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Rationale: Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.,Objectives: To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations.,Methods: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts.,The microbiome was analyzed using COPDMAP and AERIS as a discovery data set and BEAT-COPD as a validation data set.,Measurements and Main Results: The airway microbiome in neutrophilic COPD was heterogeneous, with two primary community types differentiated by the predominance of Haemophilus.,The Haemophilus-predominant subgroup had elevated sputum IL-1β and TNFα (tumor necrosis factor α) and was relatively stable over time.,The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic.,Patients in this state at stability were susceptible to the greatest microbiome shifts during exacerbations.,This subgroup can temporally switch to both neutrophilic Haemophilus-predominant and eosinophilic states that were otherwise mutually exclusive.,Time-series analysis on the microbiome showed that the temporal trajectories of Campylobacter and Granulicatella were indicative of intrapatient switches from neutrophilic to eosinophilic inflammation, in track with patient sputum eosinophilia over time.,Network analysis revealed distinct host-microbiome interaction patterns among neutrophilic Haemophilus-predominant, neutrophilic balanced microbiome, and eosinophilic subgroups.,Conclusions: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies.,Neutrophilic and eosinophilic COPD are interchangeable in some patients.,Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time. | Lung macrophage subpopulations have been identified based on size.,We investigated characteristics of small and large macrophages in the alveolar spaces and lung interstitium of COPD patients and controls.,Alveolar and interstitial cells were isolated from lung resection tissue from 88 patients.,Macrophage subpopulation cell-surface expression of immunological markers and phagocytic ability were assessed by flow cytometry.,Inflammatory related gene expression was measured.,Alveolar and interstitial macrophages had subpopulations of small and large macrophages based on size and granularity.,Alveolar macrophages had similar numbers of small and large cells; interstitial macrophages were mainly small.,Small macrophages expressed significantly higher cell surface HLA-DR, CD14, CD38 and CD36 and lower CD206 compared to large macrophages.,Large alveolar macrophages showed lower marker expression in COPD current compared to ex-smokers.,Small interstitial macrophages had the highest pro-inflammatory gene expression levels, while large alveolar macrophages had the lowest.,Small alveolar macrophages had the highest phagocytic ability.,Small alveolar macrophage CD206 expression was lower in COPD patients compared to smokers.,COPD lung macrophages include distinct subpopulations; Small interstitial and small alveolar macrophages with more pro-inflammatory and phagocytic function respectively, and large alveolar macrophages with low pro-inflammatory and phagocytic ability. | 1 |
The purpose of this study was to quantitatively assess the effects of water-based Liuzijue exercise on patients with COPD and compare it with land-based Liuzijue exercise.,Participants were randomly allocated to one of three groups: the water-based Liuzijue exercise group (WG), the land-based Liuzijue exercise group (LG), and the control group (CG).,CG participants accepted no exercise intervention, while training groups performed Liuzijue exercise according to Health Qigong Liuzijue (People’s Republic of China) in different environments for 60-min sessions twice a week for 3 months.,Of the 50 patients enrolled, 45 (90%) completed the 3-month intervention.,The CG showed decreased expiratory muscle strength, extensor and flexor endurance ratio (ER) of the elbow joints and flexor peak torque (PT), total work (TW), and ER of the knee joints (p<0.05).,Both training groups showed improved respiratory muscle strength, which differed from the CG (p<0.001).,In addition, extensor and flexor TW of the elbow joints in the training groups were increased (p<0.01), and the WG differed from the CG in extensor TW and ER and flexor TW (p<0.01), while the LG differed from the CG in flexor TW and extensor ER (p<0.05).,PT, PT/body weight (BW), and TW in the knee joint extensor in the training groups were increased as well (PT and PT/BW: p<0.05, TW: p<0.01), and the WG differed from the CG in terms of knee joints outcomes, while the LG differed from the CG in flexor TW only (p<0.05).,Water-based Liuzijue exercise has beneficial effects on COPD patients’ respiratory muscle strength and peripheral skeletal muscle function, and additional benefits may exist in endurance of upper limbs and strength and endurance of lower limbs when compared with land-based Liuzijue exercise. | There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD).,It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation.,Patients were randomised to either singing classes or a film club for eight weeks.,Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist.,The singing group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline.,There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity.,In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group.,Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity.,Registration Current Controlled Trials - ISRCTN17544114 | 1 |
The fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).,This 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD.,The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin −50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84.,Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St.,George’s Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.,Trough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) −29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND.,The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference −23 mL; 95 % CI −54 to 8 mL).,The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores.,The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.,UMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.,ClinicalTrials.gov study ID NCT02257385; GSK study no.,116961.,The online version of this article (doi:10.1007/s40268-016-0131-2) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions.,A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.,Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort.,Biomarker repeatability was assessed using baseline and 3-month samples.,Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.,Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls.,Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period.,Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit.,CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.,Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD).,Further analysis of more promising biomarkers may reveal utility in subsets of patients.,Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.,SCO104960, clinicaltrials.gov identifier NCT00292552 | Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and airway inflammation, accompanied by decreased health status.,It is still unknown which factors are responsible for the impaired health status in COPD.,We postulated that airway inflammation negatively contributes to health status in COPD.,In 114 COPD patients (99 male, age: 62 ± 8 yr, 41 [31-55] pack-years, no inhaled or oral corticosteroids, postbronchodilator FEV1: 63 ± 9% pred, FEV1/IVC: 48 ± 9%) we obtained induced sputum and measured health status (St.,George's respiratory questionnaire (SGRQ)), postbronchodilator FEV1, hyperinflation (RV/TLC), and airway hyperresponsiveness to methacholine (PC20).,Sputum was induced by hypertonic saline and differential cell counts were obtained in 102 patients.,Univariate analysis showed that SGRQ total and symptom score were positively associated with % sputum macrophages (r = 0.20, p = 0.05; and r = 0.20, p = 0.04, respectively).,Multiple regression analysis confirmed these relationships, providing significant contributions of % sputum macrophages (B = 0.25, p = 0.021) and RV/TLC (B = 0.60, p = 0.002) to SGRQ total score.,Furthermore, SGRQ symptom score was associated with % sputum macrophages (B = 0.30, p = 0.03) and RV/TLC (B = 0.48, p = 0.044), whilst SGRQ activity score was associated with % sputum macrophages (B = 0.46, p = 0.002), RV/TLC (B = 0.61, p = 0.015), and PC20 (B = -9.3, p = 0.024).,Current smoking and FEV1 were not significantly associated with health status in the multiple regression analysis.,We conclude that worse health status in COPD patients is associated with higher inflammatory cell counts in induced sputum.,Our findings suggest that airway inflammation and hyperinflation independently contribute to impaired health status in COPD.,This may provide a rationale for anti-inflammatory therapy in this disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation.,Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients.,Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction.,The aim of our study was to identify genetic variants associated with TLC in COPD.,We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway).,All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry.,TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT).,Genotyping in each cohort was completed, with statistical imputation of additional markers.,To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry.,Results were summarized using fixed-effect meta-analysis.,Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10−8).,In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia.,DNAH5 could have an effect on hyperinflation in COPD.,The online version of this article (doi:10.1186/s12931-014-0097-y) contains supplementary material, which is available to authorized users. | Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population.,It is associated with smoking, but it is unknown why only a minority of smokers develops CMH.,A plausible explanation for this phenomenon is a predisposing genetic constitution.,Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.,GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts.,In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years).,Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).,A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10−6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3.,The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10−9) in lung tissue.,Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients.,SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.,Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH. | 1 |
There are only a few longitudinal studies regarding medical utilization and costs for patients with COPD.,The purpose of this study was to analyze the trend of medical utilization and costs on a long-term basis.,Using the Korean Health Insurance Review and Assessment Service (HIRA) data from 2008 to 2013, COPD patients were identified.,The trend of medical utilization and costs was also analyzed.,The number of COPD patients increased by 13.9% from 2008 to 2013.,During the same period, the cost of COPD medication increased by 78.2%.,Methylxanthine and systemic beta agonists were most widely prescribed between 2008 and 2013.,However, inhaled medications such as long-acting beta-2 agonist (LABA), long-acting muscarinic agonist, and inhaled corticosteroid plus LABA were dispensed to a relatively low proportion of patients with COPD.,The number of patients who were prescribed inhaled medications increased gradually from 2008 to 2013, while the number of patients prescribed systemic beta agonist and methylxanthine has decreased since 2010.,This study shows that there is a large gap between the COPD guidelines and clinical practice in Korea.,Training programs for primary care physicians on diagnosis and guideline-based treatment are needed to improve the management of COPD. | Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms.,Chronic respiratory symptoms are common in the general population.,There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD.,To determine the occurrence of ‘exacerbation-like’ events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts.,We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health.,The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory ‘exacerbation-like’ events in the past year.,Individuals without COPD had half the frequency of ‘exacerbation-like’ events compared with those with COPD.,In the non-COPD group, the independent associations with ‘exacerbations’ included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health.,In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001.,Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes.,They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD. | 1 |
Whole-body vibrating training (WBVT) is a modality aiming to improve neuromuscular performance of patients with COPD.,However, a consensus on the effects of WBVT has not been reached.,We aimed to clarify the effects of WBVT on functional exercise capacity, pulmonary function, and quality of life in COPD patients.,PubMed, Web of Science, and EMBASE were searched through April 5, 2018.,We calculated the pooled weight mean difference (WMD) using a random-effects model.,Quality assessment and publication bias analyses were also performed.,We included eight randomized control trials involving 365 patients.,Compared with control group, WBVT increased 6-minute walking distance (6-MWD) (WMD: 62.14 m; 95% CI: 48.12-76.16; P<0.001), the change of 6-MWD (Δ6-MWD) (WMD: 42.33 m; 95% CI: 15.21-69.45; P=0.002), the change of the time to finish five repeated sit-to-stand tests (WMD: −2.07 seconds; 95% CI: −4.00 to −0.05; P=0.04), and decreased the change of St George’s Respiratory Questionnaire score (WMD: −6.65 points; 95% CI: −10.52 to −2.78; P<0.001).,However, no significant difference was found between the two groups regarding forced expired volume in 1 second (FEV1) (% predicated), change of FEV1 (% predicated), sit-to-stand test, 6-MWD (% predicated), change of 6-MWD (% predicated), St George’s Respiratory Questionnaire score, COPD Assessment Test score, and change of COPD Assessment Test score.,WBVT has beneficial effects on functional exercise capacity for COPD patients. | Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease.,Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life.,The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.,Five databases were searched with no dates or language limits.,The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords.,The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014.,The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale.,Studies supplied by the database search strategy were assessed independently by two blinded researchers.,A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords.,Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome.,Thus, only 14 studies had postural control as their primary outcome.,Our study examiners found only seven studies that had a PEDro score higher than five points.,The examiners’ interrater agreement was 76.4%.,Six of those studies were accomplished with a control group and one study used their patients as their own controls.,The studies were published between 2004 and 2013.,Patients with COPD present postural control impairment when compared with age-matched healthy controls.,Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility. | 1 |
Few data exist on the understanding and adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in resource-limited settings, which are mostly in sub-Saharan Africa.,To assess physicians' understanding, adherence, and barriers to implementation of GOLD guidelines in Nigeria.,A questionnaire based on the recommendations of the guidelines was self-administered by 156 physicians in departments of internal and family medicine in selected hospitals to assess physician understanding of the GOLD guidelines and barriers to its implementation.,The medical records of patients with chronic obstructive pulmonary disease (COPD) were also reviewed to assess adherence to the guideline recommendations.,The performance score of all physicians was 22.37±0.39 (range 0-38).,Pulmonologists had the highest score (37.00±0.00) while medical officers had the lowest score (19.93±4.98) (F=10.16, df=5, p<0.001).,Forty one percent of physicians knew the spirometric criteria for diagnosing COPD and 26.9% could assess the severity.,In clinical practice, 32% of patients had brief smoking counselling despite 70% being smokers, 24% had spirometry and 18% had assessment of severity.,Almost 60% of patients were on oral aminophylline, 72% were on an inhaled long-acting β2-agonist and corticosteroid combination, 2% had pulmonary rehabilitation and no patients were vaccinated.,Self-reported adherence to the COPD guidelines was 23.7%.,Lack of familiarity (39.8%) was cited as the most common barrier to adherence to the guidelines.,The understanding of GOLD guidelines is satisfactory among Nigerian doctors managing patients with COPD but the level of adherence is poor.,Educational interventions are needed to improve the implementation of guideline-based management. | To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS).,The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007.,The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS.,Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data.,We examined the baseline characteristics of these patients along with their healthcare resource utilization.,Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines.,A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results.,The adherent subgroup received COPD medications consistent with current GOLD guidelines.,Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines.,In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines.,In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines.,GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts.,Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD.,Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers. | 1 |
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. | 1 |
To evaluate the value of soluble urokinase-type plasminogen activator receptor (suPAR) in the diagnosis of acute exacerbation of COPD (AECOPD) and in monitoring treatment response, analyzing the relationship between suPAR and fibrinogen in AECOPD.,AECOPD leads to increased airway inflammation, contributing to an exaggerated release of inflammatory mediators.,We recruited 45 patients with AECOPD and 20 healthy control subjects.,Medical histories were taken, and all subjects underwent clinical examination, chest X-ray, pulmonary function tests, and blood gas analysis.,On day 1 (treatment initiation for the AECOPD patients) and day 14 (end of treatment), blood samples were collected for the determination of serum suPAR and plasma fibrinogen.,Serum levels of suPAR were significantly higher in the AECOPD group than in the control group.,In the AECOPD patients, there was a significant post-treatment decrease in the mean serum suPAR level.,The sensitivity, specificity, and accuracy of suPAR were 95.6%, 80.0%, and 93.0%, respectively.,The Global Initiative for Chronic Obstructive Lung Disease stage (i.e., COPD severity) correlated positively and significantly with serum levels of suPAR and plasma levels of fibrinogen.,Monitoring the serum suPAR level can be helpful in the evaluation of the COPD treatment response and might be a valuable biomarker for determining the prognosis of AECOPD.,Because serum suPAR correlated with plasma fibrinogen, both markers could be predictive of AECOPD. | Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition, and progresses with acute exacerbations.,(AE).,During AE, levels of acute phase reactants such as C-reactive protein (CRP) and inflammatory cells in the circulation increase.,Soluble urokinase-type plasminogen activator receptor (suPAR) levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation.,The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD) and response to treatment.,The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment.,We found that fibrinogen (P<0.001), CRP (P<0.001), and suPAR (P<0.001) were significantly higher in patients with AE-COPD than in healthy controls.,Fibrinogen (P<0.001), CRP (P=0.001), and suPAR (P<0.001) were significantly decreased by the seventh day of treatment.,However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD.,There was a correlation between fibrinogen, CRP, and suPAR.,However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression.,In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively).,Serum suPAR was negatively correlated with forced expiratory volume in 1 second (r=−478, P=0.001).,suPAR is a marker of acute inflammation.,It is well correlated with such inflammation markers as CRP and fibrinogen. suPAR can be used as a predictor of AE-COPD and in monitoring response to treatment. | 1 |
Computed tomography (CT) phenotypic characterization helps in understanding the clinical diversity of chronic obstructive pulmonary disease (COPD) patients, but its clinical relevance and its relationship with functional features are not clarified.,Volumetric capnography (VC) uses the principle of gas washout and analyzes the pattern of CO2 elimination as a function of expired volume.,The main variables analyzed were end-tidal concentration of carbon dioxide (ETCO2), Slope of phase 2 (Slp2), and Slope of phase 3 (Slp3) of capnogram, the curve which represents the total amount of CO2 eliminated by the lungs during each breath.,To investigate, in a group of patients with severe COPD, if the phenotypic analysis by CT could identify different subsets of patients, and if there was an association of CT findings and functional variables.,Sixty-five patients with COPD Gold III-IV were admitted for clinical evaluation, high-resolution CT, and functional evaluation (spirometry, 6-minute walk test [6MWT], and VC).,The presence and profusion of tomography findings were evaluated, and later, the patients were identified as having emphysema (EMP) or airway disease (AWD) phenotype.,EMP and AWD groups were compared; tomography findings scores were evaluated versus spirometric, 6MWT, and VC variables.,Bronchiectasis was found in 33.8% and peribronchial thickening in 69.2% of the 65 patients.,Structural findings of airways had no significant correlation with spirometric variables.,Air trapping and EMP were strongly correlated with VC variables, but in opposite directions.,There was some overlap between the EMP and AWD groups, but EMP patients had signicantly lower body mass index, worse obstruction, and shorter walked distance on 6MWT.,Concerning VC, EMP patients had signicantly lower ETCO2, Slp2 and Slp3.,Increases in Slp3 characterize heterogeneous involvement of the distal air spaces, as in AWD.,Visual assessment and phenotyping of CT in COPD patients is feasible and may help identify functional and clinically different subsets of patients.,VC may provide useful information about the heterogeneous involvement of lung structures in COPD. | Acute exacerbations of COPD (AECOPD) are often associated with infectious agents, some of which may be non-usual, including Aspergillus spp.,However, the importance of Aspergillus spp. in the clinical management of AECOPD still remains unclear.,The aims of the study were to analyze the prevalence and risk factors associated with Aspergillus spp. isolation in AECOPD, and to investigate the associated clinical outcomes during a 1-year follow-up period.,Patients presenting with an AECOPD requiring hospitalization were prospectively included from four hospitals across Spain.,Clinical, radiological and microbiological data were collected at admission and during the follow-up period (1, 6 and 12 months after discharge), and re-admissions and mortality data collected during the follow-up.,A total of 240 patients with severe AECOPD were included.,Valid sputum samples were obtained in 144 (58%) patients, and in this group, the prevalence of Aspergillus spp. isolation was 16.6% on admission and 14.1% at one-year follow-up.,Multivariate logistic-regression showed that AECOPD in the previous year (OR 12.35; 95% CI, 1.9-29.1; p < 0.001), concurrent isolation of pathogenic bacteria (OR 3.64; 95% CI 1.65-9.45, p = 0.001) and concomitant isolation of Pseudomonas aeruginosa (OR 2.80; 95% IC, 1.81-11.42; p = 0.001) were the main risk factors for Aspergillus spp. isolation.,The main risk factors for Aspergillus spp. isolation were AECOPD in the previous year and concomitant isolation of Pseudomonas aeruginosa.,However, although Aspergillus spp. is often isolated in sputum samples from patients with AECOPD, the pathogenic and clinical significance remains unclear. | 1 |
