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Pulmonary rehabilitation (PR) is a guideline-recommended multifaceted intervention that improves the physical and psychological well-being of people with chronic respiratory diseases (CRDs), though most of the evidence derives from trials in high-resource settings.,In low- and middle-income countries, PR services are under-provided.,We aimed to review the effectiveness, components and mode of delivery of PR in low-resource settings.,Following Cochrane methodology, we systematically searched (1990 to October 2018; pre-publication update March 2020) MEDLINE, EMBASE, CABI, AMED, PUBMED, and CENTRAL for controlled clinical trials of adults with CRD (including but not restricted to chronic obstructive pulmonary disease) comparing PR with usual care in low-resource settings.,After duplicate selection, we extracted data on exercise tolerance, health-related quality of life (HRQoL), breathlessness, included components, and mode of delivery.,We used Cochrane risk of bias (RoB) to assess study quality and synthesised data narratively.,From 8912 hits, we included 13 studies: 11 were at high RoB; 2 at moderate RoB.,PR improved functional exercise capacity in 10 studies, HRQoL in 12, and breathlessness in 9 studies.,One of the two studies at moderate RoB showed no benefit.,All programmes included exercise training; most provided education, chest physiotherapy, and breathing exercises.,Low cost services, adapted to the setting, used limited equipment and typically combined outpatient/centre delivery with a home/community-based service.,Multicomponent PR programmes can be delivered in low-resource settings, employing a range of modes of delivery.,There is a need for a high-quality trial to confirm the positive findings of these high/moderate RoB studies. | Low- and middle-income countries (LMICs) account for >90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings.,Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings.,We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV1/FVC z-score below the 5th percentile as the gold standard.,We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD.,We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%.,We evaluated for calibration and discrimination using standard approaches.,The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow.,We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry.,The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61-0.75) with higher scores conferring greater odds of COPD.,The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78-0.88) with a positive predictive value of 50% and a negative predictive value of 96%.,The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow.,COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings. | 1 |
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients.,In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally.,Demographics, anthropometrics, lung function and clinical data were assessed.,Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband.,Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters.,Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns.,Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data.,Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all).,Daily physical activity measures and hourly patterns are heterogeneous in COPD.,Clusters of patients were identified solely based on physical activity data.,These findings may be useful to develop interventions aiming to promote physical activity in COPD. | Multi-morbidity is common in patients with chronic obstructive pulmonary disease and low levels of physical activity are hypothesized to be an important risk factor.,The current study aimed to assess the longitudinal association between physical activity and risk of seven categories of comorbidity in chronic obstructive pulmonary disease patients.,The study included 409 patients from primary care practice in the Netherlands and Switzerland.,We assessed physical activity using the Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire at baseline and followed patients for up to 5 years.,During follow-up, patients reported their comorbidities (cardiovascular, neurological, endocrine, musculoskeletal, malignant, and infectious diseases) and completed the Hospital Anxiety and Depression Scale questionnaire for mental health assessment.,We implemented multinomial logistic regression (an approximation to discrete time survival model using death as a competing risk) for our analysis.,Study results did not suggest a statistically significant association of baseline physical activity with the development of seven categories of comorbidity.,However, when we focused on depression and anxiety symptoms, we found that higher levels of physical activity at baseline were associated with a lower risk for depression (adjusted hazard ratio, 0.85; 0.75-0.95; p = 0.005) and anxiety (adjusted hazard ratio, 0.89; 0.79-1.00; p = 0.045).,In chronic obstructive pulmonary disease patients, those with high physical activity are less likely to develop depression or anxiety symptoms over time.,Increasing physical activity in chronic obstructive pulmonary disease patients may be an approach for testing to lower the burden from incident depression and anxiety.,Patients with chronic lung disease who stay physically active could reduce their chances of depression and anxiety.,Milo Puhan at the University of Zurich, Switzerland, and co-workers assessed the association between physical activity and the risk of developing various co-existing diseases in 409 patients with chronic obstructive pulmonary disease (COPD).,Co-morbidities such as cardiovascular diseases, diabetes and depression are prevalent in patients with COPD, but the reasons why are not clear.,Puhan’s team assessed patients’ activity levels using an existing questionnaire, and administered another questionnaire to assess mental health.,They followed the cohort for 5 years.,Results indicated weak associations between physical activity levels and most physical illnesses, but there were significant links between higher levels of physical activity and a reduced risk of depression and anxiety.,The results could inform novel COPD treatment programs. | 1 |
There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD.,It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.,We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013.,Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline.,Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.,We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria.,The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies).,The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%).,The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for “real-life patients.”,The tiotropium RCTs tended to include patients with more severe disease than the observational studies. | Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD).,Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity.,The effect of withdrawing ICS from COPD patients in primary care is unknown.,In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132).,Follow-up assessments took place at three monthly intervals for a year at the patients' practice.,Our primary outcome was COPD exacerbation frequency.,Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life.,In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36).,Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05).,Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86).,Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze.,In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14).,Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration.,Patients with mild COPD may be at increased risk of exacerbation after withdrawal.,ClinicalTrials.gov NCT00440687 | 1 |
Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema.,Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development.,Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS).,Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression.,ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death.,Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal.,In this review, we summarize the main findings regarding the biological role of ROS, which may contribute to COPD development, and cytoprotective mechanisms against this disease progression. | Airway mucus is part of the lung’s native immune function that traps particulates and microorganisms, enabling their clearance from the lung by ciliary transport and cough.,Mucus hypersecretion and chronic productive cough are the features of the chronic bronchitis and chronic obstructive pulmonary disease (COPD).,Overproduction and hypersecretion by goblet cells and the decreased elimination of mucus are the primary mechanisms responsible for excessive mucus in chronic bronchitis.,Mucus accumulation in COPD patients affects several important outcomes such as lung function, health-related quality of life, COPD exacerbations, hospitalizations, and mortality.,Nonpharmacologic options for the treatment of mucus accumulation in COPD are smoking cessation and physical measures used to promote mucus clearance.,Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. | 1 |
Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD).,The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease.,(i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks.,One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS).,(i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission.,Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured.,All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients.,Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment.,There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014.,ID is common in COPD patients but is rarely looked for or treated.,Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea. | There are limited data on the risk of pulmonary disease in patients with diabetes.,The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.,We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California.,Age and sex data were available for all cohort members (n = 1,811,228).,Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.,Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort.,No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes.,These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03-1.12], COPD HR 1.22 [1.15-1.28], pulmonary fibrosis HR 1.54 [1.31-1.81], and pneumonia HR 1.92 [1.84-1.99]).,The risk of pneumonia and COPD increased significantly with increasing A1C.,Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer.,This increased risk may be a consequence of declining lung function in patients with diabetes. | 1 |
The application of telemedicine in home pulmonary rehabilitation interventions for the management of patients with chronic obstructive pulmonary disease (COPD) has achieved promising results.,This study aimed to develop a WeChat official account (Pulmonary Internet Explorer Rehabilitation [PeR]) based on social media.,It further evaluated the effect of PeR on the quality of life, symptoms, and exercise self-efficacy of patients with COPD.,The functional modules of PeR were developed by a multidisciplinary team according to the electronic health-enhanced chronic care model (eCCM) components.,A total of 106 patients were randomly selected (53 in the PeR group and 53 in the outpatient face-to-face group [FtF]).,Pulmonary rehabilitation intervention was conducted for 3 months, and the outcome was observed for 3 months.,The primary outcome was patient quality of life measured with the COPD assessment test (CAT).,The secondary outcomes were evaluated using the modified Medical Research Council scale (mMRC), exercise self-regulatory efficacy scale (Ex-SRES), and St George’s Respiratory Questionnaire (SGRQ).,The intention-to-treat analysis was used in the study.,A total of 94 participants completed the 6-month pulmonary rehabilitation program.,No statistically significant differences were observed in CAT (F1,3=7.78, P=.001), Ex-SRES (F1,3=21.91, P<.001), and mMRC scores (F1,3=29.64, P<.001) between the two groups with the variation in time tendency.,The Ex-SRES score had a significant effect on the CAT score (P=.03).,The partial regression coefficient of Ex-SRES to CAT was 0.81, and Exp (B) was 2.24.,The telemedicine technology was effective using the eCCM combined with a behavioral intervention strategy centering on self-efficacy.,Pulmonary rehabilitation at home through PeR and FtF could improve the sense of self-efficacy and quality of life and alleviate symptoms in patients with COPD.,Chinese Clinical Trial Registry ChiCTR1900022770; https://tinyurl.com/tmmvpq3 | Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management.,We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program.,Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.,We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017.,Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.,We included 13 randomized trials (801 participants).,Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])).,Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [− 6.85 to − 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])).,Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate.,Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.,Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation.,Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months.,Therefore, we recommend early supervised PR to patients with COPD-related exacerbations.,PR should be initiated during hospital admission or within 4 weeks after hospital discharge.,The online version of this article (10.1186/s12890-018-0718-1) contains supplementary material, which is available to authorized users. | 1 |
Accurate prognosis information after a diagnosis of chronic obstructive pulmonary disease (COPD) would facilitate earlier and better informed decisions about the use of prevention strategies and advanced care plans.,We therefore aimed to develop and validate an accurate prognosis model for incident COPD cases using only information present in general practitioner (GP) records at the point of diagnosis.,Incident COPD patients between 2004-2012 over the age of 35 were studied using records from 396 general practices in England.,We developed a model to predict all-cause five-year mortality at the point of COPD diagnosis, using 47,964 English patients.,Our model uses age, gender, smoking status, body mass index, forced expiratory volume in 1-second (FEV1) % predicted and 16 co-morbidities (the same number as the Charlson Co-morbidity Index).,The performance of our chosen model was validated in all countries of the UK (N = 48,304).,Our model performed well, and performed consistently in validation data.,The validation area under the curves in each country varied between 0.783-0.809 and the calibration slopes between 0.911-1.04.,Our model performed better in this context than models based on the Charlson Co-morbidity Index or Cambridge Multimorbidity Score.,We have developed and validated a model that outperforms general multimorbidity scores at predicting five-year mortality after COPD diagnosis.,Our model includes only data routinely collected before COPD diagnosis, allowing it to be readily translated into clinical practice, and has been made available through an online risk calculator (https://skiddle.shinyapps.io/incidentcopdsurvival/). | A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017.,We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications.,Patients with COPD were recruited from January 2006 to December 2017.,The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC).,A total of 553 subjects with COPD were analyzed.,The mortality rate was 48.6% during a median follow-up period of 5.2 years.,Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively.,The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively.,Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively).,The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001).,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients.,Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality.,We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients.,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor.,The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients. | 1 |
Singing is an increasingly popular activity for people with chronic obstructive pulmonary disease (COPD).,Research to date suggests that ‘Singing for Lung Health’ may improve various health measures, including health-related quality-of-life.,Singing and breathing are closely linked processes affecting one another.,In this narrative review, we explore the physiological rationale for ‘Singing for Lung Health’ as an intervention, focusing on the abnormalities of pulmonary mechanics seen in COPD and how these might be impacted by singing.,The potential beneficial physiological mechanisms outlined here require further in-depth evaluation. | Whole-body vibration training (WBV) performed on a vibration platform can significantly improve physical performance in patients with chronic obstructive pulmonary disease.,It has been suggested that an important mechanism of this improvement is based on an improvement in balance.,Therefore, the aim of this study was to investigate the effects of WBV compared to conventional balance training.,48 patients with severe COPD (FEV1: 37 ± 7%predicted) and low exercise performance (6 min walk distance (6MWD): 55 ± 10%predicted) were included in this randomized controlled trial during a 3 week inpatient pulmonary rehabilitation.,All patients completed a standardized endurance and strength training program.,Additionally, patients performed 4 different balance exercises 3x/week for 2 sets of 1 min each, either on a vibration platform (Galileo) at varying frequencies (5-26 Hz) (WBV) or on a conventional balance board (BAL).,The primary outcome parameter was the change in balance performance during a semi tandem stance with closed eyes assessed on a force measurement platform.,Muscular power during a countermovement jump, the 6MWD, and 4 m gait speed test (4MGST) were secondary outcomes.,Non-parametric tests were used for statistical analyses.,Static balance performance improved significantly more (p = 0.032) in favor of WBV (path length during semi-tandem stand: − 168 ± 231 mm vs. + 1 ± 234 mm).,Muscular power also increased significantly more (p = 0.001) in the WBV group (+ 2.3 ± 2.5 W/kg vs.,− 0.1 ± 2.0 W/kg).,6MWD improved to a similar extent in both groups (WBV: 48 ± 46 m, p < 0.001 vs.,BAL: 38 ± 32 m; p < 0.001) whereas the 4MGST increased significantly only in the WBV-group (0.08 ± 0.14 m/s2, p = 0.018 vs.,0.01 ± 0.11 m/s2, p = 0.71).,WBV can improve balance performance and muscular power significantly more compared to conventional balance training.,Trial registration: Clinical-Trials registration number: NCT03157986; date of registration: May 17, 2017. https://clinicaltrials.gov/ct2/results?,cond=&term=NCT03157986&cntry=&state=&city=&dist =,The online version contains supplementary material available at 10.1186/s12931-021-01688-x. | 1 |
Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria.,This review aimed to identify the criteria used to diagnose sarcopenia and the prevalence and impact of sarcopenia on health outcomes in people with COPD.,This review was registered in PROSPERO (CRD42018092576).,Five electronic databases were searched to August 2018 to identify studies related to sarcopenia and COPD.,Study quality was assessed using validated instruments matched to study designs.,Sarcopenia prevalence was determined using authors' definitions.,Comparisons were made between people who did and did not have sarcopenia for pulmonary function, exercise capacity, quality of life, muscle strength, gait speed, physical activity levels, inflammation/oxidative stress, and mortality.,Twenty‐three studies (70% cross‐sectional) from Europe (10), Asia (9), and North and South America (4) involving 9637 participants aged ≥40 years were included (69.5% men).,Sarcopenia criteria were typically concordant with recommendations of hEuropean and Asian consensus bodies.,Overall sarcopenia prevalence varied from 15.5% [95% confidence interval (CI) 11.8-19.1; combined muscle mass, strength, and/or physical performance criteria] to 34% (95%CI 20.6-47.3; muscle mass criteria alone) (P = 0.009 between subgroups) and was greater in people with more severe [37.6% (95%CI 24.8-50.4)] versus less severe [19.1% (95%CI 10.2-28.0)] lung disease (P = 0.020), but similar between men [41.0% (95%CI 26.2-55.9%)] and women [31.9% (95%CI 7.0-56.8%)] (P = 0.538).,People with sarcopenia had lower predicted forced expiratory volume in the first second (mean difference −7.1%; 95%CI −9.0 to −5.1%) and poorer exercise tolerance (standardized mean difference −0.8; 95%CI −1.4 to −0.2) and quality of life (standardized mean difference 0.26; 95%CI 0.2-0.4) compared with those who did not (P < 0.001 for all).,No clear relationship was observed between sarcopenia and inflammatory or oxidative stress biomarkers.,Incident mortality was unreported in the literature.,Sarcopenia is prevalent in a significant proportion of people with COPD and negatively impacts upon important clinical outcomes.,Opportunities exist to optimize its early detection and management and to evaluate its impact on mortality in this patient group. | Sarcopenia and decreased bone-mineral density (BMD) are common in elderly people, and are major comorbidities of obstructive airway disease (OAD).,However, the relationship between sarcopenia and BMD in each OAD phenotype, especially asthma-COPD overlap syndrome (ACOS), is not yet clear.,We aimed to evaluate differences in BMD according to the presence of sarcopenia in each OAD phenotype.,Among the research subjects in KNHANES IV and V (2008-2011), 5,562 were ≥50 years old and underwent qualified spirometry and dual-energy X-ray absorptiometry.,A total of 947 subjects were included in the study: 89 had asthma, 748 COPD, and 110 ACOS.,In the COPD and ACOS phenotypes, T-scores were lower in the sarcopenia group than the nonsarcopenia group.,Prevalence rates of osteopenia and osteoporosis were higher in the sarcopenia group than the nonsarcopenia group.,(P<0.001 and P=0.017, respectively).,The sarcopenia group had higher risks of developing osteopenia, osteoporosis, and low BMD than the nonsarcopenia group in the ACOS phenotype (OR 6.620, 95% CI 1.129-38.828 [P=0.036], OR 9.611, 95% CI 1.133-81.544 [P=0.038], and OR 6.935, 95% CI 1.194-40.272 [P=0.031], respectively).,However, in the asthma phenotype, the sarcopenia group showed no increased risk compared with the nonsarcopenia group.,In the ACOS phenotype, individuals with sarcopenia had a higher prevalence rate and higher risks of osteopenia and osteoporosis than those without sarcopenia among all OAD phenotypes. | 1 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Infective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum.,Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation.,Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD.,The purpose of our study was to determine if hemosiderin in sputum macrophages is related to infective exacerbations of COPD.,We undertook a retrospective observational study of 54 consecutive patients who presented with an exacerbation of COPD and had sputum examined including assessment for hemosiderin in alveolar macrophages.,The relation between infective exacerbations in the previous two years and the percent of hemosiderin-positive macrophages was analyzed with linear regression.,To account for the non-parametric distribution of infective exacerbations, negative binomial regression modelling was used to account for other covariates.,The percent of hemosiderin positive alveolar macrophages (hemosiderin index), analyzed parametrically and non-parametrically, demonstrated a significant correlation with increasing numbers of infective exacerbations in the previous two years.,In a multivariate regression analysis, hemosiderin index was an independent predictor of infective exacerbations.,COPD patients with raised hemosiderin index (≥20%) had higher levels of sputum IL-6 compared to patients with lower levels (<20%).,High hemosiderin index in sputum alveolar macrophages measured at the time of AECOPD may be related to the frequency of infective exacerbations of COPD. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies.,Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.,Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts.,A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients.,Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.,Odds ratios (ORs) were pooled by random effects models.,Fourteen observational studies were eligible for the study.,Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70).,The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. | To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort.,Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively.,Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).,Cox regression was used for analyses.,Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics curves and Youden's index were calculated.,Main causes of death were cardiovascular, respiratory and cancer.,Baseline COPD was associated with overall mortality (HR = 1.43 for FEV1/FVC<LLN; 2.01 for GOLD 2-4; 1.46 for GOLD 1-4; 1.50 for FEV1/FEV6 <LLN).,For cardiovascular mortality, significant associations were found with GOLD 2-4 (HR = 2.68) and with GOLD 1-4 (HR = 1.78) for both genders together (not among women).,Low FEV1 was risk for overall and respiratory mortality (both genders combined).,FVC was not associated with overall mortality.,For most COPD criteria sensitivity was low and specificity high.,The area under the curve for FEV1 was greater than for FVC for overall and cardiovascular mortality.,COPD and low FEV1 are important predictors for overall and cardiovascular mortality in Latin America. | 1 |
Little is known regarding the relationship between balance impairments and physical activity in COPD.,There has been no study investigating the relationship between balance and objectively measured physical activity.,Here we investigated the association between balance and physical activity measured by an activity monitor in elderly COPD patients.,Twenty-two outpatients with COPD (mean age, 72±7 years; forced expiratory volume in 1 second, 53%±21% predicted) and 13 age-matched healthy control subjects (mean age, 72±6 years) participated in the study.,We assessed all 35 subjects’ balance (one-leg standing test [OLST] times, Short Physical Performance Battery total scores, standing balance test scores, 4 m gait speed, and five-times sit-to-stand test [5STST]) and physical activity (daily steps and time spent in moderate-to-vigorous physical activity per day [MV-PA]).,Possible confounders were assessed in the COPD group.,The between-group differences in balance test scores and physical activity were analyzed.,A correlation analysis and multivariate regression analysis were conducted in the COPD group.,The COPD patients exhibited significant reductions in OLST times (P=0.033), Short Physical Performance Battery scores (P=0.013), 4 m gait speed (P<0.001), five-times sit-to-stand times (P=0.002), daily steps (P=0.003), and MV-PA (P=0.022) compared to the controls; the exception was the standing balance test scores.,The correlation and multivariate regression analyses revealed significant independent associations between OLST times and daily steps (P<0.001) and between OLST times and MV-PA (P=0.014) in the COPD group after adjusting for possible confounding factors.,Impairments in balance and reductions in physical activity were observed in the COPD group.,Deficits in balance are independently associated with physical inactivity. | 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 |
Self-management is recognised as an essential criteria for the provision of high quality care for chronic obstructive pulmonary disease (COPD).,The management of COPD is usually delivered by a wide range of healthcare practitioners.,This study aimed to understand the factors affecting self-management of COPD from the perspectives of the different multidisciplinary healthcare teams involved in COPD care.,Semi-structured interviews were conducted with participants from primary care, specialist respiratory and pulmonary rehabilitation (PR) teams.,Purposive sampling and snowballing were employed in participant recruitment.,All interviews were audio-recorded and transcribed verbatim and data were analysed thematically.,A total of 20 participants (eight primary care practitioners, seven respiratory specialists and five PR practitioners) were interviewed until data saturation was reached.,Participants identified a range of complex and interrelated factors affecting COPD self-management that were grouped into three broad categories-patient, practitioner and organisational/system-level factors.,Patient-level factors were predominantly considered as barriers, with COPD knowledge and understanding, and the individual patients’ life circumstances/context being the most prominent issues.,Practitioner-level factors identified were practitioners’ speciality, interest and experience in respiratory conditions as the overarching factor that influenced how self-management was understood and practiced.,A number of organisational/system-level factors were identified by all practitioners, including inconsistency of referral pathways and the wide variations of different self-management planning tools.,Factors affecting self-management of COPD across these three levels need to be tackled equally in order to improve the effectiveness of interventions and to embed and integrate self-management support approaches into routine practice.,Better co-ordination between healthcare services, practitioners and patients may help improve self-management for chronic lung disease.,Self-management is crucial for patients with chronic obstructive pulmonary disease (COPD), but it can be difficult for healthcare workers to monitor and support patient progress.,Oladapo Ogunbayo at Newcastle University, UK, and co-workers conducted interviews with healthcare practitioners to explore perceived barriers to successful self-management of COPD.,Three distinct categories emerged; those at patient level, practitioner level and organisational level, the needs of which should be carefully balanced to improved self-management.,Patient knowledge and understanding of COPD, alongside individual life circumstances, were often barriers to effective self-care.,Those practitioners with specialist respiratory knowledge took a more holistic approach to self-management than their primary care counterparts.,A lack of continuity between services and across self-management planning tools presented further barriers. | Major clinical gaps impede the evidence-based treatment of chronic obstructive pulmonary disease (COPD) in the primary care setting.,Studies are needed to measure the effectiveness of continuing medical education (CME) on improving physician competency and performance toward evidence-based COPD care.,Between September 26, 2009 and December 12, 2009, 769 primary care physicians participated in a series of 12 regional, live, interactive, case-based, multiformat, half-day CME programs on COPD.,A subgroup of randomly selected participants (n = 50) and demographically matched nonparticipants (n = 50) completed surveys that included case vignettes, a validated tool for measuring physician performance in clinical practice.,Cohen’s d was used to calculate the magnitude of difference between participants and nonparticipants in the delivery of evidence-based care.,Physicians who participated in CME programs were 50% more likely to provide evidence-based COPD care than physicians who did not participate.,Compared with nonparticipants, participating physicians were more likely to recognize COPD correctly in a patient presenting with dyspnea (74% versus 94%, P = 0.007), recognize that women may have a greater susceptibility than men to the toxic effects of smoking (54% versus 90%, P < 0.001), and identify the mechanisms of action of emerging therapies (33% versus 65%, P = 0.003).,Physicians who participated in a half-day regional CME program on COPD diagnosis, staging, and treatment were significantly more likely than nonparticipants to deliver evidence-based COPD care.,With multiformat, interactive, focused educational interventions, physicians can make diagnostic and therapeutic choices in the primary care setting that align more closely with current guidelines and clinical evidence in COPD management. | 1 |
Existing studies primarily explored chronic obstructive pulmonary disease (COPD) in smokers, whereas the clinical characteristics and the disease course of passive or nonsmokers have been rarely described.,In the present study, patients hospitalized and diagnosed as acute exacerbation of COPD (AECOPD) were recruited and followed up until being discharged.,Clinical and laboratory indicators were ascertained and delved into.,A total of 100 patients were covered, namely, 52 active smokers, 34 passive smokers, and 14 nonsmokers.,As revealed from the results here, passive or nonsmokers developed less severe dyspnea (patients with modified Medical Research Council scale (mMRC) <2, 0.0% vs.,8.8% vs.,14.3%, p < 0.05, active, passive, and nonsmokers, respectively), higher oxygenation index (206.4 ± 45.5 vs.,241.2 ± 51.1 vs.,242.4 ± 41.8 mmHg, p < 0.01), as well as lower arterial partial pressure of carbon dioxide (70.8 ± 12.7 vs.,58.85 ± 9.9 vs.,56.6 ± 6.5 mmHg, p < 0.001).,Despite lower treatment intensity over these patients, amelioration of dyspnea, mitigation of cough, and elevation of oxygenation index were comparable to those of active smokers.,However, in terms of patients exhibiting mMRC ≥2 and type 2 respiratory failure, amelioration of dyspnea was more common in nonsmokers as compared with passive smokers (46.4% vs.,83.3%, p < 0.05, passive and nonsmokers, respectively).,In terms of patients exhibiting Global Initiative for COPD severity <3, mMRC ≥2, and type 2 respiratory failure, active smokers achieved the least mitigation of cough symptom (8.7% vs.,35.0% vs.,44.4%, p < 0.05).,Similar results could be achieved after the effects of confounders were excluded, with the most prominent amelioration of dyspnea (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.1-13.6, p < 0.05, as compared with active smokers) and cough (OR 3.3, 95% CI 1.0-10.7, p < 0.05) in nonsmokers, and relatively better amelioration of hypoxemia in passive smokers (oxygenation index change, 39.0 ± 34.6 vs.,51.5 ± 32.4 vs.,45.3 ± 25.4 mmHg, p < 0.05).,In brief, passive or nonsmokers with AECOPD were subjected to less severe disease, and nonsmokers, especially patients with more severe disease, might achieve the optimal enhancement of clinical presentation after treatment. | Patients with chronic obstructive pulmonary disease often experience exacerbations.,These events are important as they are a major cause of morbidity and mortality.,Recently, it has been increasingly recognized that patients may experience symptoms suggestive of an exacerbation but do not seek treatment, which are referred to as unreported or untreated exacerbations.,Symptom diaries used in clinical trials have the benefit of identifying both treated and untreated exacerbation events.,The Kamada study was a multicenter, double-blind randomized controlled trial of inhaled augmentation therapy in alpha-1 antitrypsin deficiency (AATD).,A retrospective review of daily electronic symptom diary cards was undertaken from the two leading centers to identify symptomatic episodes consistent with a definition of an exacerbation.,The aims were to explore the relationship between exacerbation events and classical “Anthonisen” symptoms and to characterize treated and untreated episodes.,Forty-six AATD patients with airflow obstruction and history of exacerbations were included in the analysis.,Two hundred thirty-three exacerbation episodes were identified: 103 untreated and 130 treated.,Untreated episodes were significantly shorter (median 6 days; interquartile range [IQR] 3-10 days) than the treated episodes (median 10 days; IQR 5-18.25 days: P<0.001).,Using logistic regression analysis, Anthonisen type and length of dyspnea were significant predictors of the treatment of an exacerbation event.,Real-time electronic diary cards provide valuable information about the characterization of exacerbations.,Untreated episodes are common and are significantly shorter in duration than the treated episodes.,Dyspnea is the most important single Anthonisen symptom in the prediction and/or driver of treatment. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) have decreased physical activity (PA) compared with healthy adults.,As lower PA is associated with increased mortality, improving PA is an important objective for COPD management.,This large-scale, multicenter, non-interventional, cross-sectional study examined the activity status of COPD patients in Japan and explored factors related to PA.,Outpatients aged ≥40 years with confirmed COPD diagnosis and pulmonary function test data were enrolled.,Primary study outcomes were measurement of daily steps (over 14 consecutive days, using an activity monitor), assessment of activity time by activity intensity (using metabolic equivalents [METs]), and evaluation of correlation between PA and patient characteristics.,Secondary outcomes included further investigation of the influence of patient characteristics on PA.,Data from 417 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I (29.5%), II (43.9%), III (23.5%), and IV (3.1%) were evaluated.,Median (Q1, Q3) daily step count was 3440.8 (1831.3, 5709.3).,Median (Q1, Q3) durations of PA at ≥3 (moderate-to-vigorous) and ≥2 METs (light-to-vigorous) were 18.7 (6.5, 41.3) and 186.9 (126.9, 259.2) minutes, respectively.,For >30% of patients, time spent in ≥3 METs activity was ≤10 minutes.,Unemployment was significantly correlated with reduced activity time (≥3 and ≥2 METs) and step count.,Severe GOLD stage was significantly correlated with reduced activity time (≥3 and ≥2 METs).,High modified Medical Research Council (mMRC) dyspnea score was significantly correlated with reduced activity time (≥3 METs) and step count.,Patients tended to overestimate the time spent in activities requiring ≥2 METs in their subjective reports compared with activity monitor measurements.,Reduced PA was observed in the Japanese COPD patients with the majority of them being GOLD stage I/II.,Employment status, GOLD stage, and mMRC dyspnea score could help identify patients at risk of reduced PA.,NCT03642613 (ClinicalTrials.gov); UMIN000032962 (UMIN-CTR, umin.ac.jp). | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
One quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals.,We examined the utility of FVC/TLC in identifying features of obstructive lung disease.,The ratio of post-bronchodilator FVC and TLCCT from chest CT (FVC/TLCCT) among current and former smokers with PRISm (FEV1/FVC ≥ 0.7 and FEV1 < 80%) in COPDGene was used to stratify subjects into quartiles: very high, high, low, and very low.,We examined the associations between FVC/TLCCT quartiles and (1) baseline characteristics, (2) respiratory exacerbations, (3) progression to COPD at 5 years, and (4) all-cause mortality.,Among participants with PRISm at baseline (n = 1,131), the very low FVC/TLCCT quartile was associated with increased gas trapping and emphysema, and higher rates of progression to COPD at 5 years (36% versus 17%; p < 0.001) relative to the very high quartile.,The very low FVC/TLCCT quartile was associated with increased total (IRR = 1.65; 95% CI [1.07-2.54]) and severe (IRR = 2.24; 95% CI [1.29-3.89]) respiratory exacerbations.,Mortality was lower in the very high FVC/TLCCT quartile relative to the other quartiles combined.,Reduced FVC/TLCCT ratio in PRISm is associated with increased symptoms, radiographic emphysema and gas trapping, exacerbations, and progression to COPD. | Early life events may predispose to the development of chronic lung disease in adulthood.,To provide an update on current knowledge of early nongenetic origins of COPD.,Systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,A total of 16 studies, comprising 69,365 individuals, met the predefined criteria and were included in the present review.,Studies have shown that in utero tobacco exposure, low birth weight, preterm birth, and respiratory diseases, primarily asthma and pneumonia, in early childhood are associated with lung function impairment later in childhood, and by that predispose to subsequent development of COPD, although the causal association between childhood respiratory diseases and COPD has been questioned in one study.,Environmental tobacco exposure has also been shown to have negative impact on lung function in childhood possibly leading to COPD in adulthood, although it is at present not possible to clearly distinguish between the impact of active and the environmental tobacco exposure on subsequent development of COPD.,Tobacco exposure in utero and early life is a risk factor for subsequent development of COPD.,Furthermore, low birth weight, lower respiratory tract infections and asthma, including wheezy bronchitis, in childhood also seem to be important determinants for later development of COPD.,Early life insults may, therefore, be crucial to COPD development. | 1 |
Patients with COPD often experience skeletal muscle dysfunction.,For those who are unable or unwilling to undertake physical training, neuromuscular electrical stimulation (NMES) may provide an alternative method of rehabilitation.,The purpose of this meta-analysis was to investigate the controversial topic of whether this therapy is effective in patients with moderate-to-severe COPD.,We pooled data from nine trials published between January 9, 2002 and January 4, 2016 across PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, and relevant websites for randomized controlled trials.,In these trials, patients with moderate-to-severe COPD were randomly allocated to receive NMES.,Primary outcomes were quadricep strength and exercise capacity.,The secondary outcome was health-related quality of life.,We extracted data from 276 patients.,NMES contributed to statistically improved quadricep strength (standardized mean difference 1.12, 95% confidence interval [CI] 0.64-1.59, I2=54%; P<0.00001) and exercise capacity, including longer exercise distance (weighted mean difference 51.53, 95% CI 20.13-82.93, I2=90%; P=0.001), and longer exercise endurance (standardized mean difference 1.11, 95% CI 0.14-2.08, I2=85%; P=0.02).,There was no significant difference in St George’s Respiratory Questionnaire scores (weighted mean difference −0.07, 95% CI −2.44 to 2.30, I2=56%; P=0.95).,NMES appears an effectual means of enhancing quadricep strength and exercise capacity in moderate-to-severe COPD patients.,Further research is demanded to clarify its effect on other outcomes and determine the optimal parameters for an NMES program. | This retrospective, observational study of a routine clinical practice reports the feasibility and efficiency of home-based pulmonary rehabilitation (PR), including transcutaneous neuromuscular electrical stimulation (NMES) or usual endurance physical exercise (UEPE), on exercise tolerance, anxiety/depression, and health-related quality of life (HRQoL) in patients with COPD.,Seventy-one patients with COPD participated in home-based PR with NMES (Group NMES [GNMES]), while 117 patients participated in home-based PR with the UEPEs (Group UEPE [GUEPE]).,NMES was applied for 30 minutes twice a day, every day.,The endurance exercises in GUEPE began with a minimum 10-minute session at least 5 days a week, with the goal being 30-45 minutes per session.,Three upper and lower limb muscle strengthening exercises lasting 10-15 minutes were also proposed to both the groups for daily practice.,Moreover, PR in both the groups included a weekly 90-minute session based on an educational needs assessment.,The sessions comprised endurance physical exercise for GUEPE, NMES for GNMES, resumption of physical daily living activities, therapeutic patient education, and psychosocial support to facilitate health behavior changes.,Before and after PR, functional mobility and physical exercise capacity, anxiety, depression, and HRQoL were evaluated at home.,The study revealed that NMES significantly improved functional mobility (−18.8% in GNMES and −20.6% in GUEPE), exercise capacity (+20.8% in GNMES and +21.8% in GUEPE), depression (−15.8% in GNMES and −30.1% in GUEPE), and overall HRQoL (−7.0% in GNMES and −18.5% in GUEPE) in the patients with COPD, regardless of the group (GNMES or GUEPE) or severity of airflow obstruction.,Moreover, no significant difference was observed between the groups with respect to these data (P>0.05).,Home-based PR including self-monitored NMES seems feasible and effective for severely disabled COPD patients with severe exercise intolerance. | 1 |
While single-inhaler triple therapy (SITT) devices were not available when the Global Initiative for Chronic Obstructive Lung Disease strategy and National Institute for Health and Care Excellence guidelines were developed, two devices are now available in the UK.,This paper offers practical, patient-focused advice to optimize placement of SITT in the management of COPD.,A survey of UK health care professionals (HCPs) identified issues around, and attitudes toward, SITT, which informed a multidisciplinary expert panel’s discussions.,The survey confirmed the need to clarify the place of SITT in COPD management.,The panel suggested three criteria, any one of which identifies a high-risk patient where escalation to triple therapy from monotherapy or double combination treatment is appropriate: 1) at least two exacerbations treated with oral corticosteroids, antibiotics, or both in the previous year; 2) at least one severe exacerbation that required hospital admission in the previous year; 3) one exacerbation a year on a repeated basis for 2 consecutive years.,Appropriate non-pharmacological management is essential for all patients and should be considered before stepping up treatment.,Regular review is essential.,During each review, HCPs should consider stepping treatment up or down.,If patients exacerbate despite adhering to triple therapy, an individualized approach should be considered if the inhaled corticosteroid (ICS) confers benefit or causes side effects.,In this situation, the blood eosinophil count could aid decision making.,ICSs should be continued when the history suggests that asthma overlaps with COPD.,Training, counseling, and education should be individualized.,HCPs should consider referral: 1) when there is limited response to treatment and persistent exacerbations; 2) where there is diagnostic uncertainty or suspected comorbidity; 3) whenever they feel “out of their depth.”,Overall, the panel concurred that when used correctly, SITT has the potential to improve adherence, symptom control, and quality of life, and reduce exacerbations.,Studies using real-world evidence need to confirm these benefits. | Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required. | 1 |
Numerous instruments are available to measure health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD), covering a wide array of domains ranging from symptoms such as dyspnea, cough and wheezing, to social and emotional functioning.,Currently no information or guide is available yet to aid the selection of domains for a particular study or disease population.,The aim of this paper is to identify which domains of HRQoL are most important with respect to COPD, from the patient perspective.,Twenty-one Dutch patients with COPD were asked to describe important domains impacted by COPD freely; second, they were presented with cues (domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) framework) and were asked to select the domains that were most relevant to them.,During the interview, the patients were asked to indicate in which way the selected domains impact their lives.,Both the answers to the open question, and the patient statements motivating nomination of PROMIS domains were coded into themes.,The most relevant (sub)domains of HRQoL for patients with COPD were: physical health (fatigue, physical functioning), social health (instrumental support, ability to participate in social roles and activities, companionship, and emotional support), and coping with COPD.,We identified which domains of HRQoL are most important to patients with COPD.,One of these (coping with COPD) is not explicitly covered by PROMIS, or by traditional questionnaires that are used to measure HRQoL in COPD. | There is a need for a validated short instrument that can be used in routine practice to quantify potential short-term change in Health-Related Quality of Life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD).,Our aim is to determine the validity and reliability of the VQ11 questionnaire dedicated to the routine assessment of HRQoL.,181 COPD patients (40-85 yrs, I to IV GOLD stages) completed the VQ11, and several tests.,One week later, 49 of these patients completed the VQ11 again.,Confirmatory factor analysis supported the two-level hierarchical structure of the VQ11 with 11 items covering three components and HRQoL at a higher level.,The VQ11 showed good internal consistency and good reproducibility (r = 0.88).,Concurrent validity showed significant correlations between VQ11 total scores and St George’s Respiratory Questionnaire-C (r = 0.70), Short Form-36 (r = -0.66 for the physical component and -0.63 for the mental component).,We obtained significant correlations with MRC Dyspnea Grades (r = 0.59), the Hospital Anxiety and Depression Scale total score (r = 0.62), and the BODE index (r = 0.53).,The VQ11 has good measurement properties and provides a valid and reliable measure of COPD-specific HRQoL.,It is ready for use in routine practice.,The study was approved by the University of Montpellier 1 Ethics Committee and the Regional Ethics Committee (authorization number: A00332-53). | 1 |
Pulmonary rehabilitation (PR) provides benefit for patients with chronic obstructive pulmonary disease (COPD) in terms of quality of life (QoL) and exercise capacity; however, the effects diminish over time.,Our aim was to evaluate a maintenance programme for patients who had completed PR.,Primary and secondary care PR programmes in Norfolk.,148 patients with COPD who had completed at least 60% of a standard PR programme were randomised and data are available for 110 patients.,Patients had greater than 20 pack year smoking history and less than 80% predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection.,Patients were randomised to receive a maintenance programme or standard care.,The maintenance programme consisted of 2 h (1 h individually tailored exercise training and 1 h education programme) every 3 months for 1 year.,The Chronic Respiratory Questionnaire (CRQ) (primary outcome), endurance shuttle walk test (ESWT), EuroQol (EQ5D), hospital anxiety and depression score (HADS), body mass index (BMI), body fat, activity levels (overall score and activity diary) and exacerbations were assessed before and after 12 months.,There was no statistically significant difference between the groups for the change in CRQ dyspnoea score (primary end point) at 12 months which amounted to 0.19 (−0.26 to 0.64) units or other domains of the CRQ.,There was no difference in the ESWT duration (−10.06 (−191.16 to 171.03) seconds), BMI, body fat, EQ5D, MET-minutes, activity rating, HADS, exacerbations or admissions.,A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months.,We do not recommend that our maintenance programme is adopted.,Other methods of sustaining the benefits of PR are required.,NCT00925171. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
With the growing burden of COPD and associated morbidity and mortality, a need for self-management has been identified.,The Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease (SPACE for COPD) manual was developed to support self-management in COPD patients.,Currently, there is no literature available regarding health care professionals’ training needs when supporting patients with COPD on self-management.,This study sought to identify these needs to inform, design and develop a training program for health care professionals being trained to deliver a self-management program in COPD.,Fourteen health care professionals from both primary and secondary care COPD services participated in face-to-face semistructured interviews.,Thematic analysis was used to produce a framework and identify training needs and views on delivery of the SPACE for COPD self-management program.,Components of training were web-based knowledge training, with pre-and posttraining knowledge questionnaires, and a 1-day program to introduce the self-management manual.,Feedback was given after training to guide the development of the training program.,Health care professionals were able to identify areas where they required increased knowledge to support patients.,This was overwhelming in aspects of COPD seen to be outside of their current clinical role.,Skills in goal setting and behavioral change were not elicited as a training need, suggesting a lack of understanding of components of supporting self-management.,An increase in knowledge of COPD was demonstrated following the training program.,Both knowledge and skill gaps existed in those who would deliver self-management.,Analysis of this has enabled a training program to be designed to address these gaps and enable health care professionals to support patients in self-management. | Pulmonary rehabilitation programs only modestly enhance daily physical activity levels in patients with chronic obstructive pulmonary disease (COPD).,This randomised controlled trial investigates the additional effect of an individual activity counselling program during pulmonary rehabilitation on physical activity levels in patients with moderate to very severe COPD.,Eighty patients (66±7 years, 81% male, forced expiratory volume in 1 second 45±16% of predicted) referred for a six‐month multidisciplinary pulmonary rehabilitation program were randomised.,The intervention group was offered an additional eight-session activity counselling program.,The primary outcomes were daily walking time and time spent in at least moderate intense activities.,Baseline daily walking time was similar in the intervention and control group (median 33 [interquartile range 16-47] vs 29 [17-44]) whereas daily time spent in at least moderate intensity was somewhat higher in the intervention group (17[4-50] vs 12[2-26] min).,No significant intervention*time interaction effects were observed in daily physical activity levels.,In the whole group, daily walking time and time spent in at least moderate intense activities did not significantly change over time.,The present study identified no additional effect of eight individual activity counselling sessions during pulmonary rehabilitation to enhance physical activity levels in patients with COPD.,clinicaltrials.gov NCT00948623 | 1 |
Grouping COPD subjects into clinical phenotypes might be useful for the management of the disease, but the clinical implications of such classification are still not totally clear, especially regarding prognosis.,The primary objective of this study was to assess whether the mortality rates were different between four predefined clinical phenotypes.,This is a retrospective, observational study carried out at the COPD clinic of a University Hospital.,A total of 891 COPD patients were classified, according to the Spanish COPD guidelines, into the following four phenotypes: asthma-COPD overlap (ACO; 75 subjects), nonexacerbator (NONEX; 531 subjects), exacerbator with chronic bronchitis (EXCB; 194 subjects), and exacerbator with emphysema (EXEMPH; 91 subjects).,We compared the mortality outcomes between the phenotypes.,After a follow-up of 48.4±25.2 months, there were 194 deaths (21.8%).,There were significant differences in all-cause mortality between phenotypes.,The ACO phenotype had the best long-term prognosis, whereas EXEMPH had the highest risk of death.,NONEX and EXCB mortality figures were in between the other two groups.,We also found some differences in the causes of death, and patients with EXEMPH were at a higher risk of dying because of COPD itself.,The differences in mortality did not seem related to the classification into phenotypes in itself but to disparities in COPD severity and comorbidity load between groups.,Classifying COPD patients according to several predefined clinical phenotypes can identify clusters of subjects with different mortality outcomes.,Some phenotypes are associated with a specific cause of death.,The mechanisms that underlie these differences seem to be related to COPD severity and comorbidities. | The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report provides a framework for classifying COPD reflecting the impacts of disease on patients and for targeting treatment recommendations.,The GOLD 2017 introduced a new classification with 16 subgroups based on a composite of spirometry and symptoms/exacerbations.,Data from the population-based PLATINO study, collected at baseline and at follow-up, in three sites in Latin America were analyzed to compare the following: 1) the distribution of COPD patients according to GOLD 2007, 2013, and 2017; 2) the stability of the 2007 and 2013 classifications; and 3) the mortality rate over time stratified by GOLD 2007, 2013, and 2017.,Of the 524 COPD patients evaluated, most of them were classified as Grade I or II (GOLD 2007) and Group A or B (GOLD 2013), with ≈70% of those classified as Group A in GOLD 2013 also classified as Grade I in GOLD 2007 and the highest percentage (41%) in Group D (2013) classified as Grade III (2007).,According to GOLD 2017, among patients with Grade I airflow limitation, 69% of them were categorized into Group A, whereas Grade IV patients were more evenly distributed among Groups A-D.,Most of the patients classified by GOLD 2007 remained in the same airflow limitation group at the follow-up; a greater temporal variability was observed with GOLD 2013 classification.,Incidence-mortality rate in patients classified by GOLD 2007 was positively associated with increasing severity of airflow obstruction; for GOLD 2013 and GOLD 2017 (Groups A-D), highest mortality rates were observed in Groups C and D.,No clear pattern was observed for mortality across the GOLD 2017 subgroups.,The PLATINO study data suggest that GOLD 2007 classification shows more stability over time compared with GOLD 2013.,No clear patterns with respect to the distribution of patients or incidence-mortality rates were observed according to GOLD 2013/2017 classification. | 1 |
It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD).,We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy.,Twenty patients who completed the 12-month treatment period were analyzed.,No clinically significant adverse events were observed during azithromycin treatment.,Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01).,The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations.,Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations.,Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. | 1 |
The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung hyperinflation, and physical activity.,In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe airflow limitation received aclidinium 400 μg twice daily or placebo via Genuair®/Pressair®a for 3 weeks (2-week washout between treatment periods).,The primary endpoint was change from baseline to Week 3 in endurance time, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate.,Changes from baseline in intensity of exertional dyspnea (Borg CR10 Scale®) and trough inspiratory capacity were secondary endpoints.,Additional endpoints included changes from baseline in other spirometric, plethysmographic, and physical activity (assessed by objective accelerometer measurement) parameters.,Efficacy endpoints were analyzed using an analysis of covariance model.,In total, 112 patients were randomized and treated (mean age 60.3 years; mean post-bronchodilator forced expiratory volume in 1 s 1.7 L [56.7% predicted]; mean endurance time 485.7 s).,After 3 weeks, endurance time was significantly increased with aclidinium versus placebo (treatment difference 58.5 s; p < 0.05).,At Week 3, aclidinium significantly reduced dyspnea intensity at isotime during exercise (treatment difference -0.63; p < 0.05) and improved trough inspiratory capacity (treatment difference 78 mL; p < 0.05) versus placebo.,Significant improvements in spirometric, plethysmographic, and some physical activity parameters were observed with aclidinium versus placebo.,These results suggest that aclidinium significantly improves exercise endurance, exertional dyspnea, hyperinflation, and physical activity in patients with COPD.,ClinicalTrials.gov identifier: NCT01471171; URL: http://www.clinicaltrials.gov.,The online version of this article (doi:10.1186/1471-2466-14-209) contains supplementary material, which is available to authorized users. | 1 |
‘Finding the missing millions’ with chronic obstructive pulmonary disease became part of the Department of Health strategy for England in 2010.,Targeted case-finding within primary care is one potential pro-active strategy, but currently little is known about the views of healthcare professionals on this approach.,In this study, 36 healthcare professionals (12 GPs, 14 nurses, and 10 practice managers) from 34 UK practices participated in semi-structured telephone interviews about targeted case-finding.,Interviews followed an interview guide, were audio-recorded, transcribed verbatim, coded and analysed using ‘Framework Approach’.,Most of those interviewed practiced opportunistic case-finding.,The main perceived barriers to wider case-finding programmes were the resource implications associated with running such programmes and identifying more chronic obstructive pulmonary disease patients.,Financial incentives, support from specialist clinicians, and comprehensive guidance were viewed as facilitators.,While targeted case-finding is conceptually accepted by primary care staff, scepticism surrounding (1) the value of identifying those with mild disease and (2) the availability of effective targeted case-finding methods, may lead some to favour an opportunistic approach.,Key concerns were a lack of unequivocal evidence for the relative benefits vs. disadvantages of diagnosing patients earlier, and resource constraints in an already over-burdened system.,Barriers to practical implementation of case-finding studies may be addressed with financial, human and educational resources, such as additional staff to undertake searches and perform spirometry tests, and practical and educational support from specialist teams.,Additional staff and resources would facilitate targeted searches for patients showing symptoms of early-stage chronic lung disease.,Chronic obstructive pulmonary disease (COPD) costs the UK economy billions of pounds each year, yet disparate symptoms mean patients aren’t always diagnosed in the early, treatable stages of the disease.,Recent guidelines suggest introducing ‘targeted case-finding’, where symptomatic patients with known risk factors are identified and approached for testing by doctors.,Rachael Summers and colleagues at the University of Southampton analyzed the opinions of healthcare professionals on implementing targeted case-finding in primary care.,While most of the 36 professionals interviewed agreed that diagnosing COPD earlier had clear benefits, concerns were raised regarding negative patient responses and increased stress for patients, alongside the added strain on already stretched resources.,Employing independent staff and enhancing resources may facilitate such a program. | Up to 436,000 adult Danes suffer from chronic obstructive pulmonary disease (COPD), with only one third diagnosed at this time.,The Danish National Board of Health recommends early detection of COPD, focusing on smokers/ex-smokers over 35 years of age with at least one lung symptom.,A governmental prevention committee has suggested that the municipalities, in addition to general practice, should be a potential arena responsible for early detection of COPD.,We undertook a pilot study to investigate the feasibility and effectiveness of early detection of COPD in municipalities following the recommendations of the Danish National Board of Health.,The Municipality of Esbjerg offered spirometry to Danish citizens at risk of COPD without a previous diagnosis of the disease, following the National Board of Health’s recommendations.,Citizens with evidence of airway obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <70%) were advised to visit their general practitioner for diagnosis.,These citizens were followed up by telephone interview 3 months later.,Of 152 citizens sampled (50% females, mean age 58 years, 51% smokers) 51.3% had evidence of airway obstruction, with 87% being mild to moderate in terms of severity.,Seven of ten citizens (71%) then visited their general practitioner, with 85% of these being diagnosed with COPD.,The number of smokers embarking on smoking cessation or quitting smoking increased following COPD screening, with the highest frequency in participants with evidence of airway obstruction.,In addition to early detection of COPD in general practice, early detection of airway obstruction in defined risk populations in Danish municipalities seems feasible and effective for identifying new patients with COPD.,However, additional research is needed in larger samples to confirm the results of the present study. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | 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 |
Patients with obstructive lung diseases may be at risk of hospitalization and/or death due to COVID-19.,To estimate the frequency of severe COVID-19, and COVID-19-related mortality in a well-defined large population of patients with asthma and chronic inflammatory lung disease (COPD).,Further to assess the frequency of asthma and COPD as registered comorbidities at discharge from hospital, and in death certificates.,At the start of the pandemic, the Swedish National Airway Register (SNAR) included 271,404 patients with a physician diagnosis of asthma and/or COPD.,In September 2020, after the first COVID-19 wave in Sweden, the database was linked with the National Patient Register (NPR), the Swedish Intensive Care Register and the Swedish Cause of Death Register, which all provide data about COVID-19 based on International Classification of Diseases (ICD-10) codes.,Severe COVID-19 was defined as hospitalization and/or intensive care or death due to COVID-19.,Among patients in SNAR, 0.5% with asthma, and 1.2% with COPD were identified with severe COVID-19.,Among patients < 18 years with asthma, only 0.02% were severely infected.,Of hospitalized adults, 14% with asthma and 29% with COPD died.,Further, of patients in SNAR, 56% with asthma and 81% with COPD were also registered in the NPR, while on death certificates the agreement was lower (asthma 24% and COPD 71%).,The frequency of severe COVID-19 in asthma and COPD was relative low.,Mortality for those hospitalized was double as high in COPD compared to asthma.,Comorbid asthma and COPD were not always identified among patients with severe COVID-19. | Exacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak.,We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19.,We conducted a case-control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020.,Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated.,Baseline and episode-related clinical characteristics were analyzed.,Logistic regression analysis was performed to evaluate the risk for mortality.,During the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19.,A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19.,COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p<0.001) and had higher mortality (44.9% vs 13.6% respectively, p<0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit.,COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population.,Inhaled corticosteroid use was not associated to mortality.,Hospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis. | 1 |
Individuals with COPD may experience ambulatory difficulty due to both effort intolerance arising from respiratory dysfunction and impaired balance control during walking.,However, the trunk movement during walking has not been evaluated or adjusted for patients with COPD.,The Lissajous index (LI) visually and numerically evaluates the left-right symmetry of the trunk movement during walking and is useful in clinical practice.,In COPD patients, the LI is used as an indicator of the left-right symmetry of the trunk during walking.,Here, we used the LI to evaluate the symmetry of COPD patients based on bilateral differences in mediolateral and vertical accelerations, and we investigated the correlation between the patients’ symmetry evaluation results and their physical function.,Sixteen stable COPD patients (all males; age 71.3±9.2 years) and 26 healthy control subjects (15 males; age 68.2±6.9 years) participated in this study.,They performed the 10-minute walk test at a comfortable gait speed wearing a triaxial accelerometer, and we measured their trunk acceleration for the evaluation of symmetry.,Motor functions were also evaluated in the patients with COPD.,The average mediolateral bilateral difference and LI values of the COPD patients were significantly larger than those of the healthy subjects.,The COPD patients’ LI values were significantly correlated with their static balance.,The LI measured using a triaxial accelerometer during walking is useful in balance assessments of patients with COPD. | Functional activities, such as the sit-to-stand-to-sit (STSTS) task, are often impaired in individuals with chronic obstructive pulmonary disease (COPD).,The STSTS task places a high demand on the postural control system, which has been shown to be impaired in individuals with COPD.,It remains unknown whether postural control deficits contribute to the decreased STSTS performance in individuals with COPD.,Center of pressure displacement was determined in 18 individuals with COPD and 18 age/gender-matched controls during five consecutive STSTS movements with vision occluded.,The total duration, as well as the duration of each sit, sit-to-stand, stand and stand-to-sit phase was recorded.,Individuals with COPD needed significantly more time to perform five consecutive STSTS movements compared to healthy controls (19±6 vs. 13±4 seconds, respectively; p = 0.001).,The COPD group exhibited a significantly longer stand phase (p = 0.028) and stand-to-sit phase (p = 0.001) compared to the control group.,In contrast, the duration of the sit phase (p = 0.766) and sit-to-stand phase (p = 0.999) was not different between groups.,Compared to healthy individuals, individuals with COPD needed significantly more time to complete those phases of the STSTS task that require the greatest postural control.,These findings support the proposition that suboptimal postural control is an important contributor to the decreased STSTS performance in individuals with COPD. | 1 |
Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities.,We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks.,Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52.,Adverse events were also assessed.,In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years).,Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02-0.15) were small for all treatments.,Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score).,The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups.,Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%).,There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.,In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints.,Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful.,All treatments were well tolerated with no new or unexpected safety findings.,ClinicalTrials.gov NCT02536508.,Registered 27 August 2015.,The online version of this article (10.1186/s12931-019-1126-7) contains supplementary material, which is available to authorized users. | Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce.,Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.,The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months.,The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over.,Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization.,Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting.,The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.,The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up.,The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82).,Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]).,Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. | 1 |
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation.,Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood.,Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.,We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients.,We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II).,Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.,All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage.,These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1.,There were no severe exacerbations or other adverse events.,Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation. | 1 |
Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease.,In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators.,Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease.,The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use.,We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies.,Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.,A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease.,Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD).,While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs).,Anthony D’Urzo at the University of Toronto, Canada, and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials.,Of these, 1180 were already taking ICSs.,The team compared symptoms in the ICS group with those not taking ICSs.,The dual therapy improved lung function across both groups regardless of ICS use, though patients gained different clinical benefits depending on ICS use and disease severity. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD), although factors influencing the length and frequency of each episode are poorly understood.,This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT) deficiency (PiZ phenotype) and COPD.,Daily diary cards were collected over 2 years.,Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year.,The patients (n = 23) had a mean age of 52.5 years, forced expiratory volume in one second (FEV1) of 1.2 L (38.4% predicted), corrected gas transfer (KCO) of 0.90 mmol/min/kPa/L (59.7% predicted), and 15th percentile lung density of 44.55 g/L.,Two hundred and sixty-three exacerbations (164 treated) were identified.,The frequency of treated exacerbations correlated negatively with KCO% predicted (r = −0.432; P = 0.022).,Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available) correlated negatively with baseline 15th percentile lung density (r = −0.361; P = 0.003), and increased the longer treatment was delayed (r = 0.503; P < 0.001).,Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = −0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036, <0.001, and <0.001, respectively).,Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = −0.647; P = 0.007).,In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer.,Treatment delay adversely affected exacerbation length, and lung density was the best independent predictor of delay in starting treatment. | 1 |
In patients with chronic obstructive pulmonary disease, all efforts should be made to prevent exacerbations because each event modifies the trajectory of the disease.,Treatment recommendations are mostly built on results from randomized controlled trials (RCTs) whose methodology ensure internal validity.,However, their relevance may be compromised by the lack of generalizability, due to poor representability of study populations compared to real-life patients.,In order to delimit to whom the results of studies on current and future treatments apply, we sought to identify and characterize the fraction of COPD population that would be eligible for inclusion into RCTs aiming at decreasing exacerbation risk.,We used the Initiatives-BPCO database, a French cohort of 1309 real-life COPD patients monitored in academic centers.,We identified industry-sponsored phase III and IV trials that enrolled more than 500 patients, lasted at least one year and used exacerbations related endpoints.,Eligibility criteria were extracted from each trial and applied to the patients.,The eligibility criteria of 16 RCTs were applied to the 1309 patients.,The most discriminating eligibility criteria were FEV1, minimum exacerbation rate in the previous year and smoking history, responsible for the exclusion of 39.9, 36.7 and 16.8% of patients, respectively.,Altogether, 2.3 to 46.7% of our patients would have satisfied all eligibility criteria.,These analyses confirm that an important gap exists between real-life patients and clinical trials populations in COPD, which limits the relevance of results and therefore should be considered when grading levels of evidence and designing future studies. | Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1.,However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients.,The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.,We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center.,The inclusion criteria were as follows: age ≥40 years, postbron-chodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year.,Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist.,The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug.,Of the 587 patients enrolled in the study, 257 took tiotropium.,Following propensity score matching, 404 patients were included in the analysis.,The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively.,Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13).,Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) is high.,Health benefits can be gained in primary care by early detection and preventive measures.,To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings.,Practices were randomised on strategy and stratified on SES setting.,The Respiratory Health Screening Questionnaire (RHSQ) was distributed to all participants.,In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their RHSQ risk score and applying for a spirometry test.,The main outcome measure was the rate of COPD diagnoses after screening.,More new COPD patients were detected in the practice-managed condition (36%) than in the patient-managed condition (18%).,In low SES practices, more high-risk patients were found (16%) than in moderate-to-high SES practices (9%).,Recalculated for a standard Dutch practice (2,350 patients), the yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases.,The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practices. | 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 |
To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity.,A population-based sample of 3,797 subjects aged 40-80 years from the EPI-SCAN study was selected.,Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) or obese (BMI≥30.0 kg/m2).,Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests.,Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded.,The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8-33.9% vs.,24.3, 95%CI 22.9-25.8; and 44.7%, 95%CI 39.7-49.6% vs.,43.0%, 95%CI 41.3-44.6, respectively; p = 0.020).,In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status.,Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806-12.736, p = 0.002).,In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation.,Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity. | Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.,Data were collected from the National Health Insurance Database of Korea.,The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009.,Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.,The prevalence of GERD in COPD patients was 28% (39,987/141,057).,Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD.,Most of COPD medications except inhaled muscarinic antagonists were associated with GERD.,The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).,The prevalence of GERD in patients with COPD was high.,Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD.,The presence of GERD was associated with COPD exacerbation. | 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. | QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD.,The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD.,This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o.d.,+ FOR 12 µg twice daily (1:1) for 26 weeks.,The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George's Respiratory Questionnaire-COPD (SGRQ-C).,The prespecified non-inferiority margin was 4 units.,Secondary endpoints included Transition Dyspnoea Index (TDI) score, pre-dose FEV1, forced vital capacity (FVC) and safety.,Of the 934 patients randomised (QVA149=476 and TIO+FOR=458), 87.9% completed the study.,At week 26, non-inferiority was met for SGRQ-C (QVA149 vs TIO+FOR; difference: -0.69 units; 95% CI −2.31 to 0.92; p=0.399).,A significantly higher percentage of patients achieved a clinically relevant ≥1 point improvement in TDI total score with QVA149 (49.6%) versus TIO+FOR (42.4%; p=0.033).,QVA149 significantly increased pre-dose FEV1 (+68 mL, 95% CI 37 mL to 100 mL; p<0.001) and FVC (+74 mL, 95% CI 24 mL to 125 mL; p=0.004) compared with TIO+FOR at week 26.,The incidence of adverse events was comparable between both treatments (QVA149=43.7% and TIO+FOR=42.6%).,QVA149 is non-inferior to TIO+FOR in improving HRQoL, with clinically meaningful and significant improvements in breathlessness and lung function in patients with COPD.,NCT01120717. | 1 |
As Barthel Index (BI) quantifies motor impairment but not breathlessness, the use of only this index could underestimate disability in chronic respiratory disease (CRD).,To our knowledge, no study evaluates both motor and respiratory disability in CRD during activities of daily living (ADLs) simultaneously and with a unique tool.,The objective of this study was to propose for patients with CRD an additional tool for dyspnea assessment during ADLs based on BI items named Barthel Index dyspnea.,Comprehensibility, reliability, internal consistency, validity, responsiveness, and ability to differentiate between disease groups were assessed on 219 subjects through an observational study performed in an in-hospital rehabilitation setting.,Good comprehensibility, high reliability (interrater intraclass correlation coefficient was 0.93 [95% confidence interval 0.892-0.964] and test-retest intraclass correlation coefficient was 0.99 [95% confidence interval 0.983-0.994]), good internal consistency (Cronbach’s alpha 0.89), strong concurrent validity with 6 minute walking distance (Pearson r=−0.538, P<0.001) and Medical Research Council (Spearman rS=0.70, P<0.001), good responsiveness after rehabilitation (P<0.001), and good appropriateness of the index were found evidencing patients with different dyspnea severity.,Divergent validity showed weak correlation (Pearson r=−0.38) comparing Barthel Index dyspnea and BI.,The BI based on dyspnea perception proved to be reliable, sensitive, and adequate as a tool for measuring the level of dyspnea perceived in performing basic daily living activities.,A unique instrument simultaneously administered may provide a global assessment of disability during ADLs incorporating both motor and respiratory aspects. | 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 |
Influenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD).,Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs.,Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.,We conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD.,The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria.,The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.,Seventeen articles describing 13 different studies were found to be pertinent to this review.,Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD.,Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation.,Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo.,Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.,Additional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination.,Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.,The online version of this article (doi:10.1186/s12890-017-0420-8) contains supplementary material, which is available to authorized users. | Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression.,However, the effect on tissue structure and turnover is not well described.,There is an urgent clinical need for biomarkers of disease activity associated with disease progression.,Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity.,We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.,69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up.,Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).,Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001).,Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001).,Pro-C3 levels were unchanged.,At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.,Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity.,This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression. | 1 |
Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy. | The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.,Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.,The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years).,Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD.,Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers.,Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates.,While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods.,These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders.,In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach).,Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece.,This was a cross-sectional observational study.,Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece).,The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2).,Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach.,The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A.,Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.,The online version contains supplementary material available at 10.1186/s12890-021-01576-6. | Greece has one of the highest rates of smoking and chronic obstructive pulmonary disease (COPD) in Europe.,The study aimed to record both the disease characteristics among a sample of Greek COPD patients and the nationwide rates of newly diagnosed COPD cases.,In this noninterventional, epidemiological cross-sectional study, a representative nationwide sample of 45 respiratory centers provided data on the following: 1) the demographic and clinical characteristics of COPD patients and 2) newly diagnosed COPD cases monitored over a period of 6 months by each physician.,Data from 6,125 COPD patients were collected.,Advanced age (median age: 68 years), male predominance (71.3%), largely overweight status with median body mass index (BMI) =27.5 kg/m2, high percentage of current and ex-smokers (89.8%), and presence of comorbidities (81.9%) were evident in the sample.,According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 criteria, majority of the COPD patients had moderate or severe airflow limitation (61%).,Severity of airflow limitation was significantly associated with older age, male sex, obesity, ex-smoking status, and presence of comorbidity (all P-values <0.001).,A total of 61.3% of the patients received medication, mostly bronchodilators (64.4%) and fixed-dose combinations of long-acting β2-agonists and inhaled corticosteroids (39.9%), while 35.9% reported taking medication on demand.,The majority (81.1%) of patients reported a preference for fewer inhalations of their bronchodilator therapy.,Based on the mixed-effect Poisson model, the rate of newly diagnosed COPD cases was estimated to be 18.2% (95% confidence interval: 14.9-22.3) per pulmonologist/3 months.,Of those newly diagnosed, the majority of patients had mild or moderate airflow limitation (78.2%).,The Greek Obstructive Lung Disease Epidemiology and health ecoNomics study reflected the real-life profile of COPD patients and provided evidence on the profile of new COPD cases in Greece.,Various demographic factors were delineated, which can assist in designing more effective diagnostic and management strategies for COPD in Greece. | 1 |
There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | 1 |
Mobile health (mHealth) technology is an increasingly recognized and effective method for disease management and has the potential to intervene in pulmonary function, exacerbation risk, and psychological status of patients with chronic obstructive pulmonary disease (COPD).,This study aimed to investigate the feasibility of an mHealth-based COPD management system designed for Chinese remote areas with many potential COPD patients but limited medical resources.,The system was implemented based on a tailored closed-loop care pathway that breaks the heavy management tasks into detailed pieces to be quantified and executed by computers.,Low-cost COPD evaluation and questionnaire-based psychological intervention are the 2 main characteristics of the pathway.,A 6-month prospective observational study at the community level was performed to evaluate the effect of the system.,Primary outcomes included changes in peak expiratory flow values, quality of life measured using the COPD assessment test scale, and psychological condition.,Acute exacerbations, compliance, and adverse events were also measured during the study.,Compliance was defined as the ratio of the actual frequency of self-monitoring records to the prescribed number.,A total of 56 patients was enrolled; 39 patients completed the 6-month study.,There was no significant difference in the mean peak expiratory flow value before and after the 6-month period (366.1, SD 106.7 versus 313.1, SD 116.6; P=.11).,Psychological condition significantly improved after 6 months, especially for depression, as measured using the Patient Health Questionnaire-9 scale (median 6.0, IQR 3.0-9.0 versus median 4.0, IQR 0.0-6.0; P=.001).,The COPD assessment test score after 6 months of intervention was also lower than that at the baseline, and the difference was significant (median 4.0, IQR 1.0-6.0 versus median 3.0, IQR 0.0-6.0; P=.003).,The median overall compliance was 91.1% (IQR 67%-100%).,In terms of acute exacerbation, 110 exacerbations were detected and confirmed by health care providers (per 6 months, median 2.0, IQR 1.0-5.0).,Moreover, 72 adverse events occurred during the study, including 1 death, 19 hospitalizations, and 52 clinic visits due to persistent respiratory symptoms.,We designed and validated a feasible mHealth-based method to manage COPD in remote Chinese areas with limited medical resources.,The proposed closed-loop care pathway was effective at the community level.,Proper education and frequent communication with health care providers may encourage patients’ acceptance and use of smartphones to support COPD self-management.,In addition, WeChat might play an important role in improving patient compliance and psychological distress.,Further research might explore the effect of such systems on a larger scale and at a higher evidence level. | Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 1 |
Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter.,They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes.,Similar to macrophages in other organs and tissues, LMs have natural plasticity and can change phenotype and function depending largely on the microenvironment they reside in.,Phenotype changes in lung tissue macrophages have been implicated in chronic inflammatory responses and disease progression of various chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD).,LMs have a wide variety of functional properties that include phagocytosis (inorganic particulate matter and organic particles, such as viruses/bacteria/fungi), the processing of phagocytosed material, and the production of signaling mediators.,Functioning as janitors of the airways, they also play a key role in removing dead and dying cells, as well as cell debris (efferocytic functions).,We herein review changes in LM phenotypes during chronic lung disease, focusing on COPD, as well as changes in their functional properties as a result of such shifts.,Targeting molecular pathways involved in LM phenotypic shifts could potentially allow for future targeted therapeutic interventions in several diseases, such as COPD. | Pulmonary tuberculosis (PTB) is a risk factor for COPD, but the clinical characteristics and the chest imaging features (emphysema and bronchiectasis) of COPD with previous PTB have not been studied well.,The presence, distribution, and severity of emphysema and bronchiectasis in COPD patients with and without previous PTB were evaluated by high-resolution computed tomography (HRCT) and compared.,Demographic data, respiratory symptoms, lung function, and sputum culture of Pseudomonas aeruginosa were also compared between patients with and without previous PTB.,A total of 231 COPD patients (82.2% ex- or current smokers, 67.5% male) were consecutively enrolled.,Patients with previous PTB (45.0%) had more severe (p=0.045) and longer history (p=0.008) of dyspnea, more exacerbations in the previous year (p=0.011), and more positive culture of P. aeruginosa (p=0.001), compared with those without PTB.,Patients with previous PTB showed a higher prevalence of bronchiectasis (p<0.001), which was more significant in lungs with tuberculosis (TB) lesions, and a higher percentage of more severe bronchiectasis (Bhalla score ≥2, p=0.031), compared with those without previous PTB.,The overall prevalence of emphysema was not different between patients with and without previous PTB, but in those with previous PTB, a higher number of subjects with middle (p=0.001) and lower (p=0.019) lobe emphysema, higher severity score (p=0.028), higher prevalence of panlobular emphysema (p=0.013), and more extensive centrilobular emphysema (p=0.039) were observed.,Notably, in patients with TB lesions localized in a single lung, no difference was found in the occurrence and severity of emphysema between the 2 lungs.,COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations.,While PTB may have a local effect on bronchiectasis, its involvement in airspace damage in COPD may be extensive, probably through interactions with cigarette smoke. | 1 |
It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | 1 |
Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless.,There is a need to develop additional strategies to alleviate symptoms.,Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.,To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients.,The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist.,In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.,In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02.,Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs.,+0.8(1.7) p = 0.03.,Singing did not improve single breath counting, breath hold time or shuttle walk distance.,In the qualitative element, 8 patients from the singing group were interviewed.,Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.,Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.,Current Controlled Trials - ISRCTN17544114. | This study aimed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life (QoL) of COPD patients.,Forty-three patients were randomized to weekly classes of singing practice, or handcraft work.,They performed spirometry and completed maximal respiratory pressure measurements, evaluations of dyspnea, and the Saint George’s Respiratory Questionnaire, before and after 24 training classes.,A functional evaluation, immediately after 10 minutes of singing practice, was also performed at the end of the study.,Fifteen subjects completed the study in each group.,In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale (p = 0.02), and inspiratory capacity (p = 0.01), and decreases of expiratory reserve volume (p = 0.03), just after a short session of singing.,There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training.,While the control group showed deterioration of maximal expiratory pressure, the singing group exhibited a small improvement (p = 0.05).,Both groups showed significant improvements of QoL in within group comparisons.,We have concluded that singing classes are a well tolerated activity for selected subjects with COPD.,Regular practice of singing may improve QoL, and preserve the maximal expiratory pressure of these patients. | 1 |
Long-acting β2-agonists (LABAs) have demonstrated efficacy in patients with COPD in clinical trials.,The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis.,A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 μg twice daily [BID]; formoterol 12 μg BID; indacaterol 75, 150, and 300 μg once daily [OD]; olodaterol 5 and 10 μg OD, and vilanterol 25 μg OD).,Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV1), transition dyspnea index focal score, St George’s Respiratory Questionnaire total score, and rate of COPD exacerbations.,The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis.,At 12 and 24 weeks, indacaterol 300 and 150 μg OD were associated with statistically significant improvement in trough FEV1 compared to all other LABA monotherapies; vilanterol 25 μg OD was superior to formoterol 12 μg BID.,At 12 weeks, indacaterol 75 μg OD was associated with significant improvement in trough FEV1 compared to formoterol 12 μg BID and olodaterol (5 and 10 μg OD); salmeterol 50 μg BID was superior to formoterol 12 μg BID and olodaterol 5 μg OD.,Indacaterol 300 μg OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks.,Indacaterol 150 μg OD had significantly better results in exacerbation rates than olodaterol 5 μg and olodaterol 10 μg OD.,Indacaterol 300 μg, followed by 150 and 75 μg, were the most effective LABA monotherapies for moderate to severe COPD. | COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features.,In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry.,The severity of the airflow limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management.,However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1.,At present, there is a lack of reliable and simple blood biomarkers to confirm and further assess the diagnosis of COPD.,However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes.,Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and “frequent exacerbators”.,Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as “asthma COPD overlap syndrome”.,Several other phenotypes have been proposed, but require validation against clinical outcomes.,Defining phenotypes requires the assessment of multiple factors indicating disease severity, its impact, and its activity.,Recognition and validation of COPD phenotypes has an important role to play in the selection of evidence-based targeted therapy in the future management of COPD, but regardless of the diagnostic terms, patients with COPD should be assessed and treated according to their individual treatable characteristics. | 1 |
We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.,This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy.,Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa.,The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population.,The incidence of adverse events was also assessed.,In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population.,UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001].,Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14).,Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.,In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD.,Both treatments had similar safety profiles.,These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.,ClinicalTrials.gov identifier NCT02799784.,GlaxoSmithKline.,The online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users. | Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | 1 |
The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe exacerbations of COPD.,This is a prespecified analysis of the DYNAGITO data in Japanese patients.,Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe exacerbation in the previous 12 months.,Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese.,The primary endpoint was the annualized rate of moderate-to-severe COPD exacerbations.,The key secondary endpoint was the time to first moderate-to-severe COPD exacerbation, and other secondary endpoints included the annualized rate of exacerbations leading to hospitalization, time to first COPD exacerbation leading to hospitalization, and all-cause mortality.,Safety data were analyzed descriptively.,Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434).,The risk of a first moderate-to-severe COPD exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant.,The annualized rate of COPD exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654).,The adverse event incidence was balanced between treatment arms.,In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations.,Both treatments were well tolerated. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 1 |
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. | 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 |
Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD).,Resveratrol (trans-3,5,4′-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties.,The study aimed to investigate the effects of resveratrol in a rat model with COPD on the regulation of oxidative stress and inflammation via the activation of Sirtuin1 (SIRTl) and proliferator-activated receptor-γ coactivator-1α (PGC-1α).,Thirty Wistar rats were randomly divided into three groups: control group, COPD group and resveratrol intervention group.,The COPD model was established by instilling with lipopolysaccharide (LPS) and challenging with cigarette smoke (CS).,The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in serum were measured.,The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured.,The expression levels of SIRT1 and PGC-1α in the lung tissues were examined by immunohistochemistry as well as real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting analysis.,After the treatment with resveratrol (50 mg/kg), compared with the COPD group, alleviation of inflammation and reconstruction in the small airways of the lungs were seen.,Resveratrol might be correlated not only with the lower level of MDA and the higher activity of SOD, but also with the upregulation of SIRT1 and PGC-1α expression.,Resveratrol treatment decreased serum levels of IL-6 and IL-8.,Our findings indicate that resveratrol had a therapeutic effect in our rat COPD model, which is related to the inhibition of oxidative stress and inflammatory response.,The mechanism may be related to the activation and upgrading of the SIRT1/PGC-1α signaling pathways.,Thus resveratrol might be a therapeutic modality in COPD. | Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes.,Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown.,We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.,This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations.,Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo.,The primary end point was mean in-hospital blood glucose concentration.,Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.,52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo).,All were included in the primary end point analysis.,The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273).,No significant between-group differences were observed on any of the secondary end points.,Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.,Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.,ISRCTN66148745 and NCT01247870. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with cognitive impairment, but consequences of this association on a person’s functional limitations are unclear.,We examined the association between COPD and increased confusion and memory loss (ICML) and functional limitations among adults with COPD.,We studied adults aged 45 years or older in 21 states who participated in the 2011 Behavioral Risk Factor Surveillance System (n = 102,739).,Presence of COPD was based on self-reported physician diagnosis.,ICML was based on self-report that confusion or memory loss occurred more often or worsened during the prior year.,ICML-associated difficulties were defined as giving up household chores and former activities, decreased ability to work or engage in social activities, or needing help from family or friends during the prior year due to ICML.,General limitations were defined as needing special equipment as a result of a health condition, having had activity limitations for 2 weeks or more in the prior month, or being unable to work.,Multivariable models were adjusted for demographics, health behaviors or conditions, and frequent mental distress.,COPD was reported by 9.3% of adults.,ICML was greater among those with COPD than among those without COPD (25.8% vs 11%; adjusted prevalence ratio [aPR], 1.48; 95% confidence interval [CI], 1.32%-1.66%).,People with COPD, either with or without ICML, were more likely than those without COPD to report general functional limitations.,Among people reporting ICML, those with COPD were more likely to report interference with work or social activities than those without COPD (aPR, 1.17; 95% CI, 1.01%-1.36%).,Functional limitations were greater among those with COPD than among those without, and ICML may further affect these limitations.,Results from our study can inform future studies of self- management and functional limitations for people with COPD. | The aim was to gain insight into how patients with advanced chronic obstructive pulmonary disease (COPD) experience care in the acute phase.,The study has a qualitative design with a phenomenological approach.,The empirics consist of qualitative in-depth interviews with ten patients admitted to the intensive care units in two Norwegian hospitals.,The interviews were carried out from November 2009 to June 2011.,The data have been analysed through meaning condensation, in accordance with Amadeo Giorgi's four-step method.,Kari Martinsen's phenomenological philosophy of nursing has inspired the study.,An essential structure of the patients' experiences of care in the intensive care unit by acute COPD-exacerbation may be described as: Feelings of being trapped in a life-threatening situation in which the care system assumes control over their lives.,This experience is conditioned not only by the medical treatment, but also by the entire interaction with the caregivers.,The essence of the phenomenon is presented through three themes which describe the patient's lived experience: preserving the breath of life, vulnerable interactions and opportunities for better health.,Acute COPD-exacerbation is a traumatic experience and the patients become particularly vulnerable when they depend on others for breathing support.,The phenomenological analysis shows that the patients experience good care during breath of life preservation when the care is performed in a way that gives patients more insight into their illness and gives new opportunities for the future. | 1 |
We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.,This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy.,Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa.,The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population.,The incidence of adverse events was also assessed.,In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population.,UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001].,Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14).,Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.,In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD.,Both treatments had similar safety profiles.,These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.,ClinicalTrials.gov identifier NCT02799784.,GlaxoSmithKline.,The online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users. | The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds. | 1 |
Geographic clusters in prevalence and hospitalizations for COPD have been identified at national, state, and county levels.,The study objective is to identify county-level geographic accessibility to pulmonologists for adults with COPD.,Service locations of 12,392 practicing pulmonologists and 248,160 primary care physicians were identified from the 2013 National Provider Identifier Registry and weighted by census block-level populations within a series of circular distance buffer zones.,Model-based county-level population counts of US adults ≥ 18 years of age with COPD were estimated from the 2013 Behavioral Risk Factor Surveillance System.,The percentages of all estimated adults with potential access to at least one provider type and the county-level ratio of adults with COPD per pulmonologist were estimated for selected distances.,Most US adults (100% in urbanized areas, 99.5% in urban clusters, and 91.7% in rural areas) had geographic access to a primary care physician within a 10-mile buffer distance; almost all (≥ 99.9%) had access to a primary care physician within 50 miles.,At least one pulmonologist within 10 miles was available for 97.5% of US adults living in urbanized areas, but only for 38.3% in urban clusters and 34.5% in rural areas.,When distance increased to 50 miles, at least one pulmonologist was available for 100% in urbanized areas, 93.2% in urban clusters, and 95.2% in rural areas.,County-level ratios of adults with COPD per pulmonologist varied greatly across the United States, with residents in many counties in the Midwest having no pulmonologist within 50 miles.,County-level geographic variations in pulmonologist access for adults with COPD suggest that those adults with limited access will have to depend on care from primary care physicians. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.,Design Cluster randomised controlled parallel group trial.,Setting Ambulance service in Hobart, Tasmania, Australia.,Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.,Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.,Main outcome measure Prehospital or in-hospital mortality.,Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97).,Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm.,Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04).,Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.,Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease.,These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.,Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291. | 1 |
To obtain evidence whether the online pulmonary rehabilitation(PR) programme ‘my-PR’ is non-inferior to a conventional face-to-face PR in improving physical performance and symptom scores in patients with COPD.,A two-arm parallel single-blind, randomised controlled trial.,The online arm carried out pulmonary rehabilitation in their own homes and the face to face arm in a local rehabilitation facility.,90 patients with a diagnosis of chronic obstructive pulmonary disease (COPD), modified Medical Research Council score of 2 or greater referred for pulmonary rehabilitation (PR), randomised in a 2:1 ratio to online (n=64) or face-to-face PR (n=26).,Participants unable to use an internet-enabled device at home were excluded.,Coprimary outcomes were 6 min walk distance test and the COPD assessment test (CAT) score at completion of the programme.,A 6-week PR programme organised either as group sessions in a local rehabilitation facility, or online PR via log in and access to 'myPR’.,The adjusted mean difference for the 6 min walk test (6MWT) between groups for the intention-to-treat (ITT) population was 23.8 m with the lower 95% CI well above the non-inferiority threshold of −40.5 m at −4.5 m with an upper 95% CI of +52.2 m.,This result was consistent in the per-protocol (PP) population with a mean adjusted difference of 15 m (−13.7 to 43.8).,The CAT score difference in the ITT was −1.0 in favour of the online intervention with the upper 95% CI well below the non-inferiority threshold of 1.8 at 0.86 and the lower 95% CI of −2.9.,The PP analysis was consistent with the ITT.,PR is an evidenced-based and guideline-mandated intervention for patients with COPD with functional limitation.,A 6-week programme of online-supported PR was non-inferior to a conventional model delivered in face-to-face sessions in terms of effects on 6MWT distance, and symptom scores and was safe and well tolerated. | 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 |
Background: To validate the ‘Test of Adherence to Inhalers’ (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma.,Methods: A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study.,Patients with electronic adherence ≥80% were defined as adherents.,Construct validity, internal validity, and criterion validity were evaluated.,Self-reported adherence was compared with the Morisky-Green questionnaire.,Results: Factor analysis study demonstrated two factors, factor 1 was coincident with TAI patient domain (items 1 to 10) and factor 2 with TAI health-care professional domain (items 11 and 12).,The Cronbach's alpha was 0.860 and the test-retest reliability 0.883.,TAI scores correlated with electronic adherence (ρ=0.293, p=0.01).,According to the best cut-off for 10 items (score 50, area under the ROC curve 0.7), 569 (62.5%) patients were classified as non-adherents.,The non-adherence behavior pattern was: erratic 527 (57.9%), deliberate 375 (41.2%), and unwitting 242 (26.6%) patients.,As compared to Morisky-Green test, TAI showed better psychometric properties.,Conclusions: The TAI is a reliable and homogeneous questionnaire to identify easily non-adherence and to classify from a clinical perspective the barriers related to the use of inhalers in asthma and COPD. | The purpose of this study was to evaluate the frequency of inadequate diagnosis and factors predictive of this in patients with chronic obstructive pulmonary disease (COPD) participating in the On-Sint study.,The On-Sint cohort was recruited for a multicenter observational study in which 356 physicians (71.6% from primary care) included adult patients who had been diagnosed with COPD.,Patients’ clinical and functional information since diagnosis and details for the recruiting physicians were collected from patient files and at the inclusion visit.,We performed a multivariate analysis to evaluate the influence of these variables on diagnostic inadequacy (absence of postbronchodilator forced expiratory volume in one second/forced vital capacity [FEV1/FVC] <0.70 or, if this value was missing, prebronchodilator FEV1/FVC <0.70).,In total, 1,214 patients were included in the study.,The patients had a mean age of 66.4±9.7 years and 78.8% were male.,In total, 51.3% of patients did not have an obstructive spirometry performed, and 21.4% had a normal or non-obstructive spirometry pattern.,Patient-related factors associated with inadequate diagnosis were: years since diagnosis (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05), number of exacerbations in the previous year (OR 1.01, 95% CI 1.01-1.02), comorbidities (OR 1.05, 95% CI 1.01-1.015), and obesity (OR 1.06, 95% CI 1.02-1.10 per kg/m2 of body mass index), while a longer smoking history (OR 0.98, 95% CI 0.97-0.99 for each pack/year) and short-acting or long-acting bronchodilator therapy (OR 0.61, 95% CI 0.44-0.76 and OR 0.46, 95% CI 0.27-0.76, respectively) were inversely related.,With regard to physician-related variables, being followed up by primary care physicians (OR 3.0, 95% CI 2.11-4.34) and in rural centers (OR 1.63, 95% CI 1.12-2.38) were positively associated with an inadequate diagnosis, while having regular follow-ups in the most severe cases (OR 0.66, 95% CI 0.46-0.93) and use of quality of life questionnaires (OR 0.55, 95% CI 0.40-0.76) were negatively associated.,Diagnosis of COPD was inadequate in half of the patients from the On-Sint cohort.,There were multiple factors, both patient-related and physician-related, associated with this misdiagnosis. | 1 |
To examine the relationship between gastroesophageal reflux (GER) and COPD exacerbations.,We conducted a systematic search of various electronic databases for articles published up through December of 2012.,Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations) for the association between GER and COPD-as well as exacerbation rates.,Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment; and severity of airflow obstruction.,Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36).,The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001).,GER is a risk factor for COPD exacerbations.,The role of GER in COPD management should be studied in greater detail. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
The human α/β hydrolase domain-containing protein 2 gene (ABHD2) plays a critical role in pulmonary emphysema, a major subset of the clinical entity known as chronic obstructive pulmonary disease (COPD).,Here, we evaluated genetic variation in the ABHD2 gene in a Chinese Han population of 286 COPD patients and 326 control subjects.,The rs12442260 CT/CC genotype was associated with COPD (P < 0.001) under a dominant model.,In the former-smoker group, the rs12442260 TT genotype was associated with a decreased risk of developing COPD after adjusting for age, gender and pack-years (P = 0.012).,Rs12442260 was also associated with pre-FEV1 (the predicted bronchodilator forced expiratory volume in the first second) in controls (P = 0.027), but with FEV1/ forced vital capacity (FVC) ratios only in COPD patients (P = 0.012) under a dominant model.,Results from the current study suggest that ABHD2 gene polymorphisms contribute to COPD susceptibility in the Chinese Han population. | Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | 1 |
The study aimed to determine the relationship between throat microbiome and COPD.,Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD) were included.,Nonmetric multidimensional scaling indicated differences of microbiome between COPD and controls, but no difference was observed between COPD patients with differing degrees of lung function or disease severity.,Rarefaction analyses suggested that operational taxonomic units (OTUs, species-level) richness decreased in COPD.,The dominant taxa between COPD and controls were similar, but the proportions of taxonomic distribution were different.,The dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria.,The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Veillonella, Streptococcus, Neisseria and Prevotella.,Two dominant OTUs, otu3 (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified.,Otu3 and its father-level taxa, which were negatively correlated with predicted percent of forced expiratory volume in a second (FEV1%pred), were increased in COPD.,By contrast, otu4 and its father-level taxa, which were positively correlated with FEV1%pred, were decreased in COPD.,Otu4 also showed a slight potential as a COPD biomarker.,To conclude, the throat microbiome was different between smokers with or without COPD, which is similar to findings from the lower respiratory tract.,This study may strengthen our understanding of the relationship between microbiomes of different airway sites and COPD. | 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 |
COPD patients are often prescribed multiple medications for their respiratory disease and comorbidities.,This can lead to complex medication regimens resulting in poor adherence, medication errors, and drug-drug interactions.,The relationship between clinical outcomes and medication burden beyond medication count in COPD is largely unknown.,The aim of this study was to explore the relationships of medication burden in COPD with clinical outcomes, comorbidities, and multidimensional indices.,In a cross-sectional study, COPD patients (n=222) were assessed for demographic information, comorbidities, medication use, and clinical outcomes.,Complexity of medication regimens was quantified using the validated medication regimen complexity index (MRCI).,Participants (58.6% males) had a mean (SD) age of 69.1 (8.3) years with a postbronchodilator forced expiratory volume in 1 second % predicted of 56.5 (20.4) and a median of five comorbidities.,The median (q1, q3) total MRCI score was 24 (18.5, 31).,COPD-specific medication regimens were more complex than those of non-COPD medications (median MRCI: 14.5 versus 9, respectively; P<0.0001).,Complex dosage formulations contributed the most to higher MRCI scores of COPD-specific medications while dosing frequency primarily drove the complexity associated with non-COPD medications.,Participants in Global Initiative for Chronic Obstructive Lung Disease quadrant D had the highest median MRCI score for COPD medications (15.5) compared to those in quadrants A (13.5; P=0.0001) and B (12.5; P<0.0001).,Increased complexity of COPD-specific treatments showed significant but weak correlations with lower lung function and 6-minute walk distance, higher St George’s Respiratory Questionnaire and COPD assessment test scores, and higher number of prior year COPD exacerbations and hospitalizations.,Comorbid cardiovascular, gastrointestinal, or metabolic diseases individually contributed to higher total MRCI scores and/or medication counts for all medications.,Charlson Comorbidity Index and COPD-specific comorbidity test showed the highest degree of correlation with total MRCI score (ρ=0.289 and ρ=0.326; P<0.0001, respectively).,In COPD patients, complex medication regimens are associated with disease severity and specific class of comorbidities. | The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management.,A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD.,The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management.,Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation.,Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD.,Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations.,Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD.,In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence.,Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. | 1 |
The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD.,Differentially expressed genes (DEGs) were screened using the Limma package in R.,A protein-protein interaction (PPI) network of DEGs was built based on the STRING database.,Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID.,Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software.,In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened.,Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes.,The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction.,Additionally, 39 key AECOPD-related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a.,In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD. | Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization.,The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013.,Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years.,Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups.,Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions).,From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%.,Mean age at diagnosis was 66 years and 52.0% were male.,Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81-0.85) for GOLD A to 2.51 (95% CI: 2.47-2.55) for GOLD D.,General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74-4.93) for GOLD A to 7.44 (95% CI: 7.31-7.61) for GOLD D.,COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84).,Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits.,Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization. | 1 |
Antibiotic treatment is one of the major pharmacologic treatments for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,However, the choice of antibiotic depends on the local resistance pattern.,A multicenter, randomized, controlled trial was done in patients with AECOPD to compare the efficacy of levofloxacin with that of cefuroxime axetil.,Patients with AECOPD and without radiographic evidence of pneumonia were enrolled and randomized to either levofloxacin 500 mg daily or cefuroxime 250 mg twice daily in the mildmoderate exacerbation group, or 500 mg twice daily in the severe exacerbation group, for seven days.,Clinical efficacy and microbiologic response were evaluated 5-7 days after the last dose.,Treatment was clinically successful in 90.4% of patients in the levofloxacin group, and in 90.6% of patients in the cefuroxime group (95% confidence interval −9.40 to 10.91), within a noninferiority margin of 10%.,The microbiologic response appeared to be higher in the levofloxacin group, but the difference was not statistically significant.,The safety profile was similar in both groups.,Levofloxacin is not inferior to cefuroxime with regard to clinical efficacy in treating AECOPD. | Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment.,More evidence is needed to guide antibiotic choice.,The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study.,Patients were aged ≥60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s <60% predicted and two or more exacerbations in the last year.,Following stratification by steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days).,The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population.,Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%).,In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016).,Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003).,Patients treated with oral corticosteroids had more severe disease and higher failure rates.,The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD.,Both therapies were well tolerated. | 1 |
Observational studies suggest that immunoglobulin treatment may reduce the frequency of acute exacerbations of COPD (AECOPD).,To inform the design of a future randomised control trial (RCT) of intravenous immunoglobulin (IVIG) treatment efficacy for AECOPD prevention.,A pilot RCT was conducted.,We recruited patients with COPD hospitalized for AECOPD, or from ambulatory clinics with one severe, or two moderate AECOPD in the previous year regardless of their serum IgG level.,Patients were allocated in a 1:1 ratio with balanced randomisation to monthly IVIG or normal saline for 1 year.,The primary outcome was feasibility defined as pre-specified accrual, adherence, and follow-up rates.,Secondary outcomes included safety, tolerance, AECOPD rates, time to first AECOPD, quality of life, and healthcare costs.,Seventy patients were randomized (37 female; mean age 67.7; mean FEV1 35.1%).,Recruitment averaged 4.5±0.9 patients per month (range 0-8), 34 (49%) adhered to at least 80% of planned treatments, and four (5.7%) were lost to follow-up.,There were 35 serious adverse events including seven deaths and one thromboembolism.,None was related to IVIG.,There were 56 and 48 moderate and severe AECOPD in the IVIG vs control groups.,In patients with at least 80% treatment adherence, median time to first moderate or severe AECOPD was 275 vs 114 days, favoring the IVIG group (HR 0.76, 95% CI 0.3-1.92).,The study met feasibility criteria for recruitment and retention, but adherence was low.,A trend toward more robust treatment efficacy in adherent patients supports further study, but future trials must address treatment adherence.,NCT0290038, registered 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690038 and NCT03018652, registered January 12, 2017, https://clinicaltrials.gov/ct2/show/NCT03018652. | Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase.,The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.,Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months.,The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction.,Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase.,These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients.,In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results.,Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients.,The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations.,Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients. | 1 |
To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study.,Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan.,After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95% confidence interval [CI] =1.20-1.30), and there was an increase in the OR with increase in the average daily dosage.,Additionally, users of fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95% CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39, respectively).,In contrast, there were no statistically significant associations between the risk of pneumonia and the use of budesonide/formoterol, budesonide, or either budesonide/formoterol or budesonide.,In conclusion, ICSs are significantly associated with an increased risk of pneumonia in COPD patients.,The effect is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs. | To identify if there is a dose-dependent risk of diabetes complications in patients treated with corticosteroids who have both diabetes and chronic obstructive pulmonary disorder (COPD).,A retrospective study of administrative claims data from the Australian Government Department of Veterans’ Affairs, from 1 July 2001 to 30 June 2008, of diabetes patients newly initiated on metformin or sulfonylurea.,COPD was identified by dispensings of tiotropium or ipratropium in the 6 months preceding study entry.,Total corticosteroid use (inhaled and systemic) in the 12 months after study entry was determined.,The outcome was time to hospitalization for a diabetes-related complication.,Competing risks and Cox proportional hazard regression analyses were conducted with adjustment for a number of covariates.,A total of 18,226 subjects with diabetes were identified, of which 5.9% had COPD.,Of those with COPD, 67.2% were dispensed corticosteroids in the 12 months from study entry.,Stratification by dose of corticosteroids demonstrated a 94% increased likelihood of hospitalization for a diabetes complication for those who received a total defined daily dose (DDD) of corticosteroids ≥0.83/day (subhazard ratio 1.94 [95% CI 1.14-3.28], P = 0.014), by comparison with those who did not receive a corticosteroid.,Lower doses of corticosteroid (<0.83 DDD/day) were not associated with an increased risk of diabetes-related hospitalization.,In patients with diabetes and COPD, an increased risk of diabetes-related hospitalizations was only evident with use of high doses of corticosteroids.,This highlights the need for constant revision of corticosteroid dose in those with diabetes and COPD, to ensure that the minimally effective dose is used, together with review of appropriate response to therapy. | 1 |
People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity.,The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up.,In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR), health education with upper body resistance training (ED-UBR), or health education with gentle chair exercises (ED-Chair).,Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory.,Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up.,The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity.,Differences were observed in light physical activity (LPA) after 4 months of training, time by group interaction effect (P=0.045).,The SE-UBR group increased time spent in LPA by +20.68±29.30 minutes/day and the other groups decreased time spent in LPA by −22.43±47.88 minutes/day and -25.73±51.76 minutes/day.,Changes in LPA were not sustained at 12-month follow-up.,There were no significant changes in moderate-to-vigorous physical activity, sedentary time, or functional performance.,Subjects spent most of their waking hours sedentary: 72%±9% for SE-UBR, 68%±10% for ED-UBR, and 74%±9% for ED-Chair.,The self-efficacy enhancing intervention produced a modest short-term increase in LPA.,Further work is needed to increase the magnitude and duration of effect, possibly by targeting LPA. | In patients with COPD progressive dyspnoea leads to a sedentary lifestyle.,To date, no studies exist investigating the effects of Nordic Walking in patients with COPD.,Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages.,Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity.,Sixty COPD patients were randomised to either Nordic Walking or to a control group.,Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV1: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention.,Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD).,Assessment time points in both groups: baseline, after three, six and nine months.,After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s2) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01).,Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01).,These significant improvements were sustained six and nine months after baseline.,In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points.,Nordic Walking is a feasible, simple and effective physical training modality in COPD.,In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.,Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632 | 1 |
Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers.,We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS.,These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17.,Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD exacerbations, and emphysema.,Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs).,Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3-5% of the measurement variance on top of clinical variables.,IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years.,None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations.,We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements.,When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone.,COPDGene (ClinicalTrials.gov Identifier: NCT02445183).,Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344).,The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users. | Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs.,CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs.,The objective of this study was to investigate mechanisms of monocyte recruitment to the lung in COPD, including the role of CCR5 signalling.,Ninety one COPD patients, 29 smokers (S) and 37 non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by flow cytometry) and monocyte isolation for cell migration and quantitative polymerase chain reaction studies.,Lung tissue was used for immunohistochemistry.,Plasma IL-6 and sIL-6R levels were increased in COPD.,Greater proportions of COPD CD14++CD16+ monocytes expressed CCR5 compared to controls.,Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression.,COPD monocytes demonstrated impaired migration towards sputum supernatant compared to NS (% migration, 4.4 vs 11.5, respectively; p < 0.05).,Pulmonary microvessels showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS, (9.3% vs 83.1%, respectively).,The proportion of replicating Ki67+ alveolar macrophages was reduced in COPD compared to NS.,All alveolar macrophages from COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present in non-smokers or COPD ex-smokers.,COPD monocytes show decreased migratory ability despite increased CCR5 expression.,Increased COPD lung macrophage numbers may be due to delayed apoptosis.,The online version of this article (doi:10.1186/s12931-017-0569-y) contains supplementary material, which is available to authorized users. | 1 |
Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease.,However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD).,This is a post-hoc analysis of a study which enrolled a population of adults aged 35-79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000.,In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels.,We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia.,To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures.,In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs.,49.2 (SD 9.1); p < 0.0001].,Among patients with COPD (n = 495) the PF scores (39.9 vs.,45.4) and the PCS (41.9 vs.,45.9) were significantly lower in individuals with anemia compared to those without.,In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003).,There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD.,In patients with moderate to very severe COPD anemia may be associated with worse HRQL.,However, co-morbidities may explain part or all of this association in these patients. | 1 |
This retrospective, observational study of a routine clinical practice reports the feasibility and efficiency of home-based pulmonary rehabilitation (PR), including transcutaneous neuromuscular electrical stimulation (NMES) or usual endurance physical exercise (UEPE), on exercise tolerance, anxiety/depression, and health-related quality of life (HRQoL) in patients with COPD.,Seventy-one patients with COPD participated in home-based PR with NMES (Group NMES [GNMES]), while 117 patients participated in home-based PR with the UEPEs (Group UEPE [GUEPE]).,NMES was applied for 30 minutes twice a day, every day.,The endurance exercises in GUEPE began with a minimum 10-minute session at least 5 days a week, with the goal being 30-45 minutes per session.,Three upper and lower limb muscle strengthening exercises lasting 10-15 minutes were also proposed to both the groups for daily practice.,Moreover, PR in both the groups included a weekly 90-minute session based on an educational needs assessment.,The sessions comprised endurance physical exercise for GUEPE, NMES for GNMES, resumption of physical daily living activities, therapeutic patient education, and psychosocial support to facilitate health behavior changes.,Before and after PR, functional mobility and physical exercise capacity, anxiety, depression, and HRQoL were evaluated at home.,The study revealed that NMES significantly improved functional mobility (−18.8% in GNMES and −20.6% in GUEPE), exercise capacity (+20.8% in GNMES and +21.8% in GUEPE), depression (−15.8% in GNMES and −30.1% in GUEPE), and overall HRQoL (−7.0% in GNMES and −18.5% in GUEPE) in the patients with COPD, regardless of the group (GNMES or GUEPE) or severity of airflow obstruction.,Moreover, no significant difference was observed between the groups with respect to these data (P>0.05).,Home-based PR including self-monitored NMES seems feasible and effective for severely disabled COPD patients with severe exercise intolerance. | Neuromuscular electrical stimulation (NMES) of the lower limbs is an emerging training strategy in patients with COPD.,The efficacy of this technique is related to the intensity of the stimulation that is applied during the training sessions.,However, little is known about tolerance to stimulation current intensity and physiological factors that could determine it.,Our goal was to find potential physiological predictors of the tolerance to increasing NMES stimulation intensity in patients with mild to severe COPD.,20 patients with COPD (FEV1 = 54±14% pred.) completed 2 supervised NMES sessions followed by 5 self-directed sessions at home and one final supervised session.,NMES was applied simultaneously to both quadriceps for 45 minutes, at a stimulation frequency of 50 Hz.,Spirometry, body composition, muscle function and aerobic capacity were assessed at baseline.,Cardiorespiratory responses, leg discomfort, muscle fatigue and markers of systemic inflammation were assessed during or after the last NMES session.,Tolerance to NMES was quantified as the increase in current intensity from the initial to the final NMES session (ΔInt).,Mean ΔInt was 12±10 mA.,FEV1, fat-free-mass, quadriceps strength, aerobic capacity and leg discomfort during the last NMES session positively correlated with ΔInt (r = 0.42 to 0.64, all p≤0.06) while post/pre NMES IL-6 ratio negatively correlated with ΔInt (r = −0.57, p = 0.001).,FEV1, leg discomfort during last NMES session and post/pre IL-6 ratio to NMES were independent factors of variance in ΔInt (r2 = 0.72, p = 0.001).,Lower tolerance to NMES was associated with increasing airflow obstruction, low tolerance to leg discomfort during NMES and the magnitude of the IL-6 response after NMES.,ClinicalTrials.gov NCT00809120 | 1 |
Previous models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection.,Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable.,In a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC).,The primary outcome was health and social costs at 90 days.,Mean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI −2343 to 312).,Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1-7), UC=5 (IQR 2-12) (P=0.001).,Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected.,Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%.,There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD.,HAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients.,Compared with earlier models, selection is simpler and approximately twice as many patients are eligible.,The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge.,Registered prospectively ISRCTN29082260. | Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.,Design Cluster randomised controlled parallel group trial.,Setting Ambulance service in Hobart, Tasmania, Australia.,Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.,Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.,Main outcome measure Prehospital or in-hospital mortality.,Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97).,Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm.,Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04).,Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.,Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease.,These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.,Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291. | 1 |
There are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time.,Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations.,The CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention.,The evolution of the CAT was analyzed using linear regression.,The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen-Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors.,The median CAT at inclusion was 17 (interquartile range 13-22) points.,During the study, 25% of patients had a significant negative slope (median −7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy).,The median slope of the CAT in the overall cohort was +1 (interquartile range −3 to +6) ppy.,A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03-1.13; p<0.001).,There was an 8% increase of the risk of exacerbation per unit increase in CAT.,We detected a significant learning effect in filling out the CAT in 18.4% of patients with a median learning phase of five filled questionnaires.,Sixty-three percent of the COPD patients monitored by THC experienced a stable or improved CAT during 1-year follow-up.,We found a significant positive association between the evolution of the CAT over time and the risk of exacerbations.,In about one-fifth of patients, there was a significant learning effect in filling out the CAT, before reliable results could be obtained.,The evolution of the CAT could help to assess the risk for future exacerbations. | Telemedicine may increase accessibility to pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD), thus enhancing long-term exercise maintenance.,We aimed to explore COPD patients’ adherence and experiences in long-term telerehabilitation to understand factors affecting satisfaction and potential for service improvements.,A two-year pilot study with 10 patients with COPD was conducted.,The intervention included treadmill exercise training at home and a webpage for telemonitoring and self-management combined with weekly videoconferencing sessions with a physiotherapist.,We conducted four separate series of data collection.,Adherence was measured in terms of frequency of registrations on the webpage.,Factors affecting satisfaction and adherence, together with potential for service improvements, were explored through two semi-structured focus groups and an individual open-ended questionnaire.,Qualitative data were analysed by systematic text condensation.,User friendliness was measured by the means of a usability questionnaire.,On average, participants registered 3.0 symptom reports/week in a web-based diary and 1.7 training sessions/week.,Adherence rate decreased during the second year.,Four major themes regarding factors affecting satisfaction, adherence and potential improvements of the intervention emerged: (i) experienced health benefits; (ii) increased self-efficacy and independence; and (iii) emotional safety due to regular meetings and access to special competence; (iv) maintenance of motivation.,Participants were generally highly satisfied with the technical components of the telerehabilitation intervention.,Long-term adherence to telerehabilitation in COPD was maintained for a two-year period.,Satisfaction was supported by experienced health benefits, self-efficacy, and emotional safety.,Maintenance of motivation was a challenge and might have affected long-term adherence.,Four key factors of potential improvements in long-term telerehabilitation were identified: (i) adherence to different components of the telerehabilitation intervention is dependent on the level of focus provided by the health personnel involved; (ii) the potential for regularity that lies within the technology should be exploited to avoid relapses after vacation; (iii) motivation might be increased by tailoring individual consultations to support experiences of good health and meet individual goals and motivational strategies; (iv) interactive functionalities or gaming tools might provide peer-support, peer-modelling and enhance motivation. | 1 |
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice.,The aim of this study was to explore the factors associated with the use of ICS in these patients.,The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan.,Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients.,Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively).,The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients.,Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14-4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24-2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40-2.96; P<0.001).,The COPD assessment test score was also associated with an ICS prescription in group B (OR, 1.04; 95% CI, 1.00-1.07; P=0.038).,About one-third of the GOLD group A and B patients with COPD in Taiwan are prescribed ICS.,Our findings suggest that wheezing and COPD assessment test score are related to the prescription of ICS in these patients. | 1 |
Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Diet and nutrition may be important modifiable risk factors for the development, progression and management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).,This review examines the relationship between dietary patterns, nutrient intake and weight status in obstructive lung diseases, at different life stages, from in-utero influences through childhood and into adulthood.,In vitro and animal studies suggest important roles for various nutrients, some of which are supported by epidemiological studies.,However, few well-designed human intervention trials are available to definitively assess the efficacy of different approaches to nutritional management of respiratory diseases.,Evidence for the impact of higher intakes of fruit and vegetables is amongst the strongest, yet other dietary nutrients and dietary patterns require evidence from human clinical studies before conclusions can be made about their effectiveness. | 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 |
Necroptosis has emerged as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Here, we found that markers of necroptosis, including high mobility group box 1 release and phosphorylation of mixed lineage kinase domain-like protein (p-MLKL), were markedly induced in the late stage of cigarette smoking-induced (CS-induced) emphysema in mouse lung tissue as well as in lung epithelial cells and organoids with higher dosage of or more prolonged exposure to cigarette smoking extract (CSE).,Apoptotic signals were also detected and maximally induced in the early stage of CS-exposed mice and CSE-treated epithelial cells.,Inhibition of apoptosis by Z-VAD, a pan-caspase inhibitor, switched the cellular stress to enhanced necroptosis in lung epithelial cells and organoids treated with CSE.,Depletion or inhibition of receptor-interacting protein kinase 3 (RIP3) or MLKL attenuated the CSE-induced cell death, suggesting that necroptosis contributes to CSE-induced cell death.,Silencing or inhibition of RIP1 had no protective effect, indicating a RIP1-independent RIP3 activation pathway.,CSE-induced necroptosis released more damage-associated molecular patterns and evoked greater engulfment but slower clearance by bone marrow-derived macrophages, leading to enhanced expression of proinflammatory cytokines Tnfα and Il6.,Finally, our in vivo data verified that inhibition of necroptosis by RIP3 inhibitor GSK’872 protected mice from CS-induced emphysema and suppressed the lung inflammation.,In conclusion, we provide evidence that necroptosis contributes to the pathogenesis of COPD.,Targeting RIP3 and its downstream pathway may be an effective therapy for COPD. | Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | 1 |
Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial.,To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant.,Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis.,In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production.,Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines.,This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length.,As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts.,Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent).,Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also exists in some smokers with normal spirometry, and may contribute to development and progression of specific COPD phenotypes.,ClinicalTrials.gov as NCT00281229 | Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response.,Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β.,The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations.,While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable.,In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines.,The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor.,Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD.,The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit.,Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either.,Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned.,There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target.,Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond. | 1 |
Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear.,Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis.,MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization.,NMT patients had received short-acting bronchodilators or no treatment.,Outcomes included forced expiratory volume over 1 s (FEV1), clinically important deterioration (CID), rescue medication use, and safety.,GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV1 treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001).,GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts.,Safety profiles for all cohorts were consistent with each other and the parent studies.,NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk.,Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
The appropriate use of generic preference-based measures determines the accuracy of disease assessment and further decision on healthcare policy using quality adjusted life years.,The discriminative capacity of different instruments would differ across disease groups.,Our study was to examine the difference in utility scores for COPD patients measured by EQ-5D and SF-6D and to assist the choice of a proper instrument in this disease group.,Differences of mean utility scores of EQ-5D and SF-6D in groups defined by socio-demographic characteristics, comorbidities, health service utilisation and severity of illness were tested using Mann-Whitney test, t-test, Kruskal-Wallis test, Pearson’s correlation coefficient and ANOVA, as appropriate.,The discriminative properties of the two instruments were compared against indicators of quality of life using receiver operating characteristic curves.,The statistical significance of the area under the curves (AUC) was tested by ANOVA and F-statistics used to compare the efficiency with which each instrument discriminated between disease severity groups.,Mean utility scores of EQ-5D and SF-6D were 0.644 and 0.629 respectively in the 154 subjects included in the analysis.,EQ-5D scores were significantly higher than SF-6D in groups less severe and these differences corresponded to a minimally important difference of greater than 0.03 (p<0.001).,EQ-5D and SF-6D scores were strongly correlated across the whole sample (r = 0.677, p<0.001) and in pre-defined groups (r>0.5 and p<0.05 for all correlation coefficients).,AUCs were above 0.5 against the indicators of health-related quality of life for both instruments.,F-ratios suggested SF-6D was more efficient in discriminating cases of different disease severity than EQ-5D.,Both EQ-5D and SF-6D appeared to be valid preference-based measures in Chinese COPD patients.,SF-6D was more efficient in detecting differences among subgroups with differing health status.,EQ-5D and SF-6D measured different things and might not be used interchangeably in COPD patients. | Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined.,This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype.,A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited.,Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]).,The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions.,A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included.,In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations.,Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%).,Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006).,The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001).,Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001).,One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease.,The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment. | 1 |
Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD.,Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.,Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017.,Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.,Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events).,In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively).,In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; P=0.028] were higher in the group with eosinophil count less than 2%.,Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events.,Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment. | Current evidence suggests that a higher blood eosinophil cell count at admission for acute exacerbation of COPD (AECOPD) is associated with a favorable response to systemic steroids.,However, the impact of blood eosinophil counts at admission on post-hospitalization outcomes is still unclear.,The main objective of this study is to investigate readmission outcomes associated with blood eosinophilia following severe COPD exacerbation in patients with infrequent COPD hospitalizations.,This is an observational cohort study design.,We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013.,Patients were stratified into the eosinophilic group if the blood eosinophil count on admission was ≥200 cells/µL and/or ≥2% of the total white blood cell (WBC) count.,The primary outcome was 1-year COPD-related readmission.,Secondary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, length of stay, time to COPD-related readmission, and number of 1-year COPD-associated emergency department (ED) and ambulatory visits.,A total of 479 patients were included.,Of whom, 173 were stratified into the eosinophilic group.,Higher blood eosinophil cell count was associated with an increased risk of 1-year COPD-related readmission (OR, 1.83 [95% CI, 1.16-2.89]; P<0.01), a shorter time to first COPD-related readmission (HR, 1.64 [95% CI, 1.14-2.36]; P<0.01), and an increased number of 1-year COPD-related ED visits (incidence rate ratio, 1.78 [95% CI, 1.21-2.61]; P<0.01).,All-cause mortality, all-cause readmission, length of stay, and number of ambulatory visits did not differ between groups.,Higher blood eosinophil cell count at admission for a COPD exacerbation is associated with increased COPD readmission rates in patients with infrequent COPD hospitalizations. | 1 |
Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue reparative properties, which may be beneficial in the treatment of inflammatory diseases such as COPD.,This study examined the mechanisms by which human MSCs protect against elastase induced emphysema.,Using a novel human relevant pre-clinical model of emphysema the efficacy of human MSC therapy and optimal cell dose were investigated.,Protective effects were examined in the lung through histological examination.,Further in vivo experiments examined the reparative abilities of MSCs after tissue damage was established and the role played by soluble factors secreted by MSCs.,The mechanism of MSC action was determined in using shRNA gene knockdown.,Human MSC therapy and MSC conditioned media exerted significant cytoprotective effects when administered early at the onset of the disease.,These protective effects were due to significant anti-inflammatory, anti-fibrotic and anti-apoptotic mechanisms, mediated in part through MSC production of hepatocyte growth factor (HGF).,When MSC administration was delayed, significant protection of the lung architecture was observed but this was less extensive.,MSC cell therapy was more effective than MSC conditioned medium in this emphysema model. | Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD).,Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism.,We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages.,In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks.,Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages.,In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK.,Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways.,This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism. | 1 |
Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients.,Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide.,Data from the Lung Health Study (n = 5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5 years.,Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients.,After 4 months, ipratropium therapy increased FEV1 by 6.0% in female and 2.9% in male subjects from baseline values (p = 2.42 × 10− 16).,This effect was modified by body mass index (BMI) such that the biggest improvements in FEV1 with ipratropium were observed in thin female subjects (p for BMI ∗ sex interaction = 0.044).,The sex-related changes in FEV1 related to ipratropium persisted for 2 years (p = 0.0134).,Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p = 6.86 × 10− 8).,Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females.,Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs.,Female patients are thus more likely to benefit from ipratropium than male COPD patients.,•Ipratropium; a muscarinic antagonist bronchodilator is more effective in female COPD patients compared to males.,•The effect was modified by body mass index (BMI) such that thin female subjects respond better.,•Female compared with male lungs had greater gene expression for the M3/M2 ratio of muscarinic receptors.,Ipratropium; a muscarinic antagonist bronchodilator is more effective in female COPD patients compared to males.,The effect was modified by body mass index (BMI) such that thin female subjects respond better.,Female compared with male lungs had greater gene expression for the M3/M2 ratio of muscarinic receptors.,Most evidence used to support bronchodilator therapy in COPD has been generated in therapeutic trials with predominately male patients.,Here, we determined whether there are any significant sex-related differences in lung function responses to the bronchodilator ipratropium bromide.,After 4 months, ipratropium therapy increased lung function in females twice as much as males.,This effect was modified by body mass index (BMI) such that the biggest improvements in lung function with ipratropium were observed in thin female subjects.,Female compared with male lungs had greater gene expression for ipratropium receptors.,Female patients are likely to benefit more from ipratropium than male COPD patients. | In this perspective-based article, which is based on findings from a comprehensive literature search, we discuss the significant and growing burden of chronic obstructive pulmonary disease in women worldwide.,Chronic obstructive pulmonary disease now affects both men and women almost equally.,Despite this, there remains an outdated perception of chronic obstructive pulmonary disease as a male-dominated disease.,Primary care physicians play a central role in overseeing the multidisciplinary care of women with chronic obstructive pulmonary disease.,Many women with chronic obstructive pulmonary disease delay seeking medical assistance, due to fear of stigmatization or dismissing symptoms as a ‘smoker’s cough’.,Improving awareness is important to encourage women with symptoms to seek advice earlier.,Once women do seek help, primary care physicians need to have knowledge of the nuances of female chronic obstructive pulmonary disease disease presentation to avoid mis- or delayed diagnosis, both of which are more common in women with chronic obstructive pulmonary disease than men.,Subsequent management should consider gender-specific issues, such as differential incidences of comorbid conditions, potentially higher symptom burden, and a higher risk of exacerbations.,Chronic obstructive pulmonary disease treatment and smoking cessation management should be specifically tailored to the individual woman and reviewed regularly to optimize patient outcomes.,Finally, education should be an integral part of managing chronic obstructive pulmonary disease in women as it will help to empower them to take control of their disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology.,Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome.,We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype.,We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study.,PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity.,PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location.,PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques. | The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC).,In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks.,Those who smoked more than 8 cigarettes per day were invited to perform a spirometry.,Totally 3,887 spirometries were performed.,In this sample 10.2% fulfilled the NICE COPD-criteria, 14.0% the GOLD COPD-criteria and 21.7% the ERS COPD criteria.,The diagnosis according to NICE and GOLD guidelines is based on FVC and in the ERS guidelines the best value of either SVC or FVC is used.,Thus, substantially more subjects with COPD were found when the best of either SVC or FVC was used.,Forced VC tended to be higher than SVC when lung function was normal and in those with mild obstruction prior to bronchodilatation whereas SVC exceeded FVC after bronchodilatation in those who had severe bronchial obstruction.,The diagnosis of COPD is highly depending on which guidelines are used for defining the disease.,If FVC and not the best of SVC and FVC is used when defining COPD the diagnosis will be missed in a substantial number of patients. | 1 |
Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed.,ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated.,Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care.,Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK.,A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT.,Up to 76.1% of the total population had 0 or 1 exacerbation the previous year.,After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.441).,However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10-1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03-2.86; p = 0.036) were higher in the cessation group.,Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/μL.,In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS.,Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851). | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. | Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Few studies have focused on the quality of life (QoL) associated medical costs for COPD in China.,A cross-sectional survey of 678 COPD patients was conducted in four major cities (Beijing, Shanghai, Guangzhou and Chengdu), China, in 2011.,Data on socio-demographic information, health conditions and medical costs were collected through a face-to-face interview combined with medical record searching.,The EuroQol (EQ-5D) health questionnaire was applied to assess the QoL of COPD patients.,Among 678 patients with COPD, nearly 40% had difficulties in mobility, usual activities and pain/discomfort, one third had various degrees of anxiety/depression, and one fifth had difficulties in self-care.,The COPD patients had a median utility score of 0.768 and a median visual analog scale score of 70.,The degree of difficulties in any dimensions significantly increased, and utility and health scores decreased with severity of the disease.,Age, gender and disease severity were significantly associated with the quality of life after taking other covariates into consideration.,Poorer QoL was a significant indicator of higher direct medical costs for COPD patients.,Impaired quality of life was significantly linked to increased medical costs for COPD patients and could be an important measure for policy- and decision-making in COPD care. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required.,Despite the importance of hospitalized exacerbations, relatively little is known about their determinants.,This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients.,This was a retrospective population-based cohort study.,We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011.,We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission.,We observed exacerbation frequency over the previous year (2011) and following year (2012).,We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4).,We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year.,Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients.,A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05).,Older age and several comorbidities, such as heart failure and diabetes, were similarly associated.,Hospitalized exacerbations occurred with all grades of airflow limitation.,A history of severe exacerbations was associated with new hospitalized exacerbations and mortality. | The COPD assessment test (CAT) consists of eight nonspecific scores of quality of life.,The aim of this study was to compare the health-related quality of life and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome (ACOS) using the CAT.,We examined CAT and lung functions in 138 patients with asthma, 99 patients with COPD, 51 patients with ACOS, and 44 patients with chronic cough as a control.,The CAT score was recorded in all subjects, and the asthma control test was also administered to patients with asthma and ACOS.,The CAT scores were compared, and the relationships between the scores and lung function parameters were analyzed.,The total CAT scores and scores for cough, phlegm, and dyspnea were higher in patients with ACOS than in patients with asthma and COPD.,The total CAT scores were correlated with the percent predicted forced expiratory volume in 1 second only in patients with COPD.,The total CAT scores and dyspnea scores adjusted by the percent predicted forced expiratory volume in 1 second were higher in patients with ACOS than in patients with COPD and asthma.,The CAT scores and asthma control test scores were more closely correlated in patients with ACOS than in patients with asthma.,Patients with ACOS have higher disease impacts and dyspnea sensation unproportional to the severity of airflow limitation. | 1 |
Health care utilization and costs among US veterans with chronic obstructive pulmonary disease (COPD) were compared with those in veterans without COPD.,A cohort of veterans with COPD was matched for age, sex, race, and index fiscal year to a cohort of veterans without COPD (controls) using data from the Veterans Integrated Service Network (VISN) 16 from 10/1/1997 to 9/30/2004.,Annual total and respiratory-related health care service utilization, costs of care, comorbidities, and respiratory medication use at the time of diagnosis were assessed.,A total of 59,906 patients with COPD were identified for a 7-year period prevalence of 8.2%, or 82 per 1000 population.,Patients with COPD compared with controls had significantly higher all-cause and respiratory-related inpatient and outpatient health care utilization for every parameter examined including mean numbers of physician encounters, other outpatient encounters, emergency room visits, acute inpatient discharges, total bed days of care, and percentage of patients with any emergency room visits or any acute inpatient discharge.,Patients with COPD had statistically significantly higher mean outpatient, inpatient, pharmacy, and total costs than the control group.,The mean Charlson comorbidity index in patients with COPD was 1 point higher than in controls (2.85 versus 1.84, P < 0.001). 60% of COPD patients were prescribed medications recommended in treatment guidelines at diagnosis.,Veterans with COPD compared with those without COPD suffer a tremendous disease burden manifested by higher rates of all-cause and respiratory-related health care utilization and costs and a high prevalence of comorbidities.,Furthermore, COPD patients do not receive appropriate treatment for their disease on diagnosis. | 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 |
Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | To unpack and interpret descriptions of experiences of social relationships during pulmonary rehabilitation (PR) for people living with chronic obstructive pulmonary disease (COPD).,Inspired by interpretive phenomenology, individual qualitative interviews were conducted twice with 18 persons from COPD rehabilitation units in two general hospitals.,Qualitative content analysis was performed.,Analysis of the interviews revealed the overarching theme of belonging.,The participants emphasised social integration in rehabilitation groups as well as support from peers and health-care personnel as important dimensions of social relationships with regard to PR.,Active participation in and engagement with the groups provided opportunities for patients to share their knowledge, encouraged mutual trust, and support and increased self-confidence, and motivation for self-care and further social participation.,Integration in the groups and perceived support during PR made coping and adaptation easier and had a positive effect on quality of life.,Patients' perspectives on PR were strongly influenced by certain facets of social relationships, such as social integration and social support.,Patients', peers' and health-care professionals' strategies to promote social support and social integration should be further explored in the future, both in different contexts and for longer periods of time. | 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. | The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD).,We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy.,Twenty patients who completed the 12-month treatment period were analyzed.,No clinically significant adverse events were observed during azithromycin treatment.,Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01).,The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations.,Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations.,Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. | 1 |
Dual bronchodilation combining a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials.,The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year.,Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments.,The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population).,The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units).,Improvements in health status and lower rescue medication use were also observed with IND/GLY.,The safety profile of the study medication was similar to that observed in previous studies.,IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments.,ClinicalTrials.gov number: NCT01985334.,The online version of this article (doi:10.1186/s12931-017-0622-x) contains supplementary material, which is available to authorized users. | Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity.,The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time.,The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD.,This study is part of the European Community Respiratory Health Survey (ECRHS).,A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998-2002 (ECRHS II) and in 2008-2013 (ECRHS III).,Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported.,Subjects reporting asthma were excluded.,COPD was defined as a spirometry ratio of FEV1/FVC < 0.7.,A total of 5901 subjects were included.,Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p < 0.001) in ECRHS II (mean age 43) but not in ECHRS III (mean age 54).,In the multivariable regression model adjusted for COPD, smoking, age, BMI, and gender, non-infectious rhinitis was associated with COPD in both ECRHS II and III.,Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43.,Ten years later, the association was weaker.,The findings indicate that NIR could be associated with the early onset of COPD. | We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.,Representative population-based samples of adults aged ≥40 years were selected in participating sites.,Participants completed questionnaires and spirometry.,Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.,Data from 24 855 subjects from 33 sites in 29 countries were analysed.,There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi).,Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis.,Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.,The prevalence of chronic bronchitis symptoms varied widely across the studied sites.,Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.,Chronic bronchitis symptoms are associated with significant burden regardless of the presence of airflow obstructionhttp://ow.ly/kP9P30eFELK | 1 |
Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials.,Little is known on the correspondence between the two methods.,Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO.,Dyspnea was assessed by the mMRC scale and the BDI.,Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George’s Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained.,Correlations between mMRC and BDI scores were assessed using Spearman’s correlation coefficient.,An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores.,Data are given as median (interquartile ranges, [IQR]).,Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]).,The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8].,Both BDI and mMRC scores were significantly correlated at the group level (rho =−0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade.,In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio.,The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index.,Dyspnea is a complex symptom with multiple determinants in COPD patients.,Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable. | It is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL.,This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities.,In the population-based KORA F4 study (2006-08) 1,321 participants aged 41-61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities.,For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999-2001) and the F4L follow-up study (2010).,Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups.,7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1.,Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered.,Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (−3.5 (p = 0.008) in F4, −3.3 (p = 0.014) in S4 and −4.7 (p = 0.003) in F4L) compared to the group without airflow limitation.,The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer.,Over ten years, a small decline in PCS-12 was observed in all groups.,This decline was larger in participants with COPD grade 2+, but insignificant.,Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found.,Despite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades.,Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients. | 1 |
Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes. | Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).,This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.,Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days.,Treatment was repeated every 8 weeks for a total of six courses.,Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.,At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).,There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores.,There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006).,Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.,There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).,Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline.,There were no unexpected adverse events and there was no evidence of resistance development.,ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov). | 1 |
COPD patients have increased numbers of macrophages and neutrophils in the lungs.,Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3.,We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.,59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis.,Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.,COPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7).,COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts.,Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.,Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD.,Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.,The online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users. | Toll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown.,Lung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands.,We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants.,All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD.,In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells.,Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists.,Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD.,These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1. | 1 |
The high prevalence of COPD in the Russian Federation has been demonstrated in several epidemiological studies.,However, there are still no data on the clinical characteristics of these patients according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups and phenotypes, which could provide additional understanding of the burden of COPD, routine clinical practice, and ways to improve the treatment of patients with COPD in Russia.,SUPPORT was an observational multicenter study designed to obtain data about the distribution of patients with previously diagnosed COPD according to the severity of bronchial obstruction, symptom severity, risk of exacerbation, COPD phenotypes, and treatment of COPD.,We included patients with a previous diagnosis of COPD who visited one of 33 primary-care centers for any reason in 23 cities in Russia.,Among the 1,505 patients with a previous diagnosis of COPD who attended the primary-care centers and were screened for the study, 1,111 had a spirometry-confirmed diagnosis and were included in the analysis.,Up to 53% of the patients had severe or very severe COPD (GOLD stages III-IV), and 74.3% belonged to the GOLD D group.,The majority of patients were frequent exacerbators (exacerbators with chronic bronchitis [37.3%], exacerbators without chronic bronchitis [14%]), while 35.8% were nonexacerbators and 12.9% had asthma-COPD overlap.,Among the GOLD D group patients, >20% were treated with only short-acting bronchodilators.,COPD is still misdiagnosed in primary care in Russia.,COPD patients in primary care are usually GOLD D with frequent exacerbations and are often treated with only short-acting bronchodilators. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
The gold standard for the diagnosis of chronic obstructive pulmonary disease (COPD) is spirometry, but there are barriers to its use in primary care.,To externally validate the COPD Diagnostic Questionnaire (CDQ) as a diagnostic tool in patients at increased risk in Australian general practice and to compare its performance with other CDQ validation studies.,Patients were recruited from 36 general practices in Sydney, Australia.,Former or current smokers aged 40-85 years with no prior COPD diagnosis were invited to a case-finding appointment with the practice nurse.,The CDQ was collected and pre- and postbronchodilator spirometry was performed.,Cases for whom complete CDQ data were present and the spirometry met quality standards were analysed.,Of 1,631 patients who attended case-finding recruitment, 1,054 (65%) could be analysed.,Spirometry showed 13% had COPD.,The ability of the CDQ to discriminate between patients with and without COPD was fair, represented by the area under the receiver operating characteristic curve of 0.713.,With a CDQ cut-off point value of 16.5 the sensitivity was 80% and specificity 47% and, at a cut-off point value of 19.5, the sensitivity was 63% and specificity 70%.,The CDQ did not discriminate between patients with and without COPD accurately enough to use as a diagnostic tool in patients at increased risk of COPD in Australian general practice.,Further research is needed on the value of the CDQ as a tool for selecting patients for spirometry. | COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | 1 |
Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage. | Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function.,This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol.,This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study.,Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4-14-day washout period.,ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients.,The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.,Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point).,In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM).,The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006).,Both treatments were well tolerated.,The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar.,In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.,Trial registration number NCT00379028 | 1 |
Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | Influencing the progression of COPD has long been an elusive goal of drug therapy.,Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®).,Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced.,The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD.,The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease.,With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted. | 1 |
The C-type lectin receptor Dectin-1 is expressed mainly on myeloid cells mediating the immune response targeting respiratory pathogens such as Aspergillus fumigatus and Mycobacterium tuberculosis.,The pulmonary epithelium serves as an important interface for interactions between these pathogens and the respiratory tract.,Therefore, we analyzed the expression pattern of Dectin-1 in the human lung.,Immunohistochemically stained human lung sections from 17 out of 19 individuals were positive for Dectin-1, which was expressed mainly apically on bronchial and alveolar epithelium.,Our results showed no correlation with chronic obstructive pulmonary disease (COPD) or the smoking habits of the patients.,Nontypeable Haemophilus influenzae (NTHI), an important bacterial pathogen of the respiratory tract with significant importance in COPD, has also been proposed to be recognized by Dectin-1, suggesting a possible impact on the NTHI-dependent immune response in human airways.,Therefore, the involvement of Dectin-1 in NTHI-triggered cytokine responses was investigated in primary normal human bronchial epithelial (NHBE) cells and in the A549 cell line stably transfected with Dectin-1.,The presence of Dectin-1 significantly increased cytokine release in response to NTHI in NHBE and A549 cells.,In addition, phosphorylation of the Dectin-1 hem-immunoreceptor tyrosine-based activation motif (hemITAM) was essential for the Dectin-1-triggered response to NTHI in A549 cells.,In conclusion, in human airways, epithelium-expressed Dectin-1 may play a significant role in generating an NTHI-mediated, proinflammatory immune response.,In this study, we demonstrated, for the first time, the expression of Dectin-1 on human lung tissues and, in particular, pulmonary epithelium by making use of immunohistochemical staining.,The epithelial lining of the human airways is an important interface for host-pathogen interactions.,Therefore, our data suggest that epithelium-expressed Dectin-1 is of considerable importance for the interaction of the human airways with pathogens detected by this receptor, such as A. fumigatus and M. tuberculosis.,Moreover, we further demonstrated that, in pulmonary epithelial cells, Dectin-1 enhances the proinflammatory immune response to NTHI.,In COPD patients, NTHI is a major cause of respiratory tract infections and is associated with proinflammatory immune responses in the lower airways.,Therefore, our data suggest that the functional interaction of Dectin-1 with NTHI in human airways may have an important impact on the pathogenesis of COPD. | Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.,A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed.,Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples.,Levels in patients colonized by H. influenzae and non-colonized patients were compared.,Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test).,Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test).,Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).,Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients.,Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases. | 1 |
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