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

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

doi:10.1164/rccm.202408-1656OC

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

Journal article

Peer reviewed

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

Pallavi P Balte, John S Kim, Yifei Sun, Nori Allen, Elsa Angelini, Alexander Arynchyn, R Graham Barr, Michael Blaha, Russell Bowler, Jeff Carr, …

American journal of respiratory and critical care medicine, Vol.211(7), pp.1196-1210

07/2025

DOI: 10.1164/rccm.202408-1656OC

PMCID: PMC12264703

PMID: 40238945

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Abstract

Rationale: Increased risk of COVID-19 hospitalization and death has been reported among patients with clinical lung disease. Objective: To test the association of objective measures of pre-pandemic lung function and structure with COVID-19 outcomes in US adults. Methods: Pre-pandemic obstruction (FEV1/FVC<0.70) and restriction (FEV1/FVC≥0.7, FVC<80%) were defined based on the most recent spirometry exam conducted in 11 prospective US general population-based cohorts. Severe obstruction was classified by FEV1<50%. Percent emphysema, percent high attenuation areas (HAA), and interstitial lung abnormalities (ILA) were defined on computed tomography (CT) in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020-2023, and classified as severe (hospitalized or fatal) or non-severe. Cause-specific hazards models were adjusted for socio-demographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. Measurements and Main Results: Among 29,323 participants (mean age, 67 years), 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, aHR=2.11;95%CI:1.02-1.27), restriction (vs normal, aHR=1.40;95%CI:1.12-1.76), and percent emphysema (highest vs lowest quartile, aHR= 1.64;95%CI:1.03–2.61), but not greater HAA or ILAs. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. Conclusions: Pre-pandemic severe spirometric obstruction, spirometric restriction, and greater percent emphysema lung on CT 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

COVID-19

Lung function and structure

Obstructive physiology

Restrictive physiology

Percent emphysema

Details

Title: Subtitle: Associations of Pre-Pandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study
Creators: Pallavi P Balte
John S Kim - Charlottesville, Virginia, United States
Yifei Sun - Columbia University Irving Medical Center
Nori Allen - Northwestern University
Elsa Angelini - NIHR Imperial Biomedical Research Centre
Alexander Arynchyn - University of Alabama
R Graham Barr - Columbia University
Michael Blaha - Johns Hopkins University
Russell Bowler - National Jewish Health
Jeff Carr - Vanderbilt University Medical Center
Shelley A Cole - Texas Biomedical Research Institute, San Antonio, Texas, United States
David Couper - University of North Carolina at Chapel Hill
Ryan T Demmer - Mayo Clinic
Margaret Doyle - University of Vermont
Mitchell Elkind - Columbia University Irving Medical Center
Raúl San José Estépar - Brigham and Women's Hospital
Olga Garcia-Bedoya - University of Illinois Chicago
Suresh Garudadri - University of California, San Francisco
Nadia N Hansel - Johns Hopkins University
Emilia A Hermann - Columbia University Irving Medical Center
Eric A Hoffman - University of Iowa Carver College of Medicine, Radiology, Iowa City, Iowa, United States
Stephen M Humphries - National Jewish Health
Gary M Hunninghake - Brigham and Women's Hospital
Robert Kaplan - Albert Einstein College of Medicine
Jerry A Krishnan - University of Illinois Chicago
Andrew Laine - Columbia University
Joyce S Lee - University of Colorado, School of Medicine, Department of Medicine, Aurora, Colorado, United States
David A Lynch - National Jewish Health
Barry Make - National Jewish Health
Kunihiro Matsushita - Johns Hopkins Bloomberg School of Public Health, Baltimore, United States
Will McKleroy - Kaiser Permanente San Francisco Medical Center
Yuan-I Min - University of Mississippi Medical Center
Sneha N Naik - Columbia University
George O'Connor - Boston University School of Medicine
Olivia O'Driscoll - Columbia University
Eyal Oren - San Diego State University
Anna J Podolanczuk - Weill Cornell Medical College, Department of Medicine, New York, New York, United States
Wendy S Post - Johns Hopkins University
Tess Pottinger - Columbia University Irving Medical Center
Elizabeth Regan - National Jewish Health
Annie Rusk - Mayo Clinic
Mary Salvatore - Columbia University Irving Medical Center
David A Schwartz - University of Colorado, School of Medicine, Department of Medicine, Aurora, Colorado, United States
Benjamin Smith - Columbia University Irving Medical Center
Daniela Sotres-Alvarez - University of North Carolina Research Opportunities Initiative, Chapel Hill, North Carolina, United States
Jason G Umans - Georgetown-Howard Universities Center for Clinical and Translational Science
Ramachandran S Vasan - University of Texas School of Public Health - San Antonio Regional Campus, San Antonio, Texas, United States
George Washko - Brigham and Women's Hospital
Sally Wenzel - Dept of EOH, Pittsburgh, Pennsylvania, United States
Prescott Woodruff - UCSF, Division of Pulmonary and Critical Care Medicine, Department of Medicine and CVRI, San Francisco, California, United States
Vanessa Xanthakis - Boston University
Victor E Ortega - Mayo Clinic
Elizabeth C Oelsner - Columbia University
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.211(7), pp.1196-1210
DOI: 10.1164/rccm.202408-1656OC
PMID: 40238945
PMCID: PMC12264703
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1535-4970
eISSN: 1535-4970
Publisher: AMER THORACIC SOC
Language: English
Electronic publication date: 04/16/2025
Date published: 07/2025
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984810945302771

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