In chronic obstructive pulmonary disease (COPD), decreased progenitor cells and impairment of systemic vascular function have been suggested to confer higher cardiovascular risk.,The origin of these changes and their relationship with alterations in the pulmonary circulation are unknown.,To investigate whether changes in the number of circulating hematopoietic progenitor cells are associated with pulmonary hypertension or changes in endothelial function.,62 COPD patients and 35 controls (18 non-smokers and 17 smokers) without cardiovascular risk factors other than cigarette smoking were studied.,The number of circulating progenitors was measured as CD45+CD34+CD133+ labeled cells by flow cytometry.,Endothelial function was assessed by flow-mediated dilation.,Markers of inflammation and angiogenesis were also measured in all subjects.,Compared with controls, the number of circulating progenitor cells was reduced in COPD patients.,Progenitor cells did not differ between control smokers and non-smokers.,COPD patients with pulmonary hypertension showed greater number of progenitor cells than those without pulmonary hypertension.,Systemic endothelial function was worse in both control smokers and COPD patients.,Interleukin-6, fibrinogen, high sensitivity C-reactive protein, vascular endothelial growth factor and tumor necrosis factor were increased in COPD.,In COPD patients, the number of circulating progenitor cells was inversely related to the flow-mediated dilation of systemic arteries.,Pulmonary and systemic vascular impairment in COPD is associated with cigarette smoking but not with the reduced number of circulating hematopoietic progenitors.,The latter appears to be a consequence of the disease itself not related to smoking habit. | Little is known about limb muscle abnormalities in mild COPD.,Inactivity and systemic inflammation could play a role in the development of limb muscle dysfunction in COPD.,The objective of the present study was to characterize quadriceps function, enzymatic activities and morphometry, levels of plasma inflammatory markers and physical activity levels in daily life (PAdl) in patients with mild COPD (GOLD 1).,Mid-thigh muscle cross-sectional area (MTCSA), quadriceps strength, endurance, fiber-type distribution, capillarity, pro-angiogenesis factors (VEGF-A, angiopoietin I and II) and muscle oxidative capacity were assessed in 37 patients with mild COPD and 19 controls.,Systemic inflammatory markers (CRP, IL-6, TNF-α, Fibrinogen, SP-D) and PAdl were assessed.,MTCSA, quadriceps strength and endurance were not different between COPD and controls.,Capillarity and muscle oxidative capacity were all preserved in mild COPD.,Reduced pro-angiogenesis factor mRNA expression was seen in COPD.,The level of moderately active intensity (>3 METs) was significantly lower in mild COPD and, in multiple regression analyses, the level of physical activity was a determinant of muscle oxidative capacity and capillarization.,No between-group differences were found regarding muscle oxidative stress while circulating IL-6 levels were elevated in mild COPD.,The quadriceps muscle function was preserved in mild COPD although a reduced potential for angiogenesis was found.,The reduced level of daily activities and evidence of systemic inflammation in these individuals suggest that these factors precede the development of overt limb muscle dysfunction in COPD. | 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. | Pulmonary rehabilitation (PR) is recognized as the chief non-pharmacologic management approach for patients with COPD, but is clinically under-utilized.,In Taiwan, respiratory therapists (RTs) are one of the first-line health care providers who spend vast amounts of time with COPD patients in PR programs.,To better enhance patients’ knowledge of and participation in PR, it is necessary to understand how PR is viewed by RTs, as well as how these views influence their behavioral intentions toward promoting PR.,This study applied the Theory of Planned Behavior (TPB) to investigate both the behavioral intentions and the influential factors surrounding PR in RTs.,This cross-sectional study used structured self-administered questionnaires at a national symposium for RTs to collect data on their knowledge, attitudes, subjective norms, perceived behavioral controls, and behavioral intentions with regard to promoting PR.,Multiple linear regression analysis was used to identify significant factors affecting the intended promotion of PR by RTs.,The response rate after excluding respondents with incomplete data was 88.1% (n=379).,A majority of the participants were college graduates, aged over 30 years, and women.,The respective percentage scores derived from questionnaires gauging the knowledge, attitudes, subjective norms, self-efficacy, and behavioral intentions components of total PR scores were 63.12%, 71.33%, 68.96%, 66.46%, and 80.29%.,The factors significantly affecting RTs’ intentions to suggest PR participation to COPD patients or encourage it were attitudes, subjective norms, and self-efficacy.,The total model explained 22.5% of the variance in behavioral intentions.,The results of the study suggest that RTs strongly intend to promote PR, but are hindered by insufficient knowledge, attitudes, and self-efficacy with regard to it.,Applying TPB provided insight into which factors can be addressed, and by whom.,For example, enhancing RTs’ self-efficacy can be achieved through PR training via school curricula, further regular continuing education and/or courses, and practical experience. | 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. | Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide.,Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease.,We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors.,Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103).,We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions.,We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice.,HRVs are isolated from nasal and lung fluid from subjects with AE-COPD.,Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection.,HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells.,Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells.,Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD.,HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD.,Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD. | 1 |
Induced and spontaneous sputum are used to evaluate the airways microbiota.,Whether the sputum types can be used interchangeably in microbiota research is unknown.,Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation.,COPD patients from Bergen, Norway, were followed between 2006/2010, examined during the stable state and exacerbations. 30 patients delivered 36 sample pairs.,DNA was extracted by enzymatic and mechanical lysis methods.,The V3-V4 region of the 16S rRNA gene was PCR-amplified and prepared for paired-end sequencing.,Illumina Miseq System was used for sequencing, and Quantitative Insights Into Microbial Ecology (QIIME) and Stata were used for bioinformatics and statistical analyses.,Approximately 4 million sequences were sorted into 1004 different OTUs and further assigned to 106 different taxa.,Pair-wise comparison of both taxonomic composition and beta-diversity revealed significant differences in one or both parameters in 1/3 of sample pairs.,Alpha-diversity did not differ.,Comparing abundances for each taxa identified, showed statistically significant differences between the mean abundances in induced versus spontaneous samples for 15 taxa when disease state was considered.,This included potential pathogens like Haemophilus and Moraxella.,When studying microbiota in sputum samples one should take into consideration how samples are collected and avoid the usage of both induced and spontaneous sputum in the same study. | Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood.,As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression.,Here we show that polymeric immunoglobulin receptor-deficient (pIgR−/−) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age.,Progressive airway wall remodelling and emphysema in pIgR−/− mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase.,Re-derivation of pIgR−/− mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling.,These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.,The mechanisms driving lung inflammation and remodelling in chronic obstructive pulmonary disease (COPD) are incompletely understood.,Here the authors show that lack of secretory IgA promotes bacterial invasion in small airways, resulting in leukocyte recruitment and a COPD-like phenotype. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Patients with COPD experience exacerbations that may require hospitalization.,Patients do not always feel supported upon discharge and frequently get readmitted.,A Self-management Program of Activity, Coping, and Education for COPD (SPACE for COPD), a brief self-management program, may help address this issue.,To investigate if SPACE for COPD employed upon hospital discharge would reduce readmission rates at 3 months, compared with usual care.,This is a prospective, single-blinded, two-center trial (ISRCTN84599369) with participants admitted for an exacerbation, randomized to usual care or SPACE for COPD.,Measures, including health-related quality of life and exercise capacity, were taken at baseline (hospital discharge) and at 3 months.,The primary outcome measure was respiratory readmission at 3 months.,Seventy-eight patients were recruited (n=39 to both groups).,No differences were found in readmission rates or mortality at 3 months between the groups.,Ten control patients were readmitted within 30 days compared to five patients in the intervention group (P>0.05).,Both groups significantly improved their exercise tolerance and Chronic Respiratory Questionnaire (CRQ-SR) results, with between-group differences approaching statistical significance for CRQ-dyspnea and CRQ-emotion, in favor of the intervention.,The “Ready for Home” survey revealed that patients receiving the intervention reported feeling better able to arrange their life to cope with COPD, knew when to seek help about feeling unwell, and more often took their medications as prescribed, compared to usual care (P<0.05).,SPACE for COPD did not reduce readmission rates at 3 months above that of usual care.,However, encouraging results were seen in secondary outcomes for those receiving the intervention.,Importantly, SPACE for COPD appears to be safe and may help prevent readmission with 30 days. | 1 |
To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index.,Multicentre, observational, cross-sectional study.,Patients were aged ≥40 years, with spirometrically confirmed COPD.,Utility values were derived from EQ-5D-3 L.,Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications.,Differences in median utilities between groups were assessed by non-parametric tests.,346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years.,Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p < 0.001 for all comparisons).,Median utilities by GOLD 2013 were group A: 1.0 (0.09); group B: 0.87 (0.13); group C: 1.0 (0.16); group D: 0.74 (0.29); comparisons were statistically significant (p < 0.001) except A vs C.,Median utilities by GesEPOC phenotypes were 0.84 (0.33) for non exacerbator; 0.80 (0.26) for COPD-asthma overlap; 0.71 (0.62) for exacerbator with emphysema; 0.72 (0.57) for exacerbator with chronic bronchitis (p < 0.001).,Comparisons between patients with or without exacerbations and between patients with COPD-asthma overlap and exacerbator with chronic bronchitis were statistically-significant (p < 0.001).,Median utilities by BODEx index were: group 0-2: 0.89 (0.20); group 3-4: 0.80 (0.27); group 5-6: 0.67 (0.29); group 7-9: 0.41 (0.31).,All comparisons were significant (p < 0.001) except between groups 3-4 and 5-6.,Irrespective of the classification used utilities were associated to disease severity.,Some clinical phenotypes were associated with worse utilities, probably related to a higher frequency of exacerbations.,GOLD 2007 guidelines and BODEx index better discriminated patients with a worse health status than GOLD 2013 guidelines, while GOLD 2013 guidelines were better able to identify a smaller group of patients with the best health. | Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting.,Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course.,However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment.,Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon.,This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained. | 1 |
The Spanish Guidelines for COPD (GesEPOC) describe four clinical phenotypes: non-exacerbator (NE), asthma-COPD overlap syndrome (ACO), frequent exacerbator with emphysema (EE), and exacerbator with chronic bronchitis (ECB).,The objective of this study was to determine the frequency of COPD phenotypes, their clinical characteristics, and the availability of diagnostic tools to classify COPD phenotypes in clinical practice.,This study was an epidemiological, cross-sectional, and multi-centered study.,Patients ≥40 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.7 and who were smokers or former smokers (with at least 10 pack-years) were included.,The availability of diagnostic tools to classify COPD phenotypes was assessed by an ad hoc questionnaire.,A total of 647 patients (294 primary care [PC], 353 pulmonology centers) were included.,Most patients were male (80.8%), with a mean age (SD) of 68.2 (9.2) years, mean post-bronchodilator FEV1 was 53.2% (18.9%) and they suffered a mean of 2.2 (2.1) exacerbations in the last year.,NE was the most frequent phenotype (47.5%) found, followed by ECB (29.1%), EE (17.0%), and ACO (6.5%).,Significant differences between the four phenotypes were found regarding age; sex; body mass index; FEV1; body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE)/body mass index, airflow obstruction, dyspnea and exacerbations (BODEx) index; modified Medical Research Council dyspnea scale; respiratory symptoms; comorbidi-ties; hospitalizations; and exacerbations in the last year.,Physicians considered that >80% of the diagnostic tools needed to classify COPD phenotypes were available, with the exception of computed tomography (26.9%) and carbon monoxide transfer test (13.5%) in PC, and sputum eosinophilia count in PC and pulmonology centers (40.4% and 49.4%, respectively).,In Spanish clinical practice, almost half of the patients with COPD presented with NE phenotype.,The prevalence of ACO according to the Spanish consensus definition was very low.,In general, physicians indicated that they had the necessary tools for diagnosing COPD phenotypes. | Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study.,Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler.,Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler.,Patients demonstrated inhaler use after reading the patient information leaflet (PIL).,A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication).,If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again.,Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001).,Most patients (57-70%) made no errors using ELLIPTA and did not require investigator instruction.,Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%).,Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001).,More asthma and COPD patients preferred ELLIPTA over the other devices (all P⩽0.002).,Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers.,More asthma and COPD patients preferred ELLIPTA over comparator inhalers. | 1 |
The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA) in a single inhaler is a viable treatment option for patients with chronic obstructive pulmonary disease (COPD).,Here, we systematically review the current knowledge on double bronchodilation for the treatment of COPD, with a specific focus on its efficacy versus placebo and/or monotherapy bronchodilation.,A systematic review of clinical trials investigating LABA/LAMA combination therapies was conducted.,Articles were retrieved from PubMed, Embase, and Scopus on June 26, 2016.,We specifically selected clinical trials with a randomized controlled or crossover design published in any scientific journal showing the following characteristics: 1) comparison of different LABA/LAMA combinations in a single inhaler for patients with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo and/or bronchodilator monotherapy) in terms of lung function, respiratory symptoms, or exacerbations.,We analyzed 26 clinical trials conducted on 24,338 patients.,All LABA/LAMA combinations were consistently able to improve lung function compared with both placebo and bronchodilator monotherapy.,Improvements in symptoms were also consistent versus placebo, showing some lack of correlation for some clinical end points and combinations versus monotherapy bronchodilation.,Albeit being an exploratory end point, exacerbations showed an improvement with LABA/LAMA combinations over placebo in some trials; however, scarce information was available in comparison with bronchodilator monotherapy in most studies.,Our data show consistent improvements for LABA/LAMA combinations, albeit with some variability (depending on the clinical end point, the specific combination, and the comparison group).,Clinicians should be aware that these are average differences.,All treatments should be tailored at the individual level to optimize clinical outcomes. | This study evaluated patterns of pharmacotherapy in chronic obstructive pulmonary disease (COPD) as they relate to recommended guidelines in a prevalent COPD patient population with employer-sponsored health insurance in the US.,Health care claims data from 2007 and 2008 were retrospectively analyzed for the study population defined as patients aged 40 years and older, continuously enrolled during the study period, and having at least one inpatient or one emergency department (ED) visit, or at least two outpatient claims coded with COPD (International Classification of Diseases, 9th Revision, Clinical Modification code 491.xx, 492.xx, 496.xx).,Rates of any pharmacotherapy (both maintenance and reliever), long-acting maintenance pharmacotherapy in patients with an exacerbation history, and short-term treatment of acute exacerbations of COPD were evaluated in the overall population, newly diagnosed, and previously diagnosed patients (including maintenance-naïve and maintenance-experienced).,Stratified analyses were also conducted by age group (40-64 years, ≥65 years) and physician specialty.,A total of 55,361 patients met study criteria of whom 39% were newly diagnosed.,The mean age was 66 years, and 46% were male.,Three-fourths (74%) of all COPD patients had some pharmacotherapy (maintenance or reliever) with less than half (45%) being treated with maintenance medications.,The combination of an inhaled corticosteroid and a long-acting beta-agonist was the most prevalent drug class for maintenance treatment followed by tiotropium.,Only 64% of patients with an exacerbation history had a prescription for a long-acting maintenance medication, and short-term treatment with oral corticosteroids or antibiotics was higher for hospitalization exacerbations compared to ED visit exacerbations (68% vs 44%).,In general, the rates of pharmacotherapy were highest in patients who were maintenance-experienced followed by newly diagnosed and maintenance-naïve.,The majority of COPD patients received maintenance or reliever COPD medications, but less than half received guideline-recommended care, especially those with an exacerbation history or receiving short-term treatment for acute exacerbations. | 1 |
Objectives To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use.,Design Population based cohort study in England.,Setting UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11.,Participants Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record.,Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London.,Main outcome measure Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct.,Results Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years).,Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001).,Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers.,With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02).,Conclusions The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD.,Registration NCT01335672. | Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.,Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.,Setting Tayside, Scotland (2001-2010),Population 5977 patients aged >50 years with a diagnosis of COPD.,Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.,Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective.,There was a 22% overall reduction in all cause mortality with β blocker use.,Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD.,Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker.,There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent,Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function. | 1 |
Prediction models and prognostic scores have been increasingly popular in both clinical practice and clinical research settings, for example to aid in risk-based decision making or control for confounding.,In many medical fields, a large number of prognostic scores are available, but practitioners may find it difficult to choose between them due to lack of external validation as well as lack of comparisons between them.,Borrowing methodology from network meta-analysis, we describe an approach to Multiple Score Comparison meta-analysis (MSC) which permits concurrent external validation and comparisons of prognostic scores using individual patient data (IPD) arising from a large-scale international collaboration.,We describe the challenges in adapting network meta-analysis to the MSC setting, for instance the need to explicitly include correlations between the scores on a cohort level, and how to deal with many multi-score studies.,We propose first using IPD to make cohort-level aggregate discrimination or calibration scores, comparing all to a common comparator.,Then, standard network meta-analysis techniques can be applied, taking care to consider correlation structures in cohorts with multiple scores.,Transitivity, consistency and heterogeneity are also examined.,We provide a clinical application, comparing prognostic scores for 3-year mortality in patients with chronic obstructive pulmonary disease using data from a large-scale collaborative initiative.,We focus on the discriminative properties of the prognostic scores.,Our results show clear differences in performance, with ADO and eBODE showing higher discrimination with respect to mortality than other considered scores.,The assumptions of transitivity and local and global consistency were not violated.,Heterogeneity was small.,We applied a network meta-analytic methodology to externally validate and concurrently compare the prognostic properties of clinical scores.,Our large-scale external validation indicates that the scores with the best discriminative properties to predict 3 year mortality in patients with COPD are ADO and eBODE.,The online version of this article (doi:10.1186/s12874-017-0433-2) contains supplementary material, which is available to authorized users. | Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED).,Such information could help stratify these patients and guide medical decision-making.,The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit.,This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals.,Recruitment started in June 2008 and ended in September 2010.,Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up.,Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit.,Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample.,The score was compared with other published prediction rules for patients with stable COPD.,In total, 2,487 patients were included in the study.,Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85).,Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model.,The same variables were predictors of death at 1 month (AUC = 0.85).,Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better.,Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process. | 1 |
Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool.,We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent.,94 COPD patients (aged 43-86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV) were examined with V/P SPECT and spirometry.,Ventilation and perfusion defects were analyzed blindly according to the European guidelines.,Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease.,Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry.,Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients.,Emphysema was identified in 81 patients.,Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor.,The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages (r=0.63 and −0.60, respectively, P<0.0001).,V/P SPECT identified pulmonary embolism in 30 patients (32%).,A pattern typical for heart failure was present in 26 patients (28%).,Parenchymal changes typical for pneumonia or lung tumor were present in several cases.,V/P SPECT, using Technegas as the functional ventilation imaging agent, is a new tool to diagnose COPD and to grade its severity.,Additionally, it revealed heterogeneity of COPD caused by pulmonary comorbidities.,The characteristics of these comorbidities suggest their significant impact in clarifying symptoms, and also their influence on the prognosis. | 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. | 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. | To determine whether the pneumonia severity index (PSI) can predict in-hospital mortality for AECOPD patients and compare its usefulness with the CURB65 and BAP65 indexes to predict mortality.,Demographics, clinical signs and symptoms, comorbidities, and laboratory and radiographic findings of hospitalized AECOPD patients were obtained.,Univariate and multiple logistic regression analyses were used to identify the risk factors for in-hospital mortality.,The PSI, CURB65 and BAP65 scores were calculated.,Receiver operating characteristic (ROC) curve analysis was used to identify the PSI, CURB65 and BAP65 scores that could discriminate between non-survivors and survivors.,To control for the confounding factor of invasive mechanical ventilation (IMV) regarding the mortality of AECOPD, subgroup analysis was performed when excluded patients who had met the criteria of IMV but who had not received the cure of IMV according to their wishes.,During the in-hospital period, 73 patients died and 679 patients recovered.,Age, PaO2<60 mmHg, pH < 7.35, PaCO2≥50 mmHg, nursing home residency, congestive heart failure, liver disease, sodium<130 mmol/L, lower FEV1% and altered mental status were risk factors for in-hospital mortality.,The areas under the ROC curves (AUCs) of the PSI for death were 0.847 (95% CI: 0.799-0.895).,The cut-off value was 116.5 with a sensitivity of 82.2% and a specificity of 77.6%.,However, the AUCs of the CURB65 and BAP65 for death were only 0.744 (95% CI: 0.680-0.809) and 0.665 (95% CI: 0.594-0.736), respectively.,Subgroup analysis also showed that the PSI score could predict the mortality of AECOPD patients with an AUC = 0.857 (95% CI: 0.802-0.913), with exclusion of the patients who met the criteria of IMV but who did not receive the cure of IMV.,The PSI score may be used to predict in-hospital mortality for hospitalized AECOPD patients, with a prognostic capacity superior to CURB65 and BAP65. | 1 |
There is evidence that bacterial colonisation in chronic obstructive pulmonary disease (COPD) is associated with increased neutrophilic airway inflammation.,This study tested the hypothesis that different bacterial phyla and species cause different inflammatory profiles in COPD patients.,Sputum was analysed by quantitative polymerase chain reaction (qPCR) to quantify bacterial load and 16S rRNA gene sequencing to identify taxonomic composition.,Sputum differential cell counts (DCC) and blood DCC were obtained at baseline and 6 months.,Patients were categorised into five groups based on bacterial load defined by genome copies/ml of ≥ 1 × 104, no colonisation and colonisation by Haemophilus influenzae (H. influenzae), Moraxella catarrhalis (M. catarrhalis), Streptococcus pneumoniae (S. pneumoniae), or > 1 potentially pathogenic microorganism (PPM).,We observed an increase in sputum neutrophil (%), blood neutrophil (%) and neutrophil-lymphocyte ratio (NLR) in patients colonised with H. influenzae (82.6, 67.1, and 3.29 respectively) compared to those without PPM colonisation at baseline (69.5, 63.51 and 2.56 respectively) (p < 0.05 for all analyses), with similar findings at 6 months.,The bacterial load of H. influenzae and Haemophilus determined by qPCR and 16s rRNA gene sequencing respectively, and sputum neutrophil % were positively correlated between baseline and 6 months visits (p < 0.0001, 0.0150 and 0.0002 with r = 0.53, 0.33 and 0.44 respectively).,These results demonstrate a subgroup of COPD patients with persistent H. influenzae colonisation that is associated with increased airway and systemic neutrophilic airway inflammation, and less eosinophilic airway inflammation. | Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods.,The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation.,Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies.,Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations.,Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question ‘who is there?’,Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques.,Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation.,Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions ‘what can they do?’,and ‘what are they doing?’,This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives. | 1 |
Self-management of exacerbations in COPD patients is important to reduce exacerbation impact.,There is a need for more comprehensive and individualized interventions to improve exacerbation-related self-management behavior.,The use of mobile health (mHealth) could help to achieve a wide variety of behavioral goals.,Understanding of patients and health care providers perspectives towards using mHealth in promoting self-management will greatly enhance the development of solutions with optimal usability and feasibility.,Therefore, the aim of this study was to explore perceptions of COPD patients and their health care providers towards using mHealth for self-management of exacerbations.,A qualitative study using focus group interviews with COPD patients (n = 13) and health care providers (HCPs) (n = 6) was performed to explore perceptions towards using mHealth to support exacerbation-related self-management.,Data were analyzed by a thematic analysis.,COPD patients and HCPs perceived mostly similar benefits and barriers of using mHealth for exacerbation-related self-management.,These perceived benefits and barriers seem to be important drivers in the willingness to use mHealth.,Both patients and HCPs strengthen the need for a multi-component and tailored mHealth intervention that improves patients’ exacerbation-related self-management by determining their health status and providing adequate information, decision support and feedback on self-management behavior.,Most importantly, patients and HCPs considered an mHealth intervention as support to improve self-management and emphasized that it should never replace patients’ own feelings nor undermine their own decisions.,In addition, the intervention should be complementary to regular contact with HCPs, as personal contact with a HCP was considered to be very important.,To optimize engagement with mHealth, patients should have a positive attitude toward using mHealth and an mHealth intervention should be attractive, rewarding and safe.,This study provided insight into perceptions of COPD patients and their HCPs towards using mHealth for self-management of exacerbations.,This study points out that future mHealth interventions should focus on developing self-management skills over time by providing adequate information, decision support and feedback on self-management behavior and that mHealth should complement regular care.,To optimize engagement, mHealth interventions should be attractive, rewarding, safe and tailored to the patient needs.,The online version of this article (10.1186/s12913-018-3545-4) contains supplementary material, which is available to authorized users. | Pulmonary rehabilitation programs have been shown to increase functional exercise capacity and quality of life in COPD patients.,However, following the completion of pulmonary rehabilitation the benefits begin to decline unless the program is of longer duration or ongoing maintenance exercise is followed.,Therefore, the aim of this study is to determine if supervised, weekly, hospital-based exercise compared to home exercise will maintain the benefits gained from an eight-week pulmonary rehabilitation program in COPD subjects to twelve months.,Following completion of an eight-week pulmonary rehabilitation program, COPD subjects will be recruited and randomised (using concealed allocation in numbered envelopes) into either the maintenance exercise group (supervised, weekly, hospital-based exercise) or the control group (unsupervised home exercise) and followed for twelve months.,Measurements will be taken at baseline (post an eight-week pulmonary rehabilitation program), three, six and twelve months.,The exercise measurements will include two six-minute walk tests, two incremental shuttle walk tests, and two endurance shuttle walk tests.,Oxygen saturation, heart rate and dyspnoea will be monitored during all these tests.,Quality of life will be measured using the St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale.,Participants will be excluded if they require supplemental oxygen or have neurological or musculoskeletal co-morbidities that will prevent them from exercising independently.,Pulmonary rehabilitation plays an important part in the management of COPD and the results from this study will help determine if supervised, weekly, hospital-based exercise can successfully maintain functional exercise capacity and quality of life following an eight-week pulmonary rehabilitation program in COPD subjects in Australia. | 1 |
A high percentage of patients with COPD report chronic nasal symptoms.,The study aims to evaluate the clinical impact of a 2-month treatment with inhaled nasal budesonide (100 µg per nostril twice daily) in patients affected by COPD with chronic rhinitis comorbidity.,Fifty-three stable COPD patients in therapy according to the Global initiative for chronic Obstructive Lung Disease recommendations were enrolled; 49 completed the study.,At enrollment (visit 0), patients underwent skin prick test and rhinoscopy.,At visit 0 and after 1 month (visit 1) and 2 months (visit 2) of therapy with nasal budesonide, patients underwent spirometry, and COPD assessment test (CAT), Sinonasal Outcome Test (SNOT 22), and modified Medical Research Council dyspnea scale were administered.,Differences in continuous variables, after 2 months of treatment with nasal budesonide, were evaluated using a paired t-test or Wilcoxon matched-pairs signed-ranks test.,Two months of treatment with nasal budesonide showed a significant statistical improvement in the total scores of CAT, SNOT 22, and modified Medical Research Council (p<0.001).,A significant relationship between CAT and SNOT 22 total scores at baseline and after treatment was observed.,The results of the present study indicate the importance of careful evaluation of the presence of chronic nasal symptoms in all COPD patients and suggest beneficial clinical effect from treatment with nasal budesonide in terms of COPD symptoms and quality of life. | Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD).,We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.,Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD.,Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1-5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009.,Stepwise multivariate logistic regression estimated independent associations with dyspnoea.,Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.,The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded.,Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC≥3).,Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction.,Other factors associated with increased dyspnoea grade included female gender, older age (≥70 years), obesity (BMI ≥30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner.,Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.,Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care.,Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up. | 1 |
Saliva is increasingly promoted as an alternative diagnostic bio-sample to blood; however its role in respiratory disease requires elucidation.,Our aim was to investigate whether C-reactive protein (CRP), procalcitonin (PCT) and neutrophil elastase (NE) could be measured in unstimulated whole saliva, and to explore differences between COPD patients and controls with normal lung function.,We also determined the relationship between these salivary biomarkers and self-reported COPD-relevant metrics.,Salivary CRP, PCT and NE levels were measured at each of 3 visits over a 14-day period alongside spirometry and a daily self-assessment dairy in 143 subjects: 20 never-smokers and 25 smokers with normal spirometry; 98 COPD patients [GOLD Stage I, 16; Stage II, 32; Stage III, 39; Stage IV, 11].,Twenty-two randomly selected subjects provided simultaneous blood samples.,Levels of each salivary biomarker could distinguish between the above cohorts.,Significant differences remained for salivary CRP and NE (p < 0.05) following adjustment for age, gender, sampling time, gum disease and total co-morbidities; but not for BMI except for salivary NE, which remained higher in smokers compared to non-smokers and stable COPD subjects (p < 0.001).,Patients with acute COPD exacerbations had a median increase in all 3 salivary biomarkers (p < 0.001); CRP: median 5.74 ng/ml, [interquartile range (IQR) 2.86-12.25], PCT 0.38 ng/ml, [IQR 0.22-0.94], and NE 539 ng/ml, [IQR 112.25-1264].,In COPD patients, only salivary CRP and PCT levels correlated with breathing scores (r = 0.14, p < 0.02; r = 0.13, p < 0.03 respectively) and sputum features but not with activities of daily living.,Salivary CRP and PCT concentrations strongly correlated with serum counterparts [r = 0.82, (95 % CI: 0.72-0.87), p < 0.001 by Spearman’s; and r = 0.53, (95 % CI: 0.33-0.69), p < 0.006 respectively]; salivary NE did not.,CRP, PCT and NE were reliably and reproducibly measured in saliva, providing clinically-relevant information on health status in COPD; additionally NE distinguished smoking status.,All 3 salivary biomarkers increased during COPD exacerbations, with CRP and PCT correlating well with patient-derived clinical metrics.,These results provide the conceptual basis for further development of saliva as a viable bio-sample in COPD monitoring and exacerbation management.,The online version of this article (doi:10.1186/s12931-015-0219-1) contains supplementary material, which is available to authorized users. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide.,However, several studies that have assessed the role of traditional Chinese exercise in the management of this disease include broad variations in sample sizes and results.,Therefore, this meta-analysis was conducted to assess the effects of traditional Chinese exercise on patients with COPD.,Two investigators independently identified and extracted data from selected articles.,A computerized search of electronic databases through August 2015 was conducted.,Mean differences (MDs) and 95% confidence intervals (CIs) were calculated to analyze the combined data.,The methodological quality was evaluated using the Cochrane risk-of-bias tool.,Heterogeneity was assessed with the I2 test.,Ten randomized, controlled trials (RCTs) involving 622 patients met the inclusion criteria.,There were significant improvements in the 6-minute walking distance test (6 MWD;MWD = 12.10 m; 95% CI, 7.56-16.65 m; p<0.001); forced expiratory volume in one second (FEV1% predicted; WMD = 9.02; 95% CI, 6.80-11.23; p<0.00001); forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratio (Tiffenau Index; WMD = 6.67; 95% CI, 5.09-8.24; p<0.00001); and quality of life, as evaluated by the Chronic Respiratory Disease Questionnaire (CRDQ; WMD = 0.85 score; 95% CI, 0.52-1.18; p<0.00001).,Traditional Chinese exercise could provide an effective alternative method for managing COPD.,Larger and higher-quality trials are required. | The incidence of chronic obstructive pulmonary disease (COPD) in China is very high.,This study aimed to assess the vulnerability of COPD patients in rural areas outside Xuzhou City, Jiangsu province, in order to provide helpful guidance for future research and public policies.,The vulnerability of 8,217 COPD patients was evaluated using a face-to-face questionnaire to obtain information on general characteristics, awareness, beliefs, medication usage, acute exacerbation of the disease, and economic burdens.,Direct economic burdens were calculated based on the questionnaire, and indirect economic burdens were estimated using local per capita income and life expectancy in 2008.,The years of potential life lost were calculated using loss of life years for each age group and multiplying by the number of deaths in a given age group.,Of the 8,217 patients, 7,921 (96.4%) had not heard of COPD, and 2,638 (32.1%) did not understand that smoking was a risk factor for COPD.,No patients had used inhalers, nebulizer drugs or oxygen therapy, either regularly or sporadically.,No patients had undergone pulmonary rehabilitation or surgical treatment, while 4,215 (51.3%) took theophylline to relieve dyspnea, and 3,418 (41.6%) used antibiotics to treat exacerbations.,A total of 2,925 (35.6%) patients had been admitted to hospital during the past year because of respiratory symptoms.,The average direct and indirect economic burdens on COPD patients were 1,090 and 20,605 yuan, respectively.,The vulnerability of patients in rural Xuzhou to COPD was high.,Their awareness of COPD was poor, their treatment during both the stable and acute exacerbation stages did not meet standards, and the economic burdens were large.,Interventions are therefore needed to improve the prevention and management of COPD in this population.,Further studies are required to verify these findings. | 1 |
Rtp801, a stress - related protein triggered by adverse environmental conditions, inhibits mTOR and enhances oxidative stress - dependent cell death.,We postulated that Rtp801 acts as potential amplifying switch in the development of cigarette smoke - induced lung injury, leading to emphysema.,Rtp801 was overexpressed in human emphysematous lungs and in lungs of mice exposed to cigarette smoke.,The upregulation of Rtp801 expression by cigarette smoke in the lung relied on oxidative stress - dependent activation of the CCAAT response element.,Rtp801 was necessary and sufficient for NF - κ B activation in cultured cells and, when forcefully expressed in mouse lungs, it promoted NF - kB activation, alveolar inflammation, oxidative stress, and apoptosis of alveolar septal cells.,On the other hand, Rtp801 − / − mice were markedly protected against acute cigarette smoke - induced lung injury, partly via increased mTOR signaling, and, when exposed chronically, against emphysema.,Our data support the notion that Rtp801 may represent an important molecular sensor and mediator of lung injury to cigarette smoke. | Recent studies described association between chronic obstructive pulmonary disease (COPD) and increased risk of cardiovascular diseases (CVD).,In their analysis none of these studies accounted for sociodemographic factors, health behaviors, and patient comorbidities simultaneously.,To study whether COPD diagnosis is an independent risk factor for CVD.,Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002 National Health Interview Survey (NHIS) were included in the analysis.,Chi-squared tests and odds ratios (OR) were utilized to compare the data.,Multiple logistic regression was employed to analyze the association between COPD and CVD with simultaneous control for sociodemographic factors (age, gender, race, marital status, education, income), health behaviors (tobacco use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension, high cholesterol, and obesity).,The analysis employed NHIS sampling weights to generate data representative of the entire US population.,The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P < 0.0001).,Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having coronary heart disease (OR = 2.0, 95% CI: 1.5-2.5), angina (OR = 2.1, 95% CI: 1.6-2.7), myocardial infarction (OR = 2.2, 95% CI: 1.7-2.8), stroke (OR = 1.5, 95% CI: 1.1-2.1), congestive heart failure (OR = 3.9, 95% CI: 2.8-5.5), poor circulation in lower extremities (OR = 2.5, 95% CI: 2.0-3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0-2.8).,Overall, the presence of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3-3.2).,These findings support the conclusion that COPD is an independent risk factor for CVD. | 1 |
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. | This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | 1 |
