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Patients with chronic obstructive pulmonary disease (COPD) with frequent exacerbations (ExCOPD) are commonly treated with inhaled corticosteroids (ICS) and are at risk of infections caused by potential pathogenic bacteria (PPB) including Pseudomonas aeruginosa (PsA).,To investigate the association between the use of ICS and PsA infection among ExCOPD.,Case-control study with longitudinal follow-up that recruited ExCOPD after a hospitalisation due to exacerbation between 2012 and 2020.,Patients with isolation of PsA (COPD-PsA) in sputum either during admission or follow-up were compared with those with other or no PPB.,Clinical, functional characteristics, DDD, use of ICS and survival were evaluated.,Cox regression analysis was performed to evaluate the risk factors associated to PsA infection and mortality.,358 patients (78% male, mean age 73±9 years) were enrolled and followed up for a median of 4 years (IQR=3-8). 173 patients (48.3%) had at least a positive culture for PsA.,COPD-PsA had more frequent exacerbations, more severe airflow limitation and higher mortality (69.4% vs 46.5%, p<0.001).,There were no differences in the use of ICS between groups but the dose of ICS was significantly higher among COPD-PsA (median of 500 µg fluticasone propionate equivalents (IQR=250-1000) vs 400 µg (IQR=200-1000), p=0.007).,Blood eosinophil count (BEC) was not different between ICS users and non-users.,In multivariate analysis, the dose of ICS was an independent risk factor for PsA infection and mortality but not ICS use.,ICS dose, but not its use, could be a risk factor for PsA infection in patients with severe COPD regardless of BEC. | Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics.,This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds.,In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) - understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers.,This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis. | 1 |
Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia.,LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day.,Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT.,The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep.,The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT.,The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care.,Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings).,Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen.,The comparison is double blind.,The primary outcome is a composite of mortality from all cause or requirement for LTOT.,Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy.,The follow-up period is intended to last at least 3 years.,The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not.,The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight.,Current Controlled Trials ISRCTN50085100; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010). | Anxiety is a common comorbidity in patients with COPD in China, and it can significantly decrease patients’ quality of life.,Almost all anxiety measurements contain somatic items that can overlap with symptoms of COPD and side effects of medicines, which can lead to bias in measuring anxiety in patients with COPD.,Therefore, a brief and disease-specific non-somatic anxiety measurement scale, the Anxiety Inventory for Respiratory Disease (AIR), which has been developed and validated in its English version, is needed for patients with COPD in China.,A two-center study was conducted in two tertiary hospitals in Tianjin, China.,A total of 181 outpatients with COPD (mean age 67.21±8.10 years, 32.6% women), who met the inclusion and exclusion criteria, were enrolled in the study.,Test-retest reliability was examined using intraclass correlation coefficients.,The internal consistency was calculated by Cronbach’s α.,Content validity was examined using the Content Validity Index (CVI), scale-level CVI/universal agreement, and scale-level CVI/average agreement (S-CVI/Ave).,Besides, convergent validity and construct validity were also examined.,The AIR-C (AIR-Chinese version) scale had high test-retest reliability (intraclass correlation coefficient =0.904) and internal consistency (Cronbach’s α=0.914); the content validity of the AIR-C scale was calculated by CVI, scale-level CVI/universal agreement, and S-CVI/Ave at values of 0.89-1, 0.90, and 0.98, respectively.,Meanwhile, the AIR-C scale had good convergent validity, correlating with the Hospital Anxiety and Depression Scale-Anxiety (r=0.81, P<0.01), and there were significant correlations between the AIR-C and Clinical COPD Questionnaire (CCQ; r=0.44, P<0.01) and Activities of Daily Living Scale (ADLS; r=0.36, P<0.01).,A two-factor model of general anxiety and panic symptoms in the AIR-C scale had the best fit according to Confirmatory Factor Analysis (CFA).,The AIR-C scale had a good reliability and validity for patients with COPD and can be used as a user-friendly and valid tool for measuring anxiety symptoms among patients with COPD in China. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning.,The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation.,Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study.,A clinical symptom questionnaire was completed by patients at baseline.,In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment.,The most frequently reported COPD symptom was breathlessness (90.8%).,Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms.,The most frequently reported morning activity was getting out of bed (82.9%).,The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms.,There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment.,Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities.,These patients also have more prevalent and severe COPD symptoms.,The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations.,There are numerous reasons for the lack of disease control in asthma and COPD patients.,It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient.,This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence.,For this cross-sectional analysis, 165 asthma and COPD patients were analyzed.,Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type.,QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT).,Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).,Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler.,COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02).,Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02).,While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (P = .04).,Correct inhalation of prescribed medication is associated with improved health status and lung function.,These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients’ inhalation technique.,ClinicalTrials.gov: NCT0238672, Registered 14 February 2014. | Effective self-management in chronic obstructive pulmonary disease (COPD) is crucial to reduce hospital admissions and improve outcomes for patients.,This includes early detection and treatment of exacerbations by patients themselves.,To explore patients’ current understanding and experience of managing and identifying COPD exacerbations at home.,A qualitative, interview-based study was carried out in patients’ homes.,Interviews were audio-recorded, transcribed and analysed using a grounded theory approach.,Forty-four patients (17 women, 27 men; age range 55-85 years), with moderate-to-very-severe COPD, were recruited to the interview study from primary and secondary care settings in Oxford, UK, during 2012-2013.,Patients identified exacerbations on the basis of measurable, ‘visible’ symptoms, such as cough and sputum and ‘invisible’ symptoms, such as chest sensations and bodily knowledge.,Most patients seemed to use a combination of these approaches when identifying exacerbations, according to the symptoms that had the most impact on their well-being.,Patients used additional self-management strategies during an exacerbation, such as self-medication (antibiotics and steroids) and monitored their recovery.,Contact with health-care professionals usually occurred when patients felt no longer able to manage themselves.,Patients use both assessment of objective biomarkers, which are aligned with medical knowledge, and subjective symptoms based on their experience, to identify and manage exacerbations of COPD.,Health-care professionals and clinicians should acknowledge this ‘expert patient’ knowledge and integrate this into patients’ care plans to facilitate early recognition and treatment of exacerbations. | 1 |
Inhaled medications are the cornerstone of treatment and management of asthma and COPD.,However, inhaler device errors are common among patients and have been linked with reduced symptom control, an increased risk of exacerbations, and increased healthcare utilisation.,These observations have prompted GINA (Global INitiative for Asthma) and GOLD (Global initiative for chronic Obstructive Lung Disease) to recommend regular assessment of inhaler technique in a bid to improve therapeutic outcomes.,To better define the relationship between device errors and health outcomes (clinical outcomes, quality of life, and healthcare utilisation) in asthma and COPD, we conducted a systematic review of the literature, with a particular focus on the methods used to assess the relationship between device errors and outcomes.,Sixteen studies were identified (12 in patients with asthma, one in patients with COPD, and three in both asthma and COPD) with varying study designs, endpoints, and patient populations.,Most of the studies reported that inhalation errors were associated with worse disease outcomes in patients with asthma or COPD.,Patients who had a reduction in errors over time had improved outcomes.,These findings suggest that time invested by healthcare professionals is vital to improving inhalation technique in asthma and COPD patients to improve health outcomes. | Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | 1 |
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium.,Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations.,We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged.,Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression.,We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease.,Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts.,Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein.,The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS.,Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect.,The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression.,Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens. | 1 |
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended.,A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD.,Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks.,This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS.,A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD.,The methodologic quality and risk of bias of included studies were assessed.,Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks.,Meta-regression and sensitivity analyses were used to assess heterogeneity across studies.,Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network.,LAMA/LABA dual combinations were combined as a single treatment group to create a connected network.,Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks.,Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA.,In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD.,The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.,The online version contains supplementary material available at 10.1007/s12325-021-01703-z. | 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 |
Patients with chronic obstructive pulmonary disease (COPD) who are defined as frequent exacerbators suffer with 2 or more exacerbations every year.,The molecular mechanisms responsible for this phenotype are poorly understood.,We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort.,Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR) testing.,Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01) between frequent compared to non-exacerbators.,In sputum cells, only 6 genes were differentially expressed.,The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes.,Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10.,The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively.,There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations. | Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations.,Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis.,The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes.,We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain.,Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD.,Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis.,Results were validated using key outcomes of ECOPD evolution.,Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit.,Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C.,Subtypes A and B were primarily related to other serious complications.,Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B.,These results could help identify characteristics to categorize ECOPD patients for more appropriate care, and help test interventions and treatments in subgroups with poor evolution and outcomes. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | Prevention of chronic obstructive pulmonary disease hospital readmissions is an international priority aimed to slow disease progression and limit costs.,Evidence of the risk of readmission and of interventions that might prevent it is lacking.,We aimed to determine readmission risk for chronic obstructive pulmonary disease, factors influencing that risk, and variation in readmission risk between hospitals across 7.5 million people in London.,This retrospective longitudinal observational study included all chronic obstructive pulmonary disease admissions to any hospital in the United Kingdom among patients registered at London general practices who had emergency National Health Service chronic obstructive pulmonary disease hospital admissions between April 2006 and March 2010.,Influence of patient characteristics, geographical deprivation score, length of stay, day of week of admission or of discharge, and admitting hospital, were assessed using multiple logistic regression. 38,894 chronic obstructive pulmonary disease admissions of 20,932 patients aged ≥ 45 years registered with London general practices were recorded. 6295 patients (32.2%) had at least one chronic obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%) were readmitted within 30 days and 3471 patients (17.8%) were readmitted within 90 days.,Age and patient geographical deprivation score were very weak predictors of readmission.,Rates of chronic obstructive pulmonary disease readmissions within 30 days and within 90 days did not vary among the majority of hospitals.,The finding of lower chronic obstructive pulmonary disease readmission rates than was previously estimated and the limited variation in these rates between hospitals suggests that the opportunity to reduce chronic obstructive pulmonary disease readmission risk is small.,A managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed.,Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs.,However, few data are available to determine and ultimately reduce the risk of readmission.,Timothy Harries at King’s College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010.,They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days.,Neither age nor geographical deprivation were useful predictors of readmission.,These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further. | 1 |
Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD).,To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort.,Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed.,Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking.,The majority of these alterations occurred in a gender-independent manner.,The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers.,The correlations to clinical parameters in healthy never-smokers were minor.,The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers.,Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis.,Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals.,ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.,The online version of this article (10.1186/s12931-017-0695-6) contains supplementary material, which is available to authorized users. | Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.,To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.,3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.,An analysis of risk of COPD was carried out using ever smoking controls (n=4784).,Associations with %predicted FEV1 were tested in cases.,We followed-up signals of interest (p<10−5) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.,Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10−6, preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10−6).,In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10−6).,We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5.,No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10−7).,This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common cause of suffering and death.,Evidence-based management of COPD by general practitioners (GPs) is crucial for decreasing the impact of the disease.,Efficient strategies include early diagnosis, smoking cessation and multimodal treatment.,To describe knowledge about and skills for managing COPD in GPs in Sweden.,Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice and free-text questions about COPD.,Their knowledge and practical management skills were assessed by assigned points that were analyzed with non-parametric tests.,Overall, 250 GPs at 34 PHCCs replied (89% response rate).,Total mean score was 9.9 (maximum 26).,Scores were highest on ‘management of smoking cessation’, ‘follow-up after exacerbation’ and ‘diagnostic procedures’.,Spirometry was used frequently, although interpretation skills were suboptimal.,‘Management of maintenance therapy’, ‘management of multimorbidity’ and ‘interprofessional cooperation’ had mediocre scores.,Scores were unrelated to whether there was a nurse-led asthma/COPD clinic at the PHCC.,Swedish GPs’ knowledge of COPD and adherence to current guidelines seem insufficient.,A nurse-led asthma/COPD clinic at the PHCC does not correlate with sufficient COPD skills in the GPs.,The relevance of this study to participants’ actual clinical practice and usefulness of easy-to-access clinical guides are interesting topics for future investigation.,To identify problem areas, we suggest using questionnaires prior to educational interventions.,General practitioners (GPs) play a crucial role in providing evidence-based care for patients with chronic obstructive pulmonary disease (COPD) who are treated in primary care.,Swedish GPs’ knowledge about COPD and adherence to current guidelines seem insufficient.,Areas in greatest need of improvement are spirometry interpretation, management of maintenance therapy, management of multimorbidity in patients with COPD and interprofessional cooperation. | 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 |
As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD).,Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity.,The effect of withdrawing ICS from COPD patients in primary care is unknown.,In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132).,Follow-up assessments took place at three monthly intervals for a year at the patients' practice.,Our primary outcome was COPD exacerbation frequency.,Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life.,In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36).,Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05).,Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86).,Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze.,In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14).,Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration.,Patients with mild COPD may be at increased risk of exacerbation after withdrawal.,ClinicalTrials.gov NCT00440687 | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | 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. | 1 |
The chronic obstructive pulmonary disease (COPD) integrated care pathway (ICP) programme was designed and implemented to ensure that the care for patients with COPD is comprehensive and integrated across different care settings from primary care to acute hospital and home.,We evaluated the effectiveness of the ICP programme for patients with COPD.,A retrospective propensity score matched cohort study was conducted comparing differences between programme enrolees and propensity-matched non-enrolees in a Regional Health System in Singapore.,Data on patients diagnosed with COPD who enrolled in the programme (n=95) and patients who did not enrol (n=6330) were extracted from the COPD registry and hospital administrative databases.,Enrolees and non-enrolees were propensity score matched.,The risk of COPD hospitalisations and COPD hospital bed days savings were compared between the groups using a difference-in-difference strategy and generalised estimating equation approach.,Adherence with recommended care elements for the COPD-ICP group was measured quarterly at baseline and during a 2-year follow-up period.,Compared with non-enrolees, COPD hospitalisation risk for ICP programme enrolees was significantly lower in year 2 (incidence rate ratio (IRR): 0.73; 95% CI 0.54 to 1.00).,Similarly, COPD hospital bed days was significantly lower for enrolees in year 2 (IRR: 0.78; 95% CI 0.64 to 0.95).,ICP programme patients had sustained improvements in compliance with all recommended care elements for patients with COPD.,The overall all-or-none care bundle compliance rate had improved from 28% to 54%.,The study concluded that the COPD-ICP programme was associated with reductions in COPD hospitalisation risk and COPD health utilisation in a 2-year follow-up period. | Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, places substantial time and cost burden on the health care system, and is now the third leading cause of death in the US.,Many interventions are available to appropriately manage patients with COPD; however, fully implementing these strategies to help improve outcomes may be difficult.,Collaboration between an interprofessional team of health care professionals (which includes physicians, nurses, respiratory therapists, physical therapists, dietitians, pharmacists, and many others) and COPD patients and caregivers is necessary to optimally manage these patients and to truly impact outcomes in this devastating disease.,Prescribing evidence-based non-pharmacological and pharmacological therapies is an important start, but a true team-based approach is critical to successfully implement comprehensive care in patients with COPD.,The goal of this review is to employ a case-based approach to provide practical information regarding the roles of the interprofessional team in implementing strategies to optimally manage COPD patients. | 1 |
