Race/Ethnicity, Spirometry Reference Equations, and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

Abstract

Rationale: Normal values for FEV₁ and FVC are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. Objectives: To determine whether race/ethnicity-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared with race/ethnicity-neutral equations. Methods: The MESA Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry from 2004 to 2006. Predicted values for spirometry were calculated using race/ethnicity-based equations following guidelines and, alternatively, race/ethnicity-neutral equations without terms for race/ethnicity. Participants were followed for events through 2019. Measurements and Main Results: The mean age of 3,344 participants was 65 years, and self-reported race/ethnicity was 36% White, 25% Black, 23% Hispanic, and 17% Asian. There were 181 incident CLRD-related events and 547 deaths over a median of 11.6 years. There was no evidence that percentage predicted FEV₁ or FVC calculated using race/ethnicity-based equations improved the prediction of CLRD-related events compared with those calculated using race/ethnicity-neutral equations (difference in C statistics for FEV₁, -0.005; 95% confidence interval [CI], -0.013 to 0.003; difference in C statistic for FVC, -0.008; 95% CI, -0.016 to -0.0006). Findings were similar for mortality (difference in C statistics for FEV₁, -0.002; 95% CI, -0.008 to 0.003; difference in C statistics for FVC, -0.004; 95% CI, -0.009 to 0.001). Conclusions: There was no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.

Keywords: chronic lower respiratory disease; pulmonary function tests; race/ethnicity–based reference equations; racism; spirometry.

Figure 1.

(A and B) Distributions of percentage predicted FEV₁ (A) and percentage predicted FVC (B) among White, Black, Hispanic, and Asian participants calculated using race/ethnicity–based and race/ethnicity–neutral equations. The solid lines show the distribution of the percentage predicted lung function calculated following guideline-based application of the Global Lung Function Initiative (GLI) race/ethnicity–based reference equations. The dashed lines show the distribution of the percentage predicted lung function calculated using the race/ethnicity–neutral GLI reference equations for “Other.” For the race/ethnicity–based equations, GLI equations are not available for Hispanic individuals, so the GLI equation for White individuals was used (29); GLI equations include two equations for Asian individuals; the one for North East Asians was used.

Figure 2.

(A–D) Observed 10-year cumulative incidence of chronic lower respiratory disease–related events by percentage predicted FEV₁ (A) and percentage predicted FVC (B) and all-cause mortality risk by percentage predicted FEV₁ (C) and percentage predicted FVC (D) calculated using race/ethnicity–based and race/ethnicity–neutral equations. The red lines show the 10-year cumulative incidence of chronic lower respiratory disease–related events by percentage predicted FEV₁ and FVC (A and B), and the cumulative incidence of all-cause mortality risk by percentage predicted FEV₁ and FVC (C and D) calculated using race/ethnicity–based equations following guideline-based application of the Global Lung Function Initiative (GLI) race/ethnicity–based reference equations. The blue lines show the incidence of events calculated using the race/ethnicity–neutral GLI reference equation for “Other.” For the race/ethnicity–based equations, GLI equations are not available for Hispanic individuals, so the GLI equation for White individuals was used (29); GLI equations include two equations for Asian individuals; the one for North East Asians was used. CLRD = chronic lower respiratory disease.