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Background walking is crucial for an active and healthy ageing, but the perspectives of individuals living with walking impairment are still poorly understood. Objectives to identify and synthesise evidence describing walking as experienced by adults living with mobility-impairing health conditions and to propose an empirical conceptual framework of walking experience. Methods we performed a systematic review and meta-ethnography of qualitative evidence, searching seven electronic databases for records that explored personal experiences of walking in individuals living with conditions of diverse aetiology. Conditions included Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture, heart failure, frailty and sarcopenia. Data were extracted, critically appraised using the NICE quality checklist and synthesised using standardised best practices. Results from 2,552 unique records, 117 were eligible. Walking experience was similar across conditions and described by seven themes: (i) becoming aware of the personal walking experience, (ii) the walking experience as a link between individuals' activities and sense of self, (iii) the physical walking experience, (iv) the mental and emotional walking experience, (v) the social walking experience, (vi) the context of the walking experience and (vii) behavioural and attitudinal adaptations resulting from the walking experience. We propose a novel conceptual framework that visually represents the walking experience, informed by the interplay between these themes. Conclusion a multi-faceted and dynamic experience of walking was common across health conditions. Our conceptual framework of the walking experience provides a novel theoretical structure for patient-centred clinical practice, research and public health. [ABSTRACT FROM AUTHOR]

Background: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation.Objective: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries.Methods: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID.Results: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score.Conclusions: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables. [ABSTRACT FROM AUTHOR]

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. [ABSTRACT FROM AUTHOR]

Rationale: Most studies determining the prevalence of airway obstruction are limited to short time periods.Objectives: Because temporal trends of obstruction in populations are largely unknown, we determined the prevalence of airway obstruction over 20 years in yearly general population samples in Switzerland between 1993 and 2012.Methods: We analyzed data of 85,789 participants aged 35 years and older who provided spirometric measurements as part of the LuftiBus lung function campaign. We linked data from the 2003-2012 period to the Swiss National Cohort to adjust for annual population differences. Spirometry was performed without bronchodilation, according to American Thoracic Society guidelines. We used Global Lung Initiative (GLI) and Hankinson reference equations to identify obstruction.Results: Obstruction prevalence increased between 1993 and 2012 from 6.1% (95% confidence interval [CI], 5.5 to 6.7) to 15.6% (95% CI, 13.8 to 17.3) based on GLI estimates and from 5.3% (95% CI, 4.7 to 5.9) to 15.4% (95% CI, 13.6 to 17.1) based on Hankinson estimates. When adjusted for participant demographics, air pollutant and occupational exposures, altitude, and season, the prevalence ratios of obstruction were 1.54 (95% CI, 1.22 to 1.93) and 1.65 (95% CI, 1.33 to 2.04) for GLI- and Hankinson-defined airway obstruction, respectively, for 2012 compared with 2003.Conclusions: Though prebronchodilator measurements likely overestimate the prevalence of airway obstruction in absolute terms compared with post-bronchodilator measurements, we found an increase in airway obstruction prevalence. Even with adjustment for several well-known risk factors for obstruction to make the populations across the years more comparable, we still saw a statistically significant increase in prevalence over this time period. [ABSTRACT FROM AUTHOR]

Aims: To estimate the prevalence of chronic obstructive pulmonary disease (COPD) and related risk factors in people in opioid agonist treatment (OAT), to compare airflow limitation severity and age‐specific COPD prevalence rates with those in the general population, and to assess the OAT patients' willingness to adopt life‐style changes and to use therapeutic offers for COPD management. Design Cross‐sectional study in a random sample of OAT patients. Setting: Out‐patient centres for substance addiction medicine in Zurich, Switzerland. Participants: A total of 125 participants, recruited from November 2016 to April 2017 through invitation letters followed by phone or personal contact. Measurements Standardized questionnaires about drug use, smoking habits and medical history, completed during face‐to‐face interviews or from medical records. Spirometry without and—depending on the result—with bronchodilation. Findings Almost one‐third [30.3%; 95% confidence interval (CI) = 22.6–39.0%] of the 119 participants with valid spirometry tests were diagnosed with COPD. Among males aged 30–59 years, the age‐adjusted prevalence of at least moderate airflow limitation (GOLD grade ≥ 2) was 2.4 (95% CI = 1.3–4.4) times as high as in the ever‐smoking Swiss population in the same age group. Smoking tobacco (92.0%) and substance inhalation (cannabis = 97.6%, cocaine = 69.6%, heroin = 68.0%) were highly prevalent among all participants. The participants expressed considerable interest in life‐style changes and use of therapeutic offers for COPD management, with smoking cessation being least (20.2% of tobacco smokers interested) and pharmacological treatment to alleviate COPD symptoms most popular. Conclusions: In Switzerland, COPD prevalence and multiple risk factors for COPD appear to be high among people in OAT compared with the general population. Individuals in OAT appear to develop COPD at a younger average age compared with the general population and are open to life‐style changes and other COPD management approaches. [ABSTRACT FROM AUTHOR]

Count outcomes occur in virtually all disciplines, such as medicine, epidemiology or biology, but they often contain error. Recently, it has been shown that self-reported numbers of exacerbations of Chronic Obstructive Pulmonary Disease patients can be considerably miscounted. Motivated by this result, we reanalysed data from the Towards a Revolution in Chronic Obstructive Pulmonary Disease Health trial, a large randomized controlled trial with the self-reported number of exacerbations of Chronic Obstructive Pulmonary Disease patients as outcome. To adjust for miscounting error in the response of Poisson and (zero-inflated) negative binomial models, we introduce novel, general methodology. The key idea is to formulate a zero-inflated negative binomial model to capture the error mechanism. This parametric approach automatically circumvents drawbacks of previously suggested methodology that treats miscounted outcomes in the misclassification framework. Prior information for the response error model parameters was elicited from validation data of an external study and adaptively weighted to account for potential prior-data conflict. The results of the Bayesian hierarchical modelling approach indicated that the treatment effect has been overestimated in the original study. However, closer inspection revealed that this unexpected result was an artefact of an unaccounted time dependency of the treatment effect. [ABSTRACT FROM AUTHOR]

Background: There is a general notion that stressful life events may cause mental and physical health problems. Objectives: We aimed to describe stressful life events reported by patients with chronic obstructive pulmonary disease (COPD) and to assess their impact on health outcomes and behaviors. Methods: Two hundred and sixty-six primary care patients who participated in the ICE COLD ERIC cohort study were asked to document any stressful life events in the past 3 years. We assessed the before-after (the event) changes for symptoms of depression and anxiety, health status, dyspnea-related quality of life, exacerbations, cigarette use, and physical activity. We used linear regression analysis to estimate the crude and adjusted magnitude of the before-after changes. Results: About 41% (110/266) of patients reported the experience of any stressful life events and “death of relatives/important persons” was most common (31%). After accounting for age, sex, living status, lung function, and anxiety/depression status at baseline, experiencing any stressful life events was associated with a 0.9-point increase on the depression scale (95% CI 0.3 to 1.4), a 0.8-point increase on the anxiety scale (95% CI 0.3 to 1.3), and a 0.8-point decrease in the physical activity score (95% CI –1.6 to 0). Conclusions: Experiencing stressful life events was associated with a small to moderate increase in symptoms of depression and anxiety in COPD, but no discernable effect was found for other physical outcomes. However, confirmation of these results in other COPD cohorts and identification of patients particularly vulnerable to stressful life events are needed. [ABSTRACT FROM AUTHOR]

Background: Prediction models and prognostic scores have been increasingly popular in both clinical practice and clinical research settings, for example to aid in risk-based decision making or control for confounding. In many medical fields, a large number of prognostic scores are available, but practitioners may find it difficult to choose between them due to lack of external validation as well as lack of comparisons between them.Methods: Borrowing methodology from network meta-analysis, we describe an approach to Multiple Score Comparison meta-analysis (MSC) which permits concurrent external validation and comparisons of prognostic scores using individual patient data (IPD) arising from a large-scale international collaboration. We describe the challenges in adapting network meta-analysis to the MSC setting, for instance the need to explicitly include correlations between the scores on a cohort level, and how to deal with many multi-score studies. We propose first using IPD to make cohort-level aggregate discrimination or calibration scores, comparing all to a common comparator. Then, standard network meta-analysis techniques can be applied, taking care to consider correlation structures in cohorts with multiple scores. Transitivity, consistency and heterogeneity are also examined.Results: We provide a clinical application, comparing prognostic scores for 3-year mortality in patients with chronic obstructive pulmonary disease using data from a large-scale collaborative initiative. We focus on the discriminative properties of the prognostic scores. Our results show clear differences in performance, with ADO and eBODE showing higher discrimination with respect to mortality than other considered scores. The assumptions of transitivity and local and global consistency were not violated. Heterogeneity was small.Conclusions: We applied a network meta-analytic methodology to externally validate and concurrently compare the prognostic properties of clinical scores. Our large-scale external validation indicates that the scores with the best discriminative properties to predict 3 year mortality in patients with COPD are ADO and eBODE. [ABSTRACT FROM AUTHOR]

Background: Several cross-sectional and short-term studies suggest that patient-reported outcomes (PROs) may be useful to help predict COPD exacerbations, but evidence from long-term prospective cohort studies is lacking. Our aim was to assess if PROs add to the prediction of exacerbations.Methods: Four hundred eight primary care patients with COPD participated in the multicenter prospective International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) study. PROs included the Chronic Respiratory Disease Questionnaire, the Hospital Anxiety and Depression Scale, the Feeling Thermometer, and the LASA Physical Activity Questionnaire (LAPAQ). Exacerbations during 4½ years were adjudicated by experts. We used negative binomial regression to assess the association between PROs and exacerbations while considering age, sex, airflow obstruction, previous exacerbations, and smoking status. We then assessed if adding PROs improved the predictive properties of widely used indices.Results: Lower levels of dyspnea, fatigue, and anxiety and higher levels of physical activity were associated with a lower risk of exacerbations (adjusted incidence rate ratio [IRR], 0.90; 95% CI, 0.84-0.97; P = .01; IRR, 0.93; 95% CI, 0.86-1.00; P = .04; IRR, 1.03; 95% CI, 1.00-1.06; P = .03; IRR, 0.93; 95% CI, 0.87-0.99; P = .04, respectively). The best prediction was when LAPAQ was added to the BMI, airflow obstruction, dyspnea, and previous exacerbations (BODEx) index (area under the curve Δ+0.02, from 0.72-0.74). However, this increase was not clinically relevant (net reclassification improvement, 0.03; 95% CI, -0.03 to 0.08).Conclusions: Some domains of PROs are independently associated with exacerbations but do not lead to clearly improved prediction when added to established indices to predict exacerbations. There is still much room for improvement in the prediction of exacerbations.Trial Registry: ClinicalTrials.gov; No.: NCT00706602. [ABSTRACT FROM AUTHOR]

Background: COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there has been no systematic assessment of the reproducibility of these subtypes.Objective: We performed clustering analyses across 10 cohorts in North America and Europe in order to assess the reproducibility of (1) correlation patterns of key COPD-related clinical characteristics and (2) clustering results.Methods: We studied 17 146 individuals with COPD using identical methods and common COPD-related characteristics across cohorts (FEV1, FEV1/FVC, FVC, body mass index, Modified Medical Research Council score, asthma and cardiovascular comorbid disease). Correlation patterns between these clinical characteristics were assessed by principal components analysis (PCA). Cluster analysis was performed using k-medoids and hierarchical clustering, and concordance of clustering solutions was quantified with normalised mutual information (NMI), a metric that ranges from 0 to 1 with higher values indicating greater concordance.Results: The reproducibility of COPD clustering subtypes across studies was modest (median NMI range 0.17-0.43). For methods that excluded individuals that did not clearly belong to any cluster, agreement was better but still suboptimal (median NMI range 0.32-0.60). Continuous representations of COPD clinical characteristics derived from PCA were much more consistent across studies.Conclusions: Identical clustering analyses across multiple COPD cohorts showed modest reproducibility. COPD heterogeneity is better characterised by continuous disease traits coexisting in varying degrees within the same individual, rather than by mutually exclusive COPD subtypes. [ABSTRACT FROM AUTHOR]

Background: COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results. We aimed to investigate this association, considering well known risk factors.Methods: A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence. Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD. High altitude was defined as >1500 m above sea level. Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD.Results: Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m. COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005). However, known risk factors were significantly less frequent at high altitude. Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence. Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD. Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude.Conclusion: Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors. However, high altitude itself was associated with an increased risk of undiagnosed COPD. [ABSTRACT FROM AUTHOR]

The 1-min sit-to-stand (1-min STS) test and handgrip strength test have been proposed as simple tests of functional exercise performance in chronic obstructive pulmonary disease (COPD) patients. We assessed the long-term (5-year) predictive performance of the 1-min sit-to-stand and handgrip strength tests for mortality, health-related quality of life (HRQoL) and exacerbations in COPD patients. In 409 primary care patients, we found the 1-min STS test to be strongly associated with long-term morality (hazard ratio per 3 more repetitions: 0.81, 95% CI 0.65 to 0.86) and moderately associated with long-term HRQoL. Neither test was associated with exacerbations. Our results suggest that the 1-min STS test may be useful for assessing the health status and long-term prognosis of COPD patients. This study was registered at http://www.clinicaltrials.gov/ (NCT00706602, 25 June 2008). [ABSTRACT FROM AUTHOR]

Prediction models should be externally validated before being used in clinical practice. Many published prediction models have never been validated. Uncollected predictor variables in otherwise suitable validation cohorts are the main factor precluding external validation. We used individual patient data from 9 different cohort studies conducted in the United States, Europe, and Latin America that included 7,892 patients with chronic obstructive pulmonary disease who enrolled between 1981 and 2006. Data on 3-year mortality and the predictors of age, dyspnea, and airflow obstruction were available. We simulated missing data by omitting the predictor dyspnea cohort-wide, and we present 6 methods for handling the missing variable. We assessed model performance with regard to discriminative ability and calibration and by using 2 vignette scenarios. We showed that the use of any imputation method outperforms the omission of the cohort from the validation, which is a commonly used approach. Compared with using the full data set without the missing variable (benchmark), multiple imputation with fixed or random intercepts for cohorts was the best approach to impute the systematically missing predictor. Findings of this study may facilitate the use of cohort studies that do not include all predictors and pave the way for more widespread external validation of prediction models even if 1 or more predictors of the model are systematically missing. [ABSTRACT FROM AUTHOR]

Background: COPD exacerbation incidence rates are often ascertained retrospectively through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single-physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification.Methods: Self-reported exacerbations (event-based definition) in 409 primary care patients with COPD participating in the International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) cohort were ascertained every 6 months over 3 years. Exacerbations were adjudicated by single experienced physicians and an adjudication committee who had information from patient charts. We assessed the accuracy (sensitivities and specificities) of self-reports and single-physician chart review against a central adjudication committee (AC) (reference standard). We used multinomial logistic regression and bootstrap stability analyses to explore determinants of misclassifications.Results: The AC identified 648 exacerbations, corresponding to an incidence rate of 0.60 ± 0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate, 0.75 ± 1.01; incidence proportion, 59.7%). The sensitivity and specificity of self-reports were 84% and 76%, respectively, those of single-physician chart review were between 89% and 96% and 87% and 99%, respectively. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with underreporting and overreporting of exacerbations (underreporters: relative risk ratio [RRR], 2.16; 95% CI, 1.76-2.65 and overreporters: RRR, 1.67; 95% CI, 1.39-2.00).Conclusions: Patient 6-month recall of exacerbation events are inaccurate. This may lead to inaccurate estimates of incidence measures and underestimation of treatment effects. The use of multiple data sources combined with event adjudication could substantially reduce sample size requirements and possibly cost of studies.Clinical Trial Registration: www.ClinicalTrials.gov, NCT00706602. [ABSTRACT FROM AUTHOR]

Background: Although many studies examined determinants of physical activity in patients with chronic obstructive pulmonary disease (COPD), most were cross-sectional and focused on single determinants only. Objectives: The aim of this study was to determine how COPD patients' physical activity changes over time and to identify the determinants of physical activity using multivariable and longitudinal methods. Methods: In a prospective cohort study, 409 primary care patients with COPD in the Netherlands and Switzerland were followed for up to 5 years. Physical activity was assessed at baseline and every 6 months using the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire (LAPAQ) adapted to a 0- to 23-point scale. We studied the associations between determinants at baseline and patients' long-term physical activity levels using linear mixed models. Results: Unadjusted analysis showed an overall gradual decline in physical activity (0.22 points of the LAPAQ scale every 6 months, 95% CI: 0.17-0.28; p < 0.001). In multivariable analyses, baseline determinants that were independently associated (p ⩽ 0.05) with lower long-term physical activity levels included (starting from coefficients with the smallest p value) lower exercise capacity, older age, working, more smoking pack-years, more fatigued, male sex, lower educational levels, previously not in fitness programs, more depressed, lower lung function, lower overall health status, and more prescription drug use. Conclusions: We found that physical activity of COPD patients may decline more than reported in the healthy elderly. Longitudinal analysis identified independent determinants of physical activity, which allows the identification of patients having low physical activity levels and who may benefit from physical activity interventions. [ABSTRACT FROM AUTHOR]

Summary Background There is no universal consensus on the best staging system for chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2007) have traditionally used forced expiratory volume in 1 s (FEV 1 ) for staging, clinical parameters have been added to some guidelines (eg, GOLD 2011) to improve patient management. As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aimed to investigate how individual patients were categorised by GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents for mortality. Methods We searched reports published from Jan 1, 2008, to Dec 31, 2014. Using data from cohorts that agreed to participate and had a minimum amount of information needed for GOLD 2007 and 2011, we did a patient-based pooled analysis of existing data. With use of raw data, we recalculated all participant assignments to GOLD 2007 I–IV classes, and GOLD 2011 A–D stages. We used survival analysis, C statistics, and non-parametric regression to model time-to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict mortality. Findings We collected individual data for 15 632 patients from 22 COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the patients was 63·9 years (SD 10·1); 10 751 (69%) were men. Based on FEV 1 alone (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346 (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660 patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity distribution to more severe categories. There were nearly three times more COPD patients in stage D than in former stage IV (p<0·05). The predictive capacity for survival up to 10 years was significant for both systems (p<0·01) but area under the curves were only 0·623 (GOLD 2007) and 0·634 (GOLD 2011), and GOLD 2007 and 2011 did not differ significantly. We identified the percent predicted FEV 1 thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality, which are similar to the ones used previously. Interpretation Neither GOLD COPD classification schemes have sufficient discriminatory power to be used clinically for risk classification at the individual level to predict total mortality for 3 years of follow-up and onwards. Increasing intensity of treatment of patients with COPD due to their GOLD 2011 reclassification is not known to improve health outcomes. Evidence-based thresholds should be searched when exploring the prognostic ability of current and new COPD multicomponent indices. Funding None. [ABSTRACT FROM AUTHOR]

Importance: Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes. Materials and Methods: Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George's Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS. Results: Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV1 (p<0.001 for all comparisons). Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624–0·7676), MMRC (0·7590–0·7644), 6MWD (0·7531–0·7560) and exacerbation risk (0·6831–0·6919). Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341). Conclusions: Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD. [ABSTRACT FROM AUTHOR]

Background: Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. Objectives: Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts. Methods: Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality. Results: Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). Conclusions: The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

An abstract of the article "No Association of 25-Hydroxyvitamin D With Exacerbations in Primary Care Patients With COPD" by Milo A. Puhan and colleagues is presented.

Chronic Obstructive Pulmonary Disease (COPD) coexists with co-morbidities. While co-morbidity has been associated with poorer health status, it is unclear which conditions have the greatest impact on self-rated health. We sought to determine which, and how much, specific co-morbid conditions impact on self-rated health in current and former smokers with self-reported COPD. Using the 2001-2008 National Health and Nutrition Examination Survey we characterized the association between thirteen co-morbidities and health status among individuals self-reporting COPD. Adjusted odds ratios (ORs) were generated using ordinal logistic regression. Additionally we evaluated the impact of increasing number of co-morbidities with self-rated health. Eight illnesses had significant associations with worse self-rated health, however after mutually adjusting for these conditions, congestive heart failure (OR 3.07, 95% CI 1.69-5.58), arthritis (OR 1.69, 95% CI 1.13-2.52), diabetes (OR 1.63, 95% CI 1.01-2.64), and incontinence/prostate disease (OR 1.63, 95% CI 1.01-2.62) remained independent predictors of self-rated health. Each increase in co-morbidities was associated with a 43% higher chance of worse self-rated health (95% CI 1.27-1.62). Individuals with COPD have a substantial burden of co-morbidity, which is associated with worse self-rated health. CHF, arthritis, diabetes and incontinence/prostate disease have the most impact on self-rated health. Targeting these co-morbidities in COPD may result in improved self-rated health. [ABSTRACT FROM AUTHOR]

Background: Around the world, the timing of referral of chronic obstructive pulmonary disease (COPD) patients for pulmonary rehabilitation differs from immediately after exacerbation (early) to later on when patients are in a stable state (late). There are no trials comparing the different time points of referral for pulmonary rehabilitation. Objectives: Our aim was to compare the effects of early and late pulmonary rehabilitation on exacerbation rates and health-related quality of life (HRQOL) in COPD patients with exacerbations. Methods: We randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages II-IV) with a recent exacerbation to early (within 2 weeks) or late pulmonary rehabilitation (starting 6 months after randomization and in a stable state). The primary outcome was the exacerbation rate over 18 months, and secondary outcomes included HRQOL and mortality. We used multivariate analyses and an intention-to-treat analysis approach. Results: We randomized 36 patients to pulmonary rehabilitation. On average, patients with early rehabilitation (n = 19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43-1.63; p = 0.60). Over the 18-month period, patients with late rehabilitation experienced more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74 and on the Medical Research Council dyspnea scale 0.37), but neither these differences nor any difference in HRQOL domains reached statistical significance. Conclusions: We did not find any statistically significant differences between early and late pulmonary rehabilitation. However, our trial indicates that early rehabilitation may lead to faster recovery of HRQOL after exacerbations compared to rehabilitation later on when patients are in a stable state. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) is a systemic disease; morbidity and mortality due to COPD are on the increase, and it has great impact on patients' lives. Most COPD patients are managed by general practitioners (GP). Too often, GPs base their initial assessment of patient's disease severity mainly on lung function. However, lung function correlates poorly with COPD-specific health-related quality of life and exacerbation frequency. A validated COPD disease risk index that better represents the clinical manifestations of COPD and is feasible in primary care seems to be useful. The objective of this study is to develop and validate a practical COPD disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2-4. Methods/Design: We will conduct 2 linked prospective cohort studies with COPD patients from GPs in Switzerland and the Netherlands. We will perform a baseline assessment including detailed patient history, questionnaires, lung function, history of exacerbations, measurement of exercise capacity and blood sampling. During the follow-up of at least 2 years, we will update the patients' profile by registering exacerbations, health-related quality of life and any changes in the use of medication. The primary outcome will be health-related quality of life. Secondary outcomes will be exacerbation frequency and mortality. Using multivariable regression analysis, we will identify the best combination of variables predicting these outcomes over one and two years and, depending on funding, even more years. Discussion: Despite the diversity of clinical manifestations and available treatments, assessment and management today do not reflect the multifaceted character of the disease. This is in contrast to preventive cardiology where, nowadays, the treatment in primary care is based on patient-specific and fairly refined cardiovascular risk profile corresponding to differences in prognosis. After completion of this study, we will have a practical COPD-disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2-4. In a second step we will incorporate evidence-based treatment effects into this model, such that the instrument may guide physicians in selecting treatment based on the individual patients' prognosis. Trial registration: ClinicalTrials.gov Archive NCT00706602 [ABSTRACT FROM AUTHOR]

Background: The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment. Methods: We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier) to 7 (no agreement with statement = no recruitment barrier). Results: 38 of 55 recruiting physicians returned questionnaires (69% response rate), of which 35 could be analyzed (64% useable response rate). Recruiting physicians reported that "time constraints" (median agreement of 3, interquartile range 2-5) had the most negative impact on recruitment followed by "difficulties including identified eligible patients" (median agreement of 5, IQR 3-6). Other barriers such as "trial design barriers", "lack of access to treatment", "individual barriers of recruiting physicians" or "insufficient training of recruiting physicians" were perceived to have little or no impact on patient recruitment. Conclusion: Physicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be developed and tested in randomized trials. Trial registration: ISRCTN84612310 [ABSTRACT FROM AUTHOR]

Background: Interpretation of the Hospital Anxiety and Depression Scale (HADS), commonly used to assess anxiety and depression in COPD patients, is unclear. Since its minimal important difference has never been established, our aim was to determine it using several approaches.Methods: 88 COPD patients with FEV1 /= 0.5 we performed linear regression analyses to predict the minimal important difference from the anchors. As distribution-based approach we used the Effect Size approach.Results: Based on CRQ emotional function and mastery domain as well as on total scores, the minimal important difference was 1.41 (95% CI 1.18-1.63) and 1.57 (1.37-1.76) for the HADS anxiety score and 1.68 (1.48-1.87) and 1.60 (1.38-1.82) for the HADS total score. Correlations of the HADS depression score and CRQ domain and Feeling Thermometer scores were < 0.5. Based on the Effect Size approach the MID of the HADS anxiety and depression score was 1.32 and 1.40, respectively.Conclusion: The minimal important difference of the HADS is around 1.5 in COPD patients corresponding to a change from baseline of around 20%. It can be used for the planning and interpretation of trials. [ABSTRACT FROM AUTHOR]

Background: Randomised trials comparing different drugs head-to-head are extremely valuable for clinical decision-making. However, it is scientifically and ethically sensible to demand strong evidence that a drug is effective by showing superiority over a placebo before embarking on head-to-head comparisons of potentially ineffective drugs. Our aim was to study the evolvement of evidence from placebo-controlled and head-to-head trials on the effects of antibiotics for the treatment of mild to moderate exacerbations of chronic obstructive pulmonary disease. Methods: We conducted a historical systematic review. Through electronic databases and hand-searches, we identified placebo-controlled and head-to-head antibiotic trials for the treatment of mild to moderate chronic obstructive pulmonary disease exacerbations. We compared the numbers of patients recruited in placebo-controlled and head-to-head trials between 1957 and 2005. Using cumulative meta-analysis of placebo-controlled trials, we determined when, if ever, placebo-controlled trials had shown convincing evidence that antibiotics are effective in preventing treatment failure in patients with mild to moderate chronic obstructive pulmonary disease exacerbations. Results: The first head-to-head trial was published in 1963. It was followed by another 100 trials comparing different antibiotics in a total of 34,029 patients with mild to moderate chronic obstructive pulmonary disease exacerbations. Over time, the cumulative odds ratio in placebo-controlled trials remained inconclusive throughout with odds ratios ranging from 0.39 (95% confidence intervals 0.04-4.22) to the most recent estimate (1995) of 0.81 (95% confidence intervals 0.52-1.28, P = 0.37). Conclusion: Placebo-controlled trials do not support the use of antibiotics in chronic obstructive pulmonary disease patients with mild to moderate exacerbations. Conducting head-to-head trials is, therefore, scientifically and ethically questionable. This underscores the requirement to perform or study systematic reviews of placebo-controlled trials before conducting head-to-head trials. [ABSTRACT FROM AUTHOR]

Background: For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations. Methods: We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment. Results: We included 13 trials (1557 patients) of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I2 = 82%). Metaregression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.016): Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.09, 95% CI 0.75-1.59, I2 = 18%). Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16-0.39, I2 = 0%; number-needed to treat of 4, 95% CI 3-5) and on mortality (pooled odds ratio of 0.20, 95% CI 0.06-0.62, I2 = 0%; number-needed to treat of 14, 95% CI 12-30). Conclusion: Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend high-intensity continuous exercise to reduce peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease but acknowledge that interval exercise might be an equally effective alternative that is better tolerated by patients. Objective: To assess whether interval exercise is no less effective than high-intensity continuous exercise and whether it is tolerated better by patients with severe chronic obstructive pulmonary disease. Design: Randomized, noninferiority trial. Setting: Publicly funded rehabilitation hospital in Switzerland. Patients: 98 patients with severe chronic obstructive pulmonary disease, with or without recent exacerbations. Intervention: 12 to 15 supervised interval or high-intensity continuous exercise sessions (over 3 weeks) followed by exercise at home. Measurements: Health-related quality of life determined by using the Chronic Respiratory Questionnaire (CRQ) (scores from 1 [most severe impairment] to 7 [no impairment]) after 5 weeks and number of unintended breaks during supervised exercise. Results: Both groups experienced large improvements in healthrelated quality of life (increase of CRQ total scores of 1.00 [SD, 0.98] for the interval exercise group and 1.02 [SD, 1.05] for the continuous exercise group). Adjusted between-group differences between the interval exercise group and the continuous exercise group (-0.05 [95% CI, -0.42 to -0.32] for CRQ and 1.1 meters [CI, -25.4 to 27.6 meters] for 6-minute walking distance) were within the a priori defined boundaries of noninferiority (0.5 for CRQ and 45 meters for 6-minute walking distance). Twenty-one (47.9%) patients using interval exercise and 11 (24.0%) patients using continuous exercise were able to adhere to the protocol (difference, 23.9 percentage points [CI, 5.0 to 42.8 percentage points]; P = 0.014). The median number of unintended breaks lasting 1 minute or more was 2 (interquartile range, 0 to 16) for patients in the interval exercise group and 11 (interquartile range, 2 to 26) for patients in the continuous exercise group (P = 0.023). Limitations: The study focused on initiation of exercise and not on outpatient or home-based maintenance of exercise. Conclusions: Clinicians and patients can choose either of the 2 exercise plans to initiate physical exercise. [ABSTRACT FROM AUTHOR]

The chronic respiratory questionnaire, available as an interviewer and a self-administered instrument, includes 20 items across four domains: dyspnea (5 items), fatigue (4 items), emotional function (7 items), and mastery (4 items). When completing this instrument, patients rate their experience on a 7-point scale ranging from 1 (maximum impairment) to 7 (no impairment). The Chronic Respiratory Questionnaire has demonstrated excellent measurement properties for both discriminative and evaluative purposes and served as a model in numerous methodological studies in chronic airflow limitation and patients with chronic obstructive pulmonary disease. We performed a systematic review of the literature on the chronic respiratory questionnaire to summarize the key qualities of the chronic respiratory questionnaire and to appraise the work regarding the minimal important difference of the chronic respiratory questionnaire. This paper includes a revision of our initial definition of the minimal important difference and a methodological framework for using anchor based approaches to establish the minimal important difference pioneered by Jaeschke and colleagues. Other approaches to evaluate the minimal important difference include distribution-based methods and panel-based methods. Investigators have used all of these approaches to establish the minimal important difference for the chronic respiratory questionnaire and the results are in general agreement with the minimal important difference of 0.5 for the mean domain scores of the chronic respiratory questionnaire. As a result of this literature review and discussion at the workshop, we established several research objectives. These objectives include the exploration of presentation of quality of life information and prospective anchor-based approaches. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems. Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity. To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses. Methods: Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings. We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation. Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality. We pooled the results using fixed effects models where statistically significant heterogeneity (p = 0.1) was absent. Results: We identified six trials including 230 patients. Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and mortality (0.45 [0.22-0.91]). Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain, 1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery. Weighted mean differences for the St. Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials, rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115). Conclusion: Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation. Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD. [ABSTRACT FROM AUTHOR]

Background: Whether responsiveness represents a measurement property of health-related quality of life (HRQL) instruments that is distinct from reliability and validity is an issue of debate. We addressed the claims of a recent study, which suggested that investigators could rely on internal consistency to reflect instrument responsiveness. Methods: 516 patients with chronic obstructive pulmonary disease or knee injury participating in four longitudinal studies completed generic and disease-specific HRQL questionnaires before and after an intervention that impacted on HRQL. We used Pearson correlation coefficients and linear regression to assess the relationship between internal consistency reliability (expressed as Cronbach's alpha), instrument type (generic and disease-specific) and responsiveness (expressed as the standardised response mean, SRM). Results: Mean Cronbach's alpha was 0.83 (SD 0.08) and mean SRM was 0.59 (SD 0.33). The correlation between Cronbach's alpha and SRMs was 0.10 (95% CI -0.12 to 0.32) across all studies. Cronbach's alpha alone did not explain variability in SRMs (p = 0.59, r² = 0.01) whereas the type of instrument was a strong predictor of the SRM (p = 0.012, r2 = 0.37). In multivariable models applied to individual studies Cronbach's alpha consistently failed to predict SRMs (regression coefficients between -0.45 and 1.58, p-values between 0.15 and 0.98) whereas the type of instrument did predict SRMs (regression coefficients between -0.25 to -0.59, p-values between <0.01 and 0.05). Conclusion: Investigators must look to data other than internal consistency reliability to select a responsive instrument for use as an outcome in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Assessment of health-related quality of life (HRQL) is important in patients with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD in Germany, Switzerland and Austria there is no validated disease-specific instrument available. The objective of this study was to translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely used respiratory HRQL questionnaires, into German, develop an interviewer- and self-administered version including both standardised and individualised dyspnoea questions, and validate these versions in two randomised studies. Methods: We recruited three groups of patients with COPD in Switzerland, Germany and Austria. The 44 patients of the first group completed the CRQ during pilot testing to adapt the CRQ to German-speaking patients. We then recruited 80 patients participating in pulmonary rehabilitation programs to assess internal consistency reliability and cross-sectional validity of the CRQ. The third group consisted of 38 patients with stable COPD without an intervention to assess test-retest reliability. To compare the interviewer- and self-administered versions, we randomised patients in groups 2 and 3 to the interviewer- or self-administered CRQ. Patients completed both the standardised and individualised dyspnoea questions. Results: For both administration formats and all domains, we found good internal consistency reliability (Crohnbach's alpha between 0.73 and 0.89). Cross-sectional validity tended to be better for the standardised compared to the individualised dyspnoea questions and cross-sectional validity was slightly better for the self-administered format. Test-retest reliability was good for both the interviewer-administered CRQ (intraclass correlation coefficients for different domains between 0.81 and 0.95) and the self-administered format (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person variability was responsible for the higher test-retest reliability of the interviewer-administered format while between person variability was similar for both formats. Conclusions: Investigators in German-speaking countries can choose between valid and reliable self-and interviewer-administered CRQ formats. [ABSTRACT FROM AUTHOR]

Background: Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation. Methods/Design: We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12-15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out. Discussion: Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Exercise training is an important component of pulmonary rehabilitation (PR) programmes in chronic obstructive pulmonary disease (COPD), but the great majority of COPD patients who would benefit from PR never follow such programmes or fail to maintain exercise training after PR completion. Against this background, we developed an exercise training programme that requires minimal equipment and can be implemented long-term in the patient's home-setting. The aims of the HOMEX-1 and HOMEX-2 trials are to assess the effectiveness of this home-based exercise training programme in two groups of COPD patients over the course of one year: patients who have completed PR (HOMEX-1 trial) and patients who did not enrol in existing PR programmes within the last two years (HOMEX-2 trial).Methods: HOMEX-1 and HOMEX-2 are multicentre, parallel group, randomised controlled trials. For both trials each, it is planned to include 120 study participants with a diagnosis of COPD. Participants will be randomised with a 1:1 ratio into the intervention group or the control group (usual care/no intervention). The intervention consists of minimal-equipment exercise training elements with progressive level of intensity, conducted by the participant during six days per week and instructed and coached by a trained health care professional during three home visits and regular telephone calls during one year. Primary outcome is change in dyspnoea (domain of Chronic Respiratory Questionnaire) from baseline to 12-months follow-up. Secondary outcomes are change in dyspnoea over the course of the year (assessed at 3, 6 and 12 month) and change in functional exercise capacity, physical activity, health-related quality of life, health status, exacerbations and symptoms from baseline to 12 months follow-up. In addition, explanatory, safety and cost-effectiveness outcomes will be assessed. We will conduct intention-to-treat analyses separately per trial and per protocol analyses as sensitivity analyses.Discussion: The HOMEX-1 and HOMEX-2 trials assess a novel intervention that provides an innovative way of making exercise training as accessible as possible for COPD patients. If the intervention proves to be effective long-term, it will fill the gap of providing an easily accessible and feasible intervention so that more COPD patients can follow an exercise programme.Trial Registration: ClinicalTrials.gov Identifier: HOMEX-1 NCT03461887 (registration date: March 12, 2018; retrospectively registered); HOMEX-2 NCT03654092 (registration date: August 31, 2018). [ABSTRACT FROM AUTHOR]

The author discusses the prediction model developed by Z. Zafari and colleagues to predict lung-function trajectories in individual patients and its effectiveness in the prevention and early treatment of chronic obstructive pulmonary disease (COPD). He says that the prediction tool can be used to identify the risk of a rapid decline in lung function, particularly among smokers.

The article discusses an analysis of to identify role of handgrip strength in mortality of patients suffering with chronic obstructive pulmonary disease (COPD).

See article, page 1063 [ABSTRACT FROM AUTHOR]

A response by Milo Puhan et al, to letters to the editor about their article "Expansion of the Prognostic Assessment of Patients With Chronic Obstructive Pulmonary Disease: The Updated BODE Index and the ADO Index," published in a 2009 issue of the journal "The Lancet" is presented.

Abstract: Objectives: Recent studies suggest that rating clinical marker states (CMS) does not improve the measurement properties of the standard gamble (SG) and only slightly improves those of the feeling thermometer (FT). The poor intrarater (test–retest) reliability of CMS may explain their meager performance. Further, lack of interrater reliability may compromise the use of CMS in interpreting health state ratings. The aim of this study was to assess the reliability of CMS ratings for the SG and the FT. Study Design and Setting: Two similar studies in patients with chronic obstructive pulmonary disease (COPD, n =91) and in patients with gastroesophageal reflux disease (GERD, n =112) provided data for this analysis. Patients rated three different CMS (mild, moderate, and severe disease) twice several weeks apart. We used generalizability theory to calculate reliability coefficients. Results: Test–retest reliability for CMS ratings was higher for the FT compared to the SG (COPD: 0.86 vs. 0.67; GERD: 0.86 vs. 0.67). Interrater reliability was much higher for the FT compared to the SG (COPD: 0.78 vs. 0.46; GERD: 0.71 vs. 0.26). Conclusions: These results suggest that the markedly poorer reliability of CMS for the SG than the FT is driven largely by poor interrater reliability. [Copyright &y& Elsevier]