The role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established.,More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has been realised.,These studies position ABCA1 as a potential therapeutic target in a diverse range of diseases where inflammation is an underlying cause.,Chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) are driven by inflammation, and as such, there is now a growing recognition that we need a greater understanding of the signaling pathways responsible for regulation of ABCA1 expression in this clinical context.,While the signaling pathways responsible for cholesterol-mediated ABCA1 expression have been clearly delineated through decades of studies in the atherosclerosis field, and thus far appear to be translatable to the respiratory field, less is known about the cholesterol-independent signaling pathways that can modulate ABCA1 expression in inflammatory lung disease.,This review will identify the various signaling pathways and ligands that are associated with the regulation of ABCA1 expression and may be exploited in future as therapeutic targets in the setting of chronic inflammatory lung diseases. | Smoke exposure is known to decrease total pulmonary surfactant and alter its composition, but the role of surfactant in chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to analyze the compositional changes in the surfactant lipidome in COPD and identify specific lipids associated with pulmonary function decline.,Bronchoalveolar lavage (BAL) fluid was obtained from 12 former smokers with COPD and 5 non-smoking, non-asthmatic healthy control volunteers.,Lipids were extracted and analyzed by liquid chromatography and mass spectrometry.,Pulmonary function data were obtained by spirometry, and correlations of lung function with lipid species were determined.,Wild-type C57BL/6 mice were exposed to 6 months of second-hand smoke in a full-body chamber.,Surfactant lipids were decreased by 60% in subjects with COPD.,All phospholipid classes were dramatically decreased, including ether phospholipids, which have not been studied in pulmonary surfactant.,Availability of phospholipid, cholesterol, and sphingomyelin in BAL strongly correlated with pulmonary function and this was attributable to specific lipid species of phosphatidylcholine with surface tension reducing properties, and of phosphatidylglycerol with antimicrobial roles, as well as to other less studied lipid species.,Mice exposed to smoke for six months recapitulated surfactant lipidomic changes observed in human subjects with COPD.,In summary, we show that the surfactant lipidome is substantially altered in subjects with COPD, and decreased availability of phospholipids correlated with decreased pulmonary function.,Further investigation of surfactant alterations in COPD would improve our understanding of its physiopathology and reveal new potential therapeutic targets. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that primarily resides in airway epithelial cells.,Decreased CFTR expression and/or function lead to impaired airway surface liquid (ASL) volume homeostasis, resulting in accumulation of mucus, reduced clearance of bacteria, and chronic infection and inflammation.,Expression of CFTR and the cigarette smoke metal content were assessed in lung samples of controls and COPD patients with established GOLD stage 4.,CFTR protein and mRNA were quantified by immunohistochemistry and quantitative RT-PCR, respectively.,Metals present in lung samples were quantified by ICP-AES.,The effect of cigarette smoke on down-regulation of CFTR expression and function was assessed using primary human airway epithelial cells.,The role of leading metal(s) found in lung samples of GOLD 4 COPD patients involved in the alteration of CFTR was confirmed by exposing human bronchial epithelial cells 16HBE14o- to metal-depleted cigarette smoke extracts.,We found that CFTR expression is reduced in the lungs of GOLD 4 COPD patients, especially in bronchial epithelial cells.,Assessment of metals present in lung samples revealed that cadmium and manganese were significantly higher in GOLD 4 COPD patients when compared to control smokers (GOLD 0).,Primary human airway epithelial cells exposed to cigarette smoke resulted in decreased expression of CFTR protein and reduced airway surface liquid height.,16HBE14o-cells exposed to cigarette smoke also exhibited reduced levels of CFTR protein and mRNA.,Removal and/or addition of metals to cigarette smoke extracts before exposure established their role in decrease of CFTR in airway epithelial cells.,CFTR expression is reduced in the lungs of patients with severe COPD.,This effect is associated with the accumulation of cadmium and manganese suggesting a role for these metals in the pathogenesis of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs.,To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population.,A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan.,Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period).,Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three).,HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively.,A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models.,Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively.,HCRU was significantly different among cohorts (all P<0.001).,In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively.,Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001).,COPD patients frequently experience exacerbations.,Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs.,This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management. | COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs).,Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations.,In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count.,We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St.,George's Respiratory Questionnaire Activity Score (SGRQ-AS).,AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months.,Mean daily step count was 5804±3141 steps.,Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year).,Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42).,There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003).,Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations.,Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations.,Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history.,These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential. | Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer.,Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis.,We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis.,The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals.,CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers.,COPD patients were monitored annually by low-dose spiral CT.,CTCs were detected in 3% of COPD patients (5 out of 168 patients).,The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer.,Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence.,CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype.,No CTCs were detected in control smoking and non-smoking healthy individuals.,CTCs can be detected in patients with COPD without clinically detectable lung cancer.,Monitoring “sentinel” CTC-positive COPD patients may allow early diagnosis of lung cancer. | 1 |
Lung function, measured as forced expiratory volume in one second (FEV1), and exacerbations are two endpoints evaluated in chronic obstructive pulmonary disease (COPD) clinical trials.,Joint analysis of these endpoints could potentially increase statistical power and enable assessment of efficacy in shorter and smaller clinical trials.,To evaluate joint modelling as a tool for analyzing treatment effects in COPD clinical trials by quantifying the association between longitudinal improvements in FEV1 and exacerbation risk reduction.,A joint model of longitudinal FEV1 and exacerbation risk was developed based on patient-level data from a Phase III clinical study in moderate-to-severe COPD (1740 patients), evaluating efficacy of fixed-dose combinations of a long-acting bronchodilator, formoterol, and an inhaled corticosteroid, budesonide.,Two additional studies (1604 and 1042 patients) were used for external model validation and parameter re-estimation.,A significant (p<0.0001) association between FEV1 and exacerbation risk was estimated, with an approximate 10% reduction in exacerbation risk per 100 mL improvement in FEV1, consistent across trials and treatment arms.,The risk reduction associated with improvements in FEV1 was relatively small compared to the overall exacerbation risk reduction for treatment arms including budesonide (10-15% per 160 µg budesonide).,High baseline breathlessness score and previous history of exacerbations also influenced the risk of exacerbation.,Joint modelling can be used to co-analyze longitudinal FEV1 and exacerbation data in COPD clinical trials.,The association between the endpoints was consistent and appeared unrelated to treatment mechanism, suggesting that improved lung function is indicative of an exacerbation risk reduction.,The risk reduction associated with improved FEV1 was, however, generally small and no major impact on exacerbation trial design can be expected based on FEV1 alone.,Further exploration with other longitudinal endpoints should be considered to further evaluate the use of joint modelling in analyzing COPD clinical trials. | Health-related quality of life (HRQL) is an important patient-reported outcome for chronic obstructive pulmonary disease (COPD).,We developed models predicting chronic respiratory questionnaire (CRQ) dyspnoea, fatigue, emotional function, mastery and overall HRQL at 6 and 24 months using predictors easily available in primary care.,We used the “least absolute shrinkage and selection operator” (lasso) method to build the models and assessed their predictive performance.,Results were displayed using nomograms.,For each domain-specific CRQ outcome, the corresponding score at baseline was the best predictor.,Depending on the domain, these predictions could be improved by adding one to six other predictors, such as the other domain-specific CRQ scores, health status and depression score.,To predict overall HRQL, fatigue and dyspnoea scores were the best predictors.,Predicted and observed values were on average the same, indicating good calibration.,Explained variance ranged from 0.23 to 0.58, indicating good discrimination.,To predict COPD-specific HRQL in primary care COPD patients, previous HRQL was the best predictor in our models.,Asking patients explicitly about dyspnoea, fatigue, depression and how they cope with COPD provides additional important information about future HRQL whereas FEV1 or other commonly used predictors add little to the prediction of HRQL. | 1 |
Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema.,No cohorts have examined the association between sRAGE and progressive decline of lung function.,There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population.,This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction.,A meta-analysis is used to quantify sRAGE associations with clinical phenotypes.,sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399).,We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity).,Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV1 (P < 0.001), and emphysema severity (P < 0.001).,In an inverse-variance weighted meta-analysis, one SD lower log10-transformed sRAGE was associated with 105 ± 22 mL lower FEV1 and 4.14 ± 0.55 g/L lower adjusted lung density.,After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 decline and emphysema progression only in the ECLIPSE cohort.,Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar.,Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed.,In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling.,Thus, genotype should be included in sRAGE evaluations.,The online version contains supplementary material available at 10.1186/s12931-021-01686-z. | A growing number of studies clearly demonstrate a substantial association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD), although little is known about the shared genetics that contribute to this association.,We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (Ncase = 12,550, Ncontrol = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N = 458,969), high blood pressure (HBP) (Ncase = 144,793, Ncontrol = 313,761), coronary artery disease (CAD)(Ncase = 60,801, Ncontrol = 123,504), and stroke (Ncase = 40,585, Ncontrol = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data.,RHR and HBP had modest genetic correlation, and CAD had borderline evidence with COPD at a genome-wide level.,We found evidence of local genetic correlation with particular regions of the genome.,Cross-trait meta-analysis of COPD identified 21 loci jointly associated with RHR, 22 loci with HBP, and 3 loci with CAD.,Functional analysis revealed that shared genes were enriched in smoking-related pathways and in cardiovascular, nervous, and immune system tissues.,An examination of smoking-related genetic variants identified SNPs located in 15q25.1 region associated with cigarettes per day, with effects on RHR and CAD.,A Mendelian randomization analysis showed a significant positive causal effect of COPD on RHR (causal estimate = 0.1374, P = 0.008).,In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.,The online version of this article (10.1186/s12931-019-1036-8) contains supplementary material, which is available to authorized users. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality, and treatments require a multidisciplinary approach to address patient needs.,This review considers different models of care across the continuum of exacerbations (1) chronic care and self-management interventions with the action plan, (2) domiciliary care for severe exacerbation and the impact on readmission prevention and (3) the discharge care bundle for management beyond the acute exacerbation episode.,Self-management strategies include written action plans and coaching with patient and family support.,Self-management interventions facilitate the delivery of good care, can reduce exacerbations associated with admission, be cost-effective and improve quality of life.,Hospitalization as a complication of exacerbation is not always unavoidable.,Domiciliary care has been proposed as a solution to replace part, and perhaps even all, of the patient’s in-hospital stay, and to reduce hospital bed days, readmission rates and costs; low-risk patients can be identified using risk stratification tools.,A COPD discharge bundle is another potentially important approach that can be considered to improve the management of COPD exacerbations complicated by hospital admission; it comprised treatments that have demonstrated efficacy, such as smoking cessation, personalized pharmacotherapy and non-pharmacotherapy such as pulmonary rehabilitation.,COPD bundles may also improve the transition of care from the hospital to the community following exacerbation and may reduce readmission rates.,Future models of care should be personalized - providing patient education aiming at behaviour changes, identifying and treating co-morbidities, and including outcomes that measure quality of care rather than focusing only on readmission quantity within 30 days. | National surveys have revealed significant differences in patient outcomes following admission to hospital with acute exacerbation of COPD which are likely to be due to variations in care.,We developed a care bundle, comprising a short list of evidence-based practices to be implemented prior to discharge for all patients admitted with this condition, based on a review of national guidelines and other relevant literature, expert opinion and patient consultation.,Implementation was then piloted using action research methodologies with patient input.,Actively involving staff was vital to ensure that the changes introduced were understood and the process followed.,Implementation of a care bundle has the potential to produce a dramatic improvement in compliance with optimum health care practice. | 1 |
Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD).,Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism.,We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages.,In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks.,Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages.,In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK.,Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways.,This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism. | We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route.,Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month.,After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT.,After 1 week, mice were euthanized.,Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue.,In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC).,Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor.,Only BM-MSCs (IV > IT) increased the number of M2 macrophages.,In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk.,The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard.,Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD.,COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP’s office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %).,Significant agreement for forced expiratory volume in 1 s measured at GP’s office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all).,Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD).,Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral.,ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered | 1 |
Several different applications of telehealth technologies have been used in the care of respiratory patients, including telemonitoring, teleconsultations, tele-education, and telehealth-pulmonary rehabilitation (PR).,Telehealth technology provides an opportunity to assist in the management of chronic respiratory diseases and improve access to PR programs.,While there is inconclusive evidence as to the effectiveness of telemonitoring to reduce healthcare utilization and detection of exacerbations, teleconsultations have been shown to be an effective means to assess patients’ disease prior to the initiation of PR, and telehealth PR has been shown to be as effective as institution-based PR at improving functional exercise capacity and health-related quality of life.,To improve PR access across Canada and ensure a high standard of program quality, a team of clinicians and researchers has developed and begun to implement a national standardized PR program that can be delivered across different settings of practice, including remote satellite sites via telehealth PR.,The program has adapted the “Living Well with COPD” self-management program and includes standardized reference guides and resources for patients and practitioners.,A progressive and iterative process will evaluate the success of program implementation and outcomes.,This initiative will address nationwide accessibility challenges and provide PR content as well as evaluations that are in accordance with clinical standards and established self-management practices. | We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE‚ sElf-management anD support proGrammE) in improving quality of life and clinical outcomes.,We compared daily use of EDGE with usual care for 12 months.,The primary outcome was COPD-specific health status measured with the St George’s Respiratory Questionnaire for COPD (SGRQ-C).,A total of 166 patients were randomized (110 EDGE, 56 usual care).,All patients were included in an intention to treat analysis.,The estimated difference in SGRQ-C at 12 months (EDGE−usual care) was −1.7 with a 95% CI of −6.6 to 3.2 (P=.49).,The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care.,Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03).,The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively.,The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention.,However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6pmfIJ9KK) | 1 |
COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow.,It is mainly associated with exposure to cigarette smoke.,In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide.,Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells.,Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways.,The aims of these molecules are differentiation, proliferation and recruitment of neutrophils.,Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight.,In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract.,Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity. | We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke.,The exact mechanisms for this defect are unknown.,Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P) are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function.,We compared mRNA expression of sphingosine kinases (SPHK1/2), S1P receptors (S1PR1-5) and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1) in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers) using Real-Time PCR.,Phagocytosis of apoptotic cells was investigated using flow cytometry.,Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD.,To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5.,The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model.,We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively), S1PR2 and 5 (4.3- and 14.6-fold increases respectively), and SGPL1 (4.5-fold increase) in COPD vs. controls.,S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD “disease effect” rather than smoke effect per se.,Significant associations were noted between S1PR5 and both lung function and phagocytosis.,Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient-derived macrophages.,Antagonising SIPR5 significantly improved phagocytosis.,Our results suggest a potential link between the S1P signalling system and defective macrophage phagocytic function in COPD and advise therapeutic targets. | 1 |
COPD, characterized by chronic inflammation and airway remodeling, has significant pathological alterations in composition and deposition of the extracellular matrix.,The expression of procollagen 1 C-terminal peptide (PICP) and collagen type 1 C-terminal telopeptide (ICTP), two major by-products in the synthesis and degradation of collagen, was shown to be positively correlated with inflammatory mediator levels in previous studies.,In this study, we investigated whether the serum concentrations of PICP and ICTP were associated with the inflammation level for patients with stable COPD.,We collected serum samples from 25 control subjects and 20 patients with stable COPD from December 2011 to October 2012 in Shanghai Zhongshan Hospital and Shanghai Dahua Hospital.,We determined concentrations of PICP, ICTP, C-reactive protein (CRP), IL-6, IL-8, and tumor necrosis factor (TNF)-α by using enzyme-linked immunosorbent assay methods.,Demographic characteristics were comparable between the two groups.,In patients with stable COPD, serum levels of CRP, IL-6, IL-8, and TNF-α were all elevated compared to control subjects, but only changes of IL-6 achieved statistical significance.,Serum concentration of PICP was significantly elevated in patients with COPD, and level of ICTP was slightly decreased.,Moreover, serum concentrations of PICP were positively correlated with the levels of both IL-6 and IL-8.,The increased levels of serum PICP in COPD might indicate the condition of airway remodeling, and IL-6 and/or IL-8 might play an important role in stimulating collagen synthesis. | Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | 1 |