The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape.,The pandemic’s impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood.,We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations.,We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments.,Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years.,For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes.,Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations.,Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages.,There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33).,In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81).,The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths.,This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.,The online version contains supplementary material available at 10.1186/s12916-021-02000-w. | Across Europe, COPD affects 23 million people leading to annual health care costs of ~€25.1 billion.,This burden is particularly severe during winter months in association with the peak incidence of exacerbation events.,Seasonal variation in the health status of patients with COPD places additional and often critical pressure on already strained health care resources.,COPD exacerbations are characterized by worsening day-to-day symptoms of an individual and often triggered by respiratory infections, but the process by which this occurs in a seasonal fashion is likely to be multifactorial.,In this review, we discuss recent population studies that highlight the impact of seasonality in COPD and review the proposed biological mechanisms underlying this.,An appraisal of the role of the host susceptibility and response, environmental triggers and the biology of respiratory pathogens is detailed.,The impact of each aspect is considered, and an integrated model of the context for the whole individual and society in general is explored. | 1 |
Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | 1 |
Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries.,However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown.,This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE.,The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE.,Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks.,Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded.,The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494.,The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications.,Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries.,There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD.,The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
Exposure to biomass smoke (BMS) has been implicated in chronic obstructive pulmonary disease (COPD).,About 3 billion people worldwide use biomass fuel for cooking and heating.,Women in rural communities of low- and lower-middle-income countries are disproportionately exposed to massive amounts of BMS during active cooking hours (4-6 h/day).,Therefore, BMS exposure is considered as a risk factor for COPD in the same order of magnitude as tobacco smoke.,In rural India, due to cultural reasons, women are the primary cook of the family and are mostly nonsmokers.,Thus, BMS-induced COPD is predominant among rural Indian women.,However, BMS-COPD remains a relatively unexplored health problem globally.,Therefore, we investigated the serum chemokine and cytokine signatures of BMS-COPD and tobacco smoke-induced COPD (TS-COPD) patients compared to their control in a rural South Indian population for this field study.,Concentrations of 40 serum chemokines and cytokines were measured using a multiplexed immunoassay.,The study cohort consisted of BMS-COPD (female; n = 29) and BMS-exposed subjects without COPD (BMS-CONTROL; female; n = 24).,For comparison, data from TS-COPD patients (male, n = 23) and tobacco smokers without COPD (TS-CONTROL; male, n = 22) were investigated.,Subjects were matched for age, sex, and biomass exposure.,Tobacco consumption was slightly higher in TS-COPD subjects compared to TS-CONTROL.,BMS-exposed and TS-exposed subjects (currently exposed) were from the same locality with similar dwelling habits and socioeconomic status.,A validated structured questionnaire-based survey and spirometry was performed.,An additional control group with no tobacco and BMS exposure (TS-BMS-CONTROL; n = 15) was included.,Statistical significance was set at p ≤ 0.01.,Serum median concentrations (pg/ml) of CCL15 [8799.35; 5977.22], CCL27 [1409.14; 1024.99], and CXCL13 [37.14; 26.03] were significantly higher in BMS-CONTROL compared to BMS-COPD subjects.,Nine analytes exhibited higher concentrations in TS-CONTROL compared to TS-COPD subjects.,Comparison of chemokine and cytokine concentrations among BMS-COPD versus TS-COPD and BMS-CONTROL versus TS-CONTROL subjects also revealed distinct molecular signatures.,Our data identifies CCL27 and CXCL13 as putative, plausibly homeostatic/protective biomarkers for BMS-COPD within the investigated population that warrants validation in larger and multiple cohorts.,The findings further indicate exposure-specific systemic response of chemokines and cytokines. | COPD is the third leading cause of death in the world and its global burden is predicted to increase further.,Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner.,In a prospective population-based cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV1/FVC < 0.70).,In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician.,Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk.,In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones.,The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4.,The IR was higher in males and in smokers.,The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males.,The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers.,The proportion of never-smokers among female COPD cases is substantial.,The online version of this article (doi:10.1007/s10654-016-0132-z) contains supplementary material, which is available to authorized users. | 1 |
Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease.,This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed‐up during a 12‐month pilot study.,Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event.,Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum.,Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically.,Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively.,Intracellular bacteria were not found in sputum by PCR.,Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae.,Viral or virus and bacteria co‐infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases.,Patients with co‐infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4).,These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD.,These findings indicate that viral or virus and bacterial co‐infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months.,J.,Med.,Virol.,85:866-873, 2013.,© 2013 Wiley Periodicals, Inc. | COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes. | 1 |
There are no validated measures of disease activity in COPD.,Since “active” disease is expected to have worse outcomes (e.g. mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality.,We investigated 1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; 2) whether these variables inter-relate; and 3) if any clinical, imaging and/or biological marker measured cross-sectionally at baseline relates to any activity component.,Results showed that 1) after 1 year, hospitalisation for COPD, exacerbation frequency, worsening of body mass index, airflow obstruction, dyspnoea and exercise (BODE) index or health status (St George's Respiratory Questionnaire (SGRQ)) and persistence of systemic inflammation were significantly associated with 8-year mortality; 2) at 3 years, the same markers, plus forced expiratory volume in 1 s (FEV1) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; 3) changes in FEV1, inflammatory cytokines and CT emphysema were not inter-related, while the multidimensional indices (BODE and SGRQ) showed modest correlations; and 4) changes in these markers could not be predicted by any baseline cross-sectional measure.,In COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores and FEV1 decline are independent markers of disease activity associated with 8-year all-cause mortality.,These disease activity markers are generally independent and not predictable from baseline measurements.,In patients with COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores, and FEV1 decline, are independent markers of disease activity associated with 8-year all-cause mortalityhttps://bit.ly/2CyifcN | Public health is a priority for the Chinese Government.,Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance.,This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.,We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017.,We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk.,We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).,Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017.,Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017.,Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017.,Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs.,All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88.,The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain.,The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).,China has made substantial progress in reducing the burden of many diseases and disabilities.,Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.,China National Key Research and Development Program and Bill & Melinda Gates Foundation. | 1 |
COPD is a global health concern, and is a major cause of chronic morbidity and mortality worldwide.,According to the World Health Organization, it is currently the sixth leading cause of death in the world, and further increases in the prevalence and mortality of the disease is predicted for the coming decades.,These increases are mainly linked to the epidemic of tobacco exposure and indoor and outdoor air pollution in Asian countries.,The burden of COPD in Asia is currently greater than that in developed Western countries, both in terms of the total number of deaths and the burden of disease, as measured in years of life lost and years spent living with disability.,The types of health-care policies and the practice of medicine vary considerably among the regions of Asia and have an impact on the burden of disease.,Treatment aims in Asian countries are based on evidence-based management guidelines.,Barriers to the implementation of disease management guidelines are related to issues of resource conflict and lack of organizational support rather than cultural differences in medical practice.,To reduce this burden of COPD in Asian countries, there is a need for a multifaceted approach in improving awareness of prevalence and disease burden, in facilitating accurate diagnosis of COPD among chronic respiratory diseases, in championing health policies that reduce the burden of the main risk factors for COPD and in the wider use of evidence-based management for COPD. | COPD is an inflammatory disease with major co-morbidities.,It has recently been suggested that depression may be the result of systemic inflammation.,We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales.,We assessed 120 patients with moderate COPD (FEV1% 52, men 62%, age 66).,Depression was assessed using the BASDEC and CES-D scales.,Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS) and the Borg scale before and after 6MWT.,We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6.,A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007).,TNF-α remained positively correlated with depression (p = 0.024) after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV1%, and pack-years.,Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044).,Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7) had higher mean CES-D depression score than the rest of the sample (p = 0.03).,Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT.,Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054).,This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue. | 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. | 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 |
People with chronic obstructive pulmonary disease (COPD) sometimes experience anxiety, depression and comorbid cognitive deficits.,Rather than being merely a consequence of symptom-related physical impairments these additional problems may be part of the clinical course of the condition.,The relationship between the physical and psychological aspects of the condition is illustrated by the patterns of use of non-invasive ventilation (NIV); NIV is often rejected or used inappropriately, resulting in clinical deterioration and an increase in health care costs.,The study aims to analyse the effects of psychological support on the acceptance of, and adherence to, NIV.,The primary outcome will be a latent variable related to indices of use of NIV equipment and adherence to treatment regime; while survival rates and psychological variables will constitute the secondary outcomes.,A two-arm randomised controlled trial will be conducted.,We aim to recruit 150 COPD patients for whom NIV is indicated.,The experimental group will receive a brief course of psychological support that will include counselling, relaxation and mindfulness-based exercises.,In some cases, it will also include neuropsychological rehabilitation exercises.,Support will be delivered via four to eight meetings at the HD Respiratory Rehabilitation Unit, at home or via telemedicine.,Controls will receive standard care and watch educational videos related to the management of their disease.,This investigation will gain insight about the role of a psychological intervention as part of a treatment plan during the process of adaptation to NIV in COPD patients.,ClinicalTrials.gov, ID: NCT02499653.,Registered on 14 July 2015.,The online version of this article (doi:10.1186/s13063-017-1802-1) contains supplementary material, which is available to authorized users. | A key goal of chronic obstructive pulmonary disease (COPD) care is to improve patients’ quality of life (QoL).,For outcomes such as QoL, illness perceptions and coping are important determinants.,The primary aim was to assess the associations between illness perceptions, coping and QoL in COPD patients.,A secondary aim was to compare illness perceptions and coping of patients with reference values derived from the literature.,A total of 100 patients were included in the study.,Patients were asked to complete the Brief Illness Perception Questionnaire (B-IPQ), the Utrecht Proactive Coping Competence scale (UPCC), and a QoL item.,Correlations and linear regression models were used to analyze the data.,Student’s t-tests were used to compare patients with COPD with reference values derived from the literature.,Patients with better understanding of COPD utilized more proactive coping strategies (P=0.04).,A more intense emotional response to COPD was related to less proactive coping (P=0.02).,Patients who reported using more proactive coping techniques also reported to have a better QoL (P<0.01).,Illness perceptions were also related to QoL: more positive illness perceptions were related to a better QoL (all P<0.05).,Patients with COPD reported more negative illness perceptions than people with a common cold or patients with asthma (all P<0.01), but reported similar perceptions compared with patients with diabetes.,Patients with COPD reported a moderate QoL, but appeared to be proficient in proactive coping.,Illness perceptions, coping, and QoL were all associated with each other.,Patients reported more strongly affected illness perceptions compared to people with a cold and patients with asthma.,We postulate that a self-management intervention targeting patients’ illness perceptions leads to improved QoL. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users. | A suggested role for T cells in COPD pathogenesis is based on associations between increased lung cytotoxic T lymphocyte (CD8+) numbers and airflow limitation.,CD69 is an early T cell activation marker.,Natural Killer cell group 2 D (NKG2D) receptors are co-stimulatory molecules induced on CD8+ T cells upon activation.,The activating function of NKG2 D is triggered by binding to MHC class 1 chain-related (MIC) molecules A and B, expressed on surface of stressed epithelial cells.,The aim of this study was to evaluate the expression of MIC A and B in the bronchial epithelium and NKG2 D and CD69 on BAL lymphocytes in subjects with COPD, compared to smokers with normal lung function and healthy never-smokers.,Bronchoscopy with airway lavages and endobronchial mucosal biopsy sampling was performed in 35 patients with COPD, 21 healthy never-smokers and 16 smokers with normal lung function.,Biopsies were immunohistochemically stained and BAL lymphocyte subsets were determined using flow cytometry.,Epithelial CD3+ lymphocytes in bronchial biopsies were increased in both smokers with normal lung function and in COPD patients, compared to never-smokers.,Epithelial CD8+ lymphocyte numbers were higher in the COPD group compared to never-smoking controls.,Among gated CD3+cells in BAL, the percentage of CD8+ NKG2D+ cells was enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers.,The percentage of CD8+ CD69+ cells and cell surface expression of CD69 were enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers.,No changes in the expression of MIC A or MIC B in the airway epithelium could be detected between the groups, whereas significantly decreased soluble MICB was detected in bronchial wash from smokers with normal lung function, compared to never-smokers.,In COPD, we found increased numbers of cytotoxic T cells in both bronchial epithelium and airway lumen.,Further, the proportions of CD69- and NKG2D-expressing cytotoxic T cells in BAL fluid were enhanced in both subjects with COPD and smokers with normal lung function and increased expression of CD69 was found on CD8+ cells, indicating the cigarette smoke exposure-induced expansion of activated cytotoxic T cells, which potentially can respond to stressed epithelial cells. | 1 |
COPD is characterized by persistent respiratory symptoms and airflow limitation, caused by a mixture of small airway disease and pulmonary emphysema.,Programmed cell death has drawn the attention of COPD researchers because emphysema is thought to result from epithelial cell death caused by smoking.,Although apoptosis has long been thought to be the sole form of programmed cell death, recent studies have reported the existence of a genetically programmed and regulated form of necrosis called necroptosis.,Autophagy was also previously considered a form of programmed cell death, but this has been reconsidered.,However, recent studies have revealed that autophagy can regulate programmed cell death, including apoptosis and necroptosis.,It is also becoming clear that autophagy can selectively degrade specific proteins, organelles, and invading bacteria by a process termed “selective autophagy” and that this process is related to the pathogenesis of human diseases.,In this review, we outline the most recent studies implicating autophagy, selective autophagy, and necroptosis in COPD.,Strategies targeting these pathways may yield novel therapies for COPD. | COPD is a multi-pathogenesis disease mainly caused by smoking.,A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages.,This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.,COPD models were built in the C57BL/6 mouse by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE).,The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E) staining.,The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS) of CD206, CD86 and CD68 on the lung tissue paraffin section.,The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer.,The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR).,The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β) in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.,The COPD model is well established, which is confirmed by the lung function test and lung H&E staining.,The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05).,The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer.,The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05) in CES-treated M2 macrophages, which is detected by RT-PCR.,The protein levels of TGF-β/Smad pathway-related markers are all increased in alveolar M2 macrophages of the model group.,This study found an increased deposition of alveolar M2 macrophages in the mouse COPD model and an increased expression level of TGF-β/Smad pathway in M2 macrophages, both in vitro and in vivo, induced by CSE and/or CS exposure, indicating that M2 macrophages might contribute to COPD through changing of phenotype and TGF-β/Smad pathway. | 1 |
Ambient particulate matter (PM) can trigger adverse reactions in the respiratory system, but less is known about the effect of indoor PM.,In this longitudinal study, we investigated the relationships between indoor PM and clinical parameters in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Indoor air quality (PM2.5 and PM10 levels) was monitored in the patients’ bedroom, kitchen, living room, and front door at baseline and every two months for one year.,At each home visit, the patients were asked to complete spirometry and questionnaire testing.,Exacerbations were assessed by chart review and questionnaires during home visits.,Generalized estimating equation (GEE) analysis (n = 83) showed that the level of wheezing was significantly higher in patients whose living room and kitchen had abnormal (higher than ambient air quality standards in Taiwan) PM2.5 and PM10 levels.,Patients who lived in houses with abnormal outdoor PM2.5 levels had higher COPD Assessment Test scores (physical domain), and those who lived in houses with abnormal PM10 levels in the living room and kitchen had higher London Chest Activity of Daily Living scores.,Increased PM levels were associated with worse respiratory symptoms and increased risk of exacerbation in patients with moderate to very severe COPD. | Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | 1 |
The prevalence of chronic obstructive pulmonary disease (COPD) in Anhui Province of eastern China remain uncertain.,The present study provides the first estimate of the prevalence and risk factors of COPD in Anhui.,A population-based survey was conducted in a representative sample of population aged 40 years or older in 2015.,COPD was diagnosed based on 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,A total of 2770 participants had reliable post-bronchodilator results and were included in the final analysis.,The overall prevalence of COPD was 9.8% (95% CI: 8.2, 11.7).,Prevalence was higher in men (14.8, 95% CI: 12.6, 17.2) than it was in women (5.2, 95% CI: 3.1, 8.7).,Among adults with COPD, 45.0% (95% CI: 39.1, 51.0) had moderate or severe disease (GOLD stage II-IV), 0.7% (95% CI: 0.2, 2.9) reported that they had a previous pulmonary function test, and only 0.4% (95% CI: 0.1, 2.6) knew their diagnosis of COPD.,Risk factors for COPD included older age (OR 1.06, 95% CI: 1.04, 1.08), male sex (OR 2.01, 95% CI: 1.22, 3.33), current smoking status (OR 2.63, 95% CI: 1.86, 3.73), primary school or lower education (OR 1.61, 95% CI: 1.12, 2.31), family history of lung disease (OR 1.50, 95% CI: 1.17, 1.93), and indoor exposure to coal for cooking or heating (OR 1.55, 95% CI: 1.11, 2.15).,In addition, people in north region has a significantly higher risk for developing COPD than people in south region of Anhui (OR 1.98, 95% CI:1.44, 2.71).,COPD is prevalent in Anhui and the prevalence is highest in north region.,Strategies aiming at prevention, early detection and treatment of COPD are urgently needed to reduce COPD-related burden.,The online version of this article (10.1186/s12890-019-0864-0) contains supplementary material, which is available to authorized users. | In patients with chronic obstructive pulmonary disease (COPD), the extent of physical activity (PA) is correlated with disease severity and prognosis.,However, factors associated with low-level PA in elderly COPD patients are not known.,We assessed the levels of PA and clinical factors associated with low-level of PA in elderly COPD patients.,This was a secondary analysis of a multicenter, prospective study of 245 patients with COPD.,Among them, 160 patients with 65 years or more were included.,Three PA groups were defined with respect to daily activity time (low, moderate, and high).,Health related quality of life (HRQL) was measured using St.,George’s respiratory questionnaire (SGRQ) and 36-item short-form health survey.,Anxiety and depression status were assessed employing the hospital anxiety and depression scale (HADS).,Multivariate logistic regression was performed to identify independent predictors of low-level PA in elderly COPD patients.,Of all the 160 patients, 103 (64.4%) engaged in low-level PA.,Upon univariate analysis, a decreased exercise capacity (6-minute walk test < 250 m), an increased dyspnea (the modified medical research council [MMRC] dyspnea scale ≥ 2), a decreased HRQL (total SGRQ score), and a presence of depression (HADS-D ≥ 8) were significantly associated with low-level PA.,Upon multivariate analysis, an MMRC grade ≥ 2 (hazard ratio [HR], 2.550; p = 0.034), and HADS-D ≥ 8 (HR, 2.076; p = 0.045) were independently associated with low-level PA in elderly COPD patients.,Two-thirds of elderly patients with COPD reported low-level of PA.,More severe dyspnea and a presence of depression were independently associated with low-level PA in elderly COPD patients. | 1 |
Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | Exercise intolerance, exertional dyspnea, reduced health-related quality of life, and acute exacerbations are features characteristic of chronic obstructive pulmonary disease (COPD).,Patients with a primary diagnosis of COPD often report comorbidities and other secondary manifestations, which diversifies the clinical presentation.,Pulmonary rehabilitation that includes whole body exercise training is a critical part of management, and core programs involve endurance and resistance training for the upper and lower limbs.,Improvement in maximal and submaximal exercise capacity, dyspnea, fatigue, health-related quality of life, and psychological symptoms are outcomes associated with exercise training in pulmonary rehabilitation, irrespective of the clinical state in which it is commenced.,There may be benefits for the health care system as well as the individual patient, with fewer exacerbations and subsequent hospitalization reported with exercise training.,The varying clinical profile of COPD may direct the need for modification to traditional training strategies for some patients.,Interval training, one-legged cycling (partitioning) and non-linear periodized training appear to be equally or more effective than continuous training.,Inspiratory muscle training may have a role as an adjunct to whole body training in selected patients.,The benefits of balance training are also emerging.,Strategies to ensure that health enhancing behaviors are adopted and maintained are essential.,These may include training for an extended duration, alternative environments to undertake the initial program, maintenance programs following initial exercise training, program repetition, and incorporation of approaches to address behavioral change.,This may be complemented by methods designed to maximize uptake and completion of a pulmonary rehabilitation program. | 1 |
There is an ongoing demand for easily accessible biomarkers that reflect the physiological and pathophysiological mechanisms of COPD.,To test if an exercise challenge could help to identify clinically relevant metabolic biomarkers in COPD.,We performed two constant-load exercise challenges separated by 4 weeks including smokers with COPD (n=23/19) and sex- and age-matched healthy smokers (n=23/20).,Two hours after a standardized meal venous blood samples were obtained before, 5 mins after the start, at the end of submaximal exercise, and following a recovery of 20 mins.,Data analysis was performed using mixed- effects model, with the metabolite level as a function of disease, time point and interaction terms and using each individual's resting level as reference.,Exercise duration was longer in healthy smokers but lactate levels were comparable between groups at all four time points.,Glucose levels were increased in COPD.,Glutamine was lower, while glutamate and arginine were higher in COPD.,Branched-chain amino acids showed a stronger decline during exercise in healthy smokers.,Carnitine and the acyl-carnitines C16 and C18:1 were increased in COPD.,These metabolite levels and changes were reproducible in the second challenge.,Higher serum glucose, evidence for impaired utilization of amino acids during exercise and a shift of energy metabolism to enhanced consumption of lipids could be early signs for a developing metabolic syndrome in COPD.,In COPD patients, deviations of energy and nitrogen metabolism are amplified by an exercise challenge. | Caveolae are vesicular invaginations of the plasma membrane.,Caveolin-1 is the structural protein component of caveolae.,Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signaling molecules within caveolar membranes.,Cigarette smoke, a source of oxidants, is an environmental hazard that causes pulmonary emphysema.,Recently, we reported that the development of cigarette smoking-induced pulmonary emphysema was inhibited in caveolin-1 null mice, which do not express caveolin-1.,We demonstrated that lack of caveolin-1 expression in lung fibroblasts dramatically inhibited premature senescence induced by oxidants contained in cigarette smoke.,Mechanistically, we uncovered that premature senescence of lung fibroblasts induced by oxidative stress occurred through activation of an ataxia telangiectasia-mutated (ATM)/p53-depedent pathway following sequestration of the catalytic subunit of protein phosphatase 2A (PP2A-C), an inhibitor of ATM, by caveolin-1 into caveolar membranes.,We propose caveolin-1 as a key player of a novel signaling pathway that links cigarette smoke to premature senescence of lung fibroblasts and development of pulmonary emphysema. | 1 |
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. | Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD. | 1 |
In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear.,Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen.,We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD.,Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality.,A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD.,Patients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047).,MBL deficiency did not affect rate of FEV1 decline or mortality.,In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp.,There were lower levels of airway inflammation in patients with MBL deficiency.,Patients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota.,This is the first study to identify a genetic association with the lung microbiota in COPD. | The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD.,We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts.,We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653).,All samples were collected from clinically stable participants upon entry into both studies.,IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L.,To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders.,One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively.,Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results.,Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization.,In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts.,Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies.,Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts.,This study used serum samples from participants of the MACRO (NCT00325897) and STATCOPE (NCT01061671) trials.,The online version of this article (10.1186/s12931-018-0733-z) contains supplementary material, which is available to authorized users. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | The GOLD guidelines suggest that the presence of a post-bronchodilator forced expiratory volume in one second (FEV1) < 80% of the predicted value in combination with a FEV1/forced vital capacity (FVC) < 70% confirms the diagnosis of COPD.,Limited data exist regarding the accuracy of these criteria to distinguish between COPD and asthma.,The aim of this study therefore was to investigate the diagnostic value of post-bronchodilator lung function parameters in obstructive lung disease.,The pulmonary function tests of 43 (22 = COPD, 21 = asthma) patients with similar baseline characteristics were evaluated (baseline FEV1 were 55.7% ± 7.6%, and 59.3% ± 8.4% predicted for COPD and asthma, respectively).,Bronchodilator responsiveness (BDR) was calculated according to three recognized pulmonary function test criteria.,The first criteria, post-bronchodilator FEV1 < 80% of the predicted value in combination with a post-bronchodilator FEV1/FVC ratio of <70%, had an accuracy of 70% to diagnose COPD.,This combination was very sensitive (100%) in diagnosing COPD, but it was not specific (38%).,The second BDR criteria, defined as an increase of <12% and 200 mL of initial FEV1 and criterion number 3, an increase of < 9% of predicted FEV1, were less sensitive (55% and 59%, respectively), but more specific (81% and 76% respectively) to diagnose COPD.,Our findings suggest that the current recommended spirometric indices are not optimal in differentiating between COPD and asthma. | 1 |
Background: Inhaled corticosteroid (ICS)-containing medications slow rate of decline of FEV1.,Blood eosinophil (EOS) levels are associated with the degree of exacerbation reduction with ICS.,Purpose: We investigated whether FEV1 decline differs between patients with and without ICS, stratified by blood EOS level.,Patients and methods: The UK Clinical Practice Research Datalink (primary care records) and Hospital Episode Statistics (hospital records) were used to identify COPD patients aged 35 years or older, who were current or ex-smokers with ≥2 FEV1 measurements ≥6 months apart.,Prevalent ICS use and the nearest EOS count to start of follow-up were identified.,Patients were classified at baseline as higher stratum EOS (≥150 cell/µL) on ICS; higher stratum EOS not on ICS; lower stratum EOS (<150 cells/µL) on ICS; and lower stratum EOS not on ICS.,In addition, an incident ICS cohort was used to investigate the rate of FEV1 change by EOS and incident ICS use.,Mixed-effects linear regression was used to compare rates of FEV1 change in mL/year.,Results: A total of 26,675 COPD patients met our inclusion criteria (median age 69, 46% female).,The median duration of follow up was 4.2 years.,The rate of FEV1 change in prevalent ICS users was slower than non-ICS users (−12.6 mL/year vs −21.1 mL/year; P =0.001).,The rate of FEV1 change was not significantly different when stratified by EOS level.,The rate of FEV1 change in incident ICS users increased (+4.2 mL/year) vs −21.2 mL/year loss in non-ICS users; P<0.001.,In patients with high EOS, incident ICS patients showed an increase in FEV1 (+12 mL/year) compared to non-ICS users whose FEV1 decreased (−20.8 mL/year); P<0.001.,No statistical difference was seen in low EOS patients.,Incident ICS use is associated with an improvement in FEV1 change, however, over time this association is lost.,Conclusion: Regardless of blood EOS level, prevalent ICS use is associated with slower rates of FEV1 decline in COPD. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
Despite the positive impact of Palliative Care (PC) on the quality of life for patients and their relatives, the implementation of PC in non-cancer health-care delivery in the EU seems scarcely addressed.,The aim of this study is to assess guidelines/pathways for integrated PC in patients with advanced Chronic Heart Failure (CHF) and Chronic Obstructive Pulmonary Disease (COPD) in Europe via a systematic literature review.,Search results were screened by two reviewers.,Eligible studies of adult patients with CHF or COPD published between 01/01/1995 and 31/12/2013 in Europe in 6 languages were included.,Nine electronic databases were searched, 6 journals were hand-searched and citation tracking was also performed.,For the analysis, a narrative synthesis was employed.,The search strategy revealed 26,256 studies without duplicates.,From these, 19 studies were included in the review; 17 guidelines and 2 pathways. 18 out of 19 focused on suffering reduction interventions, 13/19 on a holistic approach and 15/19 on discussions of illness prognosis and limitations.,The involvement of a PC team was mentioned in 13/19 studies, the assessment of the patients’ goals of care in 12/19 and the advance care planning in 11/19.,Only 4/19 studies elaborated on aspects such as grief and bereavement care, 7/19 on treatment in the last hours of life and 8/19 on the continuation of goal adjustment.,The results illustrate that there is a growing awareness for the importance of integrated PC in patients with advanced CHF or COPD.,At the same time, however, they signal the need for the development of standardized strategies so that existing barriers are alleviated. | Despite a well-recognised burden of disabling physical symptoms compounded by co-morbidities, psychological distress and social isolation, the needs of people with severe chronic obstructive pulmonary disease (COPD) are typically poorly addressed.,To assess the effectiveness of interventions designed to deliver holistic care for people with severe COPD.,We searched 11 biomedical databases, three trial repositories (January 1990-March 2012; no language restrictions) and contacted international experts to locate published, unpublished and in-progress randomised controlled trials (RCTs), quasi-RCTs and controlled clinical trials (CCTs) that investigated holistic interventions to support patients with severe COPD in any healthcare context.,The primary outcome was health-related quality of life (HRQoL).,Quality assessment and data extraction followed Cochrane Collaboration methodology.,We used a piloted data extraction sheet and undertook narrative synthesis.,From 2,866 potentially relevant papers, we identified three trials: two RCTs (from United States and Australia), and one CCT (from Thailand): total 216 patients.,Risk of bias was assessed as moderate in two studies and high in the third.,All the interventions were led by nurses acting in a co-ordinating role (e.g. facilitating community support in Thailand, providing case-management in the USA, or co-ordinating inpatient care in Australia).,HRQoL improved significantly in the Thai CCT compared to the (very limited) usual care (p<0.001), in two sub-domains in the American trial, but showed no significant changes in the Australian trial.,Exercise tolerance, dyspnoea, and satisfaction with care also improved in the Thai trial.,Some 15 years after reports first highlighted the unmet needs of people with severe COPD, we have been unable to find robust trial evidence about interventions that can address those needs.,There is an urgent need to develop and evaluate holistic care interventions designed improve HRQoL for people with severe COPD.,PROSPERO (CRD42012002430). | 1 |
The mechanisms underlying airflow obstruction in COPD cannot be distinguished by standard spirometry.,We ascertain whether mathematical modeling of airway biomechanical properties, as assessed from spirometry, could provide estimates of emphysema presence and severity, as quantified by computed tomography (CT) metrics and CT-based radiomics.,We quantified presence and severity of emphysema by standard CT metrics (VIDA) and co-registration analysis (ImbioLDA) of inspiratory-expiratory CT in 194 COPD patients who underwent pulmonary function testing.,According to percentages of low attenuation area below − 950 Hounsfield Units (%LAA-950insp) patients were classified as having no emphysema (NE) with %LAA-950insp < 6, moderate emphysema (ME) with %LAA-950insp ≥ 6 and < 14, and severe emphysema (SE) with %LAA-950insp ≥ 14.,We also obtained stratified clusters of emphysema CT features by an automated unsupervised radiomics approach (CALIPER).,An emphysema severity index (ESI), derived from mathematical modeling of the maximum expiratory flow-volume curve descending limb, was compared with pulmonary function data and the three CT classifications of emphysema presence and severity as derived from CT metrics and radiomics.,ESI mean values and pulmonary function data differed significantly in the subgroups with different emphysema degree classified by VIDA, ImbioLDA and CALIPER (p < 0.001 by ANOVA).,ESI differentiated NE from ME/SE CT-classified patients (sensitivity 0.80, specificity 0.85, AUC 0.86) and SE from ME CT-classified patients (sensitivity 0.82, specificity 0.87, AUC 0.88).,Presence and severity of emphysema in patients with COPD, as quantified by CT metrics and radiomics can be estimated by mathematical modeling of airway function as derived from standard spirometry.,The online version of this article (10.1186/s12931-019-1049-3) contains supplementary material, which is available to authorized users. | The objective of this study was to investigate the relationship between the extent of emphysema and heart size in patients with chronic obstructive pulmonary disease (COPD) using inspiratory and expiratory chest computed tomography (CT).,This retrospective study was approved by the institutional review board and informed consent was waived.,We measured lung volume (LV), low attenuation area percent (%LAA; less than or equal to −950 HU), maximum cardiac area, and maximum transverse cardiac diameter on inspiratory/expiratory chest CT in 60 patients with COPD.,Spearman rank correlation analysis was used to determine the correlations between the heart and lung CT measurements, and the correlations between these measurements and spirometric values.,On inspiratory CT, the maximum transverse cardiac diameter was negatively correlated with LV (ρ = −0.42; p < 0.01) and %LAA (ρ = −0.43; p < 0.001).,Furthermore, on expiratory CT, the maximum cardiac area was negatively correlated with LV (ρ = −0.35; p < 0.01) and %LAA (ρ = −0.37; p < 0.01), and there was a negative correlation between transverse cardiac diameter and %LAA (ρ = −0.34; p < 0.01).,Although inspiratory cardiac size was not correlated with any of the spirometric values, the maximum cardiac area and transverse diameter on expiratory scans were significantly correlated with the reduced airflow values on spirometry (p < 0.01).,In patients with COPD, the transverse cardiac diameter decreased as the emphysema progressed.,A smaller cardiac area on expiratory CT suggested the presence of large LVs, emphysema, and airflow limitation in COPD. | 1 |
Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases.,However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood.,Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes.,There are few data on regional methylation changes in relation to smoking.,Few data link differential methylation in blood to differential gene expression in lung tissue.,We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing corrected p < 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip.,Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking.,Of the 87 DMRs, 66 were mapped to novel loci.,Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs.,Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank, n = 188).,Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking.,Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease.,The online version of this article (doi:10.1186/s13148-016-0266-6) contains supplementary material, which is available to authorized users. | Dysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD).,Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll-like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling.,While the role of TLR single nucleotide polymorphisms is increasingly recognized in inflammatory diseases, TLR single nucleotide polymorphisms in COPD have only recently been explored.,We hypothesized that specific TLR polymorphisms are associated with dysfunctional innate immune COPD alveolar macrophage responses and investigated polymorphisms of TLR2(Arg753Gln), TLR4(Thr399Ile; Asp299Gly), and TLR9(T1486C; T1237C).,DNA was purified from cells of 1) healthy nonsmokers (n = 20); 2) COPD ex-smokers (n = 83); 3) COPD active smokers (n = 93).,DNA amplifications (polymerase chain reaction) were performed for each SNP.,Alveolar macrophages from each group were incubated with nontypeable H. influenzae, M. catarrhalis and S. pneumoniae.,Cytokine induction of macrophage supernatants was measured and the association with TLR single nucleotide polymorphism expression was determined.,No significant inter-group differences in frequency of any TLR SNP existed.,However both TLR9 single nucleotide polymorphisms were expressed in high frequency.,Among COPD ex-smokers, diminished IL-8 responsiveness to nontypeable H. influenzae, M. catarrhalis and S. pneumoniae was strongly associated with carriage of TLR9(T1237C) (p = 0.02; p = 0.008; p = 0.02), but not TLR9(T1486C).,Carriage of TLR9(T1237C), but not TLR9(T1486C), correlated with diminished FEV1%predicted (p = 0.037).,Our results demonstrate a notable association of TLR9(T1237C) expression with dysfunctional innate alveolar macrophage responses to respiratory pathogens and with severity of COPD. | 1 |
Cigarette smoke (CS) induces lung cellular senescence that plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,How aging influences cellular senescence and other molecular hallmarks, and increases the risk of CS-induced damage remains unknown.,We hypothesized that aging-associated changes in lungs worsen the COPD/emphysema by CS exposure.,Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls.,CS caused a decline in lung function and affected the lung structure of both groups of mice.,No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation.,Aging per se increased lung cellular senescence and significant changes in damage-associated molecular patterns marker S100A8.,Gene transcript analysis using the nanoString nCounter showed a significant upregulation of key pro-senescence targets by CS (Mmp12, Ccl2, Cdkn2a, Tert, Wrn, and Bub1b).,Aging independently influenced lung function and structure, as well as increased susceptibility to CS-induced inflammation in emphysema, but had a negligible effect on cellular senescence.,Thus, aging solely does not contribute to the induction of cellular senescence by CS in a mouse model of COPD/emphysema. | Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema.,In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations.,Six unused donor lungs served as controls.,Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1).,The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate.,The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09).,The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1).,An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05).,TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05).,A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r2 = 0.8).,A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r2 = 0.99),Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease.,The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease.,Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types. | 1 |
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). | In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD).,The aim of this study was to analyze this overlap phenotype of asthma with COPD feature.,A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV1) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled.,Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV1/forced vital capacity (FVC) <70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up.,We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data.,All of the tests mentioned above were performed within one week.,The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV1/FVC ≥70) and overlap group (38%, n=97, postbronchodilator FEV1/FVC <70).,The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group.,Significantly lower FEV1 and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group.,Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group.,Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible.,The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations.,Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD.,Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective.,Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.,This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed.,A number of studies have evaluated the accuracy of screening tests for COPD, but their findings have not been formally summarised.,We therefore sought to determine and compare the diagnostic accuracy of such screening tests in primary care.,Systematic review and meta-analysis of the diagnostic accuracy of screening tests for COPD confirmed by spirometry in primary care.,We searched MEDLINE, EMBASE and other bibliographic databases from 1997 to 2013 for diagnostic accuracy studies that evaluated 1 or more index tests in primary care among individuals aged ≥35 years with no prior diagnosis of COPD.,Bivariate meta-analysis of sensitivity and specificity was performed where appropriate.,Methodological quality was assessed independently by 2 reviewers using the QUADAS-2 tool.,10 studies were included. 8 assessed screening questionnaires (the COPD Diagnostic Questionnaire (CDQ) was the most evaluated, n=4), 4 assessed handheld flow meters (eg, COPD-6) and 1 assessed their combination.,Among ever smokers, the CDQ (score threshold ≥19.5; n=4) had a pooled sensitivity of 64.5% (95% CI 59.9% to 68.8%) and specificity of 65.2% (52.9% to 75.8%), and handheld flow meters (n=3) had a sensitivity of 79.9% (95% CI 74.2% to 84.7%) and specificity of 84.4% (68.9% to 93.0%).,Inadequate blinding between index tests and spirometry was the main risk of bias.,Handheld flow meters demonstrated higher test accuracy than the CDQ for COPD screening in primary care.,The choice of alternative screening tests within whole screening programmes should now be fully evaluated.,CRD42012002074. | It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD).,We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use.,We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno.,We defined COPD as a post-bronchodilator FEV1/FVC < 70%.,Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001).,Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%).,Rather, we found that PARs of COPD varied by setting.,In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively).,In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%.,The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking.,This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas. | 1 |
Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).,Data were pooled from clinical studies of 3-12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214).,Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.,The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments.,The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo.,COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo.,Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses.,Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol.,The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07-0.660], P = 0.008).,Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD. | Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD).,This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD.,Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms).,Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs.,Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150 μg o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study.,Trough FEV1 (LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p < 0.001).,Trough FEV1 after one dose was significantly higher with indacaterol than placebo (p < 0.001).,Indacaterol demonstrated significantly higher peak FEV1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p < 0.001) and 160 ± 28 mL (p < 0.001), respectively.,Standardised AUC measurements for FEV1 (between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose) at Week 12 were all significantly greater with indacaterol than placebo (p < 0.001), with LSM (± SEM) differences of 170 ± 24, 180 ± 24, and 170 ± 24 mL, respectively.,Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p < 0.001) and was also associated with significantly reduced use of rescue medication (p < 0.001).,The overall rates of AEs were comparable between the groups (indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%).,One patient died in the placebo group.,Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms.,Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo.,NCT00624286 | 1 |
Genome-wide association studies (GWAS) and candidate gene studies have identified a number of risk loci associated with the smoking-related disease COPD, a disorder that originates in the airway epithelium.,Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome, enriched, in part, at known GWAS/candidate gene loci.,Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n = 10) and healthy smokers (n = 7).,The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS to confer risk for COPD.,Smoker BC have 676 genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation.,Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10−4 compared to chance), including 4 genes (NFKBIB, LTBP4, EGLN2 and TGFB1) associated with risk for COPD.,These observations provide the first direct connection between known genetic risks for smoking-related lung disease and airway BC, the population of lung cells that undergo the earliest changes associated with smoking. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Self-management of exacerbations in COPD patients is important to reduce exacerbation impact.,There is a need for more comprehensive and individualized interventions to improve exacerbation-related self-management behavior.,The use of mobile health (mHealth) could help to achieve a wide variety of behavioral goals.,Understanding of patients and health care providers perspectives towards using mHealth in promoting self-management will greatly enhance the development of solutions with optimal usability and feasibility.,Therefore, the aim of this study was to explore perceptions of COPD patients and their health care providers towards using mHealth for self-management of exacerbations.,A qualitative study using focus group interviews with COPD patients (n = 13) and health care providers (HCPs) (n = 6) was performed to explore perceptions towards using mHealth to support exacerbation-related self-management.,Data were analyzed by a thematic analysis.,COPD patients and HCPs perceived mostly similar benefits and barriers of using mHealth for exacerbation-related self-management.,These perceived benefits and barriers seem to be important drivers in the willingness to use mHealth.,Both patients and HCPs strengthen the need for a multi-component and tailored mHealth intervention that improves patients’ exacerbation-related self-management by determining their health status and providing adequate information, decision support and feedback on self-management behavior.,Most importantly, patients and HCPs considered an mHealth intervention as support to improve self-management and emphasized that it should never replace patients’ own feelings nor undermine their own decisions.,In addition, the intervention should be complementary to regular contact with HCPs, as personal contact with a HCP was considered to be very important.,To optimize engagement with mHealth, patients should have a positive attitude toward using mHealth and an mHealth intervention should be attractive, rewarding and safe.,This study provided insight into perceptions of COPD patients and their HCPs towards using mHealth for self-management of exacerbations.,This study points out that future mHealth interventions should focus on developing self-management skills over time by providing adequate information, decision support and feedback on self-management behavior and that mHealth should complement regular care.,To optimize engagement, mHealth interventions should be attractive, rewarding, safe and tailored to the patient needs.,The online version of this article (10.1186/s12913-018-3545-4) contains supplementary material, which is available to authorized users. | Telerehabilitation (TR) aimed at patients with COPD has shown promising effects on symptoms, physical function, and quality of life, but little research has been conducted to understand the impact of implementation on frontline health professionals.,Therefore, the aim of this study was to examine the barriers and enablers of health professionals to online exercise-based TR in patients with COPD, to support a successful implementation process.,Semistructured individual and focus group interviews were conducted with 25 health professionals working with conventional COPD rehabilitation or TR.,Interviews were audio-taped and transcribed verbatim.,Investigator triangulation was applied during data generation.,The Theoretical Domains Framework directed the interview guide and was used as a coding framework in the analysis.,We identified six predominant domains essential in understanding the enablers and barriers of TR from a staff perspective: 1) skills, 2) professional role and identity, 3) beliefs about capabilities, 4) beliefs about consequences, 5) environmental context and resources, and 6) social influences.,We found that health professionals held both enablers and barriers important for the implementation process of TR.,TR introduces new work tasks and new ways for the health professionals to communicate and exercise with the patients, which influence their professional role and self-perceived capability.,Specific attention toward involvement of the health professionals in the decision process combined with sufficient education and skill training is highly essential to support a successful implementation of TR in clinical practice. | 1 |
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | 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 |
Patients with COPD might not report mild exacerbation.,The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown.,The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD.,An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities.,This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311).,Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year.,Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year.,Findings of the COPD assessment test and the symptom component of the St George’s Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them.,Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to ≥2 per year.,The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD. | Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease.,To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations.,This was a 2-year prospective cohort study of COPD patients.,Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared.,Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002).,For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001).,Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation.,In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices. | 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. | Acute exacerbations of COPD are a major cause of morbidity and mortality.,Bacteria are implicated in about half of all cases.,The frequency of exacerbations is related to decline in lung function and poorer quality of life. 25% of patients with COPD have bacterial colonization of the lower airways in stable state whereas non-smokers without COPD have airways that are sterile.,The significance of the colonization is unclear, but there is emerging evidence that it may be detrimental.,Much of the data recommending antibiotic treatment are based on findings more than 10 years old and do not take into account emerging bacterial resistance.,This article reviews these data and that from newer antibiotic trials.,It also reviews current antibiotic prescribing guidelines from major respiratory societies around the world.,Recent antibiotic trials have compared fluoroquinolones with “standard” antibiotics and found, in the main, longer exacerbation-free intervals and better bacterial eradication rates in those treated with fluoroquinolones. | 1 |
N-Acetylcysteine (NAC) demonstrates applications in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD).,COPD is often characterized by fibrosis of the small airways.,This study aims at investigating the physiological mechanisms by which NAC might mediate the pulmonary fibrosis in COPD.,A total of 10 non-smokers without COPD and 10 smokers with COPD were recruited in this study, and COPD rat models were established.,Cigarette smoke extract (CSE) cell models were constructed.,The gain- or loss-of-function experiments were adopted to determine the expression of VWF and the extent of p38 MAPK phosphorylation, levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and immunoglobulins (IgG, IgM and IgA) in the serum of COPD rats and supernatant of alveolar epithelial cells and to detect cell invasion and migration and the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes.,Expression of VWF and the extent of p38 MAPK phosphorylation were increased in COPD.,NAC inhibited p38 MAPK phosphorylation by reducing the VWF expression.,NAC could inhibit cell migration and invasion, elevate E-cadherin expression, the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes, and levels of IgG, IgA, and IgM, and reduce N-cadherin expression and levels of IL-6 and TNF-α in CSE cells and serum of COPD rats.,NAC promoted immune response and suppressed epithelial-mesenchymal transformation (EMT) to relieve COPD-induced pulmonary fibrosis in vitro and in vivo by inhibiting the VWF/p38 MAPK axis.,Collectively, NAC could ameliorate COPD-induced pulmonary fibrosis by promoting immune response and inhibiting EMT process via the VWF/p38 MAPK axis, therefore providing us with a potential therapeutic target for treating COPD.,The online version contains supplementary material available at 10.1186/s10020-021-00342-y. | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 1 |
Chronic obstructive pulmonary disease (COPD) is 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. | Acute Exacerbations of COPD (AECOPD) identified from electronic healthcare records (EHR) are important for research, public health and to inform healthcare utilisation and service provision.,However, there is no standardised method of identifying AECOPD in UK EHR.,We aimed to validate the recording of AECOPD in UK EHR.,We randomly selected 1385 patients with COPD from the Clinical Practice Research Datalink.,We selected dates of possible AECOPD based on 15 different algorithms between January 2004 and August 2013.,Questionnaires were sent to GPs asking for confirmation of their patients’ AECOPD on the dates identified and for any additional relevant information.,Responses were reviewed independently by two respiratory physicians.,Positive predictive value (PPV) and sensitivity were calculated.,The response rate was 71.3%.,AECOPD diagnostic codes, lower respiratory tract infection (LRTI) codes, and prescriptions of antibiotics and oral corticosteroids (OCS) together for 5-14 days had a high PPV (>75%) for identifying AECOPD.,Symptom-based algorithms and prescription of antibiotics or OCS alone had lower PPVs (60-75%).,A combined strategy of antibiotic and OCS prescriptions for 5-14 days, or LRTI or AECOPD code resulted in a PPV of 85.5% (95% CI, 82.7-88.3%) and a sensitivity of 62.9% (55.4-70.4%).,Using a combination of diagnostic and therapy codes, the validity of AECOPD identified from EHR can be high.,These strategies are useful for understanding health-care utilisation for AECOPD, informing service provision and for researchers.,These results highlight the need for common coding strategies to be adopted in primary care to allow easy and accurate identification of events. | 1 |
There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations.,The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls.,Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients.,Performance was assessed using an independent validation set of patients who were not included in the discovery set.,Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time.,Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80).,These data were replicated in a validation cohort with an AUC of 0.88.,A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD. | Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations.,Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.,Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations.,The bacteria were identified by the semiquantitative culture of the expectorated sputum.,The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.,Viruses were isolated from 16 (22.2%) of the 72 patients enrolled.,The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus.,A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae.,Five patients (6.9%) had both positive sputum cultures and virus identification.,The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different.,Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.,WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits.,Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD).,We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD.,Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients.,Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models.,Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells.,None of the TLR4 SNPs was associated with FEV1 level.,Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time.,This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD. | 1 |
Exposure to air pollution is associated with chronic obstructive pulmonary disease (COPD).,However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce.,This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China.,We enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China.,Follow-ups were performed every 3 months for each participant.,Serum levels of 20 cytokines were detected every 6 months.,Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing.,Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures.,A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up.,A total of 84 COPD patients were enrolled at baseline.,Of those, 75 COPD patients completed the first-year of follow-up.,We found adverse cumulative effects of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD.,Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L).,Acute exposures to PM2.5, NO2, SO2 and CO were associated with a reduction in FVC % pred in COPD patients.,Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines. | Chronic obstructive pulmonary disease (COPD) has become one of the major public health problems worldwide due to its high morbidity and mortality.,Up until now, COPD is still under-diagnosed and under-treated, especially for mild or moderate patients.,It is widely accepted that the majority of patients with COPD are in the early stages, yet this subpopulation is underestimated.,In recent years, growing evidence indicates that substantial physiological and clinical abnormalities exist in patients with mild COPD compared with healthy controls.,Furthermore, recent studies suggest that pharmacologic intervention in early COPD has the potential to alter clinical outcomes.,The main objective of this review is to summarize recent research regarding the heterogeneous pathophysiology, clinical features, and treatment of mild and moderate COPD.,We also discuss promising markers of disease progression, which may contribute to the development of precision medicine in early COPD. | 1 |
Objective.,Several studies have evaluated the association between CYP1A1 polymorphisms and the susceptibility of chronic obstructive pulmonary disease (COPD) with inconclusive results.,We performed the first comprehensive meta-analysis to summarize the association between CYP1A1 polymorphisms and COPD risk.,Method.,A systematic literature search was conducted (up to April 2015) in five online databases: PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WeiPu, and WanFang databases.,The strength of association was calculated by odds ratio (OR) and corresponding 95% confidence interval (CI).,Results.,Seven case-control studies with 1050 cases and 1202 controls were included.,Our study suggested a significant association between the MspI polymorphism and COPD risk (CC versus TC + TT: OR = 1.57, CI: 1.09-2.26, P = 0.02; CC versus TT: OR = 1.73, CI: 1.18-2.55, P = 0.005).,For the Ile/Val polymorphism, a significant association with COPD risk was observed (GG versus AG + AA: OR = 2.75, CI: 1.29-5.84, P = 0.009; GG versus AA: OR = 3.23, CI: 1.50-6.93, P = 0.003; AG versus AA: OR = 1.39, CI: 1.01-1.90, P = 0.04).,Subgroup analysis indicated a significant association between the MspI variation and COPD risk among Asians (CC versus TC + TT: OR = 1.70, CI: 1.06-2.71, P = 0.03; CC versus TT: OR = 1.84, CI: 1.11-3.06, P = 0.02).,Conclusion.,The MspI and Ile/Val polymorphisms might alter the susceptibility of COPD, and MspI polymorphism might play a role in COPD risk among Asian population. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Pulmonary rehabilitation is effective in all stages of COPD.,The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden.,Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers.,Multivariable logistic regression examined associations with having received rehabilitation in the previous year.,In primary care, nurse-based asthma/COPD clinics were common (87%), with additional separate access to other rehabilitation professionals.,In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%).,In total, 36% of the patients met an asthma/COPD nurse in the previous year.,Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%), occupational therapists (3% vs 10%), nutritionists (5% vs 13%), and counselors (1% vs 4%).,A higher COPD Assessment Test score and frequent exacerbations were associated with higher utilization of all rehabilitation professionals.,Pulmonary rehabilitation resources are available but underutilized, and receiving rehabilitation is more common in severe COPD.,Treatment recommendations need to be better implemented, especially in mild and moderate COPD. | Objective To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients’ management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice.,Design 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial.,Setting 15 general practices in the eastern part of the Netherlands.,Participants Patients with COPD confirmed by spirometry and treated in general practice.,Patients with very severe COPD or treated by a respiratory physician were excluded.,Interventions A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients’ own initiative).,Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score.,Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale.,Results 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55).,At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant.,Secondary outcomes did not differ, except for exacerbation management.,Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58).,Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice.,Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group.,Trial registration Clinical trials NCT00128765. | 1 |
There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages.,Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease.,This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.,Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls.,However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials.,Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.,The online version of this article (10.1186/s12931-019-1108-9) contains supplementary material, which is available to authorized users. | Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia.,This study assessed the risk of pneumonia associated with ICS in patients with COPD.,Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014).,Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed.,Patients were categorized by airflow limitation severity.,A total of 6623 patients with COPD and 48,566 controls were analyzed.,Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06).,ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS.,Asthma was an independent risk factor for pneumonia in the COPD population.,Multivariate analysis identified independent predictors of pneumonia in the overall population.,The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62).,Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further. | 1 |
A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear.,Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable.,To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases.,We recruited 59 outpatients with MetS and 76 outpatients with COPD.,After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29).,A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%.,More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease.,MetS+COPD patients exhibited significantly higher C-peptide levels.,We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers.,Finally, a negative association emerged between smoking and vitamin D.,We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance.,Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development. | Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α).,Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH).,The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD).,The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.,We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls.,COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema).,Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.,Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001).,A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001).,Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).,Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD.,Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later. | 1 |
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. | Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown.,We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS.,CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells.,CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium.,CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice.,The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis.,Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages.,These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers. | 1 |
It has been scientifically proven that pulmonary rehabilitation improves exercise tolerance and facilitates the carrying out of daily physical activities.,To optimize the physical and physiological benefits, it is necessary to individualize the training intensity for each patient.,The aim of this study is to compare the heart rate (HR) responses to three exercise modalities measuring aerobic fitness in chronic obstructive pulmonary disease patients, in order to easily prescribe individual target HRs for endurance training.,Fifty COPD patients (mean age: 60.1±8.5 years) were included in the study.,Each patient carried out a cardiopulmonary exercise test, a 6-minute walk test (6MWT) and a 6-minute stepper test (6MST).,During these tests, HR was recorded continuously.,After the cardiopulmonary exercise test, the HR was noted at the ventilatory threshold (VT) and at the end of the two exercise field tests (6MWTpeak and 6MSTpeak).,The values of the HR during the last 3 minutes of both field tests were averaged (6MWT456 and 6MST456).,Finally, the HR at 60% of the HR reserve was calculated with the values of the HR measured during 6MWT and 6MST (HRr60%walk, HRr60%step).,The HRs measured during the 6MST were significantly higher than those measured during the 6MWT.,The HRr60%step was not significantly different from 6MWT456 and 6MWTpeak HR (P=0.51; P=0.48).,A significant correlation was observed between 6MWT456 and 6MWTpeak (r=0.58).,The 6MWT456 and 6MWTpeak HR were correlated with HRr60%step (r=0.68 and r=0.62).,The VT could be determined in 28 patients.,The HRVT was not different from 6MWT456, 6MWTpeak, and HRr60%step (P=0.57, P=0.41 and P=0.88) and was correlated to 6MWT456, 6MWTpeak, and HRr60%step (r=0.45, r=0.40, r=0.48).,An individualized target HR for endurance training can be prescribed from the HR measured during routine tests, such as 6MWT or 6MST. | Individuals with COPD may present reduced peripheral muscle strength, leading to impaired mobility.,Comprehensive pulmonary rehabilitation (PR) should include strength training, in particular to lower limbs.,Furthermore, simple tools for the assessment of peripheral muscle performance are required.,To assess the peripheral muscle performance of COPD patients by the sit-to-stand test (STST), as compared to the one-repetition maximum (1-RM), considered as the gold standard for assessing muscle strength in non-laboratory situations, and to evaluate the responsiveness of STST to a PR program.,Sixty moderate-to-severe COPD inpatients were randomly included into either the specific strength training group or into the usual PR program group.,Patients were assessed on a 30-second STST and 1-minute STST, 1-RM, and 6-minute walking test (6MWT), before and after PR.,Bland-Altman plots were used to evaluate the agreement between 1-RM and STST.,The two groups were not different at baseline.,In all patients, 1-RM was significantly related to the 30-second STST (r=0.48, P<0.001) and to 1-minute STST (r=0.36, P=0.005).,The 30-second STST was better tolerated in terms of the perceived fatigue (P=0.002) and less time consuming (P<0.001) test.,In the specific strength training group significant improvements were observed in the 30-second STST (P<0.001), 1-minute STST (P=0.005), 1-RM (P<0.001), and in the 6MWT (P=0.001).,In the usual PR program group, significant improvement was observed in the 30-second STST (P=0.042) and in the 6MWT (P=0.001).,Our study shows that in stable moderate-to-severe inpatients with COPD, STST is a valid and reliable tool to assess peripheral muscle performance of lower limbs, and is sensitive to a specific PR program. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | To establish the dose−response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulized formulation of the long acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebulizer in patients with chronic obstructive pulmonary disease (COPD).,Patients with moderate to severe COPD (GOLD II/III), with reversible lung function, were enrolled into this randomized, double-blind, placebo-controlled, six period crossover study (n = 42).,Patients received single doses of EP-101 (12.5-400 μg) and placebo via a high efficiency nebulizer (eFlow® PARI nebulizer), with washout between treatments.,Plasma pharmacokinetics were assessed in a subset of patients (n = 11).,All treatments were well tolerated with similar adverse event rates reported with placebo and at all doses.,There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval.,Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5 min.,Significant improvements in mean change from baseline FEV1 at 24 h were reported at doses ≥50 μg compared with placebo, with a clear dose−response relationship.,Mean changes in FEV1 were 0.10 l (95% CI 0.06, 0.14) and 0.12 l (95% CI 0.08, 0.16) for 100 μg and 200 μg, respectively.,Single doses of EP-101 ranging from 12.5 μg to 400 μg were well tolerated.,EP-101 delivered by high efficiency nebulizer device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 h period at all doses >50 μg. | 1 |
Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction.,Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms.,To evaluate ‘targeted lung denervation’ (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD.,This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted).,Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators.,Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD.,The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year.,Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life.,Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W).,The procedures were technically feasible 93% of the time.,Primary safety endpoint was achieved in 95%.,Asymptomatic bronchial wall effects were observed in 3 patients at 20 W.,The clinical safety profiles were similar between the two energy doses.,At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (−11.1 points ±9.1 vs −0.9 points ±8.6, p=0.044).,Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated.,Further investigation of this novel therapy is warranted.,NCT01483534. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS).,The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007.,The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS.,Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data.,We examined the baseline characteristics of these patients along with their healthcare resource utilization.,Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines.,A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results.,The adherent subgroup received COPD medications consistent with current GOLD guidelines.,Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines.,In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines.,In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines.,GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts.,Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD.,Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers. | We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | 1 |
The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear.,Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing.,The microbiome composition was analysed with QIIME.,We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera.,The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.,The online version of this article (10.1186/s12890-019-0867-x) contains supplementary material, which is available to authorized users. | 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 |
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler.,Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes.,In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated.,The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter.,Semi-structured, in-depth, qualitative interviews were carried out 2-4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI.,Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach.,Participants also rated the performance of the inhaler on several criteria, using a subjective 1-10 scale.,Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI.,It was frequently described as straightforward to operate and easy to use by interview participants.,Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler.,Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers.,Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers.,Overall average performance scores were >9 (out of 10) in participants with asthma and COPD.,The ELLIPTA DPI was associated with high patient satisfaction and was preferred to other inhalers by interview participants with asthma and COPD.,The development of an inhaler that is regarded as easy and intuitive to use may have positive implications for adherence to therapy in asthma and COPD.,Asthma: NCT01165138, NCT01431950.,COPD: NCT01053988, NCT01054885, NCT01009463, NCT01017952. | 1 |
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. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
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. | Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β2 agonists have been shown to improve COPD outcomes.,Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures.,We investigated this using record linkage in a Dundee COPD population.,A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number.,A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders.,A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias.,4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study.,There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions.,The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively.,The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation.,There was however an association with increased cataracts and pneumonia hospitalisations. | 1 |
Human lung single-cell atlas reveals the complexity and diversity of aberrant cellular populations in pulmonary fibrosis.,We provide a single-cell atlas of idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, by profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs.,Among epithelial cells enriched in IPF, we identify a previously unidentified population of aberrant basaloid cells that coexpress basal epithelial, mesenchymal, senescence, and developmental markers and are located at the edge of myofibroblast foci in the IPF lung.,Among vascular endothelial cells, we identify an ectopically expanded cell population transcriptomically identical to bronchial restricted vascular endothelial cells in IPF.,We confirm the presence of both populations by immunohistochemistry and independent datasets.,Among stromal cells, we identify IPF myofibroblasts and invasive fibroblasts with partially overlapping cells in control and COPD lungs.,Last, we confirm previous findings of profibrotic macrophage populations in the IPF lung.,Our comprehensive catalog reveals the complexity and diversity of aberrant cellular populations in IPF. | The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process.,We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state.,Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD.,Thirty-three of 56 known Wnt-related genes were expressed in the SAE.,Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes.,Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry.,Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro.,Smoking down-regulates the Wnt pathway in the human airway epithelium.,In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders. | 1 |
To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil.,This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states.,All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry.,Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels.,Those with serum AAT levels of < 113 mg/dL underwent genotyping.,In case of conflicting results, SERPINA1 gene sequencing was performed.,Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL.,Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%).,In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8%,The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | 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 |
Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible.,The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations.,Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD.,Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective.,Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.,This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD. | Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations.,We assessed risk factors for bacterial colonisation in COPD.,Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis.,Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥102 colony-forming units (CFU)/mL on quantitative bacterial culture.,Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load.,A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated.,Bacterial colonisation was demonstrated in 58 (48.7%) patients.,Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour.,Thirty-six patients (62% of those colonised) had a high bacterial load.,More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture.,In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001).,Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum.,Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs.,Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised. | 1 |
Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI).,The impact of undiagnosed COPD in these patients is unknown.,We aimed to evaluate the prognostic impact of COPD - previously or newly diagnosed - in patients with IHD treated with PCI.,Patients with IHD confirmed by PCI were consecutively included.,After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors.,All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed.,A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included.,Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed.,IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction.,Median follow-up was 934 days (interquartile range [25%-75%]: 546-1,160).,COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76-44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04-3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12-2.83).,These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08-3.1).,Prevalence and underdiagnosis of COPD in patients with IHD who undergo PCI are both high.,These patients have an independent greater mortality and a higher number of cardiovascular events during follow-up. | Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors.,The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown.,The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD.,A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation.,In a multicenter observational prospective study conducted at 17 centers across Japan, the prevalence of airflow limitation compatible with COPD (defined as forced expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in cardiac outpatients ≥40 years old with a smoking history who routinely visited the clinic for their CVD.,Each patient completed the COPD Assessment Test prior to spirometry testing.,Data were available for 995 patients with a mean age of 66.6±10.0 years, of whom 95.5% were male.,The prevalence of airflow limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients (n=236) did not have a prior diagnosis of COPD.,The prevalence of previously diagnosed airflow limitation was higher in sites with higher usage of lung function testing (14.0%, 15.2% respectively) compared against sites where it is performed seldom (11.1%), but was still low.,The prevalence of airflow limitation in this study indicates that a quarter of outpatients with CVD have COPD, almost all of whom are undiagnosed.,This suggests that it is important to look routinely for COPD in CVD outpatients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | Fundamental physical properties, such as the intrinsic recoil of the lung, are governed by the extracellular matrix.,The prototypical roles of the matrix proteins, collagen and elastin, in pulmonary fibrosis and emphysema have long been recognized, and much research effort has been devoted to understanding mechanisms of extracellular matrix synthesis and turnover in the lung.,Yet, despite extensive knowledge of the biochemical properties of collagen and elastin, none of the present clinical strategies for treating COPD directly target the extracellular matrix.,From a matrix perspective, therapeutic interventions that limit elastic fiber destruction and/or restore function to damaged alveolar units merit particular consideration as clinical strategies for treating the emphysema component of COPD.,Effective treatment of the bronchiolar component of COPD requires a better understanding of the relationship between airway fibrosis and airflow obstruction.,Translating basic knowledge of extracellular matrix biology into the clinical venue will be essential in the development of new approaches to COPD treatment. | 1 |
Indacaterol is a long-acting beta-2 agonist for once-daily treatment of COPD.,We evaluated the effects of indacaterol 150 μg on lung hyperinflation compared with placebo and open-label tiotropium 18 μg.,We measured physical activity during treatment with indacaterol 150 μg and matched placebo.,We performed a randomized, three-period, cross-over study (21 days of treatment separated by two wash-out periods of 13 days) with indacaterol 150 μg or matching placebo and tiotropium 18 μg.,Lung function was assessed by body plethysmography and spirometry.,Physical activity was measured for one week by a multisensory armband at the end of both treatment periods with indacaterol/matched placebo.,The primary endpoint was peak inspiratory capacity at the end of each treatment period.,129 patients (mean age, 61 years; mean post-bronchodilator FEV1, 64%), were randomized and 110 patients completed the study.,Peak inspiratory capacity was 0.22 L greater with Indacaterol at day 21 compared to placebo (p < 0.001).,Similar results were observed for tiotropium.,Both bronchodilators also significantly improved other parameters of lung hyperinflation compared with placebo.,All parameters of physical activity were significantly increased during treatment with indacaterol versus placebo.,Indacaterol 150 μg improved lung hyperinflation in patients with moderate COPD, which was associated with an increase of physical activity.,ClinicalTrials.gov registration number: NCT01012765. | The 65-item Functional Performance Inventory (FPI), developed to quantify functional performance in patients with chronic obstructive pulmonary disease (COPD), has been shown to be reliable and valid.,The purpose of this study was to create a shorter version of the FPI while preserving the integrity and psychometric properties of the original.,Secondary analyses were performed on qualitative and quantitative data used to develop and validate the FPI long form.,Seventeen men and women with COPD participated in the qualitative work, while 154 took part in the mail survey; 54 completed 2-week reproducibility assessment, and 40 relatives contributed validation data.,Following a systematic process of item reduction, performance properties of the 32-item short form (FPI-SF) were examined.,The FPI-SF was internally consistent (total scale α = 0.93; subscales: 0.76-0.89) and reproducible (r = 0.88; subscales: 0.69-0.86).,Validity was maintained, with significant (P < 0.001) correlations between the FPI-SF and the Functional Status Questionnaire (activities of daily living, r = 0.71; instrumental activities of daily living, r = 0.73), Duke Activity Status Index (r = 0.65), Bronchitis-Emphysema Symptom Checklist (r = −0.61), Basic Need Satisfaction Inventory (r = 0.61) and Cantril’s Ladder of Life Satisfaction (r = 0.63), and Katz Adjustment Scale for Relatives (socially expected activities, r = 0.51; free-time activities, r = −0.49, P < 0.01).,The FPI-SF differentiated patients with an FEVl% predicted greater than and less than 50% (t = 4.26, P < 0.001), and those with severe and moderate levels of perceived severity and activity limitation (t = 9.91, P < 0.001).,Results suggest the FPI-SF is a viable alternative to the FPI for situations in which a shorter instrument is desired.,Further assessment of the instrument’s performance properties in new samples of patients with COPD is warranted. | 1 |
The airway smooth muscle (ASM) plays an indispensable role in airway structure and function.,Dysfunction in ASM plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and contributes to alterations of contractility, inflammatory response, immunoreaction, phenotype, quantity, and size of airways.,ASM makes a key contribution in COPD by various mechanisms including altered contractility and relaxation induce by [Ca2+]i, cell proliferation and hypertrophy, production and modulation of extracellular cytokines, and release of pro-and-anti-inflammatory mediators.,Multiple dysfunctions of ASM contribute to modulating airway responses to stimuli, remodeling, and fibrosis, as well as influence the compliance of lungs.,The present review highlights regulatory roles of multiple factors in the development of ASM dysfunction in COPD, aims to understand the regulatory mechanism by which ASM dysfunctions are initiated, and explores the clinical significance of ASM on alterations of airway structure and function in COPD and development of novel therapeutic strategies for COPD. | Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is suggested as the consequence of emphysematous destruction of vascular bed and hypoxia of pulmonary microenvironment, mechanisms underpinning its pathogenesis however remain elusive.,The dysregulated expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases and superoxide generation by pulmonary vasculatures have significant implications in the hypoxia-induced PH.,In this study, the involvement of NADPH oxidase subunit 4 (NOX4) in pulmonary arteriolar remodeling of PH in COPD was investigated by ascertaining the morphological alteration of pulmonary arteries and pulmonary blood flow using cardiac magnetic resonance imaging (cMRI), and the expression and correlation of NOX4 with pulmonary vascular remodeling and pulmonary functions in COPD lungs.,Results demonstrated that an augmented expression of NOX4 was correlated with the increased volume of pulmonary vascular wall in COPD lung.,While the volume of distal pulmonary arteries was inversely correlated with pulmonary functions, despite it was positively associated with the main pulmonary artery distensibility, right ventricular myocardial mass end-systolic and right ventricular myocardial mass end-diastolic in COPD.,In addition, an increased malondialdehyde and a decreased superoxide dismutase were observed in sera of COPD patients.,Mechanistically, the abundance of NOX4 and production of reactive oxygen species (ROS) in pulmonary artery smooth muscle cells could be dynamically induced by transforming growth factor-beta (TGF-β), which in turn led pulmonary arteriolar remodeling in COPD lungs.,These results suggest that the NOX4-derived ROS production may play a key role in the development of PH in COPD by promoting distal pulmonary vascular remodeling. | 1 |
Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD).,The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD.,Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009.,Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George’s Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status.,In total, 1859 COPD patients of mean age (± standard deviation) 64.3 ± 9.7 years and with a forced expiratory volume in one second (FEV1) of 44.7% ± 18.2% were included.,On average, patients used 3.5 ± 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores.,FEV1 (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy.,Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages.,Use of corticosteroids was not restricted to patients with frequent exacerbations.,Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms.,In addition to severity of disease, health status is an independent predictor of polypharmacy.,Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with irreversible persistent airflow limitation and enhanced inflammation.,The episodes of acute exacerbation (AECOPD) largely depend on the colonized pathogens such as nontypeable Haemophilus influenzae (NTHi), one of the most commonly isolated bacteria.,Regulatory T cells (Tregs) are critical in controlling inflammatory immune responses and maintaining tolerance; however, their role in AECOPD is poorly understood.,In this study, we hypothesized a regulatory role of Tregs, as NTHi participated in the progress of COPD.,Immunological pathogenesis was investigated in a murine COPD model induced by cigarette smoke (CS).,NTHi was administrated through intratracheal instillation for an acute exacerbation.,Weight loss and lung function decline were observed in smoke-exposed mice.,Mice in experimental groups exhibited serious inflammatory responses via histological and cytokine assessment.,Expression levels of Tregs and Th17 cells with specific cytokines TGF-β1 and IL-17 were detected to assess the balance of pro-/anti-inflammatory influence partially.,Our findings suggested an anti-inflammatory activity of Tregs in CS-induced model.,But this activity was suppressed after NTHi administration.,Collectively, these data suggested that NTHi might play a necessary role in downregulating Foxp3 to impair the function of Tregs, helping development into AECOPD. | Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD).,We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD.,Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients.,Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models.,Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells.,None of the TLR4 SNPs was associated with FEV1 level.,Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time.,This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD. | 1 |
Many people with COPD report difficulties falling asleep or staying asleep, insufficient sleep duration, or nonrestorative sleep.,Cognitive behavioral therapy for insomnia (CBT-I) has proved effective not only in people with primary insomnia but also in people with insomnia comorbid with psychiatric and medical illness (eg, depression, cancer, and chronic pain).,However, CBT-I has rarely been tested in those with COPD who have disease-related features that interfere with sleep and may lessen the effectiveness of such therapies.,The purpose of this study was to determine the feasibility of applying a CBT-I intervention for people with COPD and to assess the impact of CBT-I on insomnia severity and sleep-related outcomes, fatigue, mood, and daytime functioning.,The study had two phases.,In Phase 1, a 6-weekly session CBT-I intervention protocol in participants with COPD was assessed to examine feasibility and acceptability.,Phase 2 was a small trial utilizing a prospective two-group pre- and post-test design with random assignment to the six-session CBT-I or a six-session wellness education (WE) program to determine the effects of each intervention, with both interventions being provided by a nurse behavioral sleep medicine specialist.,Fourteen participants (five in Phase 1 and nine in Phase 2) completed six sessions of CBT-I and nine participants completed six sessions of WE.,Participants indicated that both interventions were acceptable.,Significant positive treatment-related effects of the CBT-I intervention were noted for insomnia severity (P = 0.000), global sleep quality (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02), fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000).,Significant positive effects were noted for depressed mood after WE (P = 0.005).,Results suggest that using CBT-I in COPD is feasible and the outcomes compare favorably with those obtained in older adults with insomnia in the context of other chronic illnesses. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
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. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Aside from smoking, which is already recognized as a strong risk factor for COPD, interest in the impact of particulate matter (PM) on COPD is increasing.,This study aimed to investigate the effect of PM, especially with an aerodynamic diameter ≤2.5 µm (PM2.5), and its chemical constituents on the exacerbation of COPD.,Data on hospital visits including admission and outpatient clinic visits for exacerbation of COPD in Chuncheon, Korea, between 2006 and 2012 were extracted from the National Health Insurance Service database.,PM2.5 and its chemical constituents were measured on the roof of the four-story Kangwon National University Natural Sciences building once every 3 days.,Meteorological data were provided by the Korean Meteorological Administration.,During the study period, the mean level of PM2.5 was 35.0±25.2 µg/m3, and the number of daily hospital visits were 6.42±4.28 and 2.07±1.93 for males and females, respectively.,The number of COPD-related hospital visits increased with increasing PM2.5 after adjusting for meteorological covariates and females tended to be more affected sooner than males.,Among the PM2.5 constituents, Al, Si, and elemental carbon were associated with increased hospital visits and there was a difference according to sex.,In males, some constituents of PM2.5 were related to an increased risk of a hospital visit, mainly on the first and second days of measurement (Lag1 and Lag2).,In contrast, there was no significant increase in the risk of hospital visits due to any of the PM2.5 constituents in females.,Concentrations of PM2.5 mass and some of the PM2.5 constituents were associated with increased COPD-related hospital visits in Chuncheon. | Epidemiological research into the role of traffic pollution on chronic respiratory and allergic disease has focused primarily on children.,Studies in adults, in particular those based on objective outcomes such as bronchial hyperresponsiveness, skin sensitisation, and lung function, are limited.,We have used an existing cohort of 2644 adults aged 18-70 living in Nottingham, UK, for whom baseline health and demographic data were collected in 1991 and computed two markers of exposure to traffic: distance between the home and nearest main road and modelled outdoor nitrogen dioxide (NO2) concentration at the home location.,Using multiple regression techniques, we analysed cross-sectional associations with bronchial hyperresponsiveness, FEV1, spirometry-defined COPD, skin test positivity, total IgE and questionnaire-reported wheeze, asthma, eczema and hayfever in 2599 subjects, and longitudinal associations with decline in FEV1 in 1329 subjects followed-up nine years later in 2000.,There were no significant cross-sectional associations between home proximity to the roadside or NO2 level on any of the outcomes studied (adjusted OR of bronchial hyperresponsiveness in relation to living ≤150 m vs >150 m from a road = 0.92, 95% CI 0.68 to 1.24).,Furthermore, neither exposure was associated with a significantly greater decline in FEV1 over time (adjusted mean difference in ΔFEV1 for living ≤150 m vs >150 m of a road = 10.03 ml, 95% CI, -33.98 to 54.04).,This study found no evidence to suggest that living in close proximity to traffic is a major determinant of asthma, allergic disease or COPD in adults. | 1 |
This paper reviews evidence and quality of Systematic Reviews (SRs) on the effects of breathing control exercises (BCEs) and respiratory muscle training (RMT) on breathlessness/dyspnea and other symptoms, and quality of life (QOL) for individuals with chronic obstructive pulmonary disease (COPD).,A search for BCE and RMT literature in COPD published between January 1, 2002 and December 31, 2013 was performed in the following databases: PubMed, Ovid, CINAHL, PsycINFO, AMED, Cochrane and PEDro.,The AMSTAR criteria were used to evaluate quality.,After reviewing 642 reports, seven SRs were identified on RMT and BCEs.,Three SRs were of high quality, three were of moderate quality, and one was of low quality.,Two high-quality SRs reported significantly beneficial effects of RMT on dyspnea, and one reported significant effects on disease-specific QOL and fatigue.,In these SRs, pooled data analyses were performed with three to fourteen single randomised control trials (RCTs) included in the analysis.,In one of the SRs the quality of the single RCTs were rated by the authors to be between 5-7 (with10 best) and in the other one the quality of the single RCTs were rated to be between 30-83% of the maximum score.,One high-quality SR found a significant positive effect of BCE based on pooled data analysis with two single RCTs in regard to pursed-lip breathing (PLB) on breathlessness.,In this SR, one single RCT on diaphragmatic breathing (DB) and another one on yoga breathing (YB) showed effect on disease-specific QOL.,The single RCTs included in the SR were rated by the authors in the SRs to be of low and moderate quality.,Based on three high-quality SRs performing pooled data analyses, there is evidence that RMT has effect on breathlessness, fatigue and disease-specific QOL and PLB on breathlessness.,There is also evidence that single studies on DB and YB has effect on disease-specific QOL.,Few RCTs are available and the variable quality of the single RCTs in the SRs, seem to require more RCTs in particular for BCEs, but also RMT before conclusions regarding effects and high quality SRs can be written.,The online version of this article (doi:10.1186/1471-2466-14-184) contains supplementary material, which is available to authorized users. | Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor.,This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy.,The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique.,One-year follow-ups with three visits were performed.,The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques.,Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group.,The main outcome measure was adherence to the medication regimen.,Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count.,Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group).,When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046).,Number needed to treat is 6.37.,In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%.,The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment; activity (OR = 1.03) and impact (OR = 1.03) scales of the Saint George Respiratory Questionnaire.,Application of the multifactorial intervention designed for this study (COPD information, dose reminders, audio-visual material, motivational aspects and training in inhalation techniques) resulted in an improvement in therapeutic adherence in COPD patients with scheduled inhalation therapy.,Current Controlled Trials ISRCTN18841601. | 1 |
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported.,However, CRP is a systemic inflammatory biomarker that is related to many other diseases.,The objective of this study is to discover a diagnostic biomarker for COPD.,Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study.,Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected.,CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects.,Receiver operating characteristic values of CRP and the identified biomarkers were determined.,A validation COPD cohort was used to reexamine the identified biomarker.,Correlation of the biomarker with 1-year lung function decline was determined.,Proteoglycan 4 (PRG4) was identified as a biomarker in COPD.,The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05).,PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency.,There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R2=0.91, P=0.013).,PRG4 may be a biomarker for identification of severity in COPD.,It was related to the 1-year forced vital capacity decline in COPD patients. | Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction.,The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessment of patients, prediction of risk, and guidance of treatment.,The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD.,The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease and hard clinical outcomes, their modification by interventions, and whether changes in clinical outcomes are reflected by changes in the biomarker. | 1 |
The main causes of COPD are tobacco smoking (COPD-TS) and biomass smoke exposure (COPD-BS).,COPD-TS is known to induce changes in adipokines, incretins, and peptide hormones, frequent biomarkers of inflammation; however, it is unknown if similar changes occur in COPD-BS.,Clinical and physiological characteristics, and serum concentration of C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin were measured in women with COPD-BS, COPD-TS, and healthy controls.,Data were compared with one-way ANOVA and Tukey’s post hoc test; nonparametric were expressed as median (interquartile ranges), with Kruskal-Wallis and Dunn’s post-hoc test.,Multivariate analysis, age, BMI, MS, and FEV1% pred with levels of inflammatory mediators in COPD women.,FEV1% pred, FVC% pred, and FEV1/FVC ratio were decremented in COPD.,In COPD-TS increased C-peptide, ghrelin, GIP, GLP-1, and leptin, and reduced glucagon, PAI-1, resistin, and visfatin.,In COPD-BS enlarged ghrelin, insulin, leptin, and PAI-1 comparatively with COPD-TS and control, while C-peptide and GLP-1 relatively with controls; conversely, glucagon, and resistin were reduced.,Multivariate analysis showed association of ghrelin, insulin, PAI-1, and visfatin with BS exposure.,women with COPD-BS have a distinct profile of adipokines, incretins, and peptide hormones, and specifically with ghrelin, insulin, PAI-1, and visfatin related to BS exposure. | A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear.,Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable.,To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases.,We recruited 59 outpatients with MetS and 76 outpatients with COPD.,After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29).,A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%.,More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease.,MetS+COPD patients exhibited significantly higher C-peptide levels.,We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers.,Finally, a negative association emerged between smoking and vitamin D.,We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance.,Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development. | 1 |
Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.,Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity.,In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling.,The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.,Patients scheduled for lung resection were prospectively recruited.,Demographic, clinical data and pulmonary function tests results were recorded.,Emphysema was visually scored and histological remodeling features were noted.,Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.,We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding.,In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.,13 COPD and 7 non COPD patients were included.,The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03] respectively).,Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD, p = 0.04).,The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs 12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]).,Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively).,Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels.,Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).,Our results showed an abnormal bronchial epithelial wound closure process in severe COPD.,Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.,The online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users. | Levels of precursor proteins of collagen I and III are increased in fibrotic pulmonary diseases.,This study determined whether the expression of precursors of type I and III collagen proteins would be increased in small and large airways of COPD patients in various stages of the disease reflecting fibrogenesis.,The levels of precursor proteins of collagen I and III were studied by immunohistochemistry and quantified by image analysis in lung tissue of 16 non-smokers, 20 smokers with normal lung function, 20 smokers with stage I-II COPD and 8 ex-smokers with stage IV COPD.,In large airways, the subepithelial layer which was positive for precursor proteins of collagen I and III was thicker in smokers and in stage I-II COPD compared to non-smokers.,Large airways in stage IV COPD showed reduced expression of precursor protein of collagen I whereas precursor of collagen III was increased.,The amount of precursor protein of collagen III was increased in small airways of smokers and stage I-II COPD but reduced in stage IV COPD.,Precursor proteins of collagen I and III revealed different expression profiles in large and small airways in various stages of COPD.,Smoking enhanced expression of both precursors in large airways with a positive correlation with pack-years. | 1 |
Phosphodiesterase-4 inhibitors (PDE4Is) are potent anti-inf lammatory agents and roflumilast has been used to prevent acute exacerbation of chronic obstructive pulmonary disease (COPD).,Roflumilast decreases neutrophil migration, restores cystic fibrosis transmembrane conductance regulator activity, and recovers glucocorticoid effects.,A forced expiratory volume in 1 second of < 50%, a chronic bronchitis phenotype, high blood eosinophil levels, and a history of hospitalization are biomarkers for predicting responses to roflumilast.,Adverse effects are common in clinical practice.,An inhaled PDE4I has recently been developed and is under clinical trial.,CHF6001 and RPL554 exhibit promise and may be future treatment options for COPD. | Evidence suggests that suppressor of cytokine signaling 1 (SOCS1) is crucial for the negative regulation of inflammation.,We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4) in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1) antagonist on inflammation.,SOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction.,We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF) by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay.,In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay.,Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells.,We obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects) and BALF (20 COPD patients and 20 non-COPD control subjects), and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients.,Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels.,Further, the BLT1 antagonist restored SOCS1 expression and in turn inhibited inflammatory cytokine secretion in vitro.,Long-term cigarette smoke exposure induced SOCS1 degradation and LTB4 accumulation, which was associated with emphysema and inflammation.,A BLT1 antagonist might be a potential therapeutic candidate for the treatment of COPD. | 1 |
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