Increased mortality associated with frequent exacerbations in COPD patients with mild-to-moderate lung function impairment, and smokers with normal spirometry

Spyridon Fortis; Emily S Wan; Ken Kunisaki; Patrick Tel Eyck; Zuhair K Ballas; Russell P Bowler; James D Crapo; John E Hokanson; Chris Wendt; Edwin K Silverman; Alejandro P Comellas

doi:10.1016/j.yrmex.2020.100025

Increased mortality associated with frequent exacerbations in COPD patients with mild-to-moderate lung function impairment, and smokers with normal spirometry

Respir Med X. 2021 Nov:3:100025. doi: 10.1016/j.yrmex.2020.100025. Epub 2020 Dec 29.

Authors

Spyridon Fortis^{1

2}, Emily S Wan^{3

4}, Ken Kunisaki^{5

6}, Patrick Tel Eyck⁷, Zuhair K Ballas⁸, Russell P Bowler⁹, James D Crapo⁹, John E Hokanson¹⁰, Chris Wendt^{5

6}, Edwin K Silverman³, Alejandro P Comellas²

Affiliations

¹ Center for Access & Delivery Research & Evaluation (CADRE), Iowa City VA Health Care System, Iowa City, IA, USA.
² Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, IA, USA.
³ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁴ VA Boston Healthcare System, Jamaica Plain, MA, USA.
⁵ Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA.
⁶ University of Minnesota, Minneapolis, MN, USA.
⁷ Biostatistics and Research Design, Institute for Clinical and Translational Science, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
⁸ Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
⁹ Department of Medicine, National Jewish Health, Denver, CO, USA.
¹⁰ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract

Background: The burden of frequent respiratory exacerbations in COPD patients with mild-to-moderate spirometric impairment and smokers with preserved lung function is unknown.

Methods: We categorized COPD participants in COPDGene with post-bronchodilator FEV1%predicted≥50% by the annual exacerbation frequency into three groups: i)frequent exacerbators (top 5%; n = 109), ii)exacerbators (>0 but less than frequent exacerbators; n = 1,009), and iii)No exacerbation (n = 981). Exacerbations were defined as respiratory episodes requiring antibiotics and/or systemic steroids. We performed a Cox proportional hazards regression analysis to examine the association with mortality. We repeated the same process in current/former smokers with preserved spirometry (FEV1≥80%predicted and FEV1/FVC≥0.7).

Results: Among 2,099 COPD participants, frequent exacerbators had ≥1.8 exacerbations/year and were responsible for 34.3% of the total exacerbations. There were 102 (10.4%) deaths in the group with no exacerbations, 119 (11.8%) in the exacerbator group, and 24 (22%) in the frequent exacerbators. Adjusted mortality in frequent exacerbators was higher relative to individuals with no exacerbations (hazard ratio (HR) = 1.98; 95%CI = 1.25-3.13). An increase in frequency of exacerbations by one exacerbation/year was associated with increased mortality (HR = 1.40,95%CI = 1.21-1.62). Among 3,143 participants with preserved spirometry, frequent exacerbators had ≥0.8 exacerbations/year and were responsible for more than half of the exacerbations. There were 93 (4.2%) deaths in the group with no exacerbations, 28 (3.8%) in the exacerbator group, and 14 (7.6%) in the frequent exacerbators. The adjusted mortality was increased in frequent exacerbators with preserved spirometry relative to those with no exacerbations (HR = 2.25; 95%CI = 1.26-4.01).

Conclusions: In COPD participants with mild-to-moderate spirometric impairment and smokers with preserved spirometry, the frequent exacerbator phenotype is responsible for a large proportion of total exacerbations and associated with high mortality.

Keywords: Chronic obstructive pulmonary disease; Exacerbations; Mortality.

Abstract

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