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Original Research |

Reduced COPD exacerbation risk correlates with improved FEV1: A meta-regression analysis

Alexander D. Zider, MD; Xiaoyan Wang, PhD; Russell G. Buhr, MD; Worawan Sirichana, MD; Igor Z. Barjaktarevic, MD; Christopher B. Cooper, MD
Author and Funding Information

CONFLICTS OF INTEREST:

AZ reports that his spouse is an employee and stockholder of Shire

RB and XW report no conflicts of interest

WS reports that she has received grants and/or personal fees from Boehringer Ingelheim, Novartis, AstraZeneca, and Chiesi Farmaceutici S.p.A, none in relation to this work.

IB reports that he has received personal fees from AstraZeneca and Grifols, none in relation to this work.

CBC reports that he has received grants and/or personal fees from Amgen, Spiration, PulmonX, Boehringer Ingelheim, GlaxoSmithKline, and Equinox health clubs, none in relation to this work. In addition, he is currently employed as a Global Medical Expert in the GlaxoSmithKline respiratory franchise.

SOURCES OF FUNDING:

UCLA Exercise Physiology Research Laboratory unrestricted funding. In addition, RB is supported by NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number TL1TR001883.

NOTIFICATION OF PRIOR ABSTRACT PRESENTATION

Some of this work has been previously presented in the form of an abstract at the 2016 American Thoracic Society Annual Meeting in San Francisco.

1Division of Pulmonary & Critical Care, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA

2Division of General Internal Medicine and Health Services Research, Department of Medicine, University of California, Los Angeles, USA

3Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand

4Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, USA

Corresponding author: Christopher B Cooper, MD, Professor Emeritus of Medicine and Physiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, 37-131 CHS, Los Angeles, CA 90095.


Copyright 2017, . All Rights Reserved.


Chest. 2017. doi:10.1016/j.chest.2017.04.174
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Abstract

Background  The mechanism by which various classes of medication reduce COPD exacerbation risk remains unknown. We hypothesized a correlation between reduced exacerbation risk and improvement in airway patency as measured by the forced expiratory volume in 1 second (FEV1).

Methods  By systematic review, we identified COPD trials that reported therapeutic changes in pre-dose FEV1 (dFEV1) and occurrence of moderate to severe exacerbations. Using meta-regression analysis, we generated a model with dFEV1 as moderator variable, and absolute difference in exacerbation rate (RD), ratio of exacerbation rates (RR), or hazard ratio (HR) as dependent variables.

Results  The analysis of RD and RR included 119,227 patients, and that of HR 73,475 patients. For every 100 mL change in pre-dose FEV1, the HR decreased by 21% (95% CI: 17-26%, P<0.001, R2 = 0.85) and the absolute exacerbation rate decreased by 0.06 per patient per year (95% CI: 0.02-0.11, P=0.009, R2 = 0.05), which corresponded to a RR of 0.86 (95% CI: 0.81-0.91, P<0.001, R2 = 0.20). The relationship with exacerbation risk remained statistically significant across multiple subgroup analyses.

Conclusions  A significant correlation between increased FEV1 and lower COPD exacerbation risk suggests airway patency is an important mechanism responsible for this effect.


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