Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations

Abstract

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Keywords: COPD; dyspnea; early disease; health inequities; race-specific spirometry prediction equations.

Figure 1.

Disease characteristics of smokers in COPDGene phase 1 by self-reported race and disease severity derived from race-specific prediction equations. In each category of disease severity (using a modified Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage classification that adds GOLD stage 0 and preserved ratio impaired spirometry [PRISm]), African American (AA) participants have worse symptoms, function, and quality of life. The effects are more pronounced in the early disease groups but persist across all stages. Spirometry prediction equations for classification in this figure are the NHANES race-specific equations. PRISm generally shows worse characteristics in each measure than GOLD stage 0 or GOLD stage 1 and is more similar to GOLD stage 2 for St. George’s Respiratory Questionnaire (SGRQ) score, modified Medical Research Council (MMRC) dyspnea scale score, and 6MWD. (A) SGRQ total score, a disease-specific quality-of-life measure. SGRQ score increases across GOLD stages 1–4 but also demonstrates that there are measurable effects in the GOLD and PRISm groups and differences between AA and NHW participants across each group. (B) Reduced physical function on the 6-minute-walk test with advancing GOLD stage and significant reductions in each group for AA participants. (C) Significantly greater reports of dyspnea as defined by the MMRC dyspnea scale score ⩾ 2 in AA participants except in GOLD stage 4. This is particularly notable in the GOLD stage 0 group. (D) Although severe respiratory events or exacerbations are reported across all groups, they are more common in advanced disease and significantly increased in AA participants in all GOLD stages except PRISm and GOLD stage 1. 6MWD = 6-minute-walk distance; COPDGene = Genetic Epidemiology of Chronic Obstructive Pulmonary Disease; NHANES = National Health and Nutrition Examination Survey; NHW = non-Hispanic White. *P < 0.0001.

Figure 2.

Reclassification of African American (AA) participants with chronic obstructive pulmonary disease (COPD) and undiagnosed participants using different prediction equations. (A1–A3) Each panel demonstrates the shifts of participants from the reference NHANES (National Health and Nutrition Examination Survey) AA race-specific classification to an alternative prediction equation (Global Lung Function Initiative [GLI] Other, GLI Global, and the NHANES non-Hispanic White (NHW) race-specific “race-reversed”). The overall pattern shows that the AA race-specific equations classify individuals as less severely diseased compared with other equations. GLI Other and GLI Global are similar, but there were slightly more reclassifications under GLI Global (198 vs. 210 out of a total of 1,050 AA participants classified as having COPD [approximately 20%]). (A1) GLI Other classifications, whereby 89 AA participants were reclassified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2. Similar reclassification occurred at each GOLD stage, and in all cases, participants were reclassified to worse disease stages. (A2) GLI Global equations and their impact on classification, with 101 participants reclassified from GOLD stage 1 to GOLD stage 2. (A3) The greatest impact was noted using race-reversed equations and applying the NHW NHANES equations to AA participants. In this scenario, 131 of the initial 191 GOLD stage 1 participants were reclassified to GOLD stage 2. The trend continued with a large number of AA participants reclassified from GOLD stage 2 to GOLD stage 3, while the reclassifications to more advanced disease from GOLD stage 3 to GOLD stage 4 were fewer. (B1–B3). The proportion of AA participants (70%) who did not meet the fixed-ratio criteria (FEV₁:FVC < 0.7) for COPD was greater than that of NHW (49%) in the COPDGene cohort and was consequent to the effect of lower FVC values in a portion of the AA group, as previously reported (21). Thus