Pooled Cohort Probability Score for Subclinical Airflow Obstruction

Surya P. Bhatt, Pallavi P. Balte, Joseph E. Schwartz, Byron C. Jaeger, Patricia A. Cassano, Paulo H. Chaves, David Couper, David R. Jacobs, Ravi Kalhan, Robert Kaplan, Donald Lloyd-Jones, Anne B. Newman, George O’Connor, Jason L. Sanders, Benjamin M. Smith, Yifei Sun, Jason G. Umans, Wendy B. White, Sachin Yende, Elizabeth C. Oelsner

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Rationale: Early detection of chronic obstructive pulmonary disease (COPD) is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. Objectives: To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. Methods: Lung function and clinical data were harmonized and pooled across nine U.S. general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (forced expiratory volume in 1 second/forced vital capacity, 0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES [National Health and Nutrition Examination Survey] 2011–2012). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in four of nine cohorts. Results: Of 33,546 participants (mean age 52 yr, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events (Nat-risk = 14,024) was threefold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years) was well calibrated and showed excellent discrimination in both the testing sample (C-statistic, 0.81; 95% confidence interval [CI], 0.80–0.82) and in NHANES (C-statistic, 0.83; 95% CI, 0.80–0.86). Among participants with predicted probabilities > 15%, 3.2 would need to undergo spirometry to detect one case of SAO. Conclusions: Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies.

Original languageEnglish (US)
Pages (from-to)1294-1304
Number of pages11
JournalAnnals of the American Thoracic Society
Issue number8
StatePublished - Aug 2022

Bibliographical note

Funding Information:
Supported by National Institutes of Health (NIH) grants R01HL151421, K23 HL133438, and R21EB027891 (S.P.B.); and NIH grants R21 HL129924 and K23 HL130627 (E.C.O.). The ARIC (Atherosclerosis Risk in Communities) study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute (NHLBI), NIH, Department of Health and Human Services, under contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. The CHS (Cardiovascular Health Study) was supported by NIH NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and grants U01HL080295 and U01HL130114, with additional contributions from the National Institute of Neurological Disorders and Stroke. Additional support was provided by National Institute on Aging (NIA) grant R01AG023629. The HABC (Health, Aging, and Body Composition) study was funded by grants N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050; National Institute of Nursing Research grant R01-NR012459; and in part by the intramural research program at the NIA. The MESA (Multi-Ethnic Study of Atherosclerosis) study was funded by NIH/NHLBI grants R01-HL-077612, R01-HL-093081, RC1-HL-100543, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169. The FHS (Framingham Heart Study) Offspring Cohort was funded by the NHLBI contracts N01-HC-25195 and HHSN268201500001I. The CARDIA (Coronary Artery Risk Development in Young Adults) Study is supported by NHLBI contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I. The JHS (Jackson Heart Study) is supported by NHLBI and the National Institute for Minority Health and Health Disparities and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I). The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) was funded by NHLBI contracts HHSN268201300001I/N01-HC-65233 to the University of North Carolina, HHSN268201300004I/N01-HC-65234 to the University of Miami, HHSN268201300002I/N01-HC65235 to the Albert Einstein College of Medicine, HHSN268201300003I to the University of Illinois at Chicago, N01-HC-65236 to Northwestern University, and HHSN268201300005I/N01-HC-65237 to San Diego State University. The Strong Heart Study was funded by the NHLBI cooperative agreement grants U01-HL41642, U01-HL41652, U01-HL41654, U01-HL65520, and U01-HL65521 and research grants R01-HL109315, R01HL109301, R01HL109284, R01HL109282, and R01HL109319. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
Copyright © 2022 by the American Thoracic Society.


  • airflow obstruction
  • chronic obstructive pulmonary disease
  • probability score
  • subclinical

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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