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. 2019 Jun 25;321(24):2438-2447.
doi: 10.1001/jama.2019.7233.

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

Surya P Bhatt  1 , Pallavi P Balte  2 , Joseph E Schwartz  2 , Patricia A Cassano  3 , David Couper  4 , David R Jacobs Jr  5 , Ravi Kalhan  6 , George T O'Connor  7 , Sachin Yende  8 , Jason L Sanders  9 , Jason G Umans  10 , Mark T Dransfield  1 , Paulo H Chaves  11 , Wendy B White  12 , Elizabeth C Oelsner  2   13
Affiliations

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

Surya P Bhatt et al. JAMA. .

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Incidence Density Rates for COPD-Related Hospitalization and Mortality According to Initial FEV1:FVC
The incidence density rate (IDR) for chronic obstructive pulmonary disease (COPD)-related hospitalization and mortality was inversely related to the ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) without clear evidence of an inflection point. IDRs and 95% CIs were computed per 1000 person-years via Poisson regression in mutually exclusive, incremental categories of initial FEV1:FVC. The predicted IDR (curved black line) is generated from the best function (quadratic 0.40 to 0.77; piecewise linear 0.77 to 0.80) describing the FEV1:FVC and the corresponding IDR relationship. The blue line indicates IDR per 1000 person-years (95% CI indicated by blue shading), computed via Poisson regression, for all patients with an FEV1:FVC less than the lower limit of normal per Global Lung Function Initiative reference equations.
Figure 2.
Figure 2.. Discriminative Accuracy of Various Fixed FEV1:FVC Thresholds for Airflow Obstruction With Respect to COPD-Related Hospitalization and Mortality
The C statistics (95% CI) for fixed-ratio thresholds (dots) were estimated separately in unadjusted Cox proportional hazards models that included only 1 dichotomous predictor (ie, whether a participant had a baseline ratio of forced expiratory volume in the first second to forced vital capacity [FEV1:FVC] that was above or below a given ratio threshold). The C statistic for the lower-limit-of-normal (LLN) threshold is indicated by the solid blue horizontal line (95% CI indicated by blue shading). The optimal threshold based on highest C statistic was 0.71, but C statistics were not significantly different for 0.70 to 0.72. Fixed ratio thresholds 0.66 to 0.74 yielded C statistics that were significantly higher than the LLN threshold (P values <.05).
Figure 3.
Figure 3.. Weighted Youden Index for Various FEV1:FVC Thresholds Across a Range of Relative Weights for Sensitivity and Specificity
The weighted Youden index for the 0.70 threshold was higher than the lower limit of normal (LLN) threshold for weights of 0.35 or greater. Where weight equals 0.5, sensitivity and specificity are weighted equally. For each ratio threshold, the sensitivity and specificity were estimated from unadjusted Cox proportional hazards models including ratio thresholds only. Weight (x-axis) indicates relative weight assigned to sensitivity vs specificity. FEV1:FVC indicates the ratio of the forced expiratory volume in the first second to the forced vital capacity.
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