The relationship between chronic obstructive pulmonary disease (COPD) and diabetes remains incompletely understood.,This study evaluated diabetes risk and post-diabetes outcomes in COPD patients with and without exacerbations.,We identified 4671 adults newly diagnosed with COPD exacerbations and 9342 adults newly diagnosed with COPD without exacerbations during 2000-2008 using Taiwan’s National Health Insurance Research Database.,A comparison cohort of 18684 adults without COPD, matched by age and sex, was randomly selected from the same dataset for the control group.,Diabetes events during 2000-2013 were ascertained from medical claims during the follow-up period.,Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes associated with COPD with or without exacerbations were calculated.,We conducted another nested cohort study of 395516 patients with diabetes hospitalization during 2002-2013 and calculated adjusted odds ratios (ORs) and 95% CIs of histories of COPD and COPD exacerbations associated with adverse events after diabetes admission.,During the follow-up period, the incidences of diabetes for patients without COPD and for patients with COPD without or with exacerbations were 3.4, 4.1 and 7.4 per 1000 person-years, respectively (P < 0.0001).,Increased risk of diabetes for patients with COPD without exacerbations (HR 1.09, 95% CI 1.02-1.17) and COPD with exacerbations (HR 2.18, 95% CI 1.88-2.52) was noted.,Post-diabetes pneumonia (OR 3.28, 95% CI 3.13-3.43), intensive care admission (OR 1.32, 95% CI 1.26-1.39) and mortality (OR 2.06, 95% CI 1.88-2.25) were associated with COPD exacerbations.,Prevention and intervention strategies for diabetes and post-diabetes outcomes are needed for this susceptible population. | The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD.,Data derived from population studies can advance our understanding of the true burden of COPD.,The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.,All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV1/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004.,Mortality was observed until the end of year 2007.,Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV1 % predicted) and reported heart disease.,The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001).,Mortality was associated with higher age, being a current smoker, male gender, and COPD.,Replacing COPD with FEV1 % predicted in the multivariate model resulted in the decreasing level of FEV1 being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.,In this cohort COPD and decreased FEV1 were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure (HF) in clinical practice since they share the same pathogenic mechanism.,Both conditions incur significant morbidity and mortality.,Therefore, the prognosis of COPD and HF combined is poorer than for either disease alone.,Nevertheless, usually only one of them is diagnosed.,An active search for each condition using clinical examination and additional tests including plasma natriuretic peptides, lung function testing, and echocardiography should be obtained.,The combination of COPD and HF presents many therapeutic challenges.,The beneficial effects of selective β1-blockers should not be denied in stable patients who have HF and coexisting COPD.,Additionally, statins, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers may reduce the morbidity and mortality of COPD patients.,Moreover, caution is advised with use of inhaled β2-agonists for the treatment of COPD in patients with HF.,Finally, noninvasive ventilation, added to conventional therapy, improves the outcome of patients with acute respiratory failure due to hypercapnic exacerbation of COPD or HF in situations of acute pulmonary edema.,The establishment of a combined and integrated approach to managing these comorbidities would seem an appropriate strategy.,Additional studies providing new data on the pathogenesis and management of patients with COPD and HF are needed, with the purpose of trying to improve quality of life as well as survival of these patients. | Chronic obstructive pulmonary disease (COPD) is an underdiagnosed cause of morbidity and mortality worldwide.,Prevalence of COPD has been shown to be highly associated with positive smoking history and increasing age.,Spirometry is the method used for diagnosing COPD.,However, identifying patients at risk of COPD to undergo spirometry tests has been challenging.,Therefore, there is a need for new cost-effective and feasible diagnostic screening procedures for use in primary care centers.,Our aim was to describe the prevalence and severity of undiagnosed COPD in a group of patients with respiratory infections attending urgent primary care, and to identify those variables in patients' history that could be used to detect the disease.,Patients of 40-75 years (n = 138) attending urgent primary care center with acute respiratory tract infection, positive smoking history and no previously known pulmonary disease underwent pre- and post bronchodilator spirometry testing four to five weeks after the acute infection.,Prevalence and severity of COPD were estimated following the Global Initiative for COPD (GOLD) criteria.,Variables such as sex, age, current smoking status, smoking intensity (pack years) and type of infection diagnosis were assessed for possible associations with COPD.,The prevalence of previously undiagnosed COPD in our study group was 27%, of which 45% were in stage 1 (FEV1 ≥ 80% of predicted), 53% in stage 2 (50 ≤ FEV1 < 80% of predicted), 3% in stage 3 (30 ≤ FEV1 < 50% of predicted) and 0% in stage 4 (FEV1 < 30% of predicted).,We found a significant association between COPD and age ≥ 55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack years > 20) (OR = 3.2 [95% CI 1.2-8.5]).,Sex, current smoking status and type of infection diagnosis were not shown to be significantly associated with COPD.,A middle-aged or older patient with any type of common respiratory tract infection, positive smoking history and no previously known pulmonary disease has an increased likelihood of having underlying COPD.,These patients should be offered spirometry testing for diagnosis of COPD. | 1 |
Individuals with respiratory disease are being increasingly exposed to wildfire smoke as populations encroach further into forested regions and climate change continues to bring higher temperatures with lower rainfall.,Frequent exposures have significant potential to accelerate conditions such as chronic obstructive pulmonary disease (COPD) which is characterised by an exaggerated inflammatory response to environmental stimuli.,Here we employ models of human airway epithelium exposed to wildfire smoke-extract (WFSE) to examine modulation in airway epithelial cell (AEC) survival, fragility and barrier function.,Submerged cultures of small airway epithelial cells (SAEC) and differentiated air-liquid interface (ALI) cultures of primary bronchial AEC (bAEC) were treated for 1-24 h with 1-10% WFSE generated from plant species found in the Australian bushland.,Autophagy (LC3-II and Sequestosome), apoptosis (Poly-(ADP)-Ribose Polymerase (PARP) cleavage) and tight junction proteins were measured using western blot.,Barrier function was assessed via permeability of fluorescein tracers and measuring trans-epithelial electrical resistance.,The production of IL-6 was assessed using ELISA.,Primary epithelial models exposed to WFSE exhibited a significant blockade in autophagy as evidenced by an increase in LC3-II coupled with a concomitant elevation in Sequestosome abundance.,These exposures also induced significant PARP cleavage indicative of apoptotic changes.,ALI cultures of bAEC treated with 5% WFSE demonstrated barrier dysfunction with significant increases in paracellular molecular permeability and ionic conductance, and a reduction in the abundance of the tight junction proteins ZO-1 and Claudin-1.,These cultures also exhibited increased IL-6 secretion consistent with the aberrant and pro-inflammatory repair response observed in the COPD airways.,Further, blocks in autophagy and barrier disruption were significantly elevated in response to WFSE in comparison to similar exposures with cigarette smoke-extract.,WFSE inhibits autophagic flux and induces barrier dysfunction in the airway epithelium.,As autophagy is a central regulator of cellular repair, viability, and inflammation, targeting the block in autophagic flux may ameliorate the consequences of wildfire smoke-exposure for individuals with pre-existing respiratory conditions.,The online version of this article (10.1186/s12931-018-0945-2) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible.,Cigarette smoke and oxidative stress are main etiological risks in COPD.,Interestingly, recent studies suggest a considerable overlap between chronic bronchitis (CB) phenotypic COPD and cystic fibrosis (CF), a common fatal hereditary lung disease caused by genetic mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.,Phenotypically, CF and COPD are associated with an impaired mucociliary clearance and mucus hypersecretion, although they are two distinct entities of unrelated origin.,Mechanistically, the cigarette smoke-increased oxidative stress-induced CFTR dysfunction is implicated in COPD.,This underscores CFTR in understanding and improving therapies for COPD by altering CFTR function with antioxidant agents and CFTR modulators as a great promising strategy for COPD treatments.,Indeed, treatments that restore CFTR function, including mucolytic therapy, antioxidant ROS scavenger, CFTR stimulator (roflumilast), and CFTR potentiator (ivacaftor), have been tested in COPD.,This review article is aimed at summarizing the molecular, cellular, and clinical evidence of oxidative stress, particularly the cigarette smoke-increased oxidative stress-impaired CFTR function, as well as signaling pathways of CFTR involved in the pathogenesis of COPD, with a highlight on the therapeutic potential of targeting CFTR for COPD treatment. | 1 |
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. | Nontypeable Haemophilus influenzae colonizes and infects the airways of adults with chronic obstructive pulmonary disease, the fourth most common cause of death worldwide.Thus, H. influenzae, an exclusively human pathogen, has adapted to survive in the hostile environment of the human airways.To characterize proteins expressed by H. influenzae in the airways, a prototype strain was grown in pooled human sputum to simulate conditions in the human respiratory tract.The proteins from whole bacterial cell lysates were solubilized with a strong buffer and then quantitatively cleaned with an optimized precipitation/on-pellet enzymatic digestion procedure.Proteomic profiling was accomplished by Nano-flow liquid chromatography/mass spectroscopy with low void volume and high separation efficiency with a shallow, long gradient.,A total of 1402 proteins were identified with high confidence, including 170 proteins that were encoded by genes that are annotated as conserved hypothetical proteins.Thirty-one proteins were present in greater abundance in sputum-grown conditions at a ratio of > 1.5 compared to chemically defined media.These included 8 anti-oxidant and 5 stress-related proteins, suggesting that expression of antioxidant activity and stress responses is important for survival in the airways.Four proteins involved in uptake of divalent anions and 9 proteins that function in uptake of various molecules were present in greater abundance in sputum-grown conditions.,Proteomic expression profiling of H. influenzae grown in pooled human sputum revealed increased expression of antioxidant, stress-response proteins and cofactor and nutrient uptake systems compared to media grown cells.These observations suggest that H. influenzae adapts to the oxidative and nutritionally limited conditions of the airways in adults with chronic obstructive pulmonary disease by increasing expression of molecules necessary for survival in these conditions. | 1 |
Individuals with COPD may experience ambulatory difficulty due to both effort intolerance arising from respiratory dysfunction and impaired balance control during walking.,However, the trunk movement during walking has not been evaluated or adjusted for patients with COPD.,The Lissajous index (LI) visually and numerically evaluates the left-right symmetry of the trunk movement during walking and is useful in clinical practice.,In COPD patients, the LI is used as an indicator of the left-right symmetry of the trunk during walking.,Here, we used the LI to evaluate the symmetry of COPD patients based on bilateral differences in mediolateral and vertical accelerations, and we investigated the correlation between the patients’ symmetry evaluation results and their physical function.,Sixteen stable COPD patients (all males; age 71.3±9.2 years) and 26 healthy control subjects (15 males; age 68.2±6.9 years) participated in this study.,They performed the 10-minute walk test at a comfortable gait speed wearing a triaxial accelerometer, and we measured their trunk acceleration for the evaluation of symmetry.,Motor functions were also evaluated in the patients with COPD.,The average mediolateral bilateral difference and LI values of the COPD patients were significantly larger than those of the healthy subjects.,The COPD patients’ LI values were significantly correlated with their static balance.,The LI measured using a triaxial accelerometer during walking is useful in balance assessments of patients with COPD. | To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD).,Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects.,79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk.,The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups.,Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models.,COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects.,Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD.,In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%).,COPD patients have an altered walking pattern during 6MWT compared to healthy subjects.,These differences in walking pattern partially explain the lower 6MWD in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 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. | 1 |
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ. | 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. | 1 |
Recent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e.,GOLD groups C and D.,However, it is known that ICS is frequently prescribed for patients with less severe COPD.,Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use.,The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen.,Linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used.,For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy.,Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms.,Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing.,Treatment acquisition costs were not assessed.,Results showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group.,Rate ratios favoured the non-ICS group for eight of nine outcomes assessed.,Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 < 50% predicted), one prior exacerbation or elevated blood eosinophils.,These data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.,The online version of this article (10.1186/s12931-018-0767-2) contains supplementary material, which is available to authorized users. | Initial use of inhaled corticosteroid therapy is common in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) A or B chronic obstructive pulmonary disease, contrary to GOLD guidelines.,We investigated UK prescribing of inhaled corticosteroid therapy in these patients, to identify predictors of inhaled corticosteroid use in newly diagnosed chronic obstructive pulmonary disease patients.,A cohort of newly diagnosed GOLD A/B chronic obstructive pulmonary disease patients was identified from the UK Clinical Practice Research Datalink (June 2005-June 2015).,Patients were classified by prescribed treatment, with those receiving inhaled corticosteroid-containing therapy compared with those receiving long-acting bronchodilators without inhaled corticosteroid.,In all, 29,815 patients with spirometry-confirmed chronic obstructive pulmonary disease were identified.,Of those prescribed maintenance therapy within 3 months of diagnosis, 63% were prescribed inhaled corticosteroid-containing therapy vs. 37% prescribed non-inhaled corticosteroid therapy.,FEV1% predicted, concurrent asthma diagnosis, region, and moderate exacerbation were the strongest predictors of inhaled corticosteroid use in the overall cohort.,When concurrent asthma patients were excluded, all other co-variates remained significant predictors.,Other significant predictors included general practitioner practice, younger age, and co-prescription with short-acting bronchodilators.,Trends over time showed that initial inhaled corticosteroid prescriptions reduced throughout the study, but still accounted for 47% of initial prescriptions in 2015.,These results suggest that inhaled corticosteroid prescribing in GOLD A/B patients is common, with significant regional variation that is independent of FEV1% predicted.,Inhaled steroids are often prescribed to early-stage chronic lung disease patients in the UK despite guidelines to the contrary.,Patients newly diagnosed with early-stage chronic obstructive pulmonary disease (COPD) should not be prescribed inhaled corticosteroids (ICS), because they carry an increased risk of side effects such as pneumonia and osteoporosis.,ICS should be reserved for patients with severe COPD and frequent exacerbations.,James Chalmers at the Scottish Centre for Respiratory Research, Dundee, and co-workers examined prescribed medication data from the UK spanning 10 years, to determine key predictors of ICS prescription during early-stage COPD.,Of 29,815 patients identified, an average of 63% were prescribed ICS upon diagnosis, regardless of disease severity.,Younger patients were more likely to receive ICS, possibly due to co-morbidity with chronic asthma, and particular UK regions and medical practices prescribed ICS more readily than others. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | 1 |
Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs.,Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated.,Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.,Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.,Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%).,No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline.,No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001).,In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02].,The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).,In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D.,This association was independent of patients’ characteristics and comorbidities.,The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users. | There are limited data on the risk of pulmonary disease in patients with diabetes.,The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.,We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California.,Age and sex data were available for all cohort members (n = 1,811,228).,Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.,Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort.,No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes.,These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03-1.12], COPD HR 1.22 [1.15-1.28], pulmonary fibrosis HR 1.54 [1.31-1.81], and pneumonia HR 1.92 [1.84-1.99]).,The risk of pneumonia and COPD increased significantly with increasing A1C.,Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer.,This increased risk may be a consequence of declining lung function in patients with diabetes. | 1 |
To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection.,The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020.,Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected.,Patients with COPD were selected and compared to patients without COPD.,Factors associated with a poor prognosis were analyzed.,Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD.,Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male.,They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001).,The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001).,Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients.,Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037).,Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis.,COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
To investigate the prevalence and the risk factors of COPD in the Uyghur population in the Kashi region.,From August 2018 to March 2019, we recruited participants of Uyghur ethnicity and aged ≥40 years old from the Kashi region using a combined cluster sampling and random sampling method.,We collected potential risk factors using questionnaire, and conduced lung function using a portable pulmonary function instrument.,A total of 2963 participants were included in this analysis, of whom 1268 were males and 1695 were females.,There were 504 participants with COPD, generating a prevalence of 17.01%.,With the increase of age, the prevalence of COPD in different genders increased significantly.,The results of different regions were χ2= 627.89, p < 0.01, indicating significant differences in the prevalence in different regions.,Among them, based on the existing survey data, it is speculated that Shache county has the highest crude prevalence, but the sample size needs to be further expanded.,The participants with high age, smoking, lower BMI, high waist circumference, systolic blood pressure, fried cooking and barbecue share more COPD than those who partake of fruits and vegetables in this study.,The prevalence of COPD among the Uyghur population in the Kashi region is higher than the national rural average.,Among them, high age, smoking, low BMI, high waist circumference, high systolic blood pressure, cooking methods that may be stir-fried and deep-fried barbecue are risk factors for COPD, and vegetable and fruit intake may be a protective factor for COPD. | Bodyweight and fat distribution may be related to COPD risk.,Limited prospective evidence linked COPD to abdominal adiposity.,We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.,The China Kadoorie Biobank recruited participants aged 30-79 years from 10 areas across China.,Anthropometric indexes were objectively measured at the baseline survey during 2004-2008.,After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016.,We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.,Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported.,Compared with subjects with normal BMI (18.5-<24.0 kg·m−2), underweight (BMI <18.5 kg·m−2) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66-1.89).,Overweight (BMI 24.0-<28.0 kg·m−2) and obesity (BMI ≥28.0 kg·m−2) were not associated with an increased risk after adjustment for waist circumference.,A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI.,Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.http://bit.ly/36To4fk | 1 |
Only very few studies have investigated the influence of eosinophils on the functional progression of COPD.,We aimed at retrospectively analyzing the trend of pulmonary function tests over time in patients with COPD according to two baseline blood eosinophil cell count strata (<2% [EOS−] and ≥2% [EOS+]).,We used the last 9-year data present in the database of our outpatient clinic and selected only those who had two blood counts that would guarantee the stability of the value of eosinophils and serial spirometry for 4 consecutive years.,The analysis of the time course of the spirometric variables analysed showed differences in FEV1 and FVC decline between the subjects of the EOS− group and those of the EOS+ group.,The integrated evaluation of our results suggests that the different level of blood eosinophils in the two groups may have influenced independently the time course of the pulmonary function tests and identify two subgroups of subjects with specific disease characteristics: the hyperinflator and the rapid decliner, respectively. | Blood eosinophil counts have been documented as a good biomarker for patients with chronic obstructive pulmonary disease (COPD) using inhaled corticosteroid (ICS) therapy.,However, the effectiveness and safety of prescribing high or medium dose of ICS for patients with different eosinophil counts are unknown.,A post hoc analysis of a previous prospective randomized study was performed for COPD patients using higher dose (HD: Fluticasone 1,000 μg/day) or medium dose (MD: Fluticasone 500 μg/day) of ICS combined with Salmeterol (100 μg/day).,Patients were classified into two groups: those with high eosinophil counts (HE ≥3%) and those with low eosinophil counts (LE <3%).,Lung function was evaluated with forced expiratory volume in 1 second, forced vital capacity, and COPD assessment test.,Frequencies of acute exacerbation and pneumonia were also measured.,Two hundred and forty-eight patients were studied and classified into higher eosinophil (HE) (n=85, 34.3%) and lower eosinophil (LE) groups (n=163, 65.7%).,The levels of forced expiratory volume in 1 second were significantly increased in patients of HE group treated with HD therapy, compared with the other groups (HE/HD: 125.9±27.2 mL vs HE/MD: 94.3±23.7 mL, vs LE/HD: 70.4±20.5 mL, vs LE/MD: 49.8±16.7 mL; P<0.05) at the end of the study.,Quality of life (COPD assessment test) markedly improved in HE/HD group than in MD/LE group (HE/HD: 9±5 vs LE/MD: 16±7, P=0.02).,The frequency of acute exacerbation was more decreased in HE/HD group patients, compared with that in LE/MD group (HE/HD: 13.5% vs LE/MD: 28.7%, P<0.01).,Pneumonia incidence was similar in the treatment groups (HE/HD: 3.2%, HE/MD: 2.6%, LE/HD: 3.5%, LE/MD 2.8%; P=0.38).,The study results support using blood eosinophil counts as a biomarker of ICS response and show the benefits of greater improvement of lung function, quality of life, and decreased exacerbation frequency in COPD patients with blood eosinophil counts higher than 3%, especially treated with higher dose of ICS. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations.,We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.,Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013.,Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days.,Exacerbations occurring within this period were considered as one event.,Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC).,To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported.,The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.,The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden.,Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.,Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations. | To map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease (COPD).,Systematic review.,PubMed until November 2018 and hand searched references from eligible articles.,Studies developing, validating, or updating a prediction model in COPD patients and focusing on any potential clinical outcome.,The systematic search yielded 228 eligible articles, describing the development of 408 prognostic models, the external validation of 38 models, and the validation of 20 prognostic models derived for diseases other than COPD.,The 408 prognostic models were developed in three clinical settings: outpatients (n=239; 59%), patients admitted to hospital (n=155; 38%), and patients attending the emergency department (n=14; 3%).,Among the 408 prognostic models, the most prevalent endpoints were mortality (n=209; 51%), risk for acute exacerbation of COPD (n=42; 10%), and risk for readmission after the index hospital admission (n=36; 9%).,Overall, the most commonly used predictors were age (n=166; 41%), forced expiratory volume in one second (n=85; 21%), sex (n=74; 18%), body mass index (n=66; 16%), and smoking (n=65; 16%).,Of the 408 prognostic models, 100 (25%) were internally validated and 91 (23%) examined the calibration of the developed model.,For 286 (70%) models a model presentation was not available, and only 56 (14%) models were presented through the full equation.,Model discrimination using the C statistic was available for 311 (76%) models. 38 models were externally validated, but in only 12 of these was the validation performed by a fully independent team.,Only seven prognostic models with an overall low risk of bias according to PROBAST were identified.,These models were ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE, and a model developed by Bertens et al.,A meta-analysis of C statistics was performed for 12 prognostic models, and the summary estimates ranged from 0.611 to 0.769.,This study constitutes a detailed mapping and assessment of the prognostic models for outcome prediction in COPD patients.,The findings indicate several methodological pitfalls in their development and a low rate of external validation.,Future research should focus on the improvement of existing models through update and external validation, as well as the assessment of the safety, clinical effectiveness, and cost effectiveness of the application of these prognostic models in clinical practice through impact studies.,PROSPERO CRD42017069247 | 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. | Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | 1 |
To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Lymphotoxin β-receptor (LTβR)-signalling orchestrates lymphoid neogenesis and subsequent tertiary lymphoid structures (TLS)1,2, associated with severe chronic inflammatory diseases spanning multiple organ systems3-6.,How LTβR-signalling drives chronic tissue damage particularly in the lung, which mechanism(s) regulate this process, and whether LTβR-blockade might be of therapeutic value has remained unclear.,Here we demonstrate increased expression of LTβR-ligands on adaptive and innate immune-cells, enhanced non-canonical NF-κB signalling and enriched LTβR-target gene expression in epithelial cells of lungs from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and mice exposed to chronic cigarette smoke.,Therapeutic inhibition of LTβR-signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue (iBALT), induced lung tissue regeneration, and reverted airway-fibrosis and systemic muscle wasting.,Mechanistically, LTβR-signalling blockade dampened epithelial non-canonical NF-κB activation, reduced TGFβ-signalling in airways, induced regeneration by preventing epithelial cell-death and by activating Wnt/β-catenin-signalling in alveolar epithelial progenitor cells.,These findings highlight that LTβR-signalling inhibition represents a viable therapeutic option combining anti-TLS, anti-apoptotic with tissue regenerative strategies. | Cigarette smoke (CS) is the leading risk factor to develop COPD.,Therefore, the pathologic effects of whole CS on the differentiation of primary small airway epithelial cells (SAEC) were investigated, using cells from three healthy donors and three COPD patients, cultured under ALI (air-liquid interface) conditions.,The analysis of the epithelial physiology demonstrated that CS impaired barrier formation and reduced cilia beat activity.,Although, COPD-derived ALI cultures preserved some features known from COPD patients, CS-induced effects were similarly pronounced in ALI cultures from patients compared to healthy controls.,RNA sequencing analyses revealed the deregulation of marker genes for basal and secretory cells upon CS exposure.,The comparison between gene signatures obtained from the in vitro model (CS vs. air) with a published data set from human epithelial brushes (smoker vs. non-smoker) revealed a high degree of similarity between deregulated genes and pathways induced by CS.,Taken together, whole cigarette smoke alters the differentiation of small airway basal cells in vitro.,The established model showed a good translatability to the situation in vivo.,Thus, the model can help to identify and test novel therapeutic approaches to restore the impaired epithelial repair mechanisms in COPD, which is still a high medical need. | 1 |
Chronic obstructive pulmonary disease (COPD) is a devastating lung disease, mainly due to cigarette smoking, which represents the third cause of mortality worldwide.,The mechanisms driving its epithelial salient features remain largely elusive.,We aimed to evaluate the activation and the role of the canonical, β-catenin-dependant WNT pathway in the airway epithelium from COPD patients.,The WNT/β-catenin pathway was first assessed by WNT-targeted RNA sequencing of the air/liquid interface-reconstituted bronchial epithelium from COPD and control patients.,Airway expression of total and active β-catenin was assessed in lung sections, as well as WNT components in laser-microdissected airway epithelium.,Finally, we evaluated the role of WNT at the bronchial epithelial level by modulating the pathway in the reconstituted COPD epithelium.,We show that the WNT/β-catenin pathway is upregulated in the COPD airway epithelium as compared with that of non-smokers and control smokers, in targeted RNA-sequencing of in vitro reconstituted airway epithelium, and in situ in lung tissue and laser-microdissected epithelium.,Extrinsic activation of this pathway in COPD-derived airway epithelium inhibited epithelial differentiation, polarity and barrier function, and induced TGF-β-related epithelial-to-mesenchymal transition (EMT).,Conversely, canonical WNT inhibition increased ciliated cell numbers, epithelial polarity and barrier function, whilst inhibiting EMT, thus reversing COPD features.,In conclusion, the aberrant reactivation of the canonical WNT pathway in the adult airway epithelium recapitulates the diseased phenotype observed in COPD patients, suggesting that this pathway or its downstream effectors could represent a future therapeutic target.,This study was supported by the Fondation Mont-Godinne, the FNRS and the WELBIO. | Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential. | 1 |
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. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Angiotensin-converting enzyme 2 (ACE2) has been identified as the cell entry receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2].,Importantly, smokers and patients with COPD are at an increased risk of severe complications and a higher mortality upon SARS-CoV-2 infection [3].,We hypothesised that ACE2 expression is increased in lungs of smokers and patients with COPD, which may at least partially explain their higher risk of a more severe course of coronavirus disease 2019 (COVID-19).,Therefore, we aimed to investigate the expression of ACE2 on both mRNA and protein level in a large number of lung tissue specimens of well-phenotyped subjects, including never-smokers, current smokers without airflow limitation, and patients with COPD.,This study demonstrates increased protein levels of ACE2 in alveolar and bronchial epithelium of smokers and subjects with COPD, which might facilitate host cell entry of SARS-CoV-2https://bit.ly/2ZazOrd | Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with exercise limitation and physical inactivity, which are believed to have significant long-term negative health consequences for patients.,While a number of COPD treatments and exercise training programmes increase exercise capacity, there is limited evidence for their effects on physical activity levels, with no clear association between exercise capacity and physical activity in clinical trials.,Physical activity depends on a number of behaviour, environmental and physiological factors.,We describe the design of the PHYSACTO trial, which is investigating the effects of bronchodilators, either alone or with exercise training, in combination with a standardised behaviour-change self-management programme, on exercise capacity and physical activity in patients with COPD.,It is hypothesised that bronchodilators in conjunction with a behaviour-change self-management programme will improve physical activity and that this effect will be amplified by the addition of exercise training.,Patients are being recruited from 34 sites in Australia, New Zealand, the USA, Canada and Europe.,Patients receiving a multicomponent intervention designed to support behaviour change related to physical activity are randomised to four treatment arms: placebo, tiotropium, tiotropium+olodaterol, and tiotropium+olodaterol+exercise training.,The primary outcome is improvement in exercise capacity after 8 weeks, measured by endurance time during a shuttle walk test.,The secondary outcome is improvement in physical activity, including objective accelerometer assessment and patient-reported functioning using the Functional Performance Inventory-Short Form and the novel hybrid PROactive instrument.,Additionally, the influence of moderating variables (ie, factors influencing a patient's choice to be physically active) on increases in physical activity is also explored.,The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations.,The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.,NCT02085161. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
After the development of the COPD Strategy of the National Health Service in Spain, all scientific societies, patient organisations, and central and regional governments formed a partnership to enhance care and research in COPD.,At the same time, the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) took the initiative to convene the various scientific societies involved in the National COPD Strategy and invited them to participate in the development of the new Spanish guidelines for COPD (Guía Española de la EPOC; GesEPOC).,Probably the more innovative approach of GesEPOC is to base treatment of stable COPD on clinical phenotypes, a term which has become increasingly used in recent years to refer to the different clinical forms of COPD with different prognostic implications.,The proposed phenotypes are: (A) infrequent exacerbators with either chronic bronchitis or emphysema; (B) overlap COPD-asthma; (C) frequent exacerbators with emphysema predominant; and (D) frequent exacerbators with chronic bronchitis predominant.,The assessment of severity has also been updated with the incorporation of multidimensional indices.,The severity of the obstruction, as measured by forced expiratory volume in 1 second, is essential but not sufficient.,Multidimensional indices such as the BODE index have shown excellent prognostic value.,If the 6-minute walking test is not performed routinely, its substitution by the frequency of exacerbations (BODEx index) provides similar prognostic properties.,This proposal aims to achieve a more personalised management of COPD according to the clinical characteristics and multidimensional assessment of severity. | The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD).,The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD.,This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD.,It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers.,The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report.,This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations.,The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient.,The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma-COPD overlap syndrome (ACOS).,These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions.,For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol-ipratropium) is recommended in patients with less symptoms.,If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended.,For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice.,Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic.,If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast.,ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD.,Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD.,Thus, evidence-based recommendation of treatment cannot be given.,The treatment should cover both diseases.,Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both). | 1 |
In study “Effect of high-flow nasal therapy during early pulmonary rehabilitation in patients with severe AECOPD: a randomized controlled study” by Tung et al., authors concluded HFNT utilization led to enhanced exercise tolerance and a reduction of systemic inflammation.,Nevertheless, some points requires additional discussion, the conclusion of the trial seems overstated.,The baseline differences between groups induces substantial modifications in the conclusions of this trial.,HFNT does not seem to add any benefit on exercise tolerance or systemic inflammation, nor on pulmonary function.,The only difference that remained significant in homogenous statistical significance is dyspnea on the mMRC scale but clinical significance is highly questionable. | Chest physiotherapy is an important tool in the treatment of COPD.,Intrapulmonary percussive ventilation (IPV) and high-frequency chest wall oscillation (HFCWO) are techniques designed to create a global percussion of the lung which removes secretions and probably clears the peripheral bronchial tree.,We tested the hypothesis that adding IPV or HFCWO to the best pharmacological therapy (PT) may provide additional clinical benefit over chest physiotherapy in patients with severe COPD.,Sixty patients were randomized into three groups (20 patients in each group): IPV group (treated with PT and IPV), PT group with (treated with PT and HFCWO), and control group (treated with PT alone).,Primary outcome measures included results on the dyspnea scale (modified Medical Research Council) and Breathlessness, Cough, and Sputum scale (BCSS), as well as an evaluation of daily life activity (COPD Assessment Test [CAT]).,Secondary outcome measures were pulmonary function testing, arterial blood gas analysis, and hematological examinations.,Moreover, sputum cell counts were performed at the beginning and at the end of the study.,Patients in both the IPV group and the HFCWO group showed a significant improvement in the tests of dyspnea and daily life activity evaluations (modified Medical Research Council scale, BCSS, and CAT) compared to the control group, as well as in pulmonary function tests (forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity%, total lung capacity, residual volume, diffusing lung capacity monoxide, maximal inspiratory pressure, maximal expiratory pressure) and arterial blood gas values.,However, in the group comparison analysis for the same variables between IPV group and HFCWO group, we observed a significant improvement in the IPV group maximal inspiratory pressure, maximal expiratory pressure, BCSS, and CAT.,Similar results were observed in changes of sputum cytology with reduction of inflammatory cells (neutrophils and macrophages).,The two techniques improved daily life activities and lung function in patients with severe COPD.,IPV demonstrated a significantly greater effectiveness in improving some pulmonary function tests linked to the small bronchial airways obstruction and respiratory muscle strength and scores on health status assessment scales (BCSS and CAT) as well as a reduction of sputum inflammatory cells compared with HFCWO. | 1 |
This multicenter, prospective, observational study aimed to supplement real-world evidence on the effects of aclidinium bromide on the quality of life (QoL), symptoms, and activity impairment of patients with COPD.,Eligible patients were ≥40 years of age, newly initiated on aclidinium bromide as monotherapy or add-on therapy according to the product’s approved label.,Patient-reported COPD assessment test (CAT), the severity of symptoms and their impact on daily activities, and the features of the Genuair® inhaler device were assessed at enrollment and at 12 weeks post-treatment onset.,Between 13 March 2015 and 29 January 2016, 285 eligible consenting patients (76.3% males; median age: 69.0 years; 26.0% newly diagnosed with COPD) were enrolled by 15 hospital-based respiratory medicine specialists in Greece.,Aclidinium bromide was initiated as add-on therapy to other inhaled maintenance medications in 73.1% of evaluable patients.,The median (interquartile range [IQR]) baseline CAT score decreased from 14.0 (9.0-20.0) to 10.0 (6.0-15.0) points (p<0.001) after 12 weeks of treatment, with 76.5% of the patients achieving a ≥2-point decrease.,The severity of night-time and early-morning symptoms, assessed using a 5-point Likert-type scale, decreased from a median (IQR) of 1.0 (0.0-2.0) to 0.0 (0.0-1.0), and from 2.0 (1.0-2.0) to 1.0 (1.0-2.0), respectively (p<0.001 for both).,In patients with paired data, the prevalence of at least moderate night-time symptoms, early-morning symptoms, and daily activity impairment decreased from 28.2% to 19.1%, from 63.6% to 34.2%, and from 59.5% to 38.7%, respectively (p<0.001 for all).,Inhaler device features were assessed as “very good”/“good” by more than 90% of the patients.,The adverse drug reaction rate was 1.4%.,The study provides real-world evidence on the beneficial effects of aclidinium bromide on the patients’ QoL, symptom severity, and daily activity impairment, which are complemented by a favorable safety profile and high patient satisfaction with the inhaler device. | Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO | 1 |
Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions.,Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis.,Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity.,Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells.,NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment.,CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD.,These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.,Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases.,Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD. | Rationale: Aberrant bronchial epithelium-fibroblast communication is essential for the airway remodeling that contributes to chronic obstructive pulmonary disease (COPD).,Exosomes have emerged as novel mediators of intercellular communication, but their role in cigarette smoke (CS)-induced COPD is unknown.,Here, we investigated the role of exosomal miR-21 in the dysfunctional epithelium-fibroblast cross-talk caused by CS.,Methods: Normal or CS extract (CSE)-treated human bronchial epithelial (HBE) cells were co-cultured with bronchial fibroblasts (MRC-5 cells).,Exosomes were obtained from culture media or serum by use of commercial kits.,The size distribution and concentration of exosomes were analyzed by nanoparticle tracking analysis using a ZetaView particle tracker from ParticleMetrix.,Inhibition of miR-21 levels by tail vein injection of antagomir-21 into mice exposed to CS was used to demonstrate the role of miR-21 in airway remodeling leading to COPD in animals.,Results: For MRC-5 cells, co-culture with CSE-treated HBE cells or with exosomes derived from CSE-treated HBE cells resulted in the myofibroblast differentiation phenotype.,Exosomal miR-21 was responsible for myofibroblast differentiation through hypoxia-inducible factor 1α (HIF-1α) signaling by targeting the von Hippel-Lindau protein (pVHL); HIF-1α transcriptionally regulated the α-SMA gene.,For mice, downregulation of miR-21 prevented CS-induced airway remodeling.,The levels of exosomal miR-21 were high in sera of smokers and COPD patients and inversely correlated with FEV1/FVC.,Conclusion: We demonstrate that CS triggers the modification of exosome components and identify miR-21 derived from bronchial epithelial cells as a mediator of myofibroblast differentiation through the pVHL/HIF-1α signaling pathway, which has potential value for diagnosis and treatment of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) guidelines recommend early access to palliative care together with optimal, disease-directed therapy for people with advanced disease, however, this occurs infrequently.,This study explored the approaches of respiratory and palliative medicine specialists to palliative care and advance care planning (ACP) in advanced COPD.,An online survey was emailed to all specialists and trainees in respiratory medicine in Australia and New Zealand (ANZ), and to all palliative medicine specialists and trainees in ANZ and the United Kingdom.,Five hundred seventy-seven (33.1%) responses were received, with 440 (25.2%) complete questionnaires included from 177 respiratory and 263 palliative medicine doctors.,Most respiratory doctors (140, 80.9%) were very or quite comfortable providing a palliative approach themselves to people with COPD.,113 (63.8%) respiratory doctors recommended referring people with advanced COPD to specialist palliative care, mainly for access to: psychosocial and spiritual care (105, 59.3%), carer support (104, 58.5%), and end-of-life care (94, 53.1%).,432 (98.2%) participants recommended initiating ACP discussions.,Palliative medicine doctors were more likely to recommend discussing: what palliative care is (p < 0.0001), what death and dying might be like (p < 0.0001) and prognosis (p = 0.004).,Themes highlighted in open responses included: inadequate, fragmented models of care, with limited collaboration or support from palliative care services.,While both specialties recognised the significant palliative care and ACP needs of people with advanced COPD, in reality few patients access these elements of care.,Formal collaboration and bi-directional support between respiratory and palliative medicine, are required to address these unmet needs. | The chronic obstructive pulmonary disease (COPD) assessment test (CAT) was recently introduced for use in assessing disease-specific quality of life and follow-up of patients with COPD.,The purpose of this study was to evaluate the effect of the dyspnea on disease-specific quality of life detected by CAT score in patients with COPD.,In this study, 90 stable patients with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were included.,The level of dyspnea was assessed with the Medical Research Council (MRC) dyspnea scale, and disease-specific quality of life was assessed with CAT score.,The mean±SD age was 68.5±10.9 (range 41-97) years.,A significant relationship was established between CAT score, MRC dyspnea scale score and GOLD stage in patients with COPD.,There was also a positive correlation between dyspnea scale scores and GOLD stage in the patients (p<0.001), as well as positive correlation between CAT score and dyspnea scale score (p<0.001).,CAT score showed a significant correlation with hospitalization and exacerbations (p<0.05).,Dyspnea is an important symptom that may impact quality of life in patients with COPD.,CAT was shown to be a simple, fast and intelligible measurement of disease-specific quality of life, and was correlated with levels of dyspnea in patients with COPD. | 1 |
‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users. | Quantifying physical activity in chronic obstructive pulmonary disease (COPD) is important as physical inactivity is related to poor health outcomes.,This study analyzed the relationship between patients’ self-reported daily walking time and relevant characteristics related to COPD severity.,Pooled analysis was performed on data from four observational studies on which daily walking time was gathered from a personal interview.,Patients were classified as physically inactive if walking time was <30 min/day.,Walking times were described and compared according to several markers of disease severity.,The mean daily walking time of 5,969 patients was 66 (standard deviation [SD] 47) min/day; 893 (15%) patients were inactive.,A linear dose-response relationship was observed between walking time and the modified Medical Research Council (mMRC) dyspnea score, admissions, COPD assessment test (CAT), body mass index, airway obstruction, dyspnea, exacerbation (BODEx) index, and Charlson index (P<0.001).,Daily walking times were lower in patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B and D (P<0.001).,Often, inactive patients had mMRC or Charlson index >3, post-bronchodilator forced expiratory volume in the first second <30% predicted, at least one hospitalization for COPD, classified as GOLD B or D, BODEx >4, and CAT score >30.,Lower self-reported walking times are related to worse markers of disease severity in COPD. | 1 |
Acute exacerbations (AE) affect the prognosis of hospitalized patients with chronic obstructive pulmonary disease (COPD).,Pneumonia further affects their prognosis and early diagnosis of pneumonia in AECOPD is important to initiate treatments.,This study aimed to examine the differences between hospitalized AECOPD patients with and without pneumonia in order to identify risk factors of pneumonia among hospitalized patients with AECOPD.,This was a retrospective case-control study of patients with COPD hospitalized at the respiratory ward of Beijing Shijitan Hospital, Capital Medical University, from October 2010 to October 2013.,Patients were divided into the pneumonia and nonpneumonia groups based on exudations or opacities on chest computed tomography (CT) at admission.,Data were analyzed using the chi-square test and independent 2-sample ANOVA in SPSS 20.0.,Logistic regression analysis was used to identify the factors independently associated with pneumonia.,P < .05 was considered statistically significant.,A total of 164 patients were included.,Smoking history (OR = 2.646, 95%CI 1.153-6.074, P = .022), use of drugs during the stable stage (OR = 0.435, 95%CI 0.216-0.877, P = .020), D-dimer levels (OR = 1.001, 95%CI 1.000-1.002, P = .049), percentage of neutrophils (OR = 0.271, 95%CI 0.078-0.940, P = .040), and magnitude of neutrophils increase (OR = 0.946, 95%CI 0.896-0.999, P = .046) were independently associated with pneumonia in patients with AECOPD.,For severe and very severe COPD patients, smoking history (OR = 4.426, 95%CI 1.458-13.435, P = .009), use of drugs during the stable stage (OR = 0.384, 95%CI 0.168-0.877, P = .042), and fever (OR = 0.426, 95%CI 0.187-0.969, P = .023) were independently associated with pneumonia.,Smoking history, use of drugs during the stable stage, and percentage of neutrophils are independently associated with CT-diagnosed pneumonia among hospitalized AECOPD patients. | There is little data surrounding the survival of patients with chronic obstructive pulmonary disease (COPD) who are admitted to the critical care unit with exacerbation of symptoms.,We conducted a study to measure the in-hospital and intensive care unit (ICU) outcomes of patients admitted with COPD exacerbation, and identified the related prognostic factors.,We performed a retrospective cohort study of patients who were admitted to the adult ICU between January 2006 and July 2011 for COPD exacerbation in King Abdulaziz National Guard Hospital, Al-Hasa, Saudi Arabia.,During the study period, a total of 119 patients were admitted to the ICU with acute respiratory failure attributed to COPD exacerbation.,The mean age was 72 ± 13 years, and 44 (37%) were females.,The main cause of respiratory failure was infection, which occurred in 102 (86%) patients.,Thirty-nine (33%) of the admitted patients were mechanically ventilated, and the median duration was 2.6 (1-42) days.,The median lengths of the ICU and hospital stays were 3 (1-40) and 9 (2-43) days, respectively.,The ICU mortality was 6%, and hospital mortality was 11%.,Low Glasgow Coma Scale on admission, intubation, duration of mechanical ventilation, current smoking, tracheostomy, cardiopulmonary arrest, and the development of acute renal failure were associated with higher hospital mortality.,Early ICU and hospital mortality is low for COPD patients who have been admitted to the ICU with exacerbation.,Low Glasgow Coma Scale scores on admission, intubation, prolonged use of mechanical ventilation, and the development of acute renal failure were identified as risk factors associated with increased hospital mortality. | 1 |
To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis of randomised controlled trials.,PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.,Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible.,Efficacy and safety outcomes of interest were also available.,Data were collected independently.,Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals.,Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).,21 trials (19 publications) were included.,Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS).,Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91).,Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy.,The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).,Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.,Prospero CRD42018077033. | Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality.,Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD.,The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial.,Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70, and post-bronchodilator FEV1 ≤70% of predicted.,Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded.,Primary endpoint is change from baseline in aPWV after 24 weeks of treatment.,Safety analyses included adverse events (AEs).,The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141).,Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV1 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening.,At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo).,AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients.,No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo. | 1 |
The prevalence of Non Communicable Diseases (NCDs) is still unknown in Nepal.,The Ministry of Health and Population, Government of Nepal has not yet formulated policy regarding NCDs in the absence of evidence based finding.,The study aims to find out the hospital based prevalence of NCDs in Nepal, thus directing the concerned authorities at policy level.,A cross sectional study was conducted to identify the hospital based prevalence of 4 NCDs (cancer, cardiovascular disease, diabetes mellitus and chronic obstructive pulmonary disease), wherein 400 indoor patients admitted during 2009 were randomly selected from each of the 31 selected health institutions which included all non-specialist tertiary level hospitals outside the Kathmandu valley (n = 25), all specialist tertiary level hospitals in the country (n = 3) and 3 non-specialist tertiary level hospitals inside the Kathmandu valley.,In case of Kathmandu valley, 3 non-specialist health institutions- one central hospital, one medical college and one private hospital were randomly selected.,The main analyses are based on the 28 non-specialist hospitals.,Univariate (frequency and percentage) and bivariate (cross-tabulation) analysis were used.,In non-specialist institutions, the hospital based NCD prevalence was 31%.,Chronic obstructive pulmonary disease (43%) was the most common NCD followed by cardiovascular disease (40%), diabetes mellitus (12%) and cancer (5%).,Ovarian (14%), stomach (14%) and lung cancer (10%) were the main cancers accounting for 38% of distribution.,Majority of CVD cases were hypertension (47%) followed by cerebrovascular accident (16%), congestive cardiac failure (11%), ischemic heart disease (7%), rheumatic heart disease (5%) and myocardial infarction (2%).,CVD was common in younger age groups while COPD in older age groups.,Majority among males (42%) and females (45%) were suffering from COPD.,The study was able to reveal that Nepal is also facing the surging burden of NCDs similar to other developing nations in South East Asia.,Furthermore, the study has provided a background data on NCDs in Nepal which should prove useful for the concerned organizations to focus and contribute towards the prevention, control and reduction of NCD burden and its risk factors. | One hundred million deaths were caused by tobacco in the 20th century, and it is estimated that there will be up to one billion deaths attributed to tobacco use in the 21st century.,Chronic obstructive pulmonary disease (COPD) is rapidly becoming a global public health crisis with smoking being recognized as its most important causative factor.,The most effective available treatment for COPD is smoking cessation.,There is mounting evidence that the rate of progression of COPD can be reduced when patients at risk of developing the disease stop smoking, while lifelong smokers have a 50% probability of developing COPD during their lifetime.,More significantly, there is also evidence that the risk of developing COPD falls by about half with smoking cessation.,Several pharmacological interventions now exist to aid smokers in cessation; these include nicotine replacement therapy, bupropion, and varenicline.,All pharmacotherapies for smoking cessation are more efficacious than placebo, with odds ratios of about 2.,Pharmacologic therapy should be combined with nonpharmacologic (behavioral) therapy.,Unfortunately, despite the documented efficacy of these agents, the absolute number of patients who are abstinent from smoking at 12 months of follow-up is low. | 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation.,Why some patients are susceptible to colonisation is not understood.,We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity.,The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD.,Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.,BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls.,NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation.,When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM.,We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway.,Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients.,This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi. | 1 |
Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
The aim of this study was to determine the influence of selected physiological, psychological and situational factors on experience of fatigue, and functional limitations due to fatigue in patients with stable chronic obstructive pulmonary disease (COPD).,In total 101 patients with COPD and 34 control patients were assessed for experience of fatigue, functional limitation due to fatigue (Fatigue Impact Scale), physiological [lung function, 6-minute walk distance (6MWD), body mass index (BMI), dyspnoea, interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hs-CRP), surfactant protein D], psychological (anxiety, depression, insomnia), situational variables (age, sex, smoking, living alone, education), and quality of life.,Fatigue was more common in patients with COPD than in control patients (72% versus 56%, p < 0.001).,Patients with COPD and fatigue had lower lung function, shorter 6MWD, more dyspnoea, anxiety and depressive symptoms, and worse health status compared with patients without fatigue (all p < 0.01).,No differences were found for markers of systemic inflammation.,In logistic regression, experience of fatigue was associated with depression [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.28-2.25) and insomnia (OR 1.75, 95% CI 1.19-2.54).,In linear regression models, depression, surfactant protein D and dyspnoea explained 35% (R2) of the variation in physical impact of fatigue.,Current smoking and depression explained 33% (R2) of the cognitive impact of fatigue.,Depression and surfactant protein D explained 48% (R2) of the psychosocial impact of fatigue.,Experiences of fatigue and functional limitation due to fatigue seem to be related mainly to psychological but also to physiological influencing factors, with depressive symptoms, insomnia problems and dyspnoea as the most prominent factors.,Systemic inflammation was not associated with perception of fatigue but surfactant protein D was connected to some dimensions of the impact of fatigue | Cardiovascular diseases and skeletal muscle dysfunction are common comorbidities in COPD.,Hand grip strength (HGS) is related to general muscle strength and is associated with cardiovascular disease and all-cause mortality, while the results from small selected COPD populations are contradictory.,The aim of this population-based study was to compare HGS among the subjects with and without COPD, to evaluate HGS in relation to COPD severity, and to evaluate the impact of heart disease.,Data were collected from the Obstructive Lung disease in Northern Sweden COPD study, where the subjects with and without COPD have been invited to annual examinations since 2005.,In 2009-2010, 441 subjects with COPD (postbronchodilator forced expiratory volume in 1 second [FEV1]/vital capacity <0.70) and 570 without COPD participated in structured interviews, spirometry, and measurements of HGS.,The mean HGS was similar when comparing subjects with and without COPD, but those with heart disease had lower HGS than those without.,When compared by Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, the subjects with GOLD 3-4 had lower HGS than those without COPD in both sexes (females 21.4 kg vs 26.9 kg, P=0.010; males 41.5 kg vs 46.3 kg, P=0.038), and the difference persisted also when adjusted for confounders.,Among the subjects with COPD, HGS was associated with FEV1% of predicted value but not heart disease when adjusted for height, age, sex, and smoking habits, and the pattern was similar among males and females.,In this population-based study, the subjects with GOLD 3-4 had lower HGS than the subjects without COPD.,Among those with COPD, HGS was associated with FEV1% of predicted value but not heart disease, and the pattern was similar in both sexes. | 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. | Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | GOLD guidelines classify COPD patients into A-D groups based on health status as assessed by COPD Assessment Test (CAT) or mMRC tools and exacerbations and recommend single or dual long-acting bronchodilators as maintenance therapy, with additional inhaled corticosteroids (ICS) if the disease remains uncontrolled.,We aimed to classify primary care COPD patients into A-D groups, assess usual treatment and adherence to guidelines, potential mismatches between CAT-and mMRC-based classification and described symptoms within groups.,A total of 257 primary care COPD patients were enrolled between 2015 and 2016 in Greece.,Physicians used structured interviews to collect cross-sectional data including demographics, symptoms, CAT, mMRC scores, and medications.,Patients were classified into A-D groups based on CAT and mMRC, and prevalence of symptoms and medication was estimated within A-D groups.,Interviews with physicians were also performed to explore additional issues about treatment and adherence to guidelines.,Mean (SD) age was 65 (12.3) years with 79% males.,The majority of patients reported uncontrolled symptoms (91% and 61% with ≥10 CAT or ≥2 mMRC scores, respectively).,Thirty-seven percentage had $2 exacerbations in the past year.,Group B was the largest followed by Groups D, A, and C.,Patients were classified as more severe by CAT than by mMRC.,In all groups, the majority were treated with combined long-acting beta agonist/ICS (> 50%).,When patients were asked to report their main symptoms, dyspnea and cough were the most important symptoms mentioned, and there was a great variation between the A-D groups.,However, Groups A-C reported mainly morning symptoms, whereas Group D suffered symptoms all day.,Physicians reported a significant number of barriers to implementing guidelines, eg, frequent lack of guideline updates, access to diagnostic procedures, and prescription-reimbursement issues.,Our study confirms poor adherence to guidelines regarding treatment with an overuse of ICS and important barriers to implementation.,A mismatch in classification occurs depending on the tool used, which can mislead clinicians in their choice of treatment. | 1 |
In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation.,EFL can be measured by the forced oscillation technique (FOT); however, the relevance to clinical parameters is not fully understood.,We hypothesized that emphysema extent and pulmonary function would contribute independently to the degree of EFL.,Broadband frequency FOT and pulmonary function tests were performed in 74 patients with COPD to derive respiratory system resistance (Rrs) and reactance (Xrs), and the EFL index as expressed by the differences between inspiratory and expiratory phases of Xrs at 5 Hz (ΔX5).,Emphysema extent was measured by high-resolution computed tomography and scored.,On the basis of the median value of ΔX5 (0.55 cmH2O/L/s), patients were classified into a high or low EFL index group.,In multivariate regression analyses, a high EFL index was independently predicted by emphysema score, peripheral airway obstruction (forced expiratory flow between 25% and 75% of forced vital capacity), hyperinflation (functional residual capacity), and airway caliber (whole-breath Rrs at 5 Hz).,EFL measured by FOT is a global measure of COPD that has separable etiologies and is useful for evaluating the disease condition. | 1 |
The morbidity and mortality associated with COPD exacts a considerable economic burden.,Comorbidities in COPD are associated with poor health outcomes and increased costs.,Our objective was to assess the impact of comorbidities on COPD-associated costs in a large administrative claims dataset.,This was a retrospective observational study of data from the Truven Health MarketScan Commercial Claims and Encounters and the MarketScan Medicare Supplemental Databases from January 1, 2009, to September 30, 2012.,Resource consumption was measured from the index date (date of first occurrence of non-rule-out COPD diagnosis) to 360 days after the index date.,Resource use (all-cause and disease-specific [ie, COPD- or asthma-related] ED visits, hospitalizations, office visits, other outpatient visits, and total length of hospital stay) and health-care costs (all-cause and disease-specific costs for ED visits, hospitalizations, office visits, and other outpatient visits and medical, prescription, and total health-care costs) were assessed.,Generalized linear models were used to evaluate the impact of comorbidities on total health-care costs, adjusting for age, sex, geographic location, baseline health-care use, employment status, and index COPD medication.,Among 183,681 patients with COPD, the most common comorbidities were cardiovascular disease (34.8%), diabetes (22.8%), asthma (14.7%), and anemia (14.2%).,Most patients (52.8%) had one or two comorbidities of interest.,The average all-cause total health-care costs from the index date to 360 days after the index date were highest for patients with chronic kidney disease ($41,288) and anemia ($38,870).,The impact on total health-care costs was greatest for anemia ($10,762 more, on average, than a patient with COPD without anemia).,Our analysis demonstrated that high resource use and costs were associated with COPD and multiple comorbidities. | The medico-economic impact of smoking cessation considering a smoking patient with chronic obstructive pulmonary disease (COPD) is poorly documented.,Here, considering a COPD smoking patient, the specific burden of continuous smoking was estimated, as well as the effectiveness and the cost-effectiveness of smoking cessation.,A multi-state Markov model adopting society's perspective was developed.,Simulated cohorts of English COPD patients who are active smokers (all severity stages combined or patients with the same initial severity stage) were compared to identical cohorts of patients who quit smoking at cohort initialization.,Life expectancy, quality adjusted life-years (QALY), disease-related costs, and incremental cost-effectiveness ratio (ICER: £/QALY) were estimated, considering smoking cessation programs with various possible scenarios of success rates and costs.,Sensitivity analyses included the variation of model key parameters.,At the horizon of a smoking COPD patient's remaining lifetime, smoking cessation at cohort intitialization, relapses being allowed as observed in practice, would result in gains (mean) of 1.27 life-years and 0.68 QALY, and induce savings of −1824 £/patient in the disease-related costs.,The corresponding ICER was −2686 £/QALY.,Smoking cessation resulted in 0.72, 0.69, 0.64 and 0.42 QALY respectively gained per mild, moderate, severe, and very severe COPD patient, but was nevertheless cost-effective for mild to severe COPD patients in most scenarios, even when hypothesizing expensive smoking cessation intervention programmes associated with low success rates.,Considering a ten-year time horizon, the burden of continuous smoking in English COPD patients was estimated to cost a total of 1657 M£ while 452516 QALY would be simultaneously lost.,The study results are a useful support for the setting of smoking cessation programmes specifically targeted to COPD patients. | 1 |
Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | The study aims at investigating the influence of several factors on the probability of receiving one of the two tiotropium formulations (Respimat or Handihaler).,Drug utilisation study.,All residents in the Region Umbria, Italy, aged ≥45 years, who received prescriptions of tiotropium during 2011-2012.,Two groups of patients were studied: (1) incident users of the two tiotropium formulations (ie, without tiotropium prescriptions in the previous 6 months); (2) switchers from Handihaler to Respimat.,Users of the two formulations were compared with regard to baseline characteristics and medical history.,The adjusted OR of receiving Respimat was estimated for several factors.,Incident users of the two formulations (4390 participants) had similar characteristics.,They were older and with more comorbidities than patients included in randomised control trials (RCTs).,Among prevalent users of Handihaler, the probability of switching to Respimat was greater in patients with severe respiratory disease (users of ≥4 respiratory drugs: adjusted OR=4.62; 95% CI 2.46 to 8.69) and among β-blocker users (adjusted OR=1.76; 95% CI 1.13 to 2.75).,Age above 75 years and lipid-lowering drug use reduced the probability of switching.,A positive association was also found between neurological conditions and the use of Respimat.,When starting tiotropium treatment, the choice between the two formulations is weakly affected by comorbidities and chronic obstructive pulmonary disease severity.,Instead, these characteristics influence the likelihood of switching from Handihaler to Respimat.,Since tiotropium users in clinical practice are more severe than those included in RCTs, further aetiological studies are needed to compare the safety profile of the two formulations in routine care. | 1 |
COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels. | Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD).,Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking.,The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-α), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD.,This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center.,Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry.,Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%).,On bivariate analysis, there was no association between TNF-α and BMD.,Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density.,However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability.,Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis.,The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis.,We conclude that the effect of adipokines on BMD does not appear to be independent of body mass.,However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD. | 1 |
Existing data on COPD prevalence are limited or totally lacking in many regions of Europe.,The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, when real data are few and widely separated.,Therefore, in order to represent cartographically the prevalence of COPD in Europe, an IDW interpolation mapping was performed.,The point prevalence data provided by 62 studies from 19 countries (21 from 5 Northern European countries, 11 from 3 Western European countries, 14 from 5 Central European countries, and 16 from 6 Southern European countries) were identified using validated spirometric criteria.,Despite the lack of data in many areas (including all regions of the eastern part of the continent), the IDW mapping predicted the COPD prevalence in the whole territory, even in extensive areas lacking real data.,Although the quality of the data obtained from some studies may have some limitations related to different confounding factors, this methodology may be a suitable tool for obtaining epidemiological estimates that can enable us to better address this major public health problem. | Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality.,Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties.,Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.,We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs.,The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.,Nine RCTs comprising 1666 patients met the inclusion criteria.,Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01).,Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective.,Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates.,The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups.,A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).,Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD.,However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance.,A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages. | 1 |
This study evaluated the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ (PI3Kδ) inhibitor, in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD).,In this double-blind, placebo-controlled study, 126 patients (40-80 years with a post-bronchodilator forced expiratory volume in 1 sec (FEV1) ≤80% of predicted (previously documented)) were randomized 1:1 to once daily inhaled nemiralisib (1 mg) or placebo for 84 days, added to standard of care.,The primary endpoint was specific imaging airway volume (siVaw) after 28 treatment days and was analyzed using a Bayesian repeated measures model (clintrials.gov: NCT02294734).,A total of 126 patients were randomized to treatment; 55 on active treatment and 49 on placebo completed the study.,When comparing nemiralisib and placebo-treated patients, an 18% placebo-corrected increase from baseline in distal siVaw (95% credible intervals (Cr I) (−1%, 42%)) was observed on Day 28.,The probability that the true treatment ratio was >0% (Pr(θ>0)) was 96%, suggestive of a real treatment effect.,Improvements were observed across all lung lobes.,Patients treated with nemiralisib experienced a 107.3 mL improvement in posterior median FEV1 (change from baseline, 95% Cr I (−2.1, 215.5)) at day 84, compared with placebo.,Adverse events were reported by 41 patients on placebo and 49 on nemiralisib, the most common being post-inhalation cough on nemiralisib (35%) vs placebo (3%).,These data show that addition of nemiralisib to usual care delivers more effective recovery from an acute exacerbation and improves lung function parameters including siVaw and FEV1.,Although post-inhalation cough was identified, nemiralisib was otherwise well tolerated, providing a promising novel therapy for this acutely ill patient group. | Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the induction of corticosteroid (CS) insensitivity.,Chronic ozone exposure leads to a model of COPD with lung inflammation and emphysema.,Mitogen-activated protein kinase phosphatase-1 (MKP-1) may underlie CS insensitivity in COPD.,We determined the role played by MKP-1 by studying the effect of corticosteroids in wild-type C57/BL6J and MKP-1−/− mice after chronic ozone exposure.,Mice were exposed to ozone (3 ppm, 3 h) 12 times over 6 weeks.,Dexamethasone (0.1 or 2 mg/kg; intraperitoneally) was administered before each exposure.,Mice were studied 24 h after final exposure.,In ozone-exposed C57/BL6J mice, bronchial hyperresponsiveness (BHR) was not inhibited by both doses of dexamethasone, but in MKP-1−/− mice, there was a small inhibition by high dose dexamethasone (2 mg/kg).,There was an increase in mean linear intercept after chronic ozone exposure in both strains which was CS-insensitive.,There was lesser inflammation after low dose of dexamethasone in MKP-1−/− mice compared to C57/Bl6J mice.,Epithelial and collagen areas were modulated in ozone-exposed MKP-1−/− mice treated with dexamethasone compared to C57/Bl6J mice.,MKP-1 regulated the expression of MMP-12, IL-13 and KC induced by ozone but did not alter dexamethasone׳s effects.,Bronchial hyperresponsiveness, lung inflammation and emphySEMa after chronic exposure are CS-insensitive, and the contribution of MKP-1 to CS sensitivity in this model was negligible. | 1 |
Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | The objective of this study was to analyze the clinical and management characteristics of chronic obstructive pulmonary disease (COPD) in men and women, to determine possible gender-associated differences between the two groups of patients.,An observational and descriptive epidemiological study (EPIDEPOC study).,The study included patients with stable COPD and aged ≥ 40 years, evaluated in primary care.,Data were collected relating to sociodemographic variables, clinical characteristics, quality of life (SF-12), severity of disease and treatment.,The results obtained in men and women were compared.,A total of 10,711 patients (75.6% males and 24.4% females) were evaluated.,Significant differences were found between males and females in relation to the following parameters: age (67.4 ± 9.2 years in men vs 66.1 ± 10.8 in women, p < 0.05), smoking (91.9% of the men were smokers or ex-smokers vs 30% of the women), comorbidity (the frequency of hypertension, diabetes, anxiety and depression was greater in women, while ischemic heart disease was more common in men), mental component of quality of life (49.4 ± 10.3 in men vs 44.6 ± 11.9 in women, p < 0.05) and severity of disease (56.5 ± 13.3% in men vs 60.7 ± 3.2 in women, p < 0.05).,As regards treatment, the percentage use of long-acting b2-adrenergic agonists, anticholinergic agents, theophyllines and mucolytic agents was significant greater in men.,The total annual cost of COPD was greater in males than in females (1989.20 ± 2364.47 € vs 1724.53 ± 2106.90, p < 0.05).,The women with COPD evaluated in this study were younger, smoked less and have more comorbidity, a poorer quality of life, and lesser disease severity than men with COPD.,However, they generated a lesser total annual cost of COPD than men. | 1 |
Objectives: COPD is the fourth-leading cause of mortality worldwide.,Prolonged QTc has been found to be a long-term negative prognostic factor in ambulatory COPD patients.,The aim of this study was to evaluate the extent of prolonged-QTc syndrome in COPD patients upon admission to an internal medicine department, its relationship to hypomagnesemia, hypokalemia, and hypocalcemia, and the effect of COPD treatment on mortality during hospital stay.,Methods: This prospective cohort study evaluated COPD patients hospitalized in an internal medicine department.,The study evaluated QTc, electrolyte levels, and known risk factors during hospitalization of COPD patients.,Results: A total of 67 patients were recruited.,The median QTc interval was 0.441 seconds and 0.434 seconds on days 0 and 3, respectively.,Prolonged QTc was noted in 35.8% of patients on admission and 37.3% on day 3 of hospitalization.,The median QTc in the prolonged-QTc group on admission was 0.471 seconds and in the normal-QTc group 0.430 seconds.,There was no significant difference in age, sex, electrolyte levels, renal function tests, or blood gases on admission between the two groups.,Mortality during the hospital stay was significantly higher in the prolonged-QTc group (3 deaths, 12%) than in the normal QTc group (no deaths) (P=0.04).,A subanalysis was performed, removing known causes for prolonged QTc.,We found no differences in age, electrolytes, or renal functions.,There was a small but significant difference in bicarbonate levels.,Conclusion: Our findings demonstrated that there was no correlation between QTc prolongation in hospitalized COPD patients and electrolyte levels, comorbidities, or relevant medications.,A higher rate of mortality was noted in patients with prolonged QTc in comparison to normal QTc.,As such, it is suggested that prolonged QTc could serve as a negative prognostic factor for mortality during hospitalization in COPD patients. | Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for cardiovascular (CV) disease, one of the most frequent causes of death in COPD patients.,The goal of the present study was to evaluate the prognostic value of non-invasive CV risk markers in COPD patients.,CV risk was prospectively evaluated in 287 COPD patients using non-invasive markers including the Framingham score, the Systematic Coronary Risk Evaluation (SCORE) charts, coronary arterial calcium (CAC), epicardial adipose tissue (EAT), as well as clinical, biochemical and physiological variables.,The predictive power of each parameter was explored using CV events as the main outcome.,During a median follow up of 65 months (ICR: 36-100), 44 CV events were recorded, 12 acute myocardial infarctions (27.3%), 10 ischemic heart disease/angina (22.7%), 12 peripheral artery disease events requiring surgery (27.3%) and 10 strokes (22.7%).,A total of 35 CV deaths occurred during that period.,Univariable analysis determined that age, hypertension, CRP, total Cholesterol, LDL-Cholesterol, Framingham score and CAC were independently associated with CV events.,Multivariable analysis identified CAC as the best predictor of CV events (HR; 95%CI: 1.32; 1.19-1.46, p < 001).,In COPD patients attending pulmonary clinics, CAC was the best independent non-invasive predictor of CV events.,This tool may help evaluate the risk for a CV event in patients with COPD.,Larger studies should reproduce and validate these findings. | 1 |
Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality.,Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance.,However, none of these studies were designed with physical activity as primary outcome.,This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.,In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods).,Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70.,The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure.,Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day.,Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.,A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study.,Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264).,IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days.,The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.,In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels.,This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.,ClinicalTrials.gov number: NCT01996319.,The online version of this article (doi:10.1186/s12890-016-0256-7) contains supplementary material, which is available to authorized users. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Previous studies of healthcare utilization for chronic obstructive pulmonary disease (COPD) have focused on time-trends in COPD visits or COPD treatments, or the effect of hospital volume on mortality.,Few data are available regarding outcomes after an ED visit (and subsequent hospitalization) for COPD, which are both very common in patients with COPD.,Our objective was to assess time-trends and predictors of emergency department and subsequent inpatient health care utilization and charges associated with COPD in the U.S.,We used the 2009-12 U.S.,Nationwide Emergency Department Sample (NEDS) to study the incidence of ED visits and subsequent hospitalizations with COPD as the primary diagnosis.,We used the 2012 NEDS data to study key patient/hospital factors associated with outcomes, including charges, hospitalization and dischage from hospital to home.,ED visits for COPD as the primary diagnosis increased from 1.02 million in 2009 to 1.04 in 2010 to 1.10 million in 2012 (0.79-0.82 % of all ED visits); respective charges were $2.13, $2.32, and $3.09 billion.,In 2012, mean ED charges/visit were $2,812, hospitalization charges/visit were $29,043 and the length of hospital stay was 4.3 days. 49 % were hospitalized after an ED visit.,Older age, higher median income, metropolitan residence and comorbidities (diabetes, hypertension, HF, hyperlipidemia, CHD, renal failure and osteoarthritis) were associated with higher risk whereas male sex, Medicaid or self pay insurance status, hospital location in Midwest, South or West U.S. were associated with lower risk of hospitalization.,65.4 % of all patients hospitalized for COPD from ED were discharged home.,Older age, comorbidities (diabetes, HF, CHD, renal failure, osteoarthritis) and metropolitan residence were associated with lower odds of discharge to home, whereas male sex, payer other than Medicare, Midwest, South or West U.S. hospital location were associated with higher odds.,Health care utilization and costs in patients with COPD are significant and increasing.,COPD constitutes a major public health burden in the U.S.,We identified risk factors for hospitalization, costs, and home discharge in patients with COPD that will allow future studies to investigate interventions to potentially reduce COPD-associated utilization.,The online version of this article (doi:10.1186/s12931-015-0319-y) contains supplementary material, which is available to authorized users. | Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities.,The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.,This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008.,COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded.,Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.,Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs.,36.9%), depression (20.6% vs.,12.5%), osteoporosis (16.9% vs.,8.5%), cancer (16.5% vs.,9.9%), coronary heart disease (12.7% vs.,6.1%), congestive heart failure (12.1% vs.,3.9%), and stroke (8.9% vs.,4.6%).,Subjects with COPD were also more likely to report mobility difficulty (55.6% vs.,32.5%), use of >4 prescription medications (51.8% vs.,32.1), dizziness/balance problems (41.1% vs.,23.8%), urinary incontinence (34.9% vs.,27.3%), memory problems (18.5% vs.,8.8%), low glomerular filtration rate (16.2% vs.,10.5%), and visual impairment (14.0% vs.,9.6%).,All reported comparisons have p < 0.05.,Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities.,This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity. | 1 |
Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation.,The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure.,This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators.,The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year.,Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life.,Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up.,A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min.,Primary safety end point of freedom from worsening of COPD was 100%.,There were no procedural complications reported.,Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD.,Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy.,TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years. | 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 long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD. | The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7.,Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative.,We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.,In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years.,Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated.,The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.,Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively.,The GOLD classification led to more false positives, the LLNs to more false negative diagnoses.,The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC).,Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses.,The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.,GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis.,Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice. | 1 |
Rationale: In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate/formoterol fumarate (GFF).,However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses.,Objectives: To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses.,Methods: Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320/18/9.6 μg of BGF (BGF 320), 160/18/9.6 μg of BGF (BGF 160), 18/9.6 μg of GFF, or 320/9.6 μg of budesonide/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler).,Time to death (all-cause) was a prespecified secondary endpoint.,Measurements and Main Results: In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33-0.80; unadjusted P = 0.0035).,There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44-1.16; P = 0.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator.,Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis.,Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively.,Conclusions: Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD.,Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators. | The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions.,Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs.,Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety.,Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease.,This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age.,The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy.,The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions.,The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy.,Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams. | 1 |
Several studies have confirmed the high potential of the forced oscillation technique for the assessment of respiratory modifications related to chronic obstructive pulmonary disease.,However, most of these studies did not employ within-breath analyses of the respiratory system.,The aim of this study is to analyze respiratory impedance alterations in different phases of the respiratory cycle of chronic obstructive pulmonary disease patients and to evaluate their clinical use.,39 individuals were evaluated, including 20 controls and 19 individuals with chronic obstructive pulmonary disease who experienced severe airway obstruction.,We evaluated the mean respiratory impedance (Zm) as well as values for inspiration (Zi) and expiration cycles (Ze), at the beginning of inspiration (Zbi) and expiration (Zbe).,The peak-to-peak impedance (Zpp), and the impedance change (ΔZrs) were also analyzed.,The clinical usefulness was evaluated by investigating the sensibility, specificity and the area under the receiver operating characteristic curve.,The respiratory impedance increased in individuals with chronic obstructive pulmonary disease in all of the studied parameters (Zm, Zi, Ze, Zbi, Zbe, ΔZrs and Zpp).,These changes were inversely associated with spirometric parameters.,Higher impedances were observed in the expiratory phase of individuals with chronic obstructive pulmonary disease.,All of the studied parameters, except for ΔZrs (area under the receiver operating characteristic <0.8), exhibited high accuracy for clinical use (area under the receiver operating characteristic >0.90; Sensibility ≥ 0.85; Sp ≥ 0.85).,The respiratory alterations in severe chronic obstructive pulmonary disease may be identified by the increase in respiratory system impedance, which is more evident in the expiratory phase.,These results confirm the potential of within-breath analysis of respiratory impedance for the assessment of respiratory modifications related to chronic obstructive pulmonary disease. | Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD).,The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system.,The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases.,Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects.,Results from a group of 28 smokers with a tobacco consumption of 11.2 ± 7.3 pack-years were compared with a control group formed by 28 healthy subjects using receiver operating characteristic (ROC) curves and a questionnaire as a gold standard.,The early adverse effects of smoking were adequately detected by the absolute value of the respiratory impedance (Z4Hz), the intercept resistance (R0), and the respiratory system dynamic compliance (Crs, dyn).,Z4Hz was the most accurate parameter (Se = 75%, Sp = 75%), followed by R0 and Crs, dyn.,The performances of the FOT parameters in the detection of the early effects of smoking were higher than that of spirometry (p < 0.05).,This study shows that FOT can be used to detect early smoking-induced respiratory changes while these pathologic changes are still potentially reversible.,These findings support the use of FOT as a versatile clinical diagnostic tool in aiding COPD prevention and treatment. | 1 |
Non-typeable Haemophilus influenza (NTHi) infection is common in COPD.,Corticosteroids can have limited therapeutic effects in COPD patients.,NTHi causes corticosteroid insensitive cytokine production from COPD alveolar macrophages.,We investigated the mechanisms by which NTHi causes corticosteroid insensitive inflammatory responses, and the effects of NTHi exposure on COPD macrophage polarisation.,Alveolar macrophages from COPD patients and controls were exposed to NTHi in conjunction with the corticosteroid dexamethasone and/or the p38 MAPK inhibitor BIRB-796.,Cytokine release, GR phosphorylation and modulation and macrophage phenotype were analysed.,Dexamethasone significantly inhibited NTHi induced TNF-α, IL-6 and IL-10 from COPD macrophages but, CXCL8 was not suppressed.,BIRB-796 combined with dexamethasone caused significantly greater inhibition of all cytokines than either drug alone (p < 0.05 all comparisons).,NTHi caused phosphorylation of GR S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK.,NTHi altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206, CD163 and HLA-DR.,NTHi exposure causes p38 MAPK dependent GR phosphorylation associated with decreased GR function in COPD alveolar macrophages.,Combining a p38 MAPK inhibitor with corticosteroids can enhance anti-inflammatory effects during NTHi exposure of COPD alveolar macrophages.,NTHi causes macrophage polarisation that favours bacterial persistence.,The online version of this article (doi:10.1186/s12931-017-0539-4) contains supplementary material, which is available to authorized users. | Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | 1 |
Health status questionnaires provide standardized measures of patients’ perceptions of the impact of disease on their daily life and well-being.,Factors associated with health status were examined in a sample of 58 outpatients with chronic obstructive pulmonary disease (COPD) and co-morbid anxiety and/or depression.,A cross-sectional descriptive study was conducted with the following measures: The St.,George’s Respiratory Questionnaire (SGRQ); the Beck Anxiety Inventory (BAI); the Beck Depression Inventory, 2nd edition (BDI); the Pittsburgh Sleep Quality Index (PSQI); and spirometry.,Disease severity as measured with spirometry was not related to health status.,Perceptions of poor health as implied by the health status scores were positively associated with symptoms of anxiety and depression, sleep disturbances, and level of daily functioning.,There were statistically significant differences between men and women on COPD severity, age, and the BAI scores.,The findings emphasize the importance of screening the patients at all stages of disease severity for anxiety, depression, and sleeping problems, in order to provide adequate care for these problems. | The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC).,In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks.,Those who smoked more than 8 cigarettes per day were invited to perform a spirometry.,Totally 3,887 spirometries were performed.,In this sample 10.2% fulfilled the NICE COPD-criteria, 14.0% the GOLD COPD-criteria and 21.7% the ERS COPD criteria.,The diagnosis according to NICE and GOLD guidelines is based on FVC and in the ERS guidelines the best value of either SVC or FVC is used.,Thus, substantially more subjects with COPD were found when the best of either SVC or FVC was used.,Forced VC tended to be higher than SVC when lung function was normal and in those with mild obstruction prior to bronchodilatation whereas SVC exceeded FVC after bronchodilatation in those who had severe bronchial obstruction.,The diagnosis of COPD is highly depending on which guidelines are used for defining the disease.,If FVC and not the best of SVC and FVC is used when defining COPD the diagnosis will be missed in a substantial number of patients. | 1 |
Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD).,We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS).,Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction.,Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D.,Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.,Of 1210 patients, 1167 had data available for GOLD classification.,Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted.,Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group.,The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.,Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline.,Net treatment benefit was similar in patients with low or high levels of symptoms.,ATTAIN (ClinicalTrials.gov identifier: NCT01001494) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397).,The online version of this article (doi:10.1186/s12931-016-0372-1) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is the most prevalent obstructive lung disease worldwide characterized by decline in lung function.,It is associated with airway obstruction, oxidative stress, chronic inflammation, mucus hypersecretion, and enhanced autophagy and cellular senescence.,Cigarette smoke being the major risk factor, other secondary risk factors such as the exposure to air pollutants, occupational exposure to gases and fumes in developing countries, also contribute to the pathogenesis of COPD.,Conventional therapeutic strategies of COPD are based on anti-oxidant and anti-inflammatory drugs.,However, traditional anti-oxidant pharmacological therapies are commonly used to alleviate the impact of COPD as they have many associated repercussions such as low diffusion rate and inappropriate drug pharmacokinetics.,Recent advances in nanotechnology and stem cell research have shed new light on the current treatment of chronic airway disease.,This review is focused on some of the anti-oxidant therapies currently used in the treatment and management of COPD with more emphasis on the recent advances in nanotechnology-based therapeutics including stem cell and gene therapy approaches for the treatment of chronic airway disease such as COPD and asthma. | Oxidative stress is associated with the pathogenesis of cigarette smoke related lung diseases, but longitudinal effects of smoking cessation on oxidant markers in the airways are unknown.,This study included 61 smokers; 21 with chronic bronchitis or COPD, 15 asthmatics and 25 asymptomatic smokers followed up for 3 months after smoking cessation.,Fractional exhaled nitric oxide (FeNO), sputum neutrophil counts, sputum 8-isoprostane, nitrotyrosine and matrix metalloproteinase-8 (MMP-8) were investigated at baseline and 1 and 3 months after smoking cessation.,After 3 months 15 subjects had succeeded in quitting of smoking and in these subjects symptoms improved significantly.,Unexpectedly, however, sputum neutrophils increased (p = 0.046) after smoking cessation in patients with chronic bronchitis/COPD.,At baseline, the other markers did not differ between the three groups so these results were combined for further analysis.,Sputum 8-isoprostane declined significantly during the follow-up at 3 months (p = 0.035), but levels still remained significantly higher than in non-smokers.,The levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during the 3 months after smoking cessation.,Whilst symptoms improve after smoking cessation, the oxidant and protease burden in the airways continues for months. | 1 |
Eosinophil counts increase during chronic obstructive pulmonary disease (COPD) exacerbation and influence the response to different agents (such as inhaled and systemic corticosteroids), as well as increase the production of other inflammatory cytokines.,However, few studies have evaluated the association between peripheral blood eosinophils with mortality rate.,To evaluate the association between peripheral blood eosinophils and mortality rate in COPD patients over a nine-year period.,This cohort included 133 COPD patients assessed at baseline by spirometry, pulse oximetry (SpO2), complete blood count, body composition, dyspnea intensity [Modified Medical Research Council (mMRC)] and the six-minute distance test (6MWD).,The Kaplan-Meier curve followed by a Log rank test was used to evaluate mortality rate related to eosinophil cutoff point categorization.,Multivariate Cox regression analysis was performed to identify the association between eosinophils and mortality with all subjects evaluated at baseline, adjusted for age, gender, mMRC, 6MWT, forced expiratory volume in the first second (FEV1) and SpO2.,Nineteen patients did not complete follow-up and it was not possible to identify the date of death in four others.,Therefore, 110 patients were included in the analysis.,At baseline, 81% presented ≥150 eosinophil cells and 72% presented ≥2%.,We identified a three-fold higher risk of death in those with <2% eosinophils and <150 cells.,We did not identify statistical differences when using other cutoff points.,The decrease in number of peripheral eosinophils, with cutoff points at 2% and 150 cells, may be associated with a higher risk of death in COPD patients over nine years. | Peripheral blood eosinophilic counts are susceptible to many factors and have variability over time.,There are limited studies on association of blood eosinophilia with long-term mortality of chronic obstructive pulmonary disease (COPD) patients and these results remain controversial.,Our aims were to explore the association of blood eosinophilia at index hospitalization and stability of blood eosinophilia stability over 5 years with all-cause mortality of patients hospitalized for acute exacerbation of COPD (AECOPD).,Eight hundred twenty-nine patients hospitalized for AECOPD between 2013 and 2014 were included in this study and grouped into two groups according to blood eosinophil with 150 cells/μL used as the cutoff value to form eosinophilic and non-eosinophilic groups.,Two hundred forty-one COPD inpatients with at least three blood eosinophils measured from different hospitalizations were used for analysis of longitudinally eosinophilic stability and divided into three groups according to the same cutoff value: predominantly (PE), intermittently (IE) and rarely (RE) eosinophilic groups.,Cox regression analysis was used to determine the association of blood eosinophilia and all-cause mortality.,In patients hospitalized for AECOPD, 261 (31.5%) at baseline and 41 (17%) based on at least three measurements of blood eosinophils had increased blood eosinophils.,For all-cause mortality, eosinophilic COPD patients at index hospitalization had a lower all-cause mortality compared with non-eosinophilic COPD patients (hazard ratio 0.77, 95% confidence interval 0.6-0.99, P=0.04).,In patients readmitted for AECOPD by longitudinal eosinophil stability, with the RE group used as reference, the PE group was associated with a lower all-cause mortality of AECOPD patients (hazard ratio 0.43, 95% confidence interval 0.22-0.85, P=0.016), compared to the IE group (hazard ratio 0.72, 95% confidence interval 0.47-1.11, P=0.133).,Patients with increased eosinophils (using eosinophil 150 cells/μL as a cutoff value), especially predominantly increased eosinophil levels based on multiple measurements, had a lower risk of all-cause mortality.,Blood eosinophilia can be used as a biomarker in hospitalized COPD exacerbations for predicting the risk of all-cause mortality.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/RroTKw3Hisg | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326 | 1 |
Biomass smoke is the leading cause of COPD in developing countries such as Turkey.,In rural areas of Turkey, females are more exposed to biomass smoke because of traditional lifestyles.,The aim of this study was to determine the adverse effects of biomass smoke on pulmonary functions and define the relationship between duration in years and an index (cumulative exposure index) with altered pulmonary function test results.,A total of 115 females who lived in the village of Kağizman (a borough of Kars located in the eastern part of Turkey) and were exposed to biomass smoke were included in the study.,The control group was generated with 73 individuals living in the same area who were never exposed to biomass smoke.,Twenty-seven (23.8%) females in the study group and four (5.5%) in the control group had small airway disease (P=0.038).,Twenty-two (19.1%) females in the study group and ten (13.7%) in the control group had obstruction (P=0.223).,Twenty (17.3%) females in the study group who were exposed to biomass smoke had restriction compared with ten (13%) in the control group (P=0.189).,The duration needed for the existence of small airway disease was 16 years, for obstructive airway disease was 17 years, and for restrictive airway disease was 17 years.,The intensity of biomass smoke was defined in terms of cumulative exposure index; it was calculated by multiplying hours per day, weeks per month, and total years of smoke exposure and dividing the result by three.,Exposure to biomass smoke is a serious public health problem, especially in rural areas of developing countries, because of its negative effects on pulmonary functions.,As the duration and the intensity of exposure increase, the probability of having altered pulmonary function test results is higher. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction.,Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations.,Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome.,The role of the lung microbiome in the pathogenesis of COPD remains unknown.,The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora.,Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients.,The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid.,Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats.,Our results showed a significant increase in microbial diversity with the development of COPD.,The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria.,Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity.,However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators.,Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. | 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 |
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. | Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes. | 1 |
Chronic obstructive pulmonary disease (COPD), the most common chronic respiratory disease worldwide, not only leads to the decline of pulmonary function and quality of life consecutively, but also has become a major economic burden on individuals, families, and society in China.,The purpose of this meta-analysis was to explore the risk factors for developing COPD in the Chinese population that resides in China and to provide a theoretical basis for the early prevention of COPD.,A total of 2457 cross-sectional, case-control, and cohort studies published related to risk factors for COPD in China were searched.,Based on the inclusion and exclusion criteria, 20 articles were selected.,Stata 11.0 was used for meta-analysis.,After merging the data, the pooled effect and 95% confidence intervals (CIs) were calculated to assess the association between risk factors and COPD.,Heterogeneity between studies was assessed using I2 and Cochran’s Q tests.,Begg’s test was used to assess publication bias.,Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) (pooled effect = 1.73; 95%CI: 1.16~2.58; P <0.01), smoking history (pooled effect = 2.58; 95%CI: 2.00~3.32; P <0.01), passive smoking history (pooled effect = 1.39; 95%CI: 1.03~1.87; P = 0.03), male sex(pooled effect = 1.70; 95%CI: 1.31~2.22; P <0.01), body mass index (BMI) <18.5 kg/m2 (pooled effect = 1.73; 95%CI: 1.32~2.25; P <0.01), exposure to biomass burning emissions (pooled effect = 1.65; 95%CI: 1.32~2.06; P <0.01), childhood respiratory infections (pooled effect = 3.44; 95%CI: 1.33~8.90; P = 0.01), residence (pooled effect = 1.24; 95%CI: 1.09~1.42; P <0.01), and a family history of respiratory diseases (pooled effect = 2.04; 95%CI: 1.53~2.71; P <0.01) were risk factors for COPD in the Chinese population.,Early prevention of COPD could be accomplished by quitting smoking, reducing exposure to air pollutants and biomass burning emissions, maintaining body mass index between 18.5 kg/m2 and 28 kg/m2, protecting children from respiratory infections, adopting active treatments to children with respiratory diseases, and conducting regular screening for those with family history of respiratory diseases. | Chronic obstructive pulmonary disease (COPD) ranks among the leading causes of morbidity and mortality worldwide.,COPD rarely occurs in isolation and is often combined with various diseases.,It is considered that systemic inflammation underlies the comorbid course of COPD.,The data obtained in recent years have shown the importance of violations of the cross-links of lipid metabolism and the immune response, which are links in the pathogenesis of both COPD and atherosclerosis.,The role of lipid metabolism disorders in the pathogenesis of the comorbid course of COPD and atherosclerosis and the participation of ATP-binding cassette (ABC) transporters in these processes is discussed in this article.,It is known that about 20 representatives of a large family of ABC transporters provide lipid homeostasis of cells by moving lipids inside the cell and in its plasma membrane, as well as removing lipids from the cell.,It was shown that some representatives of the ABC-transporter family are involved in various links of the pathogenesis of COPD and atherosclerosis, which can determine their comorbid course. | 1 |
Inhaled corticosteroids (ICS) might lower the risk of coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD).,This study aimed to assess the association of ICS with the development of CHD in COPD patients by using data from the Korean Nationwide study.,Patients who were newly diagnosed with COPD between 2004 and 2013 and who were not diagnosed with coronary heart disease before their diagnosis of COPD were included.,Exposure of ICS was incorporated into multivariable Cox regression models using time-dependent methods.,To accurately estimate ICS-exposure accumulation, a washout period of 2 years from 2002 to 2003 was applied.,Among a total of 4,400 newly diagnosed COPD patients, 771 patients were diagnosed as CHD incident cases during a median follow-up of one year (interquartile range 0.1-2.9).,The cumulative dose of ICS was associated with a reduced risk of CHD (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.52-0.89).,When the cumulative exposure dose of ICS was divided into quartiles, the aHR for CHD incidence was 0.70 (95% CI, 0.55-0.88) in the highest quartile ICS dose use.,The effect of ICS on reducing CHD incidence was pronounced in adults over 55 years, men under 55 years, and former smokers.,Our findings demonstrate the role of ICS for the prevention of CHD in COPD patients without a history of CHD.,Further research is needed to determine whether a certain amount of ICS exposure in COPD patients is protective against CHD. | Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations.,However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value.,Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed.,Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC).,The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations.,Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.,Compared to Q1 (<53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively).,In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC.,Neither FEV1 nor FVC was associated with cardiovascular risk.,Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase).,Our results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks. | 1 |
Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy. | Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD).,We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.,This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months.,Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2-12.,Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score.,Overall, 2,331 and 1,799 patients were included in the 0-2- and 0-12-month responder analyses, respectively, and 2,360 patients in the 2-12-month exacerbation rate analysis.,At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders.,The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters.,Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14-7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83-5.31).,Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.,Early FEV1 and SGRQ treatment responses relate to their changes at 12 months.,FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients.,This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required. | 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. | Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide.,Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown.,Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.,They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases.,Recently, EVs have attracted considerable attention in pulmonary research.,In this review, we summarize the recent findings of EV-mediated COPD pathogenesis.,We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with multiple comorbidities, which impact negatively on patients and are often underdiagnosed, thus lacking a proper management due to the absence of clear guidelines.,To elaborate expert recommendations aimed to help healthcare professionals to provide the right care for treating COPD patients with comorbidities.,A modified RAND-UCLA appropriateness method consisting of nominal groups to draw up consensus recommendations (6 Spanish experts) and 2-Delphi rounds to validate them (23 Spanish experts) was performed.,A panel of Spanish internal medicine experts reached consensus on 73 recommendations and 81 conclusions on the clinical consequences of the presence of comorbidities.,In general, the experts reached consensus on the issues raised with regard to cardiovascular comorbidity and metabolic disorders.,Consensus was reached on the use of selective serotonin reuptake inhibitors in cases of depression and the usefulness of referring patients with anxiety to respiratory rehabilitation programmes.,The results also showed consensus on the usefulness of investigating the quality of sleep, the treatment of pain with opioids and the evaluation of osteoporosis by lateral chest radiography.,This study provides conclusions and recommendations that are intended to improve the management of the complexity of patients with COPD and important comorbidities, usually excluded from clinical trials. | Chronic obstructive pulmonary disease (COPD) is an incurable, progressive illness that is the fourth commonest cause of death worldwide.,Death tends to occur after a prolonged functional decline associated with uncontrolled symptoms, emotional distress and social isolation.,There is increasing evidence that the end of life needs of those with advanced COPD are not being met by existing services.,Many barriers hinder the provision of good end of life care in COPD, including the inherent difficulties in determining prognosis.,This review provides an evidence-based approach to overcoming these barriers, summarising current evidence and highlighting areas for future research.,Topics include end of life needs, symptom control, advance care planning, and service development to improve the quality of end of life care. | 1 |
Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy.,The ELLIPTA® DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease.,It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication.,Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration.,There are three principal operating steps to administer a dose: open, inhale, close.,This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler.,Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (≥30 L/min) and over its 30-day in-use life.,Data from the human factors validation tests demonstrated that almost all participants (≥97%) were able to complete each of the steps required to prepare a dose for inhalation without error.,Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options.,It also improves patient ease-of-use when compared with the DISKUS® DPI. | Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) demonstrate a greater osteoporosis prevalence than the general population.,This osteoporosis risk may be enhanced by treatment with inhaled corticosteroids (ICSs), which are recommended for COPD management when combined with long-acting bronchodilators, but may also be associated with reduced bone mineral density (BMD).,We conducted a narrative literature review reporting results of randomized controlled trials (RCTs) of an ICS versus placebo over a treatment period of at least 12 months, with the aim of providing further insight into the link between bone fractures and ICS therapy.,As of 16 October 2017, we identified 17 RCTs for inclusion.,The ICSs studied were budesonide (six studies), fluticasone propionate (five studies), mometasone furoate (three studies), beclomethasone dipropionate, triamcinolone acetonide, and fluticasone furoate (one each).,We found no difference in the number of bone fractures among patients receiving ICSs versus placebo across the six identified RCTs reporting fracture data.,BMD data were available for subsets of patients in few studies, and baseline BMD data were rare; where these data were given, they were reported for treatment groups without stratification for factors known to affect BMD.,Risk factors for reduced BMD and fractures, such as smoking and physical activity, were also often not reported.,Furthermore, a standardized definition of the term “fracture” was not employed across these studies.,The exact relationship between long-term ICS use and bone fracture incidence in patients with stable COPD remains unclear in light of our review.,We have, however, identified several limiting factors in existing studies that may form the basis of future RCTs designed specifically to explore this relationship. | Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD).,Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity.,The effect of withdrawing ICS from COPD patients in primary care is unknown.,In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132).,Follow-up assessments took place at three monthly intervals for a year at the patients' practice.,Our primary outcome was COPD exacerbation frequency.,Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life.,In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36).,Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05).,Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86).,Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze.,In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14).,Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration.,Patients with mild COPD may be at increased risk of exacerbation after withdrawal.,ClinicalTrials.gov NCT00440687 | 1 |
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.,The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression.,Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.,Among these new drugs, we focussed on thioredoxin (Trx).,Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways.,The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.,In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF).,Taken together, these findings suggest that Trx may be the ideal drug for treating COPD. | Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD).,However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD.,We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.,Eligible participants (n = 170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months.,COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.,After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41 ± 3.56 and 11.08 ± 3.05, p < 0.0001).,The changes of CAT (p = 0.028) and mMRC scores (p = 0.049) between the two groups differed after 1 month of treatment.,In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF25% pred) was significantly improved after 3 months (4.84 ± 8.73%, p < 0.0001) and 6 months (6.21 ± 8.65%, p < 0.0001).,There was a significant difference in small airway function tests (MEF50% pred, MEF25% pred, and MMEF% pred) between the two groups after 6 month of treatment (p = 0.003, p < 0.0001, and p = 0.021, respectively).,Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up.,Additionally, this therapy also improved the indicators of small airway function.,Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).,The online version of this article (10.1007/s12325-018-0831-9) contains supplementary material, which is available to authorized users. | 1 |
Smoking and COPD are associated with decreased mucociliary clearance, and healthy smokers have shorter cilia in the large airway than nonsmokers.,We hypothesized that changes in cilia length are consistent throughout the airway, and we further hypothesized that smokers with COPD have shorter cilia than healthy smokers.,Because intraflagellar transport (IFT) is the process by which cilia of normal length are produced and maintained, and alterations in IFT lead to short cilia in model organisms, we also hypothesized that smoking induces changes in the expression of IFT-related genes in the airway epithelium of smokers and smokers with COPD.,To assess these hypotheses, airway epithelium was obtained via bronchoscopic brushing.,Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject and Affymetrix microarrays were used to evaluate IFT gene expression in nonsmokers and healthy smokers in 2 independent data sets from large and small airway as well as in COPD smokers in a data set from the small airway.,In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers.,The gene expression data confirmed that a set of 8 IFT genes were down-regulated in smokers in both data sets; however, no differences were seen in COPD smokers compared to healthy smokers.,These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers.,Strategies to normalize cilia length may be an important avenue for novel COPD therapies. | Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction.,Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations.,Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome.,The role of the lung microbiome in the pathogenesis of COPD remains unknown.,The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora.,Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients.,The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid.,Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats.,Our results showed a significant increase in microbial diversity with the development of COPD.,The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria.,Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity.,However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators.,Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. | 1 |
Background: It is the first study in Poland and one of the first in the world to assess the nutrition of patients with chronic obstructive pulmonary disease (COPD) treated with long-term oxygen therapy (LTOT).,Methods: The study group consisted of 110 COPD patients treated with LTOT.,Anthropometric measurements and spirometry were performed.,The diet of patients was assessed using a 3-day nutrition diary.,Results: When assessing the degree of airflow obstruction (FEV1% N) depending on the BMI in patients treated with LTOT, a statistically significant correlation was demonstrated between the BMI and the value of the FEV% N parameter (p = 0.0093).,Patients with COPD with a BMI >30 had statistically significantly higher values of FEV1% N than patients with a BMI in the range of 20-24.9 (p = 0.0278).,Intake of calcium, vitamins A, C, D, E and folates was lower than the recommended daily intake in more than 95% of COPD patients.,Conclusions: The diet of COPD patients treated with long-term oxygen therapy was improperly balanced, with deficiencies of important nutrients.,Airflow obstruction in the respiratory tract was significantly smaller in obese patients, and greater in patients with diagnosed malnutrition. | Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | 1 |
The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known.,The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection.,The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed.,Among these, the data sets of 364 pathological stage I patients were available.,The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated.,Emphysema was assessed on the basis of semiquantitative CT.,Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study.,Emphysema was present in 63 patients.,The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001).,On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05).,Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05).,Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively).,The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients. | The aim of this study was to determine the relationship between lobar severity of emphysema and lung cancer using automated lobe segmentation and emphysema quantification methods.,This study included 78 patients (74 males and 4 females; mean age of 72 years) with the following conditions: pathologically proven lung cancer, available chest computed tomographic (CT) scans for lobe segmentation, and quantitative scoring of emphysema.,The relationship between emphysema and lung cancer was analyzed using quantitative emphysema scoring of each pulmonary lobe.,The most common location of cancer was the left upper lobe (LUL) (n = 28), followed by the right upper lobe (RUL) (n = 27), left lower lobe (LLL) (n = 13), right lower lobe (RLL) (n = 9), and right middle lobe (RML) (n = 1).,Emphysema ratio was the highest in LUL, followed by that in RUL, LLL, RML, and RLL.,Multivariate logistic regression analysis revealed that upper lobes (odds ratio: 1.77; 95% confidence interval: 1.01-3.11, P = 0.048) and lobes with emphysema ratio ranked the 1st or the 2nd (odds ratio: 2.48; 95% confidence interval: 1.48-4.15, P < 0.001) were significantly and independently associated with lung cancer development.,In emphysema patients, lung cancer has a tendency to develop in lobes with more severe emphysema. | 1 |
Patients with stable COPD show improvements in exercise capacity and muscular function after the application of whole body vibration.,We aimed to evaluate whether this modality added to conventional physiotherapy in exacerbated hospitalised COPD patients would be safe and would improve exercise capacity and quality of life.,49 hospitalised exacerbated COPD patients were randomized (1:1) to undergo physiotherapy alone or physiotherapy with the addition of whole body vibration.,The primary endpoint was the between-group difference of the 6-minute walking test (day of discharge - day of admission).,Secondary assessments included chair rising test, quality of life, and serum marker analysis.,Whole body vibration did not cause procedure-related adverse events.,Compared to physiotherapy alone, it led to significantly stronger improvements in 6-minute walking test (95.55 ± 76.29 m vs.,6.13 ± 81.65 m; p = 0.007) and St.,Georges Respiratory Questionnaire (-6.43 ± 14.25 vs.,5.59 ± 19.15, p = 0.049).,Whole body vibration increased the expression of the transcription factor peroxisome proliferator receptor gamma coactivator-1-α and serum levels of irisin, while it decreased serum interleukin-8.,Whole body vibration during hospitalised exacerbations did not cause procedure-related adverse events and induced clinically significant benefits regarding exercise capacity and health-related quality of life that were associated with increased serum levels of irisin, a marker of muscle activity.,German Clinical Trials Register DRKS00005979.,Registered 17 March 2014. | Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | 1 |
Initial use of inhaled corticosteroid therapy is common in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) A or B chronic obstructive pulmonary disease, contrary to GOLD guidelines.,We investigated UK prescribing of inhaled corticosteroid therapy in these patients, to identify predictors of inhaled corticosteroid use in newly diagnosed chronic obstructive pulmonary disease patients.,A cohort of newly diagnosed GOLD A/B chronic obstructive pulmonary disease patients was identified from the UK Clinical Practice Research Datalink (June 2005-June 2015).,Patients were classified by prescribed treatment, with those receiving inhaled corticosteroid-containing therapy compared with those receiving long-acting bronchodilators without inhaled corticosteroid.,In all, 29,815 patients with spirometry-confirmed chronic obstructive pulmonary disease were identified.,Of those prescribed maintenance therapy within 3 months of diagnosis, 63% were prescribed inhaled corticosteroid-containing therapy vs. 37% prescribed non-inhaled corticosteroid therapy.,FEV1% predicted, concurrent asthma diagnosis, region, and moderate exacerbation were the strongest predictors of inhaled corticosteroid use in the overall cohort.,When concurrent asthma patients were excluded, all other co-variates remained significant predictors.,Other significant predictors included general practitioner practice, younger age, and co-prescription with short-acting bronchodilators.,Trends over time showed that initial inhaled corticosteroid prescriptions reduced throughout the study, but still accounted for 47% of initial prescriptions in 2015.,These results suggest that inhaled corticosteroid prescribing in GOLD A/B patients is common, with significant regional variation that is independent of FEV1% predicted.,Inhaled steroids are often prescribed to early-stage chronic lung disease patients in the UK despite guidelines to the contrary.,Patients newly diagnosed with early-stage chronic obstructive pulmonary disease (COPD) should not be prescribed inhaled corticosteroids (ICS), because they carry an increased risk of side effects such as pneumonia and osteoporosis.,ICS should be reserved for patients with severe COPD and frequent exacerbations.,James Chalmers at the Scottish Centre for Respiratory Research, Dundee, and co-workers examined prescribed medication data from the UK spanning 10 years, to determine key predictors of ICS prescription during early-stage COPD.,Of 29,815 patients identified, an average of 63% were prescribed ICS upon diagnosis, regardless of disease severity.,Younger patients were more likely to receive ICS, possibly due to co-morbidity with chronic asthma, and particular UK regions and medical practices prescribed ICS more readily than others. | Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified. | 1 |
This study was designed to evaluate errors in inhaler technique in COPD vs asthma patients and to investigate the association of poor inhaler technique with patient demographics and clinical variables.,A total of 509 adult patients with COPD (n=328) or asthma (n=181) who were currently using an inhaler device were included in this study.,Data on patient demographics, duration of disease, type and duration of inhaler therapy, and assessment of inhaler technique were recorded.,Metered dose inhaler (MDI) was the most common type of inhaler used by a similarly high percentage of patients in both COPD (83.2%) and asthma (77.3%) groups.,Failure to exhale before inhaling through device (75.8% and 68.5% for MDIs; 73.2% and 71.8% for Aerolizer®/Handihaler®; 53.1% and 66.7% for Turbuhaler®) was the most common error in inhaler technique, in both COPD and asthma groups.,Device-specific errors in inhaler techniques were more common in asthma patients as compared with COPD patients, particularly for MDIs (P-values ranged from 0.046 to 0.0005), as associated with female gender (failure to press the buttons on both sides of Aerolizer®/Handihaler®, P=0.006), shorter duration of disease (failure to hold MDI or head in a vertical position, P<0.001, and to keep Turbuhaler® upright, P=0.005), and shorter duration of inhaler usage (failure to hold head in a vertical position during MDI usage, P=0.006, and to keep Turbuhaler® upright, P=0.012).,In conclusion, our findings revealed that errors in inhaler technique in terms of inhalation maneuvers and device handling were similarly common in COPD and asthma patients.,Errors in certain device handling maneuvers, particularly with MDIs, were more common among asthma patients than among COPD patients and associated with female gender and shorter durations of disease and inhaler therapy. | With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever.,We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success.,Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions.,Inclusion eligibility, quality appraisal (Cochrane’s risk of bias tool) and data extraction were performed by two independent reviewers.,Regression analyses were performed to identify characteristics contributing to inhaler technique improvement.,Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique.,However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates.,Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p < 0.05), were shown to have an impact on effectiveness of the intervention, explaining up to 91% of the effectiveness variation.,Other factors, such as disease (asthma vs. chronic obstructive pulmonary disease), education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role.,Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time.,In conclusion, educational interventions to improve inhaler technique are effective on the short-term.,Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended. | 1 |
Exposure to high levels of particulate matter (PM) poses a major threat to human health.,Cigarette smoke is the most common irritant that causes chronic obstructive pulmonary disease (COPD); however, at least one-fourth of patients with COPD are nonsmokers, and their disease is largely attributed to air pollution.,The occurrence of pollution episodes in China has raised an emergent question of how PM leads to the pathogenesis of COPD.,In this paper, we show that deregulation of mitochondrial NADH dehydrogenase gene expression levels plays a key role in the aggravation of COPD during air pollutant exposure, which can be rescued by taurine and 3-MA treatments in both mammalian cells and animals.,Chronic obstructive pulmonary disease (COPD) has been linked to particulate matter (PM) exposure.,Using transcriptomic analysis, we demonstrate that diesel exhaust particles, one of the major sources of particulate emission, down-regulated genes located in mitochondrial complexes I and V and induced experimental COPD in a mouse model.,1-Nitropyrene was identified as a major toxic component of PM-induced COPD.,In the panel study, COPD patients were found to be more susceptible to PM than individuals with normal lung function due to an increased inflammatory response.,Mechanistically, exposure to PM in human bronchial epithelial cells led to a decline in CCAAT/enhancer-binding protein alpha (C/EBPα), which triggered aberrant expression of NADH dehydrogenase genes and ultimately led to enhanced autophagy.,ATG7-deficient mice, which have lower autophagy rates, were protected from PM-induced experimental COPD.,Using metabolomics analysis, we further established that treatment with taurine and 3-methyladenine completely restored mitochondrial gene expression levels, thereby ameliorating the PM-induced emphysema.,Our studies suggest a potential therapeutic intervention for the C/EBPα/mitochondria/autophagy axis in PM-induced COPD. | Chronic airway inflammation and airway remodeling are the major pathophysiological characteristics of chronic obstructive pulmonary disease (COPD).,Resveratrol and genistein have been previously demonstrated to have anti-inflammatory and antioxidative properties.,The present study aimed to measure the inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 concentration in patients with COPD.,Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy subjects, then randomly divided into the following four treatment groups: Control, dexamethasone (0.5 µmol/l), resveratrol (12.5 µmol/l) and genistein (25 µmol/l) groups.,After 1 h of treatment, 100 µl lymphocytes were collected for nuclear factor (NF)-κB immunocytochemical staining.,After 48 h treatment, the supernatant of the lymphocytes was collected for analysis of TNF-α and MMP-9 concentration levels.,The percentage of lymphocytes with positive nuclear NF-κB expression was analyzed by immunocytochemical staining.,The concentration levels of TNF-α and MMP-9 were measured using radioimmunoassay and enzyme-linked immunosorbent assay, respectively.,The present study demonstrated that the percentage of NF-κB-positive cells, and the levels of TNF-α and MMP-9 in lymphocytes from patients with COPD patients were significantly higher compared with healthy subjects.,Additionally, there were positive correlations between the percentage of NF-κB-positive cells, and the concentration levels of TNF-α and MMP-9 in patients with COPD.,All three factors were significantly reduced in lymphocytes treated with resveratrol and genistein, and the inhibitory effects of resveratrol on NF-κB, TNF-α and MMP-9 were more potent than the effects of genistein.,In conclusion, resveratrol and genistein may inhibit the NF-κB, TNF-α and MMP-9-associated pathways in patients with COPD.,It is suggested that resveratrol and genistein may be potential drugs candidates for use in the treatment of COPD. | 1 |
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