Associations of Prepandemic 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

Associations of Prepandemic 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

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Rationale: Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. Objective: To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Methods: Prepandemic 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 U.S. general population–based cohorts. Severe obstruction was classified by FEV₁ < 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. Measurements and Main Results: 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. Conclusions: 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.

Original language	English
Pages (from-to)	1196-1210
Number of pages	15
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	211
Issue number	7
DOIs	https://doi.org/10.1164/rccm.202408-1656OC
State	Published - 1 Jul 2025
Externally published	Yes

Keywords

COVID-19
lung function
obstructive physiology
percentage emphysema
restrictive physiology
structure

Access to Document

10.1164/rccm.202408-1656OC

Cite this

Balte, P. P., Kim, J. S., Sun, Y., Allen, N., Angelini, E., Arynchyn, A., Barr, R. G., Blaha, M., Bowler, R., Carr, J., Cole, S. A., Couper, D., Demmer, R. T., Doyle, M., Elkind, M., Estépar, R. S. J., Garcia-Bedoya, O., Garudadri, S., Hansel, N. N., ... Oelsner, E. C. (2025). Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes The C4R Study. American Journal of Respiratory and Critical Care Medicine, 211(7), 1196-1210. https://doi.org/10.1164/rccm.202408-1656OC

@article{527f62bf0dc14f18b8ecb74bbd594897,

title = "Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes The C4R Study",

abstract = "Rationale: Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. Objective: To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Methods: Prepandemic 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 U.S. general population–based cohorts. Severe obstruction was classified by FEV1 < 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. Measurements and Main Results: 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. Conclusions: 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.",

keywords = "COVID-19, lung function, obstructive physiology, percentage emphysema, restrictive physiology, structure",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2025 by the American Thoracic Society.",

year = "2025",

month = jul,

day = "1",

doi = "10.1164/rccm.202408-1656OC",

language = "English",

volume = "211",

pages = "1196--1210",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "7",

}

Balte, PP, Kim, JS, Sun, Y, Allen, N, Angelini, E, Arynchyn, A, Barr, RG, Blaha, M, Bowler, R, Carr, J, Cole, SA, Couper, D, Demmer, RT, Doyle, M, Elkind, M, Estépar, RSJ, Garcia-Bedoya, O, Garudadri, S, Hansel, NN, Hermann, EA, Hoffman, EA, Humphries, SM, Hunninghake, GM, Kaplan, R, Krishnan, JA, Laine, A, Lee, JS, Lynch, DA, Make, B, Matsushita, K, McKleroy, W, Min, YI, Naik, SN, O’Connor, G, O’Driscoll, O, Oren, E, Podolanczuk, AJ, Post, WS, Pottinger, T, Regan, E, Rusk, A, Salvatore, M, Schwartz, DA, Smith, B, Sotres-Alvarez, D, Umans, JG, Vasan, RS, Washko, G, Wenzel, S, Woodruff, P, Xanthakis, V, Ortega, VE & Oelsner, EC 2025, 'Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes The C4R Study', American Journal of Respiratory and Critical Care Medicine, vol. 211, no. 7, pp. 1196-1210. https://doi.org/10.1164/rccm.202408-1656OC

TY - JOUR

T1 - Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes The C4R Study

AU - Balte, Pallavi P.

AU - Kim, John S.

AU - Sun, Yifei

AU - Allen, Nori

AU - Angelini, Elsa

AU - Arynchyn, Alexander

AU - Barr, R. Graham

AU - Blaha, Michael

AU - Bowler, Russell

AU - Carr, Jeff

AU - Cole, Shelley A.

AU - Couper, David

AU - Demmer, Ryan T.

AU - Doyle, Margaret

AU - Elkind, Mitchell

AU - Estépar, Raúl San José

AU - Garcia-Bedoya, Olga

AU - Garudadri, Suresh

AU - Hansel, Nadia N.

AU - Hermann, Emilia A.

AU - Hoffman, Eric A.

AU - Humphries, Stephen M.

AU - Hunninghake, Gary M.

AU - Kaplan, Robert

AU - Krishnan, Jerry A.

AU - Laine, Andrew

AU - Lee, Joyce S.

AU - Lynch, David A.

AU - Make, Barry

AU - Matsushita, Kunihiro

AU - McKleroy, Will

AU - Min, Yuan I.

AU - Naik, Sneha N.

AU - O’Connor, George

AU - O’Driscoll, Olivia

AU - Oren, Eyal

AU - Podolanczuk, Anna J.

AU - Post, Wendy S.

AU - Pottinger, Tess

AU - Regan, Elizabeth

AU - Rusk, Annie

AU - Salvatore, Mary

AU - Schwartz, David A.

AU - Smith, Benjamin

AU - Sotres-Alvarez, Daniela

AU - Umans, Jason G.

AU - Vasan, Ramachandran S.

AU - Washko, George

AU - Wenzel, Sally

AU - Woodruff, Prescott

AU - Xanthakis, Vanessa

AU - Ortega, Victor E.

AU - Oelsner, Elizabeth C.

PY - 2025/7/1

Y1 - 2025/7/1

N2 - Rationale: Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. Objective: To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Methods: Prepandemic 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 U.S. general population–based cohorts. Severe obstruction was classified by FEV1 < 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. Measurements and Main Results: 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. Conclusions: 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.

AB - Rationale: Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. Objective: To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Methods: Prepandemic 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 U.S. general population–based cohorts. Severe obstruction was classified by FEV1 < 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. Measurements and Main Results: 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. Conclusions: 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.

KW - COVID-19

KW - lung function

KW - obstructive physiology

KW - percentage emphysema

KW - restrictive physiology

KW - structure

UR - https://www.scopus.com/pages/publications/105010590401

U2 - 10.1164/rccm.202408-1656OC

DO - 10.1164/rccm.202408-1656OC

M3 - Article

C2 - 40238945

AN - SCOPUS:105010590401

SN - 1073-449X

VL - 211

SP - 1196

EP - 1210

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 7

ER -

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

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Keywords

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