratory volume in 1 s 37±18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months.,Median survival was 91.9 (95% CI 80.8-103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively.,Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172-0.639; and second quartile (51-37.3%): HR 0.52, 95% CI 0.322-0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02-1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77-0.94) were the only parameters independently associated with mortality.,Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely.,Transfer factor not GOLD stage is the most powerful predictor of survival in patients with COPDhttp://ow.ly/mGmjG | 1 |
Endothelial progenitor cells (EPCs) are decreased in cardiac dysfunction morbidity associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Therefore, the present study aimed to assess the role of EPCs in AECOPD.,Patients with AECOPD (n=27) or stable COPD (n=26) were enrolled.,Systemic inflammatory markers (high-sensitivity C-reactive protein) were measured.,In addition, EPCs were counted, isolated and cultured, and their proliferative, migratory, adhesive and tube-forming capabilities were determined, in cells from patients with AECOPD and stable COPD.,EPC number was lower in patients with AECOPD (5.1±2.6×103/ml) compared with patients with stable COPD (6.0±3.2×103/ml).,Migration assay indicated that the early-EPCs isolated from patients with AECOPD were significantly less mobile than EPCs derived from stable COPD subjects, at a stromal-cell derived factor-1α concentration of 100 ng/ml (3,550/30,000 vs.,7,853/30,000, P<0.05).,C-X-C chemokine receptor-4 positivity was significantly reduced in AECOPD patients (16.1±9.9 vs.,56.33±6.3%, P<0.05).,Furthermore, fewer early-EPC clusters were formed by EPCs derived from AECOPD, compared with those derived from stable COPD (8.2±0.86 vs.,14.4±1.36, P=0.027).,Stable COPD late-EPCs were markedly deficient in intact tubule formation, however AECOPD late-EPCs formed no tubules.,The number of AECOPD- and stable COPD-derived late-EPCs adhering to Matrigel-induced tubules was 36.8±1.85 and 20.6±1.36 (P<0.05) respectively, and the cluster of differentiation 31 positivity in late-EPCs was 79.69±1.3 and 29.1±2.47%, in AECOPD and stable COPD patients, respectively (P<0.001).,The findings demonstrated that early-EPCs are decreased and dysfunctional in AECOPD patients, which may contribute to the altered vascular endothelium in this patient population. | This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are progressively limited in their ability to undertake normal everyday activities by a combination of exertional dyspnoea and peripheral muscle weakness.,COPD is characterised by expiratory flow limitation, resulting in air trapping and lung hyperinflation.,Hyperinflation increases acutely under conditions such as exercise or exacerbations, with an accompanying sharp increase in the intensity of dyspnoea to distressing and intolerable levels.,Air trapping, causing increased lung hyperinflation, can be present even in milder COPD during everyday activities.,The resulting activity-related dyspnoea leads to a vicious spiral of activity avoidance, physical deconditioning, and reduced quality of life, and has implications for the early development of comorbidities such as cardiovascular disease.,Various strategies exist to reduce hyperinflation, notably long-acting bronchodilator treatment (via reduction in flow limitation and improved lung emptying) and an exercise programme (via decreased respiratory rate, reducing ventilatory demand), or their combination.,Optimal bronchodilation can reduce exertional dyspnoea and increase a patient's ability to exercise, and improves the chance of successful outcome of a pulmonary rehabilitation programme.,There should be a lower threshold for initiating treatments appropriate to the stage of the disease, such as long-acting bronchodilators and an exercise programme for patients with mild-to-moderate disease who experience persistent dyspnoea. | Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | 1 |
To identify differentially methylated probes (DMPs) and regions (DMRs) in relation to chronic obstructive pulmonary disease (COPD) and lung function traits.,We performed an epigenome-wide association study of COPD and spirometric parameters, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC, in blood DNA using the Infinium HumanMethylation450 (n = 100, a Korean COPD cohort).,We found one significant DMP (cg03559389, DIP2C) and 104 significant DMRs after multiple-testing correction.,Of these, 34 DMRs mapped to genes differential expressed with respect to the same trait.,Five of the genes were associated with more than two traits: CTU2, USP36, ZNF516, KLK10 and CPT1B.,We identified novel differential methylation loci related to COPD and lung function in blood DNA in Koreans and confirmed previous findings in non-Asians.,Epigenetic modification could contribute to the etiology of these phenotypes. | Lung macrophage subpopulations have been identified based on size.,We investigated characteristics of small and large macrophages in the alveolar spaces and lung interstitium of COPD patients and controls.,Alveolar and interstitial cells were isolated from lung resection tissue from 88 patients.,Macrophage subpopulation cell-surface expression of immunological markers and phagocytic ability were assessed by flow cytometry.,Inflammatory related gene expression was measured.,Alveolar and interstitial macrophages had subpopulations of small and large macrophages based on size and granularity.,Alveolar macrophages had similar numbers of small and large cells; interstitial macrophages were mainly small.,Small macrophages expressed significantly higher cell surface HLA-DR, CD14, CD38 and CD36 and lower CD206 compared to large macrophages.,Large alveolar macrophages showed lower marker expression in COPD current compared to ex-smokers.,Small interstitial macrophages had the highest pro-inflammatory gene expression levels, while large alveolar macrophages had the lowest.,Small alveolar macrophages had the highest phagocytic ability.,Small alveolar macrophage CD206 expression was lower in COPD patients compared to smokers.,COPD lung macrophages include distinct subpopulations; Small interstitial and small alveolar macrophages with more pro-inflammatory and phagocytic function respectively, and large alveolar macrophages with low pro-inflammatory and phagocytic ability. | 1 |
Preserved ratio impaired spirometry (PRISm) is an incompletely understood respiratory condition.,We investigated the incidence and significant predictive factors of chronic obstructive pulmonary disease (COPD) in PRISm patients.,From 11,922 subjects registered in the Korea National Health and Nutrition Examination Survey, never or light smokers, young subjects, and those already medically diagnosed with COPD (defined by ICD-10 code and prescribed medication) were excluded.,The 2666 remaining subjects were categorized into PRISm (normal forced expiratory volume in the first second [FEV1]/force vital capacity [FVC] [≥ 0.7] and low FEV1 (< 80%); n = 313); normal (n = 1666); and unrevealed COPD groups (FEV1/FVC ratio < 0.7; n = 687).,These groups were compared using matched Health Insurance Review and Assessment Service data over a 3-year follow-up.,COPD incidence in PRISm patients (17/1000 person-year [PY]) was higher than that in normal subjects (4.3/1000 PY; P < 0.001), but lower than that in unrevealed COPD patients (45/1000 PY; P < 0.001).,PRISm patients visited hospitals, took COPD medication, and incurred hospitalization costs more frequently than normal subjects, but less frequently than unrevealed COPD patients.,In the overall sample, age, FVC, FEV1, dyspnea, and wheezing were significant predictors of COPD, but in PRISm patients, only age (OR, 1.14; P = 0.002) and wheezing (OR, 4.56; P = 0.04) were significant predictors.,PRISm patients are likely to develop COPD, and should be monitored carefully, especially older patients and those with wheezing, regardless of lung function. | Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | 1 |
Preserved ratio impaired spirometry (PRISm) is an incompletely understood respiratory condition.,We investigated the incidence and significant predictive factors of chronic obstructive pulmonary disease (COPD) in PRISm patients.,From 11,922 subjects registered in the Korea National Health and Nutrition Examination Survey, never or light smokers, young subjects, and those already medically diagnosed with COPD (defined by ICD-10 code and prescribed medication) were excluded.,The 2666 remaining subjects were categorized into PRISm (normal forced expiratory volume in the first second [FEV1]/force vital capacity [FVC] [≥ 0.7] and low FEV1 (< 80%); n = 313); normal (n = 1666); and unrevealed COPD groups (FEV1/FVC ratio < 0.7; n = 687).,These groups were compared using matched Health Insurance Review and Assessment Service data over a 3-year follow-up.,COPD incidence in PRISm patients (17/1000 person-year [PY]) was higher than that in normal subjects (4.3/1000 PY; P < 0.001), but lower than that in unrevealed COPD patients (45/1000 PY; P < 0.001).,PRISm patients visited hospitals, took COPD medication, and incurred hospitalization costs more frequently than normal subjects, but less frequently than unrevealed COPD patients.,In the overall sample, age, FVC, FEV1, dyspnea, and wheezing were significant predictors of COPD, but in PRISm patients, only age (OR, 1.14; P = 0.002) and wheezing (OR, 4.56; P = 0.04) were significant predictors.,PRISm patients are likely to develop COPD, and should be monitored carefully, especially older patients and those with wheezing, regardless of lung function. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Asthma and COPD are complex, heterogeneous conditions comprising a wide range of phenotypes, some of which are refractory to currently available treatments.,Elucidation of these phenotypes and identification of biomarkers with which to recognize them and guide appropriate treat-ment remain a priority.,This review describes the utility of blood eosinophils as a surrogate biomarker of eosinophilic airway inflammation, a common feature of specific asthma and COPD phenotypes.,The role of blood eosinophils in airway disease is described, as is their relevance in reflecting airway eosinophilia.,Each disease is discussed separately as the manner in which blood eosinophils might be used as biomarkers differs.,Focusing on patients with severe disease (persistent eosinophilic asthma and exacerbating COPD), we evaluate evidence examining eosinophils as biomarkers.,In asthma, the rationale for using blood eosinophils to guide treatment is clearly defined, backed by prospective, well-controlled studies.,Higher eosinophil counts identify patients with more se-vere disease and poorer outcomes, patients for whom biologic therapies targeting allergic and/or eosino-philic pathways are recommended.,In COPD, the evidence is less robust.,High blood eosinophil counts are a modest predictor of future exacerbations, and may predict a favourable response to ICS on top of LABA/LAMA, especially in patients with a history of frequent exacerbations.,Before extensive application in clinical practice, further evaluation of these findings in pro-spective clinical studies, and standardization of the appropriate thresholds of clinically relevant eosino-philia are needed, together with establishing whether single or multiple measurements are required in dif-ferent clinical settings | COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | 1 |
Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily).,The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles.,This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.,Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks).,Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately.,In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure.,Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted).,The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]).,The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group.,Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium.,Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.,This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. | 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 |
Pulmonary rehabilitation (PR) is recommended in the management of people with chronic obstructive pulmonary disease (COPD), but referral to this service is low.,To identify barriers to, and facilitators for, referral to PR programmes from the perspective of Australian general practitioners.,Semi-structured interviews were conducted with general practitioners involved in the care of people with COPD.,Interview questions were informed by a validated behavioural framework and asked about participants’ experience of referring people with COPD for PR, and barriers to, or facilitators of, this behaviour.,Interviews were audiotaped, transcribed verbatim, and analysed using content analysis.,Twelve general practitioners participated in this study, 10 of whom had never referred a patient to a PR programme.,Four major categories relating to barriers to referral were identified: low knowledge of PR for COPD; low knowledge of how to refer; actual or anticipated access difficulties for patients; and questioning the need to do more to promote exercise behaviour change.,Awareness of benefit was the only current facilitator.,Three major categories of potential facilitators were identified: making PR part of standard COPD care through financial incentive; improving information flow with regard to referrals and services; and informing patients and public.,Significant barriers to referral exist, but opportunities to change the organisation of practice and information management were identified.,Behaviour change strategies which directly target these barriers and incorporate facilitators should make up the key components of interventions to improve referral to PR by general practitioners who care for people with COPD. | The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care.,The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation.,Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care).,Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care.,The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32).,The program was accessed on 86% of the treatment days, especially the diary.,Patient adherence with the exercise scheme was low (21%).,Health care providers seem to play an important role in patients’ adherence to telehealth in usual care.,Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence. | 1 |
To have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.,Data were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study.,Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise.,All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.,Chronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104).,Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups.,Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p<0.001).,Submaximal ventilation, dyspnea, and leg discomfort ratings were higher for a given work rate in both GOLD groups compared with controls.,Resting inspiratory capacity, peak ventilation, and tidal volume were reduced in patients with GOLD 2 COPD compared with patients with GOLD 1 COPD and controls (p<0.001).,Lower exercise tolerance in patients with GOLD 1 and 2 COPD compared with controls was explained by greater mechanical abnormalities, greater ventilatory requirements, and increased subjective discomfort.,Lower resting inspiratory capacity in patients with GOLD 2 COPD was associated with greater mechanical constraints and lower peak ventilation compared with patients with GOLD 1 COPD and controls.,ClinicalTrials.gov: NCT01072396 | 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 |
It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | 1 |
Autophagy plays essential roles in the development of COPD.,We aim to identify and validate the potential autophagy-related genes of COPD through bioinformatics analysis and experiment validation.,The mRNA expression profile dataset GSE38974 was obtained from GEO database.,The potential differentially expressed autophagy-related genes of COPD were screened by R software.,Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed autophagy-related genes.,Finally, RNA expression of top five differentially expressed autophagy-related genes was validated in blood samples from COPD patients and healthy controls by qRT-PCR.,A total of 40 differentially expressed autophagy-related genes (14 up-regulated genes and 26 down-regulated genes) were identified between 23 COPD patients and 9 healthy controls.,The PPI results demonstrated that these autophagy-related genes interacted with each other.,The GO and KEGG enrichment analysis of differentially expressed autophagy-related genes indicated several enriched terms related to autophagy and mitophagy.,The results of qRT-PCR showed that the expression levels of HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 in COPD patients and healthy controls were consistent with the bioinformatics analysis results from mRNA microarray.,We identified 40 potential autophagy-related genes of COPD through bioinformatics analysis.,HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 may affect the development of COPD by regulating autophagy.,These results may expand our understanding of COPD and might be useful in the treatment of COPD. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by poor airflow.,The purpose of this study was to explore the mechanisms involved in the development of COPD.,The mRNA expression profile GSE100281, consisting of 79 COPD and 16 healthy samples, was acquired from the Gene Expression Omnibus database.,The differentially expressed genes (DEGs) between COPD samples and healthy samples were analyzed using the limma package.,Functional enrichment analysis for the DEGs was carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool.,Furthermore, DEG-compound pairs were predicted using the Comparative Toxicogenomics Database.,The KEGG metabolite IDs corresponding to the compounds were also obtained through the MetaboAnalyst pipeline.,Based on the diffusion algorithm, the metabolite network was constructed.,Finally, the expression levels of key genes were determined using quantitative PCR (qPCR).,There were 594 DEGs identified between the COPD and healthy samples, including 242 upregulated and 352 downregulated genes.,A total of 696 DEG-compound pairs, such as BCL2-C00469 (ethanol) and BCL2-C00389 (quercetin) pairs, were predicted.,CYP1B1, VEGFA, BCL2, and CDKN1A were included in the top 10 DEG-compound pairs.,Additionally, 57 metabolites were obtained.,In particular, hsa04750 (inflammatory mediator regulation of TRP channels)-C00469 (ethanol) and hsa04152 (AMPK signaling pathway)-C00389 (quercetin) pairs were found in the metabolite network.,The results of qPCR showed that the expression of CYP1B1, VEGFA, BCL2, and CDKN1A was consistent with that predicted using bioinformatic analysis.,CYP1B1, VEGFA, BCL2, and CDKN1A may play important functions in the development and progression of COPD. | 1 |
Previous studies have shown that progressive forms of non-alcoholic fatty liver disease (NAFLD) occur frequently in patients with obstructive lung disease (OLD).,However, few studies have written about this relationship.,This study aimed to investigate the relationship between OLD and NAFLD.,The Korea National Health and Nutrition Examination Survey is a national population-based, cross-sectional surveillance program that was initiated to assess the health and nutritional status of the Korean population.,From 2007 to 2010, 11,738 subjects were enrolled.,The subjects were defined as having NAFLD when they had scores higher than −0.640 in a NAFLD liver fat score prediction model, which was a previously validated prediction score.,Individuals with forced expiratory volume in one second/forced vital capacity <0.7 were considered to have OLD.,The subjects were divided into non-OLD and OLD groups and non-NAFLD and NAFLD groups.,All analyses were performed using sample weighting using the complex samples plan.,The prevalences of NAFLD and OLD were 30.2% and 8.9%, respectively.,Although not statistically significant, subjects in the NAFLD group involved a higher tendency of having OLD than did those in the non-NAFLD group (8.5% vs 10.0%, respectively, P=0.060).,Subjects with OLD showed a higher tendency to have NAFLD than non-OLD subjects (30.0% vs 33.7%, respectively, P=0.060).,NAFLD subjects were at higher odds of OLD (odds ratio=1.334; 95% confidence interval=1.108-1.607, P=0.002) than non-NAFLD subjects, after adjusting for age, sex, and smoking history.,OLD subjects were at higher odds of NAFLD (odds ratio=1.556; 95% confidence interval=1.288-1.879, P<0.001) than non-OLD subjects, after adjusting for age, sex, and smoking history.,This study showed that NAFLD is related to OLD.,Clinicians should be aware of possible liver comorbidities in OLD patients and that extrahepatic disease in NAFLD patients may vary more than previously thought. | Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated.,Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture.,We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013.,The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention.,Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD.,Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy).,Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture.,The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up.,This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity.,However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking.,A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted.,Patients with a diagnosis of COPD aged ≥40 years were followed up for 5 years from January 1, 2010.,CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time.,In addition, baseline factors predicting future risk of CAP and hospital admission with CAP were identified.,A total of 14,513 COPD patients were identified: 13.4% (n=1,938) had ≥1 CAP episode, of whom 18.8% suffered from recurrent (≥2) CAP.,Highest rates of both CAP and exacerbations were seen in winter.,A greater proportion of frequent, compared to infrequent, exacerbators experienced recurrent CAP (5.1% versus 2.0%, respectively, P<0.001); 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations.,Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission with CAP.,Other independent predictors of future CAP included lower body mass index, inhaled corticosteroid use, prior frequent exacerbations and comorbidities, including ischemic heart disease and diabetes.,CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission with CAP.,Highlighting this burden of COPD-associated CAP during the winter period informs us of the likely triggers and the need for more effective preventive strategies. | 1 |
Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers.,We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS.,These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17.,Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD exacerbations, and emphysema.,Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs).,Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3-5% of the measurement variance on top of clinical variables.,IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years.,None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations.,We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements.,When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone.,COPDGene (ClinicalTrials.gov Identifier: NCT02445183).,Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344).,The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death by disease worldwide and has a 30-day readmission rate of 22.6%.,In 2015, COPD was added to the Medicare Hospital Readmission Reductions Program.,The objective of this paper was to survey the current medical technologies for remote patient monitoring (RPM) tools that forecast COPD exacerbations in order to reduce COPD readmissions.,We searched literature and digital health news to find commercially available RPM devices focused on predicting COPD exacerbations.,These technologies were reviewed and compared according to four criteria: forecasting ability, cost, ease of use, and appearance.,A rating system was developed to facilitate the evaluation process.,As of June 2019, a list of handheld and hands-free devices was compiled.,We compared features and found substantial variations.,Devices that ranked higher on all criteria tended to have a high or unlisted price.,Commonly mass-marketed devices like the pulse oximeter and spirometer surprisingly fulfilled the least criteria.,The COPD RPM technologies with most technological promise and compatibility with daily living appear to have high or unlisted prices.,Consumers and providers need better access to product information to make informed decisions. | In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs.,The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand).,We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay.,Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD.,Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales.,The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES).,In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up.,Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD.,For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD).,The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD.,The SPPB can aid in clinical decision making and when prioritising healthcare resources. | 1 |
In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation.,However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.,To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.,Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry.,IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.,In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers.,IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers.,In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups.,The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects.,The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers.,IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.,Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD. | The aim of this study is to quantify the burden of chronic obstructive pulmonary disease (COPD) - incidence, prevalence, and mortality - and identify trends in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, the United Kingdom, and the United States of America.,A structured literature search was performed (January 2000 to September 2010) of PubMed and EMBASE, identifying English-language articles reporting COPD prevalence, incidence, or mortality.,Of 2838 articles identified, 299 full-text articles were reviewed, and data were extracted from 133 publications.,Prevalence data were extracted from 80 articles, incidence data from 15 articles, and mortality data from 58 articles.,Prevalence ranged from 0.2%-37%, but varied widely across countries and populations, and by COPD diagnosis and classification methods.,Prevalence and incidence were greatest in men and those aged 75 years and older.,Mortality ranged from 3-111 deaths per 100,000 population.,Mortality increased in the last 30-40 years; more recently, mortality decreased in men in several countries, while increasing or stabilizing in women.,Although COPD mortality increased over time, rates declined more recently, likely indicating improvements in COPD management.,In many countries, COPD mortality has increased in women but decreased in men.,This may be explained by differences in smoking patterns and a greater vulnerability in women to the adverse effects of smoking.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use: http://dvpr.es/Nl3LKT | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction.,Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients.,In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, FVC, TLC, IC/TLC, PaO2, PaCO2, DLCO, Pimax, P0.1, Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ.,We estimated the association between these parameters and MMRC scores.,Multivariate analysis determined the independent strength of those associations.,MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV1 % (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO2 (men:-0.59, p < 0.001), PaCO2 (men:0.27, p = 0.05), DLCO (men:-0.54, p < 0.001), P0.1/Pimax (men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001).,Regression analysis showed that P0.1/Pimax in women (r2 = 0.30) and BMI, DLCO, PaO2 and P0.1/Pimax in men (r2 = 0.81) were the strongest predictors of MMRC scores.,In mild to severe COPD patients attending a pulmonary clinic, P0.1/Pimax was the unique predictor of MMRC scores only in women.,Respiratory factors explain most of the variations of MMRC scores in men but not in women.,Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD. | 1 |
Many patients suffering from asthma or COPD have overlapping features of both diseases.,However, a phenotypical approach for evaluating asthma-COPD overlap syndrome (ACOS) has not been established.,In this report, we examined the phenotypes in patients with ACOS.,Patients diagnosed with ACOS between 2011 and 2015 were identified and classified into four phenotype groups.,Group A was composed of patients who smoked <10 pack years and had blood eosinophil counts ≥300.,Group B was composed of patients who smoked <10 pack years and had blood eosinophil counts <300.,Group C was composed of patients who smoked ≥10 pack years and had blood eosinophil counts ≥300.,Group D was composed of patients who smoked <10 pack years and had blood eosinophil counts <300.,Clinical characteristics were analyzed and compared among groups.,Comparisons were made among 103 ACOS patients.,Patients in group D were oldest, while patients in group A were youngest.,There were relatively more female patients in groups A and B; the majority of patients in groups C and D were male.,The degree of airflow obstruction was most severe in group C.,The rate of being free of severe exacerbation was significantly lower in group C than in the other groups.,In this study, each ACOS phenotype showed different characteristics.,The proportion of patients free of severe exacerbation differed significantly among groups.,At this time, further studies on the phenotypes of ACOS are required. | There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters.,We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation.,Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization.,Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001).,Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001).,Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, −964 [SD, 19.62] vs asthmatic patients: mean, −937 [SD, 22.7] and healthy subjects: mean, −937 [SD, 17.1], P < .001).,Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping.,Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors.,Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air trapping.,In asthmatic patients and patients with COPD, lung function impairment is strongly associated with air trapping, with a contribution from proximal airway narrowing in asthmatic patients. | 1 |
Public health is a priority for the Chinese Government.,Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance.,This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.,We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017.,We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk.,We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).,Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017.,Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017.,Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017.,Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs.,All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88.,The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain.,The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).,China has made substantial progress in reducing the burden of many diseases and disabilities.,Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.,China National Key Research and Development Program and Bill & Melinda Gates Foundation. | Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world.,It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD.,The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected.,The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors.,In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity.,In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke.,We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. | COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020.,It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation.,This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion.,The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood.,Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease.,Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD.,Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies.,The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD. | 1 |
Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR).,The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD).,Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin.,The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR.,The primary endpoint of the study was the 1-month rate of HUVECs apoptosis.,The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint.,In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y 12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower.,There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups.,In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).,Supplementary Material to this article is available online at www.thrombosis-online.com. | The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis.,In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD).,We obtained surgical specimens from 10 patients with COPD and 10 control participants.,Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells.,Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE).,Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE.,The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis.,However, this activation can be abolished by N1ICD overexpression.,Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis.,These results suggest that CS alters Notch signaling in pulmonary endothelial cells.,Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.,To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.,A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted.,COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected.,Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis.,All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.,Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities.,Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations.,CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations.,All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001).,CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.,This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities.,Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities. | 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 |
Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality.,Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations.,However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate.,The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.,We comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.,Eleven RCTs and one retrospective study including a total of 2,151 cases were carried out.,Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24-0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45-0.78; P<0.01).,Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months.,In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance.,The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50).,Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).,Prophylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner.,However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance.,Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks. | Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years.,Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers.,However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways.,In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly.,Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis.,Nebulizers should be considered for patients unable to use handheld inhalers properly.,What follows is a review of issues associated with COPD and its treatment in the elderly patient. | 1 |
Assessment of airflow limitation (AFL) is crucial in the clinical evaluation of patients with chronic obstructive pulmonary disease (COPD).,However, in the absence of normative reference values among adult Australian Indigenous population, the implications of utilising the Global Lung Function Initiative (GLI-2012), Global Initiative for Chronic Obstructive Lung Disease (GOLD) and the Australian concise COPD-X recommended severity classifications is not known.,Moreover, spirometry values (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) are observed to be 20%-30% lower in an apparently healthy Indigenous population in comparison to Caucasian counterparts.,Adult Indigenous patients diagnosed to have COPD on spirometry (postbronchodilator (BD) FEV1/FVC <0.7 ((GOLD, (COPD-X)) and ≤lower limit of normal (others/mixed reference equations) for GLI-2012) were assessed for AFL severity classifications on Post-BD FEV1 values (mild, moderate, severe, very severe) as per the recommended classifications.,From a total of 742 unique patient records of Indigenous Australians, 253 were identified to have COPD via GOLD/COPD-X criteria (n=238) or GLI-2012 criteria (n=238) with significant agreeance between criteria (96%, κ=0.901).,Of these, the majority were classified as having moderate or severe/very-severe AFL with significant variability across classification criteria (COPD-X (40%-43%), GOLD (33%-65%), GLI-2012 (18%-75%)).,The FVC and FEV1 values also varied significantly between classification criterion (COPD-X/GOLD/GLI-2012) within the same AFL category, with COPD-X ‘moderate’ AFL almost matching ‘severe’ AFL categorisation by GOLD or GLI-2012.,Health professionals caring for Indigenous patients with COPD should be aware of the clinical implications and consequences of utilising various recommended AFL classifications in the absence of validated spirometry reference norms among adult Indigenous patients. | COPD among Aboriginal peoples in Canada is a major public health concern.,This study was conducted in order to determine the prevalence and association between certain risk factors and COPD among the 35-year-old or older Aboriginal peoples in Canada.,This is a cross-sectional study.,It uses data from Statistics Canada’s Aboriginal Peoples Survey (APS), 2012.,It consists of 8,117 self-identified Aboriginal peoples, aged 35 years old or older from all Canadian provinces and territories.,The study outcomes centered on evaluating the prevalence and associated factors of COPD.,This study found that 6.80% of the participants self-reported having COPD.,Results of the logistic regression analysis show that COPD was significantly higher among daily smokers (odds ratio [OR], 2.28; 95% confidence interval [95% CI], 1.65-3.14), aged 55 years or older (OR, 3.04; 95% CI, 2.14-4.30), who earned $5,000-$9,999 per annum (OR, 4.21; 95% CI, 2.39-7.41) and needed health care over the past 12 months and did not receive it (OR, 1.83; 95% CI, 1.27-2.65).,The findings of our study show that COPD is strongly associated with Aboriginal peoples, who are older, smoke, have a low socioeconomic status (SES) and do not have access to health care when needed.,Clinicians, health care professionals, medical/public health organizations, researchers and patients will greatly benefit from additional research in this common, serious and often overlooked disease among Aboriginal peoples in Canada. | 1 |
Inhaled bronchodilator medications are central to the management of COPD and are frequently given on a regular basis to prevent or reduce symptoms.,While short-acting bronchodilators are a treatment option for people with relatively few COPD symptoms and at low risk of exacerbations, for the majority of patients with significant breathlessness at the time of diagnosis, long-acting bronchodilators may be required.,Dual bronchodilation with a long-acting β2-agonist and long-acting muscarinic antagonist may be more effective treatment for some of these patients, with the aim of improving symptoms.,This combination may also reduce the rate of exacerbations compared with a bronchodilator-inhaled corticosteroid combination in those with a history of exacerbations.,However, there is currently a lack of guidance on clinical indicators suggesting which patients should step up from mono- to dual bronchodilation.,In this article, we discuss a number of clinical indicators that could prompt a patient and physician to consider treatment escalation, while being mindful of the need to avoid unnecessary polypharmacy.,These indicators include insufficient symptomatic response, a sustained increased requirement for rescue medication, suboptimal 24-hour symptom control, deteriorating symptoms, the occurrence of exacerbations, COPD-related hospitalization, and reductions in lung function.,Future research is required to provide a better understanding of the optimal timing and benefits of treatment escalation and to identify the appropriate tools to inform this decision. | Chronic obstructive pulmonary disease is associated with significant morbidity and mortality.,Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations, while patients are much more concerned about symptoms and health status.,Our aim was to investigate the effects of tiotropium + olodaterol on patient-reported health outcomes, breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease, compared to placebo, tiotropium or olodaterol monotherapy.,Two pairs of replicate, phase III studies of 12 (OTEMTO 1 + 2) and 52 weeks’ (TONADO 1 + 2) duration were evaluated, in which patients received either tiotropium + olodaterol 2.5/5 or 5/5 μg, tiotropium 2.5 or 5 μg, olodaterol 5 μg or placebo, all delivered once daily via Respimat inhaler.,Patient-reported outcomes included breathlessness assessed by transition dyspnoea index focal score, health status assessed by St George’s Respiratory Questionnaire total score and night-time rescue medication use at 12 or 24 weeks.,Outcomes from the pooled study data are reported.,Overall, 1621 and 5162 patients were treated in the OTEMTO and TONADO trials, respectively.,Significantly larger improvements in St George’s Respiratory Questionnaire and transition dyspnoea index focal scores were observed and a greater proportion of patients were responders to therapy (based on minimum clinically important differences in St George’s Respiratory Questionnaire and transition dyspnoea index) with tiotropium + olodaterol compared to either monotherapy or to placebo.,Tiotropium + olodaterol 5/5 µg significantly reduced night-time rescue medication usage.,Results from four in-depth studies show that a combined inhaler is very effective for treatment of moderate to severe chronic lung disease.,Alleviating the symptoms of chronic obstructive pulmonary disease (COPD), particularly sleep disturbance, is crucial to enhancing patients’ quality of life.,Gary Ferguson at the Pulmonary Research Institute of Southeast Michigan, together with other scientists across the USA and Germany, analysed data from four large-scale studies to evaluate the efficacy of STIOLTO Respimat, a combination of two bronchodilators-tiotropium, and olodaterol, which tackle airway obstruction and breathlessness, improving long-term lung function.,They found that the new drug combination triggered significant improvements in patients’ quality of life and levels of breathlessness.,Use of night-time rescue medication in patients on STIOLTO Respimat was considerably reduced.,A greater number of patients responded positively to the combined inhaler than to monotherapy. | 1 |
Management of acute exacerbations of chronic obstructive pulmonary disease (COPD) is sometimes inadequate leading to either prolonged duration and/or an increased risk of recurrent exacerbations in the period following the initial event.,To evaluate the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ inhibitor, in patients experiencing an acute exacerbation of COPD.,In this double-blind, placebo-controlled study, COPD patients (40-80 years, ≥10 pack-year smoking history, current moderate/severe acute exacerbation of COPD requiring standard-of-care treatment) were randomized to placebo or nemiralisib 12.5 µg, 50 µg, 100 µg, 250 µg, 500 µg, or 750 µg (ratio of 3:1:1:1:1:1:3; N=938) for 12 weeks with an exploratory 12-week follow-up period.,The primary endpoint was change from baseline in post-bronchodilator FEV1 at week 12.,Key secondary endpoints were rate of re-exacerbations, patient-reported outcomes (Exacerbations of Chronic Pulmonary Disease Tool, COPD Assessment Test, St George's Respiratory Questionnaire-COPD), plasma pharmacokinetics (PK) and safety/tolerability.,There was no difference in change from baseline FEV1 at week 12 between the nemiralisib and placebo treatment groups (posterior adjusted median difference, nemiralisib 750 µg and placebo: −0.004L (95% CrI: −0.051L to 0.042L)).,Overall, there were also no differences between nemiralisib and placebo in secondary endpoints, including re-exacerbations.,Plasma PK increased in a dose proportional manner.,The most common adverse event for nemiralisib was post-inhalation cough which appeared to be dose-related.,The addition of nemiralisib to standard-of-care treatment for 12 weeks did not improve lung function or re-exacerbations in patients with, and following an acute exacerbation of COPD.,However, this study demonstrated that large clinical trials recruiting acutely exacerbating patients can successfully be conducted. | The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages.,We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker).,Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500.,Approximately 25% of the macrophages did not harbor classical M1 or M2 surface markers (double negative, DN), and these cells were significantly enriched in COPD patients compared with non-COPD patients (46.7% vs.,14.5%, p < 0.001). 1886 genes were differentially expressed in the DN subtype compared with all other subtypes at a 10% false discovery rate.,The 602 up-regulated genes included 15 mitochondrial genes and were enriched in 86 gene ontology (GO) biological processes including inflammatory responses.,Modules associated with cellular functions including oxidative phosphorylation were significantly down-regulated in the DN subtype.,Macrophages in the human BAL fluid, which were negative for both M1/M2 surface markers, harbored a gene signature that was pro-inflammatory and suggested dysfunction in cellular homeostasis.,These macrophages may contribute to the pathogenesis and manifestations of inflammatory lung diseases such as COPD. | 1 |
Interleukin-1 receptor 1 (IL-1R1) inhibition is a potential strategy for treating patients with chronic obstructive pulmonary disease (COPD).,MEDI8968, a fully human monoclonal antibody, binds selectively to IL-1R1, inhibiting activation by IL-1α and IL-1β.,We studied the efficacy and safety/tolerability of MEDI8968 in adults with symptomatic, moderate-to-very severe COPD.,This was a phase II, randomised, double-blind, placebo-controlled, multicentre, parallel-group study.,Subjects aged 45-75 years and receiving standard maintenance therapy with ≥2 exacerbations in the past year were randomised 1:1 to receive placebo or MEDI8968 300 mg (600 mg intravenous loading dose) subcutaneously every 4 weeks, for 52 weeks.,The primary endpoint was the moderate/severe acute exacerbations of COPD (AECOPD) rate (week 56 post-randomisation).,Secondary endpoints were severe AECOPD rate and St George’s Respiratory Questionnaire-COPD (SGRQ-C) score (week 56 post-randomisation).,Of subjects randomised to placebo (n = 164) and MEDI8968 (n = 160), 79.3% and 75.0%, respectively, completed the study.,There were neither statistically significant differences between treatment groups in moderate/severe AECOPD rate ([90% confidence interval]: 0.78 [0.63, 0.96], placebo; 0.71 [0.57, 0.90], MEDI8968), nor in severe AECOPD rate or SGRQ-C scores.,Post-hoc analysis of subject subgroups (by baseline neutrophil count or tertiles of circulating neutrophil counts) did not alter the study outcome.,The incidence of treatment-emergent adverse events (TEAEs) with placebo and MEDI8968 treatment was similar.,The most common TEAE was worsening of COPD.,In this phase II study, MEDI8968 did not produce statistically significant improvements in AECOPD rate, lung function or quality of life.,ClinicalTrials.gov, NCT01448850, date of registration: 06 October 2011.,The online version of this article (doi:10.1186/s12931-017-0633-7) contains supplementary material, which is available to authorized users. | One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients.,However, local inflammation may result and can contribute to worsening of clinical status in these patients.,We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients.,This initial study sought to investigate the safety of this approach.,For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used.,Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs.,Patients were evaluated 1, 7, 30, and 90 days after therapy.,All patients completed the study protocol and 90‐day follow‐up.,MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death.,No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease.,Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes.,However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV.,EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores.,Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy.,Stem Cells Translational Medicine 2017;6:962-969 | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a chronic, progressive disease that is not curable.,However, there are effective treatments available.,In the UK, long-acting bronchodilators are first-line treatments for COPD patients requiring maintenance therapy, and there are several options available.,The aim of this study is to establish, from the UK National Health Service (NHS) perspective, the cost-effectiveness profile of indacaterol, the first once-daily long-acting beta2-agonist (LABA), compared with tiotropium and salmeterol, in patients with moderate to severe COPD.,In assessing the cost-effectiveness of COPD therapies, this study has the advantage of using real world evidence on the resource use associated with COPD management across the spectrum of the disease.,A Markov model was developed with four health states following the GOLD classification for severity of airflow limitation.,The model time horizon was 3 years, and the cycle length was 3 months.,From each state, patients could experience a severe or non-severe exacerbation, move to a different COPD state, remain in the current state or die.,Transition probabilities were based on data from the indacaterol clinical trials.,The majority of the resource use data was taken from the Optimum Patient Care Research Database (OPCRD), which contains data from over 20,000 COPD patients in England and Scotland.,Cost data were taken from UK-based sources and published literature and presented for the cost year 2011.,Health-related quality of life was the main outcome of interest and utility data for the COPD states were based on data from the indacaterol clinical trials and disutility due to exacerbations were taken from the literature.,Both one way and probabilistic sensitivity analyses were performed to test the robustness of the results.,Indacaterol dominated in the comparison with salmeterol producing an incremental QALY gain of 0.008 and cost savings of £110 per patient over a 3-year time horizon.,In the comparison with tiotropium over the same time horizon, indacaterol remained the dominant strategy, producing an incremental QALY gain of 0.008 and cost savings of £248 per patient.,The one-way sensitivity analysis indicates that the proportion of patients in each of the COPD stages and the mortality rate associated with Very Severe COPD are the variables with the largest impact on the results.,The probabilistic sensitivity analyses showed that over 72 % and 89 % of the iterations when compared with salmeterol and tiotropium, respectively, produced dominant results for indacaterol.,The analyses demonstrate that indacaterol dominates both tiotropium and salmeterol in the base case and is likely to remain cost-effective under a range of assumptions. | The objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs.,22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5), indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7), and formoterol 12 μg (n = 4).,All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled.,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and St.,George’s Respiratory Questionnaire (SGRQ) total score at week 12.,The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained.,In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA.,Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials.,All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks.,Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses.,In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09).,In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo, whereas for tiotropium and salmeterol the credible intervals included zero for the AD results only (tiotropium: -2.99 points improvement versus placebo; 95%CrI −6.48 to 0.43; salmeterol:-2.52; 95%CrI: -5.34; 0.44).,Both IPD and AD results suggest that indacaterol 75 μg is expected to be comparable to all active treatments.,Based on a synthesis of currently available AD RCT evidence as well as an IPD network meta-analysis of six RCTs, indacaterol 75 μg is expected to be at least as efficacious as formoterol and comparable to tiotropium and salmeterol regarding FEV1.,Furthermore, indacaterol 75 μg shows comparable level of improvement in health-related quality of life to tiotropium, salmeterol, and formoterol, as measured by the SGRQ. | 1 |
Data regarding osteoporosis in COPD patients in Taiwan remain limited.,The primary end point of this study was to evaluate the prevalence and risk factors of osteoporosis in COPD patients in Taiwan.,The secondary end point was to examine the association between osteoporosis and health-related quality of life (HRQL) in COPD patients.,This prospective cross-sectional study enrolled 125 COPD patients (mean age 73.6 years, forced expiratory volume in 1 second [FEV1] 1.19±0.43 L) who had bone mineral-density measurements performed consecutively.,Demographic data, lung function, and HRQL including modified Medical Research Council dyspnea scale, St George’s Respiratory Questionnaire, oxygen-cost diagram, Center for Epidemiologic Studies - depression scale, and COPD Assessment Test scores were recorded.,A total of 50 (40%) participants were diagnosed as having osteoporosis.,In a multivariate logistic regression model including age, smoking amount (pack-year), body mass index (BMI), and FEV1, only BMI (odds ratio 0.824, 95% confidence interval 0.73-0.93; P=0.002) and FEV1 (odds ratio 0.360, 95% confidence interval 0.13-0.98; P=0.046) were negatively associated with an increased risk of osteoporosis in COPD patients.,In addition, COPD patients with osteoporosis had significantly higher modified Medical Research Council dyspnea scale scores (1.7±0.8 vs 1.4±0.8, P=0.046), St George’s Respiratory Questionnaire scores (36.6 vs 28.0, P=0.01), and COPD Assessment Test scores (14.7±8 vs 11.5±7, P=0.019), and lower oxygen-cost diagram score (4.8±1.8 vs 5.4±1.6, P=0.045) than patients without osteoporosis.,The prevalence of osteoporosis in COPD patients was high at a community hospital in Taiwan.,BMI and FEV1 were the independent risk factors for osteoporosis in COPD.,In addition, COPD patients with osteoporosis had worse HRQL than those without osteoporosis. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD).,However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear.,PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers.,The HDAC2 and NF-κB p65 expression were quantified by Western Blot.,HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit.,Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA.,HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers.,Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers.,The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients.,Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers.,HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity.,The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation.,Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function. | Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder.,COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways.,We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.,Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects.,TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood.,CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors.,PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.,No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects.,However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells.,Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression.,CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ.,Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.,Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD.,CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production.,These results provide a new perspective on the role of CD8+ T cells in COPD. | 1 |
Serum D-dimer is elevated in respiratory disease.,The objective of our study was to investigate the effect of D-dimer on in-hospital and 1-year mortality after acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Upon admission, we measured 343 AECOPD patients’ serum D-dimer levels and arterial blood gas analysis, and recorded their clinical characteristics.,The level of D-dimer that discriminated survivors and non-survivors was determined using a receiver operator curve (ROC).,The risk factors for in-hospital mortality were identified through univariate analysis and multiple logistic regression analyses.,To evaluate the predictive role of D-dimer for 1-year mortality, univariate and multivariate Cox regression analyses were performed.,In all, 28 patients died, and 315 patients survived in the in-hospital period.,The group of dead patients had lower pH levels (7.35±0.11 vs 7.39±0.05, P<0.0001), higher D-dimer, arterial carbon dioxide tension (PaCO2), C-reactive protein (CRP), and blood urea nitrogen (BUN) levels (D-dimer 2,244.9±2,310.7 vs 768.2±1,078.4 µg/L, P<0.0001; PaCO2: 58.8±29.7 vs 46.1±27.0 mmHg, P=0.018; CRP: 81.5±66, P=0.001; BUN: 10.20±6.87 vs 6.15±3.15 mmol/L, P<0.0001), and lower hemoglobin levels (118.6±29.4 vs 128.3±18.2 g/L, P=0.001).,The areas under the ROC curves of D-dimer for in-hospital death were 0.748 (95% confidence interval (CI): 0.641-0.854).,D-dimer ≥985 ng/L was a risk factor for in-hospital mortality (relative risk =6.51; 95% CI 3.06-13.83).,Multivariate logistic regression analysis also showed that D-dimer ≥985 ng/L and heart failure were independent risk factors for in-hospital mortality.,Both univariate and multivariate Cox regression analyses showed that D-dimer ≥985 ng/L was an independent risk factor for 1-year death (hazard ratio (HR) 3.48, 95% CI 2.07-5.85 for the univariate analysis; and HR 1.96, 95% CI 1.05-3.65 for the multivariate analysis).,D-dimer was a strong and independent risk factor for in-hospital and 1-year death for AECOPD patients. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients.,In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally.,Demographics, anthropometrics, lung function and clinical data were assessed.,Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband.,Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters.,Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns.,Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data.,Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all).,Daily physical activity measures and hourly patterns are heterogeneous in COPD.,Clusters of patients were identified solely based on physical activity data.,These findings may be useful to develop interventions aiming to promote physical activity in COPD. | Changes in physical activity (PA) are difficult to interpret because no framework of minimal important difference (MID) exists.,We aimed to determine the minimal important difference (MID) in physical activity (PA) in patients with Chronic Obstructive Pulmonary Disease and to clinically validate this MID by evaluating its impact on time to first COPD-related hospitalization.,PA was objectively measured for one week in 74 patients before and after three months of rehabilitation (rehabilitation sample).,In addition the intraclass correlation coefficient was measured in 30 patients (test-retest sample), by measuring PA for two consecutive weeks.,Daily number of steps was chosen as outcome measurement.,Different distribution and anchor based methods were chosen to calculate the MID.,Time to first hospitalization due to an exacerbation was compared between patients exceeding the MID and those who did not.,Calculation of the MID resulted in 599 (Standard Error of Measurement), 1029 (empirical rule effect size), 1072 (Cohen's effect size) and 1131 (0.5SD) steps.day-1.,An anchor based estimation could not be obtained because of the lack of a sufficiently related anchor.,The time to the first hospital admission was significantly different between patients exceeding the MID and patients who did not, using the Standard Error of Measurement as cutoff.,The MID after pulmonary rehabilitation lies between 600 and 1100 steps.day-1.,The clinical importance of this change is supported by a reduced risk for hospital admission in those patients with more than 600 steps improvement. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death world-wide, where chronic inflammation accelerates lung function decline.,Pathological inflammation is worsened by chronic bacterial lung infections and susceptibility to recurrent acute exacerbations of COPD (AECOPD), typically caused by viral and/or bacterial respiratory pathogens.,Despite ongoing efforts to reduce AECOPD rates with inhaled corticosteroids, COPD patients remain at heightened risk of developing serious lung infections/AECOPD, frequently leading to hospitalization and infection-dependent delirium.,Here, we review emerging mechanisms into why COPD patients are susceptible to chronic bacterial infections and highlight dysregulated inflammation and production of reactive oxygen species (ROS) as central causes.,This underlying chronic infection leaves COPD patients particularly vulnerable to acute viral infections, which further destabilize host immunity to bacteria.,The pathogeneses of bacterial and viral exacerbations are significant as clinical symptoms are more severe and there is a marked increase in neutrophilic inflammation and tissue damage.,AECOPD triggered by a bacterial and viral co-infection increases circulating levels of the systemic inflammatory marker, serum amyloid A (SAA).,SAA is a functional agonist for formyl peptide receptor 2 (FPR2/ALX), where it promotes chemotaxis and survival of neutrophils.,Excessive levels of SAA can antagonize the protective actions of FPR2/ALX that involve engagement of specialized pro-resolving mediators, such as resolvin-D1.,We propose that the anti-microbial and anti-inflammatory actions of specialized pro-resolving mediators, such as resolvin-D1 should be harnessed for the treatment of AECOPD that are complicated by the co-pathogenesis of viruses and bacteria. | Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide.,It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases.,Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea.,The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections.,Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria.,This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations.,Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response.,Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system.,These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.”,Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status.,In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients. | 1 |
Non-small cell lung cancer (NSCLC) is the predominant cause of death in patients with COPD, and the severity of COPD in NSCLC patients is classified mainly as mild to moderate.,Most advanced NSCLC patients with mild to moderate COPD are treated with chemotherapy; however, the feasibility for and prognosis after chemotherapy of these patients are not well understood.,The aim of this study was to elucidate the impact of mild to moderate COPD on the feasibility for and prognosis after chemotherapy in NSCLC patients.,A retrospective review was performed on 268 NSCLC patients who received first-line chemotherapy from 2009 to 2014 in our institution.,Finally, 85 evaluable patients were included in this study.,The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients with mild to moderate COPD and those without COPD (non-COPD).,Forty-three patients were classified as COPD (27 cases mild and 16 cases moderate) and 42 patients as non-COPD.,The COPD group were older and had fewer never-smokers than the non-COPD group.,The objective response rate did not differ between groups (p=0.14).,There was no significant difference in overall survival between COPD and non-COPD groups (15.0 and 17.0 months, log-rank test p=0.57).,In the multivariate Cox’s proportional hazard model, the adjusted hazard ratio (HRadj) was statistically significant for male sex (HRadj =5.382, 95% CI: 1.496-19.359; p=0.010), pathological diagnosis of adenocarcinoma (HRadj =0.460, 95% CI: 0.223-0.948; p=0.035), and epithelial growth factor receptor negative mutation (HRadj =6.040, 95% CI: 1.158-31.497; p=0.033), but not for the presence of COPD (HRadj =0.661, 95% CI: 0.330-1.325; p=0.24).,Toxicity profile in COPD group was favorable, as in the non-COPD group.,Mild to moderate COPD did not have a significant deleterious impact on toxicity and prognosis in NSCLC patients. | A low body mass index (BMI) is associated with increased mortality and low health-related quality of life in patients with COPD.,The Asia-Pacific classification of BMI has a lower cutoff for overweight and obese categories compared to the World Health Organization (WHO) classification.,The present study assessed patients with COPD among different BMI categories according to two BMI classification systems: WHO and Asia-Pacific.,Patients with COPD aged 40 years or older from the Korean COPD Subtype Study cohort were selected for evaluation.,We enrolled 1,462 patients.,Medical history including age, sex, St George’s Respiratory Questionnaire (SGRQ-C), the modified Medical Research Council (mMRC) dyspnea scale, and post-bronchodilator forced expiratory volume in 1 second (FEV1) were evaluated.,Patients were categorized into different BMI groups according to the two BMI classification systems.,FEV1 and the diffusing capacity of the lung for carbon monoxide (DLCO) percentage revealed an inverse “U”-shaped pattern as the BMI groups changed from underweight to obese when WHO cutoffs were applied.,When Asia-Pacific cutoffs were applied, FEV1 and DLCO (%) exhibited a linearly ascending relationship as the BMI increased, and the percentage of patients in the overweight and obese groups linearly decreased with increasing severity of the Global Initiative for Chronic Obstructive Lung Disease criteria.,From the underweight to the overweight groups, SGRQ-C and mMRC had a decreasing relationship in both the WHO and Asia-Pacific classifications.,The prevalence of comorbidities in the different BMI groups showed similar trends in both BMI classifications systems.,The present study demonstrated that patients with COPD who have a high BMI have better pulmonary function and health-related quality of life and reduced dyspnea symptoms.,Furthermore, the Asia-Pacific BMI classification more appropriately reflects the correlation of obesity and disease manifestation in Asian COPD patients than the WHO classification. | 1 |
Efficient management of COPD represents an international challenge.,Effective management strategies within the means of limited health care budgets are urgently required.,This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET).,Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET.,The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy.,Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR).,Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores.,Home-based DM was associated with improved mortality and quality-adjusted life expectancy.,DM and UM were associated with equivalent direct costs (DM reduced costs by EUR −37 per patient per year) in the pooled analysis.,DM was associated with lower costs in France (EUR −806 per patient per year) and Spain (EUR −51 per patient per year), but higher costs in Germany (EUR 391 per patient per year).,Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM.,Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany.,Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis.,DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained.,The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers. | Caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function.,However, no systematic review has examined how the caregiver role has been operationalized in interventions to improve outcomes of individuals with COPD or the quality or effectiveness of these interventions.,The aims of this review were to 1) determine whether caregivers have been involved as part of interventions to improve outcomes of individuals with COPD; 2) determine the risk of bias within included intervention studies; and 3) examine the effectiveness of interventions that have involved caregivers in improving outcomes of individuals with COPD.,The electronic databases of Medline, Embase, PsycINFO, and Cochrane Library were searched from January 2000 to November 2015.,Experimental studies testing interventions that involved a caregiver to improve COPD patient outcomes were eligible.,Nine studies involving caregivers met inclusion criteria.,No studies reported any intervention components targeted solely at caregivers, with most instead including caregivers in dyadic or group education sessions about COPD delivered by health care professionals.,The risk of bias identified in included studies was mixed.,Seven of the nine studies were effective in improving a broad range of outcomes.,These findings highlight that there is an urgent need for methodologically rigorous interventions to examine the effectiveness of strategies to assist caregivers to provide direct care, encourage adherence to health care provider recommendations, act as a health care advocate, and provide emotional and psychosocial support to individuals with COPD. | 1 |
Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD.,However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD.,The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension.,The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension.,Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography.,Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension.,There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups.,For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels.,These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients. | Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood.,A number of candidate genes have been proposed on the basis of the pathogenesis of COPD.,These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD.,Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies.,To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations.,We used logistic regression to adjust for age, gender, centre and smoking history.,Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV.,Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94).,The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129).,This implicates haplotypes of MMP-12 as modifiers of disease severity. | 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. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
To assess the impact of home telemonitoring on health service use and quality of life in patients with severe chronic lung disease.,Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring.,68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission.,Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team.,Primary outcome measure was time to first hospital admission for an acute exacerbation.,Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford).,Median (IQR) number of days to first admission showed no difference between the two groups-77 (114) telemonitoring, 77.5 (61) control (p=0.189).,Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026).,Home visits increased during telemonitoring; GP consultations were unchanged.,Self-efficacy fell, while HAD depression score improved marginally during telemonitoring.,Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients.,NCT02180919 (ClinicalTrials.gov). | To assess the effects of a home-based telehealth intervention on the use of secondary healthcare and mortality.,Observational study of a mainstream telehealth service, using person-level administrative data.,Time to event analysis (Cox regression) was performed comparing telehealth patients with controls who were matched using a machine-learning algorithm.,A predominantly rural region of England (North Yorkshire).,716 telehealth patients were recruited from community, general practice and specialist acute care, between June 2010 and March 2013.,Patients had chronic obstructive pulmonary disease, congestive heart failure or diabetes, and a history of associated inpatient admission.,Patients were matched 1:1 to control patients, also selected from North Yorkshire, with respect to demographics, diagnoses of health conditions, previous hospital use and predictive risk score.,Telehealth involved the remote exchange of medical data between patients and healthcare professionals as part of the ongoing management of the patient's health condition.,Monitoring centre staff alerted healthcare professionals if the telemonitored data exceeded preset thresholds.,Control patients received usual care, without telehealth.,Time to the first emergency (unplanned) hospital admission or death.,Secondary metrics included time to death and time to first admission, outpatient attendance and emergency department visit.,Matched controls and telehealth patients were similar at baseline.,Following enrolment, telehealth patients were more likely than matched controls to experience emergency admission or death (adjusted HR 1.34, 95% CI 1.16 to 1.56, p<0.001).,They were also more likely to have outpatient attendances (adjusted HR=1.25, 1.11 to 1.40, p<0.001), but mortality rates were similar between groups.,Sensitivity analyses showed that we were unlikely to have missed reductions in the likelihood of an emergency admission or death because of unobserved baseline differences between patient groups.,Telehealth was not associated with a reduction in secondary care utilisation. | 1 |
COPD has been identified as an etiology or related disease of bronchiectasis, and bronchiectasis has been classified as a comorbidity of COPD.,In this study, we investigated the prevalence of bronchiectasis in different phenotypes of COPD subjects and the correlation between bronchiectasis and different phenotypes, especially emphysema.,COPD patients were recruited from April 2012 to December 2015.,The presence of bronchiectasis and related information were statistically analyzed.,COPD subjects were separated into subgroups in two ways: COPD with and without bronchiectasis groups and emphysema-predominant (emphysema index, EI≥9.9%) and non-emphysema-predominant (EI<9.9%) groups.,In total, 1,739 COPD patients were incorporated into the study, among which 140 cases (8.1%) were accompanied with radiological bronchiectasis.,COPD patients with concomitant bronchiectasis presented worse pulmonary function (FEV1% predicted, P<0.001), higher EI (15.0% vs 13.4%, P<0.001), and higher proportion of pulmonary hypertension and cor pulmonale (6.4% vs 2.4%, P=0.005 and 23.6% vs 16.1%, P=0.022) than patients without bronchiectasis.,Of all the COPD patients, 787 with EI data were divided into emphysema-predominant (n=369) and non-emphysema-predominant groups (n=418).,The proportion of bronchiectasis was 16.5% and 10.3% (P=0.01), respectively.,Severity of bronchiectasis increased as the degree of airflow limitation (r=−0.371, P<0.001) and emphysema increased (r=0.226, P=0.021).,After adjusting confounding factors, FEV1% predicted (OR, 1.636; 95% CI, 1.219-2.197; P=0.001) and EI (OR, 1.993; 95% CI, 1.199-3.313; P=0.008) were significantly related with the presence of bronchiectasis in COPD patients.,The proportion of bronchiectasis is higher in emphysema-predominant COPD subjects.,Emphysema measured by EI and FEV1% predicted are independent predictors for bronchiectasis in COPD subjects, while the underlying mechanism deserves further investigation. | A high prevalence of bronchiectasis was found by chest computed tomography (CT) in patients with moderate-severe chronic obstructive pulmonary disease (COPD), and it was shown to be associated with more severe symptoms, higher frequency of exacerbations and mortality.,The risk factors for bronchiectasis in COPD are not yet clarified.,High-resolution computed tomography (HRCT) of chest was performed in patients with moderate-severe COPD, and the presence and the extent of bronchiectasis were evaluated by two radiologists.,Demographic data, respiratory symptoms, lung function, previous pulmonary tuberculosis, serum inflammatory markers, serum total immunoglobulin E (T-IgE), and sputum culture of Pseudomonas aeruginosa were compared between those with and without bronchiectasis.,Multivariate logistic regression analysis was used to determine the independent factors associated with bronchiectasis.,We enrolled 190 patients with stable COPD, of which 87 (87/190, 45.8%) had bronchiectasis on HRCT.,Compared with those without bronchiectasis, COPD patients with bronchiectasis were more likely to be males (P = 0.021), had a lower body mass index (BMI) (P = 0.019), a higher prevalence of previous tuberculosis (P = 0.005), longer history of dyspnea (P < 0.001), more severe dyspnea (P = 0.041), higher frequency of acute exacerbation (P = 0.002), higher serum concentrations of C-reactive protein (CRP) (P = 0.017), fibrinogen (P = 0.016), and T-IgE [P = 0.004; for log10(T-IgE), P <0.001].,COPD patients with bronchiectasis also showed poorer lung function (for FEV1/FVC, P = 0.013; for FEV1%predicted, P = 0.012; for global initiative for chronic obstructive lung disease (GOLD) grades, P = 0.035), and a higher positive rate of sputum P aeruginosa (P = 0.020).,Logistic regression analysis demonstrated that male gender (P = 0.021), previous tuberculosis (P = 0.021), and increased level of serum T-IgE [for log10(T-IgE), P < 0.001] were risk factors for coexistent bronchiectasis.,More notably, the level of serum T-IgE [log10(T-IgE)] was positively correlated with the extent of bronchiectasis in COPD patients (r = 0.208, P = 0.05).,Higher serum T-IgE, male gender, and previous tuberculosis are independent risk factors for coexistent bronchiectasis in COPD.,The association of T-IgE with the extent of bronchiectasis also suggests that further investigations are needed to explore the potential role of IgE in the pathogenesis of bronchiectasis in COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes. | 1 |
COPD is a civilization disease.,It affects up to 8%-10% of population >30 years of age.,Coexistence of depression occurs in 20%-40% of patients with COPD.,Depression and anxiety reduce compliance and worsen prognosis.,The aims of this study were to determine the degree of illness acceptance among patients with COPD, to examine the relation between disease acceptance and perceived anxiety and depression, and to verify which of the sociodemographic and clinical factors are associated with illness acceptance, anxiety, and depression.,The study included 102 patients with COPD (mean age 65.8 years), hospitalized due to exacerbations.,Acceptance of Illness Scale and Hospital Anxiety and Depression Scale were used.,For statistical analysis, Student’s t-test and Pearson’s r correlation coefficient were carried out.,The overall illness acceptance level was moderate with a tendency toward lack of acceptance (mean 20.6, standard deviation [SD] 7.62).,The overall scores were 10.2 (SD 3.32) for anxiety and 10.8 (SD 4.14) for depression, which indicate borderline or high intensity of these symptoms.,Acceptance of illness was negatively correlated with the intensity of depression symptoms (r=−0.46, P<0.05).,Intensity of depression was significantly associated with intensity of smoking, duration of the disease, severity of dyspnea, and living in a rural area.,Early identification and assessment of depression and anxiety symptoms allow health care providers to offer patients at risk of depression a special medical supervision.,Rapid start of antidepressant therapy may increase illness acceptance and improve prognosis among patients with COPD. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
Early diagnosis of COPD is often not achieved due to limited recognition and limited access to the pulmonary function test.,Our hypothesis was that lung function decline may be different between populations with mild COPD and those who are at high risk and do not receive treatment.,Subjects with mild COPD and those from a high-risk COPD population were recruited from a community-based COPD epidemiological study after obtaining consent.,Baseline clinical characteristics, symptom questionnaire, spirometry, low-dose computed tomography (LDCT) chest scan, and blood plasma biomarker data were collected initially and then 1 year later.,A total of 617 participants were recruited, and 438 eventually completed the first-year follow-up visit; 72 participants (46 males) were in the mild COPD group, and 225 participants (165 males) were in the high-risk group.,The mean forced expiratory volume in the first second of expiration (FEV1) decline in the mild COPD group was 129 mL, which was significantly higher than the 30 mL decline in the high-risk population group (P=0.005).,Group category (odds ratio [OR] =0.230) and COPD Assessment Test (CAT) score (OR =9.912) were independent risk factors for an FEV1% predicted decline of >15% for all participants.,In the mild COPD group, patients with a higher CAT (OR =5.310) and Emphysema Index (OR =5.681) were associated with a FEV1% predicted decline of >15% at the first-year follow-up.,No factor showed a significantly predictive effect on FEV1 decline in the high-risk COPD group.,Group category was an independent influential factor associated with FEV1 decline. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
Hand grip strength (HGS) is a simple way of predicting the risk of cardiovascular disease and all-cause mortality in the general population.,However, the practical significance of grip strength in patients with COPD is uncertain.,The aim of this study was to compare HGS between subjects with and without COPD and to evaluate its clinical relevance in patients with COPD by using a national survey.,Data were collected from the Korean National Health and Nutrition Examination Survey.,The study included 421 adults with COPD and 2,542 controls who completed questionnaires, spirometry, and a HGS test.,HGS was compared between subjects with and without COPD, and the association between grip strength, lung function, and quality of life (QoL) was evaluated.,The mean HGS was 33.3±9.1 kg in the COPD group and 29.9±9.5 kg in the non-COPD group; adjusted HGS was 30.9±0.33 kg and 30.9±0.11 kg, respectively (P=0.99).,HGS was not related to forced vital capacity (β=0.04, P=0.70) or forced expiratory volume in 1 second (β=0.11, P=0.24) in multivariable analysis.,HGS was independently associated with the EQ-5D index, but the relationship was stronger in the COPD group (β=0.30, P<0.001) than in the non-COPD group (β=0.21, P<0.001).,The results were similar for each component of the EQ-5D, including mobility (β=−0.25, P<0.001), daily activity (β=−0.19, P=0.01), pain/discomfort (β=−0.32, P<0.001), and anxiety/depression (β=−0.16, P=0.01).,HGS was not different between subjects with and without COPD, but was associated with QoL - including mobility, daily activity, pain/discomfort, and anxiety/depression - in patients with COPD.,The HGS test could be used as a marker of QoL in patients with COPD and could assist risk stratification in clinical practice. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
Few studies have evaluated the contribution of both viruses and bacteria in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,This study estimated the burden of both types of pathogens among adults seeking care for an AECOPD during two consecutive winter seasons.,Patients 50 years or older who consulted within 10 days of AECOPD onset were eligible.,Clinical data were collected on a standardized questionnaire, and nasopharyngeal aspirates (NPA), paired sera, and non-induced sputum were collected.,Polymerase chain reaction (PRC) assays were used to identify viral, atypical and bacterial pathogens in NPA specimen.,Overall, 108 patients with AECOPD were included, 88% of patients were admitted and 2 patients (2%) received intensive care.,A third of patients (31%) had evidence of a viral infection, 9% with influenza A, 7% RSV and 7% with PIV-3.,One patient was positive for Mycoplasma pneumoniae.,Bacterial pathogens were identified in 49% of patients with available sputum, most frequently Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae.,Among virus-infected patients, 14 (58%) also had bacteria in their sputum, but co-infected patients did not present with different symptoms than patients with single infections.,These results suggest that influenza and RSV are frequent contributors of AECOPD, and that coinfection with bacteria does not appear to be more severe among virus-infected patients.,Clinicians should be aware that AECOPD may be frequently triggered by viruses, and may consider antivirals and proper infection control measures in appropriate epidemiological setting. | Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | 1 |
The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care.,The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation.,Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care).,Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care.,The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32).,The program was accessed on 86% of the treatment days, especially the diary.,Patient adherence with the exercise scheme was low (21%).,Health care providers seem to play an important role in patients’ adherence to telehealth in usual care.,Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence. | A literature review was conducted to obtain a high-level view of the value of telemedicine in the management of five common chronic diseases (asthma, COPD, diabetes, heart failure, hypertension).,A total of 141 randomised controlled trials (RCTs) was identified, in which 148 telemedicine interventions of various kinds had been tested in a total of 37,695 patients.,The value of each intervention was categorised in terms of the outcomes specified by the investigators in that trial, i.e. no attempt was made to extract a common outcome from all studies, as would be required for a conventional meta-analysis.,Summarizing the value of these interventions shows, first, that most studies have reported positive effects (n = 108), and almost none have reported negative effects (n = 2).,This suggests publication bias.,Second, there were no significant differences between the chronic diseases, i.e. telemedicine seems equally effective (or ineffective) in the diseases studied.,Third, most studies have been relatively short-term (median duration 6 months).,It seems unlikely that in a chronic disease, any intervention can have much effect unless applied for a long period.,Finally, there have been very few studies of cost-effectiveness.,Thus the evidence base for the value of telemedicine in managing chronic diseases is on the whole weak and contradictory. | 1 |
Platelets may actively participate in inflammation in COPD.,Platelet distribution width (PDW), a measure of platelets’ volume heterogeneity, may increase in platelets’ activation.,We hypothesized that PDW may be a marker of hypercoagulation, which plays a significant role in conditions associated with worse survival of patients with COPD, eg, acute myocardial infarction and other forms of ischemic heart disease.,Retrospective analysis of 79 patients.,Variables were compared after grouping patients according to the upper normal limit of PDW, using Welch’s t-tests or Mann-Whitney U, and chi-square tests.,Survival in the two groups was compared using the Kaplan-Meier method and Cox proportional hazards regression.,Ten patients presented values of PDW above 16 fL, which was the upper limit of normality for our laboratory.,Compared to patients with normal PDW, they had lower forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75) - 35% of reference value vs 57% (P=0.003) and peak expiratory flow - 39% vs 54% (P<0.001).,The median survival of patients with elevated PDW was 743 days compared to those with normal PDW (1,305 days) (P=0.025).,The adjusted HR was 4.59 (95% CI: 1.1, 19.19; P=0.04).,Our analysis indicates that elevated PDW is associated with reduced survival of patients with COPD.,If our data are to be confirmed, PDW may be used as an inexpensive and repeatable prognostic tool in COPD. | 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 |
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. | Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM).,Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs.,During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes.,The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study.,The COPDGene study recruited 10,300 COPD patients in 21 centers.,A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE).,Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed.,The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05).,EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%.,C1M was inversely associated with forced expiratory volume in 1 s (FEV1) (r = −0.344, p = 0.001), as was EL-NE (r = −0.302, p = 0.004) and Pro-C6 (r = −0.259, p = 0.015).,In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36.,C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively).,These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema.,Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials. | To compare the absolute serum von Willebrand factor (vWF) levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers.,The study included 57 subjects, in three groups: COPD (n = 36); smoker (n = 12); and control (n = 9).,During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing.,Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively.,The modified Medical Research Council scale (cut-off score = 2) was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic.,Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001) and 1,865 ± 592 pg/mL (p < 0.01).,Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs.,92.8 ± 34.0%; p < 0.05), as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05).,In all three groups, there was a negative correlation between FEV1 (% of predicted) and relative serum vWF activity (r2 = −0.13; p = 0.009).,Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients.,Comparar os níveis séricos absolutos e a atividade sérica em percentual do fator de von Willebrand (FvW) em pacientes com DPOC clinicamente estáveis, tabagistas sem obstrução das vias aéreas e em indivíduos saudáveis que nunca fumaram.,Foram incluídos no estudo 57 indivíduos, em três grupos: DPOC (n = 36), tabagista (n = 12) e controle (n = 9).,Todos os participantes realizaram radiografia do tórax, espirometria e exame de sangue durante a fase de seleção.,Os níveis séricos absolutos e a atividade sérica em percentual do FvW foram obtidos por turbidimetria e ELISA, respectivamente.,A escala Medical Research Council modificada foi utilizada para classificar pacientes como sintomáticos ou assintomáticos/pouco sintomáticos no grupo DPOC (ponto de corte = 2).,Os níveis absolutos do FvW no grupo controle foram significativamente menores que os nos grupos tabagista e DPOC: 989 ± 436 pg/mL vs.,2.220 ± 746 pg/mL (p < 0,001) e 1.865 ± 592 pg/mL (p < 0,01).,Os valores em percentual de atividade do FvW no grupo DPOC foram significativamente maiores que no grupo tabagista (136,7 ± 46,0% vs. 92,8 ± 34,0%; p < 0,05), assim como foram significativamente maiores no subgrupo DPOC sintomático que no subgrupo DPOC assintomático/pouco sintomático (154 ± 48% vs. 119 ± 8%; p < 0,05).,Houve uma correlação negativa entre o VEF1 (% do previsto) e os níveis em percentual de atividade do FvW nos três grupos (r2 = −0,13; p = 0,009).,Nossos resultados sugerem que aumentos nos níveis de FvW e de sua atividade contribuem para a manutenção da inflamação sistêmica e o aumento do risco cardiovascular em pacientes com DPOC. | 1 |
Hospital readmission for acute exacerbation of COPD (AECOPD) occurs in up to 30% of patients, leading to excess morbidity and poor survival.,Physiological risk factors predict readmission, but the impact of modifiable psychosocial risk factors remains uncertain.,We aimed to evaluate whether psychosocial risk factors independently predict readmission for AECOPD in patients referred to early discharge services (EDS).,This prospective cohort study included 79 patients with AECOPD cared for by nurse led EDS in the UK, and followed up for 12 months.,Data on lung function, medical comorbidities, previous hospital admissions, medications, and sociodemographics were collected at baseline; St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS), and social support were measured at baseline, 3 and 12-months.,Exploratory multivariate models were fitted to identify psychosocial factors associated with readmission adjusted for known confounders.,26 patients were readmitted within 90 days and 60 patients were readmitted at least once during follow-up.,Depression at baseline predicted readmission adjusted for sociodemographics and forced expiratory volume in 1 second (odds ratio 1.30, 95% CI 1.06 to 1.60, p = 0.013).,Perceived social support was not significantly associated with risk of readmission.,Home ownership was associated with the total number of readmissions (B = 0.46, 95% CI -0.86 to -0.06, p = 0.024).,Compared with those not readmitted, readmitted patients had worse SGRQ and HADS scores at 12 months.,Depressive symptoms and socioeconomic status, but not perceived social support, predict risk of readmission and readmission frequency for AECOPD in patients cared for by nurse-led EDS.,Future work on reducing demand for unscheduled hospital admissions could include the design and evaluation of interventions aimed at optimising the psychosocial care of AECOPD patients managed at home. | COPD is a major cause of mortality and morbidity worldwide with an estimated 2.75 million deaths in 2000 (fourth leading cause of death).,In addition to the considerable morbidity and mortality associated with COPD, this disease incurs significant healthcare and societal costs.,Current COPD guidelines acknowledge that the following can improve COPD mortality: smoking cessation; long-term oxygen therapy; and lung volume reduction surgery in small subsets of COPD patients.,To date, no randomized controlled trials have demonstrated an effect of pharmacological treatment on mortality, although several observational studies suggest that both long-acting bronchodilators and inhaled corticosteroids may provide a survival benefit.,The possibility that these treatments reduce mortality is being investigated in ongoing large-scale clinical trials. | 1 |
Low health literacy is associated with low adherence to self-management in many chronic diseases.,Additionally, health beliefs are thought to be determinants of self-management behaviors.,In this study we sought to determine the association, if any, of health literacy and health beliefs among elderly individuals with COPD.,We enrolled a cohort of patients with COPD from two academic urban settings in New York, NY and Chicago, IL.,Health literacy was measured using the Short Test of Functional Health Literacy in Adults.,Using the framework of the Self-Regulation Model, illness and medication beliefs were measured with the Brief Illness Perception Questionnaire (B-IPQ) and Beliefs about Medications Questionnaire (BMQ).,Unadjusted analyses, with corresponding Cohen’s d effect sizes, and multiple logistic regression were used to assess the relationships between HL and illness and medication beliefs.,We enrolled 235 participants, 29% of whom had low health literacy.,Patients with low health literacy were more likely to belong to a racial minority group (p<0.001), not be married (p = 0.006), and to have lower income (p<0.001) or education (p<0.001).,In unadjusted analyses, patients with low health literacy were less likely to believe they will always have COPD (p = 0.003, Cohen’s d = 0.42), and were more likely to be concerned about their illness ((p = 0.04, Cohen’s d = 0.17).,In analyses adjusted for sociodemographic factors and other health beliefs, patients with low health literacy were less likely to believe that they will always have COPD (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.65-0.94).,In addition, the association of low health literacy with expressed concern about medications remained significant (OR: 1.20, 95% CI: 1.05-1.37) though the association of low health literacy with belief in the necessity of medications was no longer significant (OR: 0.92, 95% CI: 0.82-1.04).,In this cohort of urban individuals with COPD, low health literacy was prevalent, and associated with illness beliefs that predict decreased adherence.,Our results suggest that targeted strategies to address low health literacy and related illness and medications beliefs might improve COPD medication adherence and other self-management behaviors. | The causal association between depression, anxiety, and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) is unclear.,We therefore conducted a systematic review of prospective cohort studies that measured depression, anxiety, and HRQoL in COPD.,Electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature [CINAHL], British Nursing Index and Archive, PsycINFO and Cochrane database) were searched from inception to June 18, 2013.,Studies were eligible for inclusion if they: used a nonexperimental prospective cohort design; included patients with a diagnosis of COPD confirmed by spirometry; and used validated measures of depression, anxiety, and HRQoL.,Data were extracted and pooled using random effects models.,Six studies were included in the systematic review; of these, three were included in the meta-analysis for depression and two were included for the meta-analysis for anxiety.,Depression was significantly correlated with HRQoL at 1-year follow-up (pooled r=0.48, 95% confidence interval 0.37-0.57, P<0.001).,Anxiety was also significantly correlated with HRQoL at 1-year follow-up (pooled r=0.36, 95% confidence interval 0.23-0.48, P<0.001).,Anxiety and depression predict HRQoL in COPD.,However, this longitudinal analysis does not show cause and effect relationships between depression and anxiety and future HRQoL.,Future studies should identify psychological predictors of poor HRQoL in well designed prospective cohorts with a view to isolating the mediating role played by anxiety disorder and depression. | 1 |
Between 2006 and 2010, in 16 randomly selected villages in rural areas of Mysore district, in south India, 8,457 subjects aged 30 and above were screened for symptoms of chronic respiratory disease.,Of the 8,457 subjects, 1,692 were randomly invited for further evaluation of lung function and chronic obstructive pulmonary disease (COPD) by spirometry, and 1,085 of these subjects underwent lung function assessments for prevalent COPD and its risk factors.,These 1,085 subjects, who were then aged between 35 and 80 years, constituted the Mysuru stUdies of Determinants of Health in Rural Adults (MUDHRA) cohort.,Among other findings, threshold of biomass fuel smoke exposure suitable for use as a dichotomous risk factor for the diagnosis of chronic bronchitis was established, with a minimum biomass smoke exposure index of 60 found to be significantly associated with an elevated risk of developing chronic bronchitis.,Five years later (between 2014 and 2016), 869 of the 1,085 participants were followed up with repeat lung function assessments for incident COPD and all-cause mortality.,A subset of these participants (n=200) underwent blood tests for vitamin D levels, antioxidant activity, an assessment for anxiety and depression, and another subset (n=98) underwent a bioplex assay for 40 serum cytokines. | Exposure to air pollution due to combustion of biomass fuels remains one of the significant risk factors for chronic respiratory diseases such as chronic bronchitis.,There is a need to identify the minimum threshold level of biomass index that is significantly associated with chronic bronchitis.,This study was undertaken to identify a threshold for biomass exposure index in a rural women population in Mysore district, south India.,A cross-sectional survey was conducted in a representative population of Mysore and Nanjangud taluks.,Eight villages each from Mysore and Nanjangud were randomly selected based on the list of villages from census 2001.,A house-to-house survey was carried out by trained field workers using the Burden of Obstructive Diseases questionnaire, which evaluated the biomass smoke exposure and chronic bronchitis.,All the women aged above 30 yr were included in the study.,A total of 2011 women from Mysore and 1942 women from Nanjangud participated in the study.,All women were non-smoking and used biomass fuels as the primary fuel for cooking.,A threshold of biomass fuel exposure of 60 was identified on multivariate analysis in Mysore district after adjusting for age, passive smoking and working in a occupational exposure to dust, as the minimum required for a significant association with chronic bronchitis.,One in every 20 women in Mysore district exposed to biomass fuel exposure index of 110 or more developed chronic bronchitis.,The minimum threshold of biomass exposure index of 60 is necessary to have a significant risk of developing chronic bronchitis in women.,The number needed to harm to develop chronic bronchitis reduces with increasing biomass exposure index and women residing in rural Nanjangud have a higher risk for developing chronic bronchitis as compared to women in Mysore. | 1 |
Nuclear factor-κB (NF-κB) signaling plays essential roles in inflammatory responses.,However, whether the expression levels of NF-κB family genes affect inflammatory responses is unclear.,Moreover, little is known regarding the association between NF-κB family genes expression and the pathogenesis of chronic obstructive pulmonary disease (COPD).,The present study was undertaken to assess the relationship between the expression levels of NF-κB family genes mRNA and of inflammatory markers relevant to COPD pathogenesis.,A total of 186 unrelated patients with acute exacerbations of COPD and 180 healthy controls were recruited.,Total RNA was extracted from the peripheral fasting blood of each subject using trizol reagent.,The mRNA levels of NF-κB family genes (NF-κB1, NF-κB2 and c-REL) were measured by real-time quantitative polymerase chain reaction.,The serum levels of cyclooxygenase-2 (COX-2), C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, IL-12 and tumor necrosis factor-α were measured with enzyme-linked immunosorbent assay kits.,The relative mRNA levels of the NF-κB family genes and the levels of inflammatory molecules were significantly higher in the COPD group than in the control group after adjustment for smoking.,The IL-1β, IL-8 and COX-2 levels were significantly lower in the NF-κB2 under-expression subgroup as compared to the NF-κB2 over-expression subgroup.,The COX-2 level was significantly lower (P < 0.05) in the c-REL under-expression subgroup as compared to the c-REL over-expression subgroup.,NF-κB2 over-expression was associated with IL-1β, IL-8 and COX-2 levels, whereas c-REL overexpression was associated with COX-2 level.,Over-expression of both NF-κB2 and c-REL was found to be related to COPD. | Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration.,However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury.,In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche.,We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats.,The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemistry, and real-time PCR.,The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay.,rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats.,HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection.,Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions.,Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats.,MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling. | 1 |
While it is relatively well known that the prognosis of patients with lung cancer (LC) treated with surgery is worse in the presence of chronic obstructive pulmonary disease (COPD), it is unknown if this assessment can be extrapolated to patients with advanced disease treated with chemotherapy and/or tyrosine kinase inhibitors.,The aim of our study is to analyze the clinical characteristics and survival rates in patients with LC and COPD, and to compare these to the patients without airflow obstruction.,From 471 evaluable patients, 324 (69%) were not treated with surgery due to disseminated disease (stages 3B and 4).,Of them, 47.7% also had COPD.,All patients were treated at the moment of diagnosis according to National Comprehensive Cancer Network guidelines with platinum-based chemotherapy or tyrosine kinase inhibitors.,Kaplan-Meier curves showed no significant differences in overall survival between COPD and non-COPD patients (log-rank P=0.65).,In the multivariate Cox proportional hazard model adjusting for the most relevant variables, the adjusted hazard ratio (HRadj) was statistically significant for performance status (HRadj =1.33, 95% confidence interval [CI]: 1.11-1.59; P=0.002) and clinical stage (HRadj =0.67, 95% CI: 0.50-0.89; P=0.006), but not for COPD status (HRadj =1.20, 95% CI: 0.83-1.50; P=0.46).,Our conclusion is that at present, when using standard care in advanced LC (stages 3B and 4), COPD does not have a significant deleterious impact on overall survival. | Recent studies suggest that coexistence of chronic obstructive pulmonary disease (COPD) might be independently related to a worse prognosis for lung cancer.,However, because data on the substantial prevalence of COPD and its severity in Asian lung cancer patients remain limited, clinical impact of prevalence and severity of COPD among the population has not been fully evaluated.,Furthermore, patients with COPD often have comorbidities.,Thus, whether the decision-making process for therapeutic management of lung cancer patients might be independently affected by COPD remains elusive.,Clinical impact of prevalence and severity of COPD were evaluated in 270 Japanese patients with newly diagnosed lung cancer who were sequentially registered and underwent bronchoscopy from August 2010 to July 2012 at Nagoya University hospital.,Furthermore, to explore whether or not the severity of airflow obstruction might affect the decision to propose thoracic surgery with curative intent, we evaluated data from patients with lung cancer at stage 1A to 3A who underwent spirometry and bronchoscopy.,The prevalence rate of COPD was 54.4% among Japanese patients with lung cancer who underwent bronchoscopy.,The incidence of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2 was significantly higher than that of GOLD grade 3.,Although COPD-related comorbidities were not independent factors for proposing thoracic surgery, the number of thoracic surgeries performed was significantly less in the COPD group than the non-COPD group.,Multivariate analysis showed that more severe airway obstruction, advanced clinical staging, and higher age, were independent factors associated with the decision on thoracic surgery.,We demonstrated a high prevalence of COPD among Japanese lung cancer patients.,Based on the knowledge that severity of COPD is one of the most important factors in the therapeutic decision, comprehensive assessment of COPD at bronchoscopy might allow us to implement the optimum management for lung cancer patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by different phenotypes with either bronchial airways alterations or emphysema prevailing.,As blood biomarkers could be clinically useful for COPD stratification, we aimed at investigating the levels of blood biomarkers in COPD patients differentiated by phenotype: prevalent chronic airway disease versus emphysema.,In 23 COPD patients with prevalent airway disease (COPD-B), 22 COPD patients with prevalent emphysema (COPD-E), 9 control smokers (CSs), and 18 control nonsmokers (CNSs), we analyzed the expression levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF), monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay in plasma/serum; glutathione peroxidase and superoxide dismutase (SOD)-1 by immunochemical kits in plasma; and free F2-isoprostanes (F2-IsoPs) by gas chromatography in plasma.,F2-IsoPs level was increased in COPD-B and COPD-E compared with CSs and CNSs; in addition, CS showed higher levels than CNSs; SOD1 level was lower in COPD-B and COPD-E than that in CNSs.,Interestingly, MCP-1 level was higher only in COPD-E versus CSs and CNSs; EGF and IL-8 levels were higher in COPD-B and COPD-E versus CNSs; IL-6 level was increased in all three smoking groups (COPD-B, COPD-E, and CSs) versus CNS; IFN-γ and IL-1α levels were higher in CSs than in CNSs; and IL-1α level was also higher in CSs versus COPD-B and COPD-E.,In all subjects, F2-IsoPs level correlated positively and significantly with MCP-1, IL-2, IL-1β, IFN-γ, and TNF-α and negatively with SOD1.,When correlations were restricted to COPD-E and COPD-B groups, F2-IsoPs maintained the positive associations with IFN-γ, TNF-α, and IL-2.,We did not find any specific blood biomarkers that could differentiate COPD patients with prevalent airway disease from those with prevalent emphysema.,The MCP-1 increase in COPD-E, associated with the imbalance of oxidant/antioxidant markers, may play a role in inducing emphysema. | Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression.,However, the effect on tissue structure and turnover is not well described.,There is an urgent clinical need for biomarkers of disease activity associated with disease progression.,Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity.,We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.,69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up.,Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).,Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001).,Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001).,Pro-C3 levels were unchanged.,At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.,Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity.,This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression. | 1 |
The investigation of complex disease heterogeneity has been challenging.,Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes.,We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD).,We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants.,Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches.,Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease severity, and genetic mechanisms. | The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) gene regulates transcription of enzymes involved in cellular detoxification and lipids homeostasis.,NFE2L2 is associated with pathophysiology of atherosclerosis and chronic obstructive pulmonary disease (COPD).,Therefore we studied the relation between NFE2L2 and all-cause, cardiovascular, and COPD mortality and its associations with triglyceride and cholesterol levels.,We genotyped five tagging single nucleotide polymorphisms (SNPs) (rs4243387, rs2364723, rs13001694, rs1806649, and rs6726395) in NFE2L2 in 1,390 subjects from the Vlagtwedde-Vlaardingen cohort.,Participants were examined in 1989/1990 and followed up till the vital status evaluation on December 31st, 2008.,Associations between SNPs and mortality were estimated by Cox proportional hazards regression, and associations between SNPs and triglyceride and cholesterol levels were tested with linear regression.,After 18 yr, 284 (20.4%) subjects had died, 107 from cardiovascular disease and 20 from COPD.,Minor allele carriers of rs13001694 had a significantly reduced risk of all-cause mortality compared with wild types: hazard ratio (HR) 0.8 [95% confidence interval (CI) 0.6 to 1.0].,Minor allele carriers of rs2364723 had significantly reduced risk of cardiovascular mortality: HR = 0.5 (95% CI: 0.3-0.7).,This result was consistent in stratified analyses: females 0.4 (0.2-0.7), males 0.6 (0.3-0.9), never smokers 0.5 (0.2-1.1), ever smokers 0.5 (0.3-0.8).,Minor allele carriers of rs1806649 had a markedly reduced COPD mortality: HR = 0.3 (95% CI: 0.1-0.9).,Rs2364723 was associated with lower triglyceride levels.,None of the SNPs was associated with cholesterol levels.,This study shows for the first time that NFE2L2 is associated with reduced risk of all-cause, cardiovascular and COPD mortality in humans. | 1 |
Small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease (COPD).,A large population of patients with COPD also have pulmonary hypertension.,Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor that contributes to tissue remodeling in cardiovascular diseases.,Here, we evaluate the possible involvement of KLF5 in the remodeling of small airways and pulmonary vessels in COPD.,Lung tissues were obtained from 23 control never-smokers, 17 control ex-smokers and 24 ex-smokers with COPD.,The expression of KLF5 in the lung tissues was investigated by immunohistochemistry.,We investigated whether oxidative/nitrosative stress, which is a major cause of the pathogenesis in COPD, could augment the production of KLF5.,We examined the role of KLF5 in the stress-mediated tissue remodeling responses.,We also investigated the susceptibility of KLF5 expression to nitrosative stress using bronchial fibroblasts isolated from the lung tissues.,The expression of KLF5 was up-regulated in the small airways and pulmonary vessels of the COPD patients and it was mainly expressed in bronchial fibroblasts and cells of the pulmonary vessels.,The extent of the KLF5 expression in the small airway of the COPD group had a significant correlation with the severity of the airflow limitation.,Oxidative/nitrosative stress augmented the production of KLF5 in lung fibroblasts as well as the translocation of KLF5 into the nuclei.,Silencing of KLF5 suppressed the stress-augmented differentiation into myofibroblasts, the release of collagens and metalloproteinases.,Bronchial fibroblasts from the patients with COPD highly expressed KLF5 compared to those from the control subjects under basal condition and were more susceptible to the induction of KLF5 expression by nitrosative stress compared to those from the control subjects.,We provide the first evidence that the expression of KLF5 is up-regulated in small airways and pulmonary vessels of patients with COPD and may be involved in the tissue remodeling of COPD. | Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages.,The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs.,19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods.,Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP.,The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of α-actin and desmin.,Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically.,The expression of endothelial nitric oxide synthase (eNOS) was evaluated by Real Time-PCR.,Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p < 0.05) but not in the aorta.,Endothelial dysfunction was apparent at 3 months of exposure and did not increase further after 6 months of exposure.,Smoke-exposed animals showed proliferation of poorly differentiated smooth muscle cells in small vessels (p < 0.05) after 3 months of exposure.,Prolonged exposure resulted in full muscularization of small pulmonary vessels (p < 0.05), wall thickening (p < 0.01) and increased contractility of the main pulmonary artery (p < 0.05), and enlargement of the alveolar spaces.,Lung expression of eNOS was decreased in animals exposed to cigarette smoke.,In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS.,These changes appear after 3 months of exposure and precede the development of pulmonary emphysema. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | Prescriber disagreement is among the reasons for poor adherence to COPD treatment guidelines; it is yet not clear whether this leads to adverse outcomes.,We tested whether undertreatment according to the original Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines led to increased exacerbations.,Records of 878 patients with spirometrically confirmed COPD who were followed from 2005 to 2010 at one Veterans Administration (VA) Medical Center were analyzed.,Analysis of variance was performed to assess differences in exacerbation rates between severity groups.,Logistic regression analysis was performed to assess the relationship between noncompliance with guidelines and exacerbation rates.,About 19% were appropriately treated by guidelines; 14% overtreated, 44% under-treated, and in 23% treatment did not follow any guideline.,Logistic regression revealed a strong inverse relationship between undertreatment and exacerbation rate when severity of obstruction was held constant.,Exacerbations per year by GOLD stage were significantly different from each other: mild 0.15, moderate 0.27, severe 0.38, very severe 0.72, and substantially fewer than previously reported.,The guidelines were largely not followed.,Undertreatment predominated but, contrary to expectations, was associated with fewer exacerbations.,Thus, clinicians were likely advancing therapy primarily based upon exacerbation rates as was subsequently recommended in revised GOLD and other more recent guidelines.,In retrospect, a substantial lack of prescriber adherence to treatment guidelines may have been a signal that they required re-evaluation.,This is likely to be a general principle regarding therapeutic guidelines.,The identification of fewer exacerbations in this cohort than has been generally reported probably reflects the comprehensive nature of the VA system, which is more likely to identify relatively asymptomatic (ie, nonexacerbating) COPD patients.,Accordingly, these rates may better reflect those in the general population.,In addition, the lower rates may reflect the more complete preventive care provided by the VA. | 1 |
Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required. | Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids.,Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.,A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months’ duration was performed.,Trials had similar inclusion and exclusion criteria.,Exacerbation definition was standardized.,Patients were divided into two groups, ie, D (anticholinergics discontinued at randomization, previously prescribed) and ND (anticholinergics not discontinued, not previously prescribed).,Demographics were balanced between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in one second (FEV1)/forced vital capacity (43% versus 48%), and lower baseline FEV1 (35.8% predicted versus 42.4% predicted) in the D group.,In both groups, tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P < 0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR = 0.85, P = 0.0467 versus 0.79, P = 0.0094).,Tiotropium reduced the number of exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR = 0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]).,Tiotropium reduced exacerbations in patients who did and did not have anticholinergics discontinued upon randomization in clinical trials. | 1 |
To date there are no head-to-head studies comparing different mucolytic/antioxidant agents.,Considering the inconsistent evidence resulting from the pivotal studies on mucolytic/antioxidant agents tested in chronic obstructive pulmonary disease (COPD), and the recent publication of Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study, we have performed a meta-analysis to compare the efficacy and safety of erdosteine 600 mg/day, carbocysteine 1500 mg/day, and N-acetylcysteine (NAC) 1200 mg/day in COPD.,A pairwise and network meta-analyses were performed to assess the efficacy of erdosteine, carbocysteine, and NAC on acute exacerbation of COPD (AECOPD), duration of AECOPD, and hospitalization.,The frequency of adverse events (AEs) was also investigated.,Data obtained from 2753 COPD patients were extracted from 7 RCTs published between 2004 and 2017.,In the pairwise meta-analysis mucolytic/antioxidant agents significantly reduced the risk of AECOPD (RR 0.74 95%CI 0.68-0.80).,The network meta-analysis provided the following rank of effectiveness: erdosteine>carbocysteine>NAC.,Only erdosteine reduced the risk of experiencing at least one AECOPD (P < 0.01) and the risk of hospitalization due to AECOPD (P < 0.05).,Erdosteine and NAC both significantly reduced the duration of AECOPD (P < 0.01).,The AEs induced by erdosteine, carbocysteine, and NAC were mild in severity and generally well tolerated.,The quality of evidence of this quantitative synthesis is moderate.,The overall efficacy/safety profile of erdosteine is superior to that of both carbocysteine and NAC.,Future head-to-head studies performed on the same COPD populations are needed to definitely confirm the results of this meta-analysis.,CRD42016053762. | The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | 1 |
To evaluate the effectiveness of long-term treatment of statins for chronic obstructive pulmonary disease (COPD), and to answer which one is better.,General meta-analysis was performed to produce polled estimates of the effect of mortality, inflammatory factors, and lung function index in COPD patients by the search of PubMed, Web of Science, Embase, and China National Knowledge Infrastructure for eligible studies.,A network meta-analysis was performed to synthetically compare the effectiveness of using different statins in COPD patients.,General meta-analysis showed that using statins reduced the risk of all-cause mortality, heart disease-related mortality and COPD acute exacerbation (AECOPD) in COPD patients, the RR (95% CI) were 0.72 (0.63,0.84), 0.72 (0.53,0.98) and 0.84 (0.79,0.89), respectively.,And using statins reduced C-reactive protein (CRP) and pulmonary hypertension (PH) in COPD patients, the SMD (95% CI) were − 0.62 (− 0.52,-0.72) and − 0.71 (− 0.85,-0.57), respectively.,Network meta-analysis showed that Fluvastatin (97.7%), Atorvastatin (68.0%) and Rosuvastatin (49.3%) had higher cumulative probability than other statins in reducing CRP in COPD patients.,Fluvastatin (76.0%) and Atorvastatin (75.4%) had higher cumulative probability than other satins in reducing PH in COPD patients.,Using statins can reduce the risk of mortality, the level of CRP and PH in COPD patients.,In addition, Fluvastatin and Atorvastatin are more effective in reducing CRP and PH in COPD patients.,The online version of this article (10.1186/s12931-019-0984-3) contains supplementary material, which is available to authorized users. | In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.,The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD.,Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014.,Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography.,One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis.,Six observational studies with 881 patients were included in the meta-analysis.,The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%.,Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history.,Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation.,In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value. | 1 |
Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD) because of concerns that they might provoke bronchospasm and cause deterioration in health status.,Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown.,The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL) in patients with peripheral arterial disease and COPD.,Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up.,These COPD patients were sent the Short Form-36 (SF-36) health-related quality of life questionnaire, which was completed and returned by 326 (70%) patients.,No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all).,Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD.,Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD.,This suggests that beta-blockers can, in most circumstances, be administered to patients with COPD without impairment in HRQOL. | 1 |
Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.,Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting.,The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria.,Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.,3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap.,Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort.,There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.,The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.,Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatmenthttp://ow.ly/oMZI307ndr5 | Inhaled corticosteroid/long-acting β2-agonist combinations (ICS/LABA) have emerged as first line therapies for chronic obstructive pulmonary disease (COPD) patients with exacerbation history.,No randomized clinical trial has compared exacerbation rates among COPD patients receiving budesonide/formoterol combination (BFC) and fluticasone/salmeterol combination (FSC) to date, and only limited comparative data are available.,This study compared the real-world effectiveness of approved BFC and FSC treatments among matched cohorts of COPD patients in a large US managed care setting.,COPD patients (≥40 years) naive to ICS/LABA who initiated BFC or FSC treatments between 03/01/2009-03/31/2012 were identified in a geographically diverse US managed care database and followed for 12 months; index date was defined as first prescription fill date.,Patients with a cancer diagnosis or chronic (≥180 days) oral corticosteroid (OCS) use within 12 months prior to index were excluded.,Patients were matched 1-to-1 on demographic and pre-initiation clinical characteristics using propensity scores from a random forest model.,The primary efficacy outcome was COPD exacerbation rate, and secondary efficacy outcomes included exacerbation rates by event type and healthcare resource utilization.,Pneumonia objectives included rates of any diagnosis of pneumonia and pneumonia-related healthcare resource utilization.,Matching of the identified 3,788 BFC and 6,439 FSC patients resulted in 3,697 patients in each group.,Matched patients were well balanced on age (mean = 64 years), gender (BFC: 52% female; FSC: 54%), prior COPD-related medication use, healthcare utilization, and comorbid conditions.,During follow-up, no significant difference was seen between BFC and FSC patients for number of COPD-related exacerbations overall (rate ratio [RR] = 1.02, 95% CI = [0.96,1.09], p = 0.56) or by event type: COPD-related hospitalizations (RR = 0.96), COPD-related ED visits (RR = 1.11), and COPD-related office/outpatient visits with OCS and/or antibiotic use (RR = 1.01).,The proportion of patients diagnosed with pneumonia during the post-index period was similar for patients in each group (BFC = 17.3%, FSC = 19.0%, odds ratio = 0.92 [0.81,1.04], p = 0.19), and no difference was detected for pneumonia-related healthcare utilization by place of service.,This study demonstrated no difference in COPD-related exacerbations or pneumonia events between BFC and FSC treatment groups for patients new to ICS/LABA treatment in a real-world setting.,ClinicalTrials.gov identifier NCT01921127. | 1 |
There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. | Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress.,The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.,Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers).,Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry.,Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.,FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001.,Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers.,Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02).,Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03).,However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.,Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is predominantly associated with neutrophilic inflammation.,Active neutrophil elastase (NE) is a serine proteinase, secreted by neutrophils, in response to inflammation and pathogen invasion.,We sought to investigate if NE could be used as a biomarker for bacterial infection in patients with COPD.,NE was quantified using ProteaseTag® Active NE Immunoassay (ProAxsis, Belfast) from the sputum of COPD subjects at stable state, exacerbation and 2 weeks post treatment visit.,NE was measured in 90 samples from 30 COPD subjects (18 males) with a mean (range) age of 65 (45-81) years and mean (SD) FEV1 of 47% (18).,The geometric mean (95%CI) of NE at stable state was 2454 ng/mL (1460 to 4125 ng/mL).,There was a significant increase in NE levels at an exacerbation (p = 0.003), and NE levels were higher in a bacterial-associated exacerbation (NE log difference 3.873, 95% CI of log difference 1.396 to 10.740, p = 0.011).,NE was an accurate predictor of a bacteria-associated exacerbation (area (95%CI) under the receiver operator characteristic curve 0.812 (0.657 to 0.968).,NE is elevated during exacerbations of COPD.,NE may be a viable biomarker for distinguishing a bacterial exacerbation in patients with COPD.,Leicestershire, Northamptonshire and Rutland ethics committee (reference number: 07/H0406/157). | Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common in patients with underlying moderate to severe COPD and are associated with increased health and economic burden.,International and Chinese guidelines recommend using glucocorticoids for the management of AECOPD because glucocorticoid therapy has been shown to benefit clinical outcomes.,However, only scant data are available for current status of glucocorticoid therapy in hospitalized AECOPD patients in China.,The aim of the study was to identify current use of glucocorticoids for the treatment of AECOPD in China.,This retrospective, multicenter, noninterventional study evaluated the treatment pattern of AECOPD in patients hospitalized from January 2014 to September 2014 at 43 sites (41 tertiary hospitals and two secondary hospitals) in China.,The endpoints of the study were the percentage of patients receiving glucocorticoids by different routes of administration, doses and duration, mortality, and the mean length of hospitalization.,A total of 4569 patients (90.17%) received glucocorticoids for AECOPD treatment.,A combination of nebulized and systemic route was most frequently used (40.51%), followed by using nebulized route alone (38.00%), systemic route alone (15.45%), and inhaled route other than nebulization (6.04%).,Furthermore, the most commonly prescribed glucocorticoids of the nebulized, intravenous, inhaled (other than nebulized) and oral route was budesonide (69.4%), methylprednisolone sodium succinate (45.31%), fluticasone propionate (19.54%), and prednisone acetate (11.90%), respectively.,The in-hospital mortality rate was 1.24% and the mean length of hospitalization was 12.22 ± 6.20 days (± SD).,Our study was the first study of the treatment pattern of glucocorticoids in the management of hospitalized AECOPD patients in China.,Data indicates that there is a gap in the implementation of international guidelines for the treatment of AECOPD in China.,Further studies are warranted to clarify the appropriate glucocorticoids strategy for the management of AECOPD to determine the optimal route of administration, dose and duration, and resulting clinical outcomes. | 1 |
The prevalence of erectile dysfunction (ED) in patients with chronic obstructive pulmonary disease (COPD) seemed high; however, large scale of population-based study was absent.,We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan.,The cohort included 29,042 male patients who were newly diagnosed with COPD.,Patients were recruited between 2000 and 2011, and the date of diagnosis was defined as the index date.,Each patient was randomly matched with 1 male person from the general population without COPD according to age and the index year.,The occurrence of ED was followed up until the end of 2011.,The hazard ratios of ED were estimated using the Cox proportional hazard model after adjusting for age, index year, comorbidities, and medications.,The overall incidence of ED was 1.88-fold greater in the COPD cohort than in the non-COPD cohort (24.9 vs 13.3/1000 person-years, 95% confidence interval [CI] = 1.61-2.18).,Compared with non-COPD patients, the hazard ratio increased with the number of emergency room visits and admissions for COPD from 1.51 (95% CI 1.29-1.77) to 5.46 (95% CI 3.03-9.84) and from 1.50 (95% CI 1.28-1.76) to 11.5 (95% CI 5.83-22.6), respectively.,Patients with COPD are at a significantly higher risk of developing ED compared with the general population regardless of age and presence of comorbidity.,The results also support that poor control of COPD status is a key factor affecting ED development. | Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD).,We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD.,The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database.,Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group.,Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex.,Patients who had used hypnotics within 1 month meant active users.,The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models.,Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively.,After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11-17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68-14.2) compared with the adjusted ORs of those who never used hypnotics.,The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD. | 1 |
Long‐acting bronchodilators, i.e. beta‐2‐agonists (LABA) and tiotropium are commonly used in COPD treatment.,Choice of a specific agent is based on effectiveness and safety.,Evidence yields controversial results with respect to mortality.,The present study compared one‐year mortality associated to treatment with tiotropium versus LABA.,A population‐based cohort study using data from Italian health information systems was performed.,Patients aged 45+ years, discharged with COPD diagnosis in 2006-2009 were identified.,Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled.,The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium).,We used ‘intention to treat’ (ITT) and ‘as treated’ (AT) approaches.,We followed patients for a maximum of 12 months.,Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score.,In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group.,Among the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both.,Overall mean age was 74 years and the mortality rate was 122/1000 person‐years (py) at the ITT analysis and 108/1000 py at the AT analysis.,The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94-1.20) at the ITT analysis and 1.00 (95%CI: 0.93-1.08) at the AT analysis.,Results were robust in sensitivity analysis.,In this real‐world study use of tiotropium was not associated with an increased risk of one‐year mortality compared with LABA.,© 2016 The Authors.,Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. | There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population.,The study examined COPD patients with moderate COPD exacerbations.,COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.,This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation.,A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period.,A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs.,COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009).,COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.,21,524 patients with a moderate COPD exacerbation were identified.,Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation.,Annual costs averaged $594 per patient.,A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis.,The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04).,After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).,The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort.,However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05).,Total monthly COPD-related costs, as a result, did not differ between cohorts.,Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy.,Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC. | 1 |
It remains unclear whether eosinophilia is useful for in guiding inhaled corticosteroid (ICS) therapy in chronic obstructive pulmonary disease (COPD) patients.,The goal of this study is to evaluate the risk of acute exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality with various levels of eosinophil counts among COPD patients using ICS.,A cohort study was conducted using the UK Clinical Practice Research Datalink.,Patients were aged 40+ and had COPD (n = 32 693).,Current users of ICS were stratified by relative and absolute eosinophil counts to determine the risk of outcomes with blood eosiniphilia using Cox regression analysis.,Among COPD patients, current use of ICS was not associated with a reduced risk of acute COPD exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality.,Stratification of ICS use by absolute or relative eosinophil counts did not result in significant differences in risk of COPD exacerbations or hospitalisations/accident and emergency visits.,However, all‐cause mortality was reduced by 12% to 24% among patients with eosinophilia.,COPD‐related acute exacerbations or hospitalisations/accident and emergency visits were not reduced with eosinophilia among users of ICS with COPD.,However, all‐cause mortality was reduced by 12% to 24%.,These findings are potentially important and require further evaluation in prospective studies. | Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.,Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting.,The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria.,Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.,3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap.,Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort.,There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.,The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.,Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatmenthttp://ow.ly/oMZI307ndr5 | 1 |
Blood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD).,We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort.,Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year.,85.3% of patients with eosinophils < 100 cells/μL had stable counts.,The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds. | Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation.,Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood.,Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.,We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients.,We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II).,Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.,All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage.,These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1.,There were no severe exacerbations or other adverse events.,Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation. | 1 |
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. | The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern.,Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest.,Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases.,Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and diet appear to play roles in its pathophysiology.,Obesity has been associated with decreased lung-function measures in population-based studies, with increased prevalence of several lung diseases and with compromised pulmonary function.,In contrast, obesity has a protective effect against mortality in severe chronic obstructive pulmonary disease (COPD).,Nutrient intake and dietary patterns have also been associated with lung-function measures and the development and progression of COPD.,Taken together, this suggests that a focus on obesity and diet should be part of public health campaigns to reduce the burden of lung disease, and could have important implications for clinicians in the management of their patients.,Future research should also focus on elucidating these relationships in diverse populations and age-groups, and on understanding the complex interaction between behavior, environment, and genetics in the development and progression of COPD.,The goal of this article is to review current evidence regarding the role that obesity and diet play in the development of COPD, and in COPD-related outcomes. | 1 |
Severe exacerbations and mortality are major outcomes in COPD, and risk factors for these events are actively searched for.,Several predictors of mortality have been identified in COPD.,The inspiratory capacity/total lung capacity (IC/TLC) ratio has been shown to be a strong predictor of all cause and respiratory mortality in patients with COPD.,The major objectives of this study were to analyze which clinical parameters, including lung volumes, were the best predictors of the 5-year cumulative risk of hospital admissions or death and the 5-year risk of exacerbations, in stable COPD patients.,This study retrospectively reviewed data from 98 stable COPD patients, consecutively recruited in 2012.,Forced expiratory volume in 1 s (FEV1), modified Medical Research Council dyspnea scale, exacerbation history (ExH), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 groups, and lung volumes were reviewed.,Five years later, this population was evaluated for cumulative exacerbations, hospital admissions, and mortality.,All the population, and GOLD group D separately, were analyzed.,The cumulative 5-year combined risk of hospital admission or death was significantly predicted by the ExH and the IC/TLC ratio.,Analyzing separately group D, FEV1 was the only predictor of this outcome.,The frequency of exacerbations in the previous year was the best predictor of future cumulative 5-year risk of subsequent exacerbations, both for the total population and the GOLD D group.,ExH and IC/TLC ratio were the best predictors of the most severe outcomes in COPD (admissions or mortality), independently of COPD severity.,FEV1 was the only predictor of the cumulative 5-year combined risk of hospital admission or death in the GOLD D group.,ExH was the best predictor of 5-year cumulative future risk of exacerbations.,Besides FEV1 and ExH, the IC/TLC ratio can be a useful predictor of severe outcomes in COPD. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
The economic burden of COPD has not been well studied in China.,This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.,A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011.,The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation).,Logistic regression model was used to explore factors related to high total costs on COPD.,The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively.,The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China.,Hospitalization accounted for 56.7% of the total costs.,High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.,COPD posed a heavy economic burden in China.,Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care. | Risk factors of anxiety and depression symptoms in patients with chronic obstructive pulmonary disease (COPD) have been widely researched, but most of them cannot be addressed clinically.,The aim of this study was to investigate whether COPD knowledge level is a risk factor of anxiety and/or depression in COPD patients in addition to functional capacity and quality of life, and to determine the key topics of COPD knowledge.,A total of 364 COPD patients from four centers were recruited into this cross-sectional survey.,Subjects’ general medical information, assessments of lung function, dyspnea, quality of life, and exercise capacity, and responses to the Hospital Anxiety and Depression Scale (HAD) and the Bristol COPD Knowledge Questionnaire (BCKQ) were collected.,Partial correlation analysis was performed, and a multivariable model testing risk factors of anxiety and depression as well as a multivariable model of 13 topics of knowledge derived from BCKQ were constructed.,Subjects with anxiety or depression were more likely to have less COPD knowledge.,Partial correlation analysis revealed that HAD score was negatively correlated with BCKQ score (rho = −0.153, P = 0.004).,BCKQ score was significant in the multivariable model that tested risk factors of anxiety and depression (P = 0.001, OR = 0.944).,Topics of epidemiology (P < 0.001, OR = 0.653) and infections (P = 0.006, OR = 0.721) were significant in the multivariable model evaluating 13 topics.,The level of patients’ disease knowledge is a significant risk factor of anxiety and depression in COPD patients.,Epidemiology and infections are key topics of COPD knowledge to target in the Chinese population.,ChiCTR-OCS-12002518 | 1 |
Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase.,The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.,Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months.,The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction.,Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase.,These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients.,In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results.,Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients.,The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations.,Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients. | 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 |
Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved.,In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research.,1) AATD is a highly underdiagnosed condition.,Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed.,2) Several clinical and etiological aspects of the disease are yet to be resolved.,New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema.,Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials.,4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes. | This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | 1 |
The aim of this study was to analyse the relationship between exposure to residential radon and chronic obstructive pulmonary disease (COPD) by means of a systematic review.,A search was conducted in PubMed and OVID for papers making reference to the radon-COPD relationship.,No search filters were applied, whether by date of publication, study type or sample size.,All studies not written in English or Spanish were discarded.,A total of 174 and 57 papers were found in PubMed and OVID, respectively: of these, 13 (11 on miners and 2 on the general population) fulfilled the inclusion criteria.,Only four of the studies on cohorts of miners analysed COPD as a specific disease, and only one reported statistically significant results.,In addition, many of these studies lacked information on tobacco use among miners.,In contrast, studies conducted on the general public showed an association between mortality and hospital admissions, on the one hand, and residential radon on the other.,There are not enough studies to provide a basis for confirming or ruling out an association between radon exposure and COPD.,Nonetheless, the most recent general population studies point to evidence of a possible association.,In view of the heterogeneity of available studies, it is impossible to say whether this gas may or may not affect COPD morbidity and mortality, until such a time as further studies are carried out. | There is growing evidence about sex-related phenotypes of COPD.,However, the sex differences in COPD mainly result from smokers.,This study evaluated the sex differences in nonsmoking patients with COPD, focusing on structural changes in the lungs in airway diseases and emphysema.,Ninety-seven nonsmoking patients, defined as having <1 pack-year of lifetime cigarette smoking, diagnosed with COPD were selected from a Korean COPD cohort.,Emphysema extent and mean wall area percentage (WA%) on computed tomography were compared between the male and female groups.,The 97 patients with COPD included 62 females and 35 males.,Emphysema index was significantly lower (3.5±4.2 vs 6.2±5.7, P<0.01) and mean WA% on computed tomography was significantly higher (71.8%±5% vs 69.4%±5%, P<0.01) in females than in males, after adjusting for age, body mass index, history of biomass exposure, and postbronchodilator forced expiratory volume in 1 second (% of predicted).,WA% was higher and emphysema extent was lower in nonsmoking females with COPD than in nonsmoking males with COPD.,These findings suggest that males may be predisposed to an emphysema phenotype and females may be predisposed to an airway phenotype of COPD. | 1 |
This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity.,A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study.,Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups.,We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores.,Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment.,This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients. | Chronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis.,Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD.,Despite current available therapies to control inflammation, neutrophilic bronchitis remains common.,This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load.,We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis.,Eligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications.,Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment.,Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit.,Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment.,A sub-group of participants underwent chest computed tomography scans (n = 15).,Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL.,Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load.,The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p = 0.062).,For participants who underwent chest CT scans, no alterations were observed.,In stable COPD with neutrophilic bronchitis, add-on azithromycin therapy showed a trend to reduced severe exacerbations sputum neutrophils, CXCL8 levels and bacterial load.,Future studies with a larger sample size are warranted.,Australian New Zealand Clinical Trials Registry ACTRN12609000259246 | 1 |
Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide.,We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology.,In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain.,AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months.,It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS).,In contrast, the early-phase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected.,The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage, mitochondrial ROS production, and lung remodeling.,Our findings implicate mitochondrial respiratory inhibition as a key pathogenic mechanism of CS toxicity in the lung.,We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage. | Lung tissue from COPD patients displays oxidative DNA damage.,The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes.,The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects.,A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients.,Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE) of the VEGF promoter.,The content of VEGF mRNA also was reduced in COPD lung tissue.,Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites.,These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD. | 1 |
To explore how persons living with COPD experience transitions related to health, self-management, and follow-up from the healthcare services.,This study is part of a participatory research project.,Six males and five females living with COPD, with a COPD assessment test score of 21-29, participated; all the participants were living at home.,Data were collected in qualitative research interviews and analyzed using qualitative content analysis highlighting the participants’ experiences.,The findings showed two main themes: “The struggle to keep going” and “The need for continuity and competent facilitation”.,The participants reported complex health transitions, with changes in roles and function, demanding exacerbations and critical events, and challenges with learning needed self-management.,They expressed a great need for and had great benefit from, education, rehabilitation, and follow-up in their management of everyday life.,Not all received offers in line with current guidelines.,In-depth knowledge of patients’ experienced COPD transitions offers clinicians guidance for the timing and quality of follow-up services.,Life with COPD entails challenging transitions in health and self-management.,Good rehabilitation and follow-up from the healthcare services are needed throughout the disease trajectory.,Participation in self-management education and rehabilitation that include psychosocial aspects may facilitate health-enhancing transitions and improve self-management skills.,Experienced lack of competence and flexibility among healthcare providers hinders trust and collaboration.,Access to stable and competent follow-up in the primary health services may facilitate cohesive services and collaborative self-management. | To assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).,A cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).,Twenty-six municipal districts in the North Denmark Region of Denmark.,Patients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.,Health-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2.,Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.,In the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was −2.6 (SD 12.4) in the telehealthcare group and −2.8 (SD 11.9) in the usual practice group.,The raw mean difference in MCS scores in the same period was −4.7 (SD 16.5) and −5.3 (SD 15.5) for telehealthcare and usual practice, respectively.,The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI −1.4 to 1.7) and 0.4 (95% CI −1.7 to 2.4), respectively.,The overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.,NCT01984840; Results. | 1 |
Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of 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 |
To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations.,It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation.,To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations.,To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations.,To speculate on future therapeutic options to modify inflammation during COPD exacerbations.,During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes.,Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive.,Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations.,This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects. | 1 |
Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | COPD is considered a complex disease and global problem that is predicted to be the third most common cause of death by 2030.,While managing this chronic condition, primary health care practitioners are faced with the ongoing challenge of achieving good quality of life and overall “wellness” for those affected.,As such, a practical tool for monitoring quality of life in a clinical setting is required.,However, due to the wide variety of general and disease-specific tools from which to choose, primary health care practitioners are given minimal guidance as to which tool may be most appropriate.,To address these challenges, the International Primary Care Respiratory Group (IPCRG) proposed the creation of a user’s guide for primary health care practitioners to assess “wellness” in COPD patients in an everyday clinical setting.,This short report outlines the process by which the IPCRG Users’ Guide to COPD “Wellness” Tools was developed.,It also describes why this guide has the potential to be of great value in guiding primary health care practitioners to improve patient wellness. | 1 |
Objective To systematically review the risk of mortality associated with long term use of tiotropium delivered using a mist inhaler for symptomatic improvement in chronic obstructive pulmonary disease.,Data sources Medline, Embase, the pharmaceutical company clinical trials register, the US Food and Drug Administration website, and ClinicalTrials.gov for randomised controlled trials from inception to July 2010.,Study selection Trials were selected for inclusion if they were parallel group randomised controlled trials of tiotropium solution using a mist inhaler (Respimat Soft Mist Inhaler, Boehringer Ingelheim) versus placebo for chronic obstructive pulmonary disease; the treatment duration was more than 30 days, and they reported data on mortality.,Relative risks of all cause mortality were estimated using a fixed effect meta-analysis, and heterogeneity was assessed with the I2 statistic.,Results Five randomised controlled trials were eligible for inclusion.,Tiotropium mist inhaler was associated with a significantly increased risk of mortality (90/3686 v 47/2836; relative risk 1.52, 95% confidence interval, 1.06 to 2.16; P=0.02; I2=0%).,Both 10 µg (2.15, 1.03 to 4.51; P=0.04; I2=9%) and 5 µg (1.46, 1.01 to 2.10; P=0.04; I2=0%) doses of tiotropium mist inhaler were associated with an increased risk of mortality.,The overall estimates were not substantially changed by sensitivity analysis of the fixed effect analysis of the five trials combined using the random effects model (1.45, 1.02 to 2.07; P=0.04), limiting the analysis to three trials of one year’s duration each (1.50, 1.05 to 2.15), or the inclusion of additional data on tiotropium mist inhaler from another investigational drug programme (1.42, 1.01 to 2.00).,The number needed to treat for a year with the 5 µg dose to see one additional death was estimated to be 124 (95% confidence interval 52 to 5682) based on the average control event rate from the long term trials.,Conclusions This meta-analysis explains safety concerns by regulatory agencies and indicates a 52% increased risk of mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease. | This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study.,COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 μg, 2.5 μg, 5 μg, 10 μg, or 20 μg Respimat® SMI (a novel, propellant-free device); tiotropium 18 μg HandiHaler®; placebo Respimat®; or placebo HandiHaler® for 3 weeks.,The primary endpoint was trough FEV1 on Day 21.,Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics.,In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo.,Tiotropium 5 μg Respimat®, 20 μg Respimat®, and tiotropium 18 μg HandiHaler® were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV1 was 150 mL (both Respimat® doses) versus 20 mL (placebo Respimat®); p < 0.05; and 230 mL (HandiHaler®) versus −90 mL (placebo HandiHaler®); p ≤ 0.001).,The urinary excretion (up to 2 hours post-dose) of tiotropium 5-10 μg Respimat® was comparable with tiotropium 18 μg HandiHaler®; the overall incidence of adverse events was comparable across treatment groups.,Tiotropium 5 and 10 μg Respimat® improve lung function in COPD patients and appear to be comparable with tiotropium 18 μg HandiHaler®. | 1 |
Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD).,This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.,This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2).,A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation.,Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy.,Adverse events (AEs) were also assessed.,Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818).,Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001).,Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population.,No significant reduction in risk of a SGRQ CID was observed.,AE incidence was similar between treatment groups.,Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations.,Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.,GlaxoSmithKline (study number: 202067).,Plain language summary available for this article.,The online version of this article (10.1007/s12325-018-0771-4) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis.,We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction.,Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity <70% following inhalation of a β2-agonist) as follows: CPFE patients with airflow obstruction (CPFE OB+ group, n=11), and CPFE patients without airflow obstruction (CPFE OB− group, n=20).,Pulmonary function, including respiratory impedance evaluated using impulse oscillometry and dynamic hyperinflation following metronome-paced incremental hyperventilation, was retrospectively analyzed in comparison with that observed in 49 chronic obstructive pulmonary disease (COPD) patients (n=49).,In imaging findings, low-attenuation-area scores on chest high-resolution computed tomography, representing the degree of emphysema, were significantly lower in the CPFE OB− group than in the CPFE OB+ and COPD groups.,In contrast, the severity of pulmonary fibrosis was greater in the CPFE OB− group than in the CPFE OB+ group.,In pulmonary function, lung hyperinflation was not apparent in the CPFE OB− group.,Impairment of diffusion capacity was severe in both the CPFE OB− and CPFE OB+ groups.,Impulse oscillometry showed that respiratory resistance was not apparent in the CPFE OB− group compared with the COPD group, and that easy collapsibility of small airways during expiration of tidal breath was not apparent in the CPFE OB+ group compared with the COPD group.,Dynamic hyperinflation following metronome-paced incremental hyperventilation was significantly greater in the COPD group than in the CPFE OB− group, and also tended to be greater in the CPFE OB+ group than in the CPFE OB− group.,The mechanisms underlying impairment of physiological function may differ among CPFE OB+ patients, CPFE OB− patients, and COPD patients.,CPFE is a heterogeneous disease, and may have distinct phenotypes physiologically and radiologically. | COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function.,CT imaging is emerging as an important, noninvasive tool in phenotyping COPD.,However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.,Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation.,Airway physiology and health status were also determined.,The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively.,The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001).,There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM.,The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96).,Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.,The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD. | 1 |
To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major global health problem.,It results from chronic inflammation and causes irreversible airway damage.,Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD.,We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD.,In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21).,Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed.,Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA).,Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients.,Notably, this study identifies stem cell factor as a biomarker for COPD.,Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes.,Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD.,Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. | 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 |
Treatment of stable chronic obstructive pulmonary disease (COPD) with long-acting bronchodilator (LABD) medications is recommended by the 2014 Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines.,The primary objective of this study was to examine LABD prescription fills after a COPD-related hospitalization.,This retrospective observational study used claims from Truven Health MarketScan® Commercial and Medicare Supplemental databases.,Patients (age ≥40, commercial; age ≥65, Medicare supplemental) had a first hospitalization with a primary COPD diagnosis between April 1, 2009 and June 30, 2011 (index hospitalization) and were continuously enrolled for 1 year before and 9 months after hospitalization.,Patients were categorized according to pre-index and/or post-index pharmacy claims.,A total of 27,738 patients had an index hospitalization and met inclusion/exclusion criteria.,Of those, 19,783 patients had COPD as a primary or secondary diagnosis during the year before index hospitalization and were included in the analysis.,Approximately one quarter of the patients (26.32%) did not fill a prescription for an LABD or short-acting bronchodilator both 90 days before and 90 days after hospitalization.,During the 90-day pre-index period, 40.57% of patients filled an LABD (with or without a short-acting bronchodilator) prescription.,Over half of the patients (56.88%) filled an LABD prescription at some point during the 180-day post-index period, but, of those, a significantly greater proportion of patients filled an LABD prescription in the 1- to 90-day post-index period than in the 91- to 180-day post-index period (51.27% versus 43.66%; P<0.0001).,A significant proportion of COPD patients in this study did not fill an LABD prescription before hospitalization for COPD.,Moreover, hospitalization did not appear to greatly impact LABD initiation.,Lastly, patients who did not fill an LABD prescription within the first 90 days posthospitalization were not likely to fill an LABD prescription later.,Taken together, the results of this study suggest that many patients with COPD are undertreated. | We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | 1 |
Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD).,Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients.,No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease.,We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS).,The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD).,TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD).,In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC.,These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD. | Pro-inflammatory/cytotoxic T cells (IFNγ, TNFα, granzyme B+) are increased in the peripheral circulation in COPD.,NKT-like and NK cells are effector lymphocytes that we have also shown to be major sources of pro-inflammatory cytokines and granzymes.,P-glycoprotein 1 (Pgp1) is a transmembrane efflux pump well characterised in drug resistant cancer cells.,We hypothesized that Pgp1 would be increased in peripheral blood T, NKT-like and NK cells in patients with COPD, and that this would be accompanied by increased expression of IFNγ, TNFα and granzyme B.,We further hypothesized that treatment with cyclosporine A, a Pgp1 inhibitor, would render cells more sensitive to treatment with corticosteroids.,Pgp1, granzyme B, IFNγ and TNFα expression were measured in peripheral blood T, NK and NKT-like cells from COPD patients and control subjects (± cyclosporine A and prednisolone) following in vitro stimulation and results correlated with uptake of efflux dye Calcein-AM using flow cytometry.,There was increased Pgp1 expression by peripheral blood T, NKT-like and NK cells co-expressing IFNγ, TNFα and granzyme B in COPD patients compared with controls (e.g.,%IFNγ/Pgp1 T, NKT-like, NK for COPD (Control): 25(6), 54(27), 39(23)).,There was an inverse correlation between Pgp1 expression and Calcein-AM uptake.,Treatment with 2.5 ng/ml cylosporin A and10-6 M prednisolone resulted in synergistic inhibition of pro-inflammatory cytokines in Pgp1 + cells (p < 0.05 for all).,Treatment strategies that target Pgp1 in T, NKT-like and NK cells may reduce systemic inflammatory mediators in COPD and improve patient morbidity. | 1 |
The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | 1 |
Public health is a priority for the Chinese Government.,Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance.,This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.,We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017.,We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk.,We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).,Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017.,Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017.,Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017.,Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs.,All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88.,The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain.,The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).,China has made substantial progress in reducing the burden of many diseases and disabilities.,Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.,China National Key Research and Development Program and Bill & Melinda Gates Foundation. | Pneumoconiosis may play an important role in the development of chronic obstructive pulmonary disease (COPD), and the complication of COPD may impose a heavy burden of illness.,The study was conducted in Hunan Province in China from December 1, 2015, to December 1, 2016.,Consecutive underground male pneumoconiosis patients employed for at least 1 year were recruited from the Hunan Occupational Disease Prevention Institute.,Patient information, respiratory symptoms and clinical data were collected using a structured questionnaire.,The diagnosis of COPD were assessed using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,Logistic regression analyses were conducted to examine the clinical and demographic risk factors of COPD among pneumoconiosis patients.,The prevalence of COPD in our sample of pneumoconiosis patients was 18.65% (119/638).,In pneumoconiosis patients with and without smoking history, the prevalence of COPD was 19.32 and 16.77%.,Compared with non-COPD patients, those with COPD are older in age, have longer exposure time, have lower body mass index (BMI), have a higher smoking index and have worse pulmonary function (all p < 0.05).,For the five respiratory symptoms (cough, sputum, wheeze, dyspnea, and chest tightness), only the presence of wheeze and the severity scores for wheeze or dyspnea showed significant differences between the COPD and non-COPD groups (p < 0.01).,Multivariate logistic regression analysis revealed that advanced pneumoconiosis category, older age and the presence of wheeze symptoms were significant risk factors for the development of COPD among pneumoconiosis patients.,Pneumoconiosis patients are at a high risk of COPD, and pneumoconiosis patients with COPD may suffer more severe respiratory symptoms, such as wheeze and dyspnea, than patients without COPD.,Advanced pneumoconiosis category, older age and the presence of wheeze symptoms are associated with an increased risk of COPD in pneumoconiosis.,We proposed that a routine assessment of lung function is necessary for timely and adequate clinical management. | 1 |
BMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor β (TGF-β) signaling.,Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated.,In this study, we investigated whether TGF-β/BAMBI pathway is associated with COPD.,Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients.,Elevated Th17/Treg ratios, and increased levels of BAMBI protein and mRNA (in plasma and CD4+ T cells respectively), were observed in COPD compared with HC and HS.,BAMBI expression was first observed on human CD4+ T cells, with a typical membrane-bound pattern.,The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-β1 levels and Th17/Treg ratio.,Together, an impaired TGF-β/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD. | Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth leading cause of death worldwide.,Neutrophilic inflammation is prominent, worsened during infective exacerbations and is refractory to glucocorticosteroids (GCs).,Deregulated neutrophilic inflammation can cause excessive matrix degradation through proteinase release.,Gelatinase and azurophilic granules within neutrophils are a major source of matrix metalloproteinase (MMP)-9 and neutrophil elastase (NE), respectively, which are elevated in COPD.,Secreted MMP-9 and NE activity in BALF were stratified according to GOLD severity stages.,The regulation of secreted NE and MMP-9 in isolated blood neutrophils was investigated using a pharmacological approach.,In vivo release of MMP-9 and NE in mice exposed to cigarette smoke (CS) and/or the TLR agonist lipopolysaccharide (LPS) in the presence of dexamethasone (Dex) was investigated.,Neutrophil activation as assessed by NE release was increased in severe COPD (36-fold, GOLD II vs.,IV).,MMP-9 levels (8-fold) and activity (21-fold) were also elevated in severe COPD, and this activity was strongly associated with BALF neutrophils (r = 0.92, p<0.001), but not macrophages (r = 0.48, p = 0.13).,In vitro, release of NE and MMP-9 from fMLP stimulated blood neutrophils was insensitive to Dex and attenuated by the PI3K inhibitor, wortmannin.,In vivo, GC resistant neutrophil activation (NE release) was only seen in mice exposed to CS and LPS.,In addition, GC refractory MMP-9 expression was only associated with neutrophil activation.,As neutrophils become activated with increasing COPD severity, they become an important source of NE and MMP-9 activity, which secrete proteinases independently of TIMPs.,Furthermore, as NE and MMP-9 release was resistant to GC, targeting of the PI3K pathway may offer an alternative pathway to combating this proteinase imbalance in severe COPD. | 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. | The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry.,Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis.,We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted.,Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD).,We then used logistic regression to investigate predictors of correct interpretation.,Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care.,Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality.,Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction.,Historical records for asthma diagnosis significantly decreased odds of correct interpretation.,The quality of the spirometry procedure undertaken in primary care is high.,However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care.,The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes. | 1 |
MicroRNAs (MiRNA) are small non-coding RNAs that regulate gene expression.,The aim of this study was to identify miRNAs differentially expressed between mild and moderately emphysematous lung, as well as their functional target mRNAs.,Resected lung from patients with COPD undergoing lung cancer surgery was profiled using miRNA (Agilent Human miRNA profiler G4470 V1.01) and mRNA (OperonV2.0) microarrays.,Cells of lung origin (BEAS-2B and HFL1) were profiled using mRNA microarrays (Illumina HumanHT-12 V3) after in vitro manipulation.,COPD patients had mean (SD) age 68 (6) years, FEV1 72 (17)% predicted and gas transfer (KCO) 70 (10)% predicted.,Five miRNAs (miR-34c, miR-34b, miR-149, miR-133a and miR-133b) were significantly down-regulated in lung from patients with moderate compared to mild emphysema as defined by gas transfer (p < 0.01).,In vitro upregulation of miR-34c in respiratory cells led to down-regulation of predicted target mRNAs, including SERPINE1, MAP4K4, ZNF3, ALDOA and HNF4A.,The fold change in ex-vivo expression of all five predicted target genes inversely correlated with that of miR-34c in emphysematous lung, but this relationship was strongest for SERPINE1 (p = 0.05).,Differences in miRNA expression are associated with emphysema severity in COPD patients.,MiR-34c modulates expression of its putative target gene, SERPINE1, in vitro in respiratory cell lines and ex vivo in emphysematous lung tissue. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Exercise tolerance is an important endpoint in chronic obstructive pulmonary disease (COPD) clinical trials.,Little is known about the comparative measurement properties of constant work rate cycle ergometry (CWRCE) and the endurance shuttle walking test (ESWT).,The objective of this sub-analysis of the TORRACTO® study was to directly compare the endurance measurement properties of CWRCE and ESWT in patients with COPD in a multicentre, multinational setting.,We predicted that both tests would be similarly reliable, but that the ESWT would be more responsive to bronchodilation than CWRCE.,This analysis included 151 patients who performed CWRCE and ESWT at baseline and week 6 after receiving once-daily placebo, tiotropium/olodaterol (T/O) 2.5/5 μg or T/O 5/5 μg.,Reproducibility was assessed by comparing their respective performance at baseline and week 6 in the placebo group.,Responsiveness to bronchodilation was assessed by comparing endurance time at week 6 with T/O with baseline values and placebo.,The locus of symptom limitation and end-exercise Borg scales for breathing and leg discomfort for both tests were also analysed.,The intraclass correlation coefficients for CWRCE and ESWT were 0.56 [95% confidence interval (CI) 0.37-0.71] and 0.75 (95% CI 0.63-0.84).,More patients were limited by breathing discomfort during the ESWT than during CWRCE, whereas more patients were limited by leg discomfort or breathing/leg discomfort during CWRCE than the ESWT (p <0.0001).,Both tests were responsive to bronchodilator treatment: there was a 19% increase in endurance time from baseline at week 6 (p = 0.0006) assessed with CWRCE, and a 20% increase in endurance time assessed with ESWT (p = 0.0013).,Both exercise tests performed well in a multicentre clinical trial.,Although the locus of symptom limitation differed between the two tests, both were reliable and responsive to bronchodilation.,For future clinical trials, the choice of test should depend on the study requirements.,NCT01525615.,The reviews of this paper are available via the supplemental material section. | Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | 1 |
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