Paradoxical movement of the lower ribcage at rest and during exercise in COPD patients

Paradoxical inward displacement of the costal margin during inspiration is observed in many chronic obstructive pulmonary disease patients at rest but its importance is unclear.The current authors studied 20 patients (forced expiratory volume in one second 32.6 +/- 11.7, functional residual capacity 186 +/- 32% predicted) and 10 healthy controls at rest and during symptom-limited incremental exercise. With optoelectronic plethysmography, the phase shift between pulmonary and abdominal ribcage volumes and the percentage of inspiratory time the ribcage compartments moved in opposite directions were quantified, using control data to define the normal range of movement.Eight patients showed lower ribcage inspiratory paradox at rest (P+), while 12 patients did not (P-). This was unrelated to resting lung function or exercise tolerance. Total end-expiratory chest wall volume (EEVcw) increased immediately when exercise began in P+ patients, but later in exercise in P- patients. This difference in EEVcw was mainly due to a greater increase of end-expiratory pulmonary ribcage volume in P+ patients. During exercise, dyspnoea increased similarly in the two groups, while leg effort increased more markedly in the patients without paradox.In conclusion, lower ribcage paradox at rest is reproducible and associated with early-onset hyperinflation of the chest wall and predominant dyspnoea at end-exercise. When paradox is absent, the sense of leg effort becomes a more important symptom limiting exercise.British Lung FoundationEuropean Respiratory Society (ERS)ERS COEDPolitecn Milan, TBM Lab, Dipartimento Bioingn, I-20133 Milan, ItalyUniv Liverpool, Ctr Clin Sci, Univ Hosp Aintree, Liverpool L69 3BX, Merseyside, EnglandUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilEuropean Respiratory Society (ERS): 69Web of Scienc

Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? the REACT study protocol.

Many patients with chronic obstructive pulmonary disease (COPD) continue to suffer exacerbations, even when treated with maximum recommended therapy (eg, inhaled combinations of long-acting β(2)-agonist and high dose inhaled corticosteroids, with or without a long-acting anticholinergic [long-acting muscarinic antagonist]). Roflumilast is approved to treat severe COPD in patients with chronic bronchitis - and a history of frequent exacerbations - as an add-on to bronchodilators.PURPOSE:The REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment) study (identification number RO-2455-404-RD, clinicaltrials. gov identifier NCT01329029) will investigate whether roflumilast further reduces exacerbations when added to inhaled combination therapy in patients still suffering from frequent exacerbations.PATIENTS AND METHODS:REACT is a 1-year randomized, double-blind, multicenter, phase III/IV study of roflumilast 500 μg once daily or placebo on top of a fixed long-acting β(2)-agonist/inhaled corticosteroid combination. A concomitant long-acting muscarinic antagonist will be allowed at stable doses. The primary outcome is the rate of moderate or severe COPD exacerbations. Using a Poisson regression model with a two-sided significance level of 5%, a sample size of 967 patients per treatment group is needed for 90% power. COPD patients with severe to very severe airflow limitation, symptoms of chronic bronchitis, and at least two exacerbations in the previous year will be recruited.CONCLUSION:It is hypothesized that because roflumilast (a phosphodiesterase-4 inhibitor) has a different mode of action to bronchodilators and inhaled corticosteroids, it may provide additional benefits when added to these treatments in frequent exacerbators. REACT will be important to determine the role of roflumilast in COPD management. Here, the design and rationale for this important study is described

The Effect of Maintenance Treatment with Erdosteine on Exacerbation Treatment and Health Status in Patients with COPD: A Post-Hoc Analysis of the RESTORE Dataset.

Purpose: To explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity. Patients and methods: This post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patientreported HRQoL (St George’s Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student’s t-tests or ANCOVA as appropriate. Results: Among GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures. Conclusion: Adding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity

One-year treatment with mometasone furoate in chronic obstructive pulmonary disease

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing

Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

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

Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

A pooled analysis of mortality in patients with COPD receiving triple therapy versus dual bronchodilation

Peer reviewedPostprin

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations