The effect of posture on asynchronous chest wall movement in COPD

Priori R, Aliverti A, Albuquerque AL, Quaranta M, Albert P, Calverley PM. the effect of posture on asynchronous chest wall movement in COPD. J Appl Physiol 114: 1066-1075, 2013. First published February 14, 2013; doi:10.1152/japplphysiol.00414.2012.-Chronic obstructive pulmonary disease (COPD) patients often show asynchronous movement of the lower rib cage during spontaneous quiet breathing and exercise. We speculated that varying body position from seated to supine would influence rib cage asynchrony by changing the configuration of the respiratory muscles. Twenty-three severe COPD patients (forced expiratory volume in 1 s = 32.5 +/- 7.0% predicted) and 12 healthy age-matched controls were studied. Measurements of the phase shift between upper and lower rib cage and between upper rib cage and abdomen were performed with opto-electronic plethysmography during quiet breathing in the seated and supine position. Changes in diaphragm zone of apposition were measured by ultrasounds. Control subjects showed no compartmental asynchronous movement, whether seated or supine. in 13 COPD patients, rib cage asynchrony was noticed in the seated posture. This asynchrony disappeared in the supine posture. in COPD, upper rib cage and abdomen were synchronous when seated, but a strong asynchrony was found in supine. the relationships between changes in diaphragm zone of apposition and volume variations of chest wall compartments supported these findings. Rib cage paradox was noticed in approximately one-half of the COPD patients while seated, but was not related to impaired diaphragm motion. in the supine posture, the rib cage paradox disappeared, suggesting that, in this posture, diaphragm mechanics improves. in conclusion, changing body position induces important differences in the chest wall behavior in COPD patients.Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, ItalyUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniv Liverpool, Univ Hosp Aintree, Ctr Clin Sci, Liverpool L69 3BX, Merseyside, EnglandUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilWeb of Scienc

Clinical trials for elderly patients with multiple diseases (CHROMED) pilot study

The problem COPD (Chronic Obstructive Pulmonary Disease) is a significant socioeconomic burden which, particularly when associated with comorbidities such as Chronic Heart Failure (CHF), markedly affects patient outcomes. Care models based on telemedicine systems that enable early diagnosis and treatment of exacerbations are advocated to reduce the impact of chronic diseases on patient outcomes and health service costs. CHROMED (www.chromed.eu) is an international EU-funded project aimed at developing a multi-centre clinical trial to evaluate the impact of a new integrated home care approach to reduce care costs and improve quality of life in COPD. The approach We collaborated in a pilot study prior to the main trial which will include 300 patients from seven European countries (Italy, Spain, UK, Estonia, Slovenia, Sweden and Norway) with nine partners. The home monitoring system includes a novel forced oscillation technique (FOT) device for self-measurement of lung mechanics (RESMONPRO DIARY, Restech srl, Italy), a touch screen for collecting patients' symptoms and, where COPD is associated with CHF, by a device for measuring heart rate (HR), blood pressure (BP), pulse oximetry (SpO2) and body temperature (WRIST CLINIC, Medic4all, Israel). Findings The pilot included 16 patients (n=11 COPD, 5 COPD+CHF). The average monitoring period was 48.3±23.4 days resulting in a total of 504 patient days. The percentage of data correctly received within the period was: lung impedance and breathing pattern 90.0%; HR 91.7%, BP 91.7%; SpO2 74.0% and body temperature 71.4%. During the pilot, one patient was treated pharmacologically for an exacerbation of COPD. Offline processing demonstrated that the system identified warning of an exacerbation five days prior to admission. We also analysed qualitative data from patients and professionals about the acceptability of the telemedicine system and the interaction between patients, professionals and the monitoring system. Consequences The data suggest good acceptability and short-term compliance among patients with COPD. Lung function, HR and BP provided the most reliable data. The full RCT is currently under way and will be completed in August 2015

Blood eosinophils as a biomarker of future COPD exacerbation risk:pooled data from 11 clinical trials

Background Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear. Methods This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies. Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study. Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study. Results Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150–300 cells/μL and 20.1% with > 300 cells/μL. The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count. When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150–300 cells/μL and 0.44 for > 300 cells/μL respectively). A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively. For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150–300 cells/μL) and 1.07 (> 300 cells/μL). Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49). Conclusion We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate. Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations. Trial registration ClinicalTrials.gov Identifiers: NCT00168844, NCT00168831, NCT00387088, NCT00782210, NCT00782509, NCT00793624, NCT00796653, NCT01431274, NCT01431287, NCT02296138 and NCT00975195

Impact of pre-enrolment medication use on clinical outcomes in SUMMIT

The impact of prior treatment on results of clinical trials in chronic obstructive pulmonary disease (COPD) has been debated. We used data from the Study to Understand Mortality and Morbidity in COPD Trial to examine the impact of prior treatment on the effects of randomised study drugs on mortality and exacerbations. We used data on 16 417 patients with moderate COPD and heightened cardiovascular risk and information on prior medications to examine the effects of fluticasone furoate (FF), vilanterol (VI) and combined FF/VI compared to placebo on moderate and severe exacerbation as well as mortality. The study was event-driven with a median study exposure of 1.8 years. This study was registered with ClinicalTrials.gov, number NCT01313676. There were no consistent associations between treatment prior to study entry and the effects of FF, VI or FF/VI on exacerbations during the study. However, patients taking inhaled corticosteroids and one or more bronchodilators prior to study entry seemed to have a better effect of active treatments than of placebo on mortality (hazard ratio for FF/VI 0.65, 95% CI 0.48–0.89). Survival in those randomised to placebo was independent of treatment prior to study enrolment. Prior treatment appears to affect treatment effects on mortality but not exacerbations in a randomised controlled trial of patients with COPD and heightened cardiovascular risk

Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study

Background: 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. Methods: 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: ³ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937). Results: 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. Conclusion: 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

Withdrawal of inhaled glucocorticoids and exacerbations of COPD.

This is the final version of the article. It first appeared from Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa1407154BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. CONCLUSIONS: In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).Supported by Boehringer Ingelheim Pharma

Characterisation of COPD heterogeneity in the ECLIPSE cohort

Background 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). Methods 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. Results 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. Conclusions The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease