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Discriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality

Educational Objective
To understand the value of a diagnostic threshold for airway obstruction in patients with chronic obstructive pulmonary disease.
1 Credit CME
Key Points

Question  What is the discriminative accuracy of various thresholds for the ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) for predicting chronic obstructive pulmonary disease (COPD)-related hospitalization and mortality?

Findings  Among 24 207 participants from 4 US general population–based cohorts, the optimal fixed threshold for discriminating COPD-related events was 0.71 (C statistic for the optimal fixed threshold, 0.696). The discriminative accuracy of the 0.71 threshold was not significantly different than that of the 0.70 threshold (difference, 0.001) but it was more accurate than a lower-limit-of-normal threshold derived from population-based reference equations (difference between the optimal ratio threshold vs the model using the LLN threshold, 0.034). The 0.70 threshold provided optimal discrimination in a subgroup analysis of ever smokers and in adjusted models.

Meaning  These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

Abstract

Importance  According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial.

Objective  To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality.

Design, Setting, and Participants  The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population–based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016.

Exposures  Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN).

Main Outcomes and Measures  The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach.

Results  Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, −0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models.

Conclusions and Relevance  Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

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Article Information

Corresponding Authors: Elizabeth C. Oelsner, MD, MPH, Division of General Medicine, Columbia University Medical Center, 630 W 168th St, Presbyterian Hospital Ninth Floor, Ste 105, New York, NY 10032 (eco7@cumc.columbia.edu); Surya P. Bhatt, MD, MSPH, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 Second Ave S, Birmingham, AL 35294 (sbhatt@uabmc.edu).

Accepted for Publication: May 23, 2019.

Author Contributions: Drs Oelsner and Bhatt had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bhatt, Oelsner.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Bhatt, Oelsner.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Balte, Schwartz, Oelsner.

Obtained funding: Oelsner.

Administrative, technical, or material support: O'Connor, Umans, White, Oelsner.

Supervision: Oelsner.

Conflict of Interest Disclosures: Dr Bhatt reports support from a National Institutes of Health (NIH) grant (K23 HL 133438) during the course of the study; receipt of consulting fees from Sunovion; and other (research funds to the institution) from Proterix Bio outside the submitted work. Dr Dransfield reports receipt of grants from NIH/National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study and from the Department of Defense and the American Lung Association outside the submitted work; contracted clinical trials from GlaxoSmithKline, Novartis, AstraZeneca, Yungjin, PneumRx/BTG and PulmonX; and consulting/personal fees from Boehringer Ingelheim, GlaxoSmithKline, PneumRx/BTG, Genentech, Boston Scientific, Quark Pharmaceuticals, and Mereo. Dr Couper reports receipt of grants from NHLBI and the COPD Foundation during the conduct of the study. Dr Kalhan reports receipt of grants from NHLBI during the conduct of the study; and outside the submitted work: grants and personal fees from Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline; grants from PneumRx/BTG, Spiration, and CVS Caremark; and personal fees from Aptus Health and Boston Scientific. Dr O’Connor reports receipt of grants from NIH during the conduct of the study and from Janssen Pharmaceuticals outside the submitted work; and personal/consulting fees from AstraZeneca. Dr Schwartz reports receipt of grants from NHLBI during the conduct of the study. Dr Balte reports receipt of grants from NHLBI during the conduct of the study. Dr Yende reports receipt of personal fees from Atox Bio and grants from Bristol-Myers Squibb outside the submitted work. Dr Umans reports receipt of grants from NIH/NHLBI outside the submitted work. Dr Oelsner reports receipt of grants from NIH/NHLBI during the conduct of the study. No other disclosures were reported.

Funding/Support: Dr Bhatt is supported by NIH grant K23 HL133438. Dr Oelsner is supported by NIH grants R21 HL129924 and K23 HL130627. The Atherosclerosis Risk in Communities (ARIC) study has been funded in whole or in part with federal funds from NIH, NHLBI, and the Department of Health and Human Services (contract numbers: HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I). The Cardiovascular Health Study (CHS) was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114 from NHLBI, with an additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). The Health, Aging and Body Composition (Health ABC) study was funded by NIA contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG028050, National Institute of Nursing Research grant R01-NR012459, and supported in part by the intramural research program at NIA. the 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.

Role of the Funder/Sponsor: The NIH had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.

Additional Contributions: The authors thank the staff and participants of ARIC, CHS, Health ABC, and MESA studies for their important contributions.

Additional Information: A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

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