Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study

<b>Rationale:</b> Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. <b>Objective:</b> To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. <b>Methods:</b> Prepandemic obstruction (FEV<sub>1</sub>/FVC < 0.70) and restriction (FEV<sub>1</sub>/FVC ⩾ 0.7, FVC < 80%) were defined based on the most recent spirometry exam conducted in 11 prospective U.S. general population-based cohorts. Severe obstruction was classified by FEV<sub>1</sub> < 50%. Percentage emphysema, percentage high-attenuation areas, and interstitial lung abnormalities were defined on computed tomography in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020 to 2023 and classified as severe (hospitalized or fatal) or nonsevere. Cause-specific hazard models were adjusted for sociodemographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. <b>Measurements and Main Results:</b> Among 29,323 participants (mean age, 67 yr), there were 748 severe incident COVID-19 cases over median follow-up of 17.3 months from March 1, 2020. Greater hazards of severe COVID-19 were associated with severe obstruction (vs. normal; adjusted hazard ratio [aHR], 2.11; 95% confidence interval [CI], 1.02-1.27), restriction (vs. normal; aHR, 1.40; 95% CI, 1.12-1.76), and percentage emphysema (highest vs. lowest quartile; aHR, 1.64; 95% CI, 1.03-2.61), but not greater high-attenuation areas or interstitial lung abnormalities. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. <b>Conclusions:</b> Prepandemic severe spirometric obstruction, spirometric restriction, and greater percentage emphysema lung on computed tomography were associated with risk of severe COVID-19. These findings support enhanced COVID-19 risk mitigation for individuals with impaired lung health and warrant further mechanistic studies on interactions of lung function, structure, and vulnerability to acute respiratory illnesses.

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Publication Details

Journal
American Journal of Respiratory and Critical Care Medicine
Published
2025-04-16
DOI
https://doi.org/10.1164/rccm.202408-1656oc
Citations
2
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
Type
article
Field-Weighted Citation Impact
3.04
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article

Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study

Nadia N. Hansel, John S. Kim, Raúl San Jośe Estépar, Mary Salvatore et al.
2 citations
American Journal of Respiratory and Critical Care Medicine
Chronic Obstructive Pulmonary Disease (COPD) Research
3.04
article

Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study

Nadia N. Hansel, John S. Kim, Raúl San Jośe Estépar, Mary Salvatore, Ramachandran Srini Vasan, J. Jeffrey Carr, Michael Joseph Blaha, Elsa D. Angelini, Elizabeth A. Regan, Eric A. Hoffman, Suresh Garudadri, Eyal Oren, Russell Paul Bowler, Gary Matthew Hunninghake, Ryan T. Demmer, Sneha N. Naik, David A. Lynch, Tess D. Pottinger, Norrina B. Allen, Anna J. Podolanczuk, Benjamin M. Smith, Victor E. Ortega, Wendy S. Post, Margaret F. Doyle, Olga Garcia‐Bedoya, Barry J. Make, Daniela Sotres‐Alvarez, Elizabeth C. Oelsner, George T. O’Connor, Emilia A. Hermann, Vanessa Xanthakis, Sally E. Wenzel, George R. Washko, Jerry A. Krishnan, Pallavi Balte, Prescott G. Woodruff, A.M. Rusk, Jason G. Umans, R. Graham Barr, Alexander Arynchyn, Shelley A. Cole, Stephen M. Humphries, William McKleroy, Yifei Sun, Robert C. Kaplan, Kunihiro Matsushita, Yuan‐I Min, David Couper, Andrew F. Laine, David A. Schwartz, Joyce Lee, Mitchell S Elkind, O. O'Driscoll
article en
2 citations

Abstract

<b>Rationale:</b> Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. <b>Objective:</b> To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. <b>Methods:</b> Prepandemic obstruction (FEV<sub>1</sub>/FVC < 0.70) and restriction (FEV<sub>1</sub>/FVC ⩾ 0.7, FVC < 80%) were defined based on the most recent spirometry exam conducted in 11 prospective U.S. general population-based cohorts. Severe obstruction was classified by FEV<sub>1</sub> < 50%. Percentage emphysema, percentage high-attenuation areas, and interstitial lung abnormalities were defined on computed tomography in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020 to 2023 and classified as severe (hospitalized or fatal) or nonsevere. Cause-specific hazard models were adjusted for sociodemographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. <b>Measurements and Main Results:</b> Among 29,323 participants (mean age, 67 yr), there were 748 severe incident COVID-19 cases over median follow-up of 17.3 months from March 1, 2020. Greater hazards of severe COVID-19 were associated with severe obstruction (vs. normal; adjusted hazard ratio [aHR], 2.11; 95% confidence interval [CI], 1.02-1.27), restriction (vs. normal; aHR, 1.40; 95% CI, 1.12-1.76), and percentage emphysema (highest vs. lowest quartile; aHR, 1.64; 95% CI, 1.03-2.61), but not greater high-attenuation areas or interstitial lung abnormalities. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. <b>Conclusions:</b> Prepandemic severe spirometric obstruction, spirometric restriction, and greater percentage emphysema lung on computed tomography were associated with risk of severe COVID-19. These findings support enhanced COVID-19 risk mitigation for individuals with impaired lung health and warrant further mechanistic studies on interactions of lung function, structure, and vulnerability to acute respiratory illnesses.

American Journal of Respiratory and Critical Care MedicineVol. 211(7)
Boston University (US), University of Vermont (US), Northwestern University (US), University of North Carolina at Chapel Hill (US), University of Iowa (US), American Heart Association (US), Brigham and Women's Hospital (US), University of Colorado Hospital (US), Texas Biomedical Research Institute (US), Albert Einstein College of Medicine (US), Mayo Clinic (US), Johns Hopkins University (US), The University of Texas at San Antonio Health Science Center (US), University of Pittsburgh (US), University of California, San Francisco (US), Georgetown University (US), Cornell University (US), San Diego State University (US), Columbia University Irving Medical Center (US), British Geriatrics Society (GB), Johns Hopkins Medicine (US), MedStar Georgetown University Hospital (US), University of California System (US), University of Mississippi Medical Center (US), National Jewish Health (US), University of Alabama at Birmingham (US), University of Illinois Chicago (US), General Department of Preventive Medicine (VN), NIHR Imperial Biomedical Research Centre (GB), Georgetown-Howard Universities Center for Clinical and Translational Science (US), Pulmonary and Allergy Associates (US), Kaiser Permanente San Francisco Medical Center (US), Mayo Clinic in Arizona (US), Mayo Clinic in Florida (US), SleepMed (US), Center for Rheumatology (US), Pulmonary and Critical Care Associates (US), Weill Cornell Medicine (US), The University of Texas at San Antonio (US), McGill University (CA), University of Virginia (US), University of Colorado Anschutz Medical Campus (US), Columbia University (US), MedStar Health (US), Vanderbilt University Medical Center (US), University of Colorado Denver (US)
Good health and well-being
Openalex Percentile: Top 10%
Chronic Obstructive Pulmonary Disease (COPD) Research
3.04
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