Comments
Rationale: The impact of respiratory exacerbation on chronic obstructive pulmonary disease (COPD) is well established. The effects of respiratory exacerbations in people with cigarette smoking but normal spirometry are unknown.
Objectives: To assess the association of respiratory exacerbations with lung function decline and mortality in people with normal spirometry and current or former cigarette smoking history.
Methods: We analyzed data from COPDGene study participants with ⩾10 pack-years of cigarette smoking and normal spirometry at enrollment (Visit 1) defined as post-bronchodilator FEV1/FVC greater than or equal to the lower limit of normal and FEV1 greater than or equal to the lower limit of normal. We examined whether respiratory exacerbations occurring between Visit 1 and the 5-year follow-up visit (Visit 2) were associated with FEV1 decline and all-cause mortality.
Measurements and Main Results: Among 2,939 participants with cigarette smoking history and normal lung function at Visit 1, each additional exacerbation between Visits 1 and 2 was associated with a 2.96 ml/yr FEV1 decline (95% confidence interval [CI], 1.81 to 4.12; P < 0.001) at Visit 2. Experiencing one or more severe exacerbations between Visits 1 and 2 was associated with 14.6 ml/yr FEV1 decline relative to those with no severe exacerbations (95% CI, 8.56 to 20.6; P < 0.001). Individuals with one or more severe exacerbations between Visits 1 and 2 had increased mortality compared with those with no severe exacerbations (17.1% vs. 9.8%; adjusted hazard ratio, 1.97; 95% CI, 1.40 to 2.77; P < 0.001).
Conclusions: Respiratory exacerbations in people with cigarette smoking but normal spirometry were associated with lung function decline. Experiencing a severe respiratory exacerbation was associated with increased mortality.
A complete list of COPDGene investigators may be found before the beginning of the References.
Supported by award number U01 HL089897, award number U01 HL089856, and NIH contract 75N92023D00011 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. COPDGene is also supported by the COPD Foundation through contributions made to an industry advisory board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion. E.S.W. is supported by U.S. Department of Veterans Affairs Clinical Science Research and Development Service grant CX002193.
Author Contributions: S.F. has full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept: S.F. and A.P.C. Study design: S.F., M.S., P.T.E., and L.W. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: S.F. Critical revision of the manuscript for important intellectual content: all authors.
Deidentified data from COPDGene are publicly available on request. Further details are available online from: http://www.copdgene.org/.
A data supplement for this article is available via the Supplements tab at the top of the online article.
Artificial Intelligence Disclaimer: The first author used Copilot to correct his grammar mistakes.
Originally Published in Press as DOI: 10.1164/rccm.202401-0023OC on February 13, 2025
Author disclosures are available with the text of this article at www.atsjournals.org.
