Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation.

BACKGROUND: Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612). METHODS/DESIGN: The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1 ≤ 50% of predicted or FEV1 < 1 liter, RV/TLC ≥ 0.65 at screening, marked dyspnea score ≥ 2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥ 12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥ 1 point at the 6-month follow-up visit. DISCUSSION: If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00391612.

Sniff nasal inspiratory pressure versus IC/TLC ratio as predictors of mortality in COPD.

BACKGROUND: Hyperinflation is a recognized adverse prognostic factor in COPD. As the sniff inspiratory nasal pressure (SnIP) principally reflects the severity of hyperinflation in COPD, we hypothesized that it might also be a predictor of mortality. We therefore compared the SnIP to the inspiratory capacity-to-total lung capacity (IC/TLC) ratio as predictors of mortality in advanced COPD. METHODS: A retrospective mortality analysis of 110 patients with COPD (mean FEV(1) 1.01litres, 37% predicted; 66% male) was performed. All patients had SnIP and lung volume measurements performed. The power of each test to predict mortality was determined, and predicted survival curves were created for both the SnIP and IC/TLC ratio. RESULTS: 37 patients (34%) died during the study period (29 male, 8 female). Mortality rates were analysed with a Chi(2) test; there was a significant trend towards male death (mortality rate male vs. female; 39.7% vs. 21.6% respectively; chi(2)p=0.058, Chi 3.6). ROC curves demonstrated that both SnIP and IC/TLC ratio are predictors of mortality, but analysis by Cox proportional hazards suggested the SnIP has a stronger predictive power (SnIP vs. IC/TLC ratio; p=0.017 vs 0.525; HR 0.97 vs 0.99 respectively), and analysis of the area under ROC curves (AUC) suggest that SnIP is a better discriminator than IC/TLC ratio (AUC SnIP vs IC/TLC; 0.679 vs 0.618). CONCLUSIONS: The SnIP conveys at least as much predictive power for mortality in COPD as hyperinflation determined by IC/TLC ratio. This test is cheaper, quicker and easier than measuring lung volumes by plethysmography.

Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease.

BACKGROUND: Prognosis in chronic obstructive pulmonary disease (COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis. OBJECTIVE: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force (QMVC) is a useful predictor of mortality in patients with COPD. METHODS: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient's body mass index. The end point measured was death or lung transplantation, and median (range) follow-up was 38 (1-54) months. RESULTS: Data were obtained for 162 patients (108 men and 54 women) with a mean (SD) percentage of forced expiratory volume in 1 s (FEV1) predicted of 35.6 (16.2), giving a response rate of 88%. Transplant-free survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age (HR 1.72 (95% CI 1.14 to 2.6); p = 0.01) and QMVC (HR 0.91 (95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis. CONCLUSION: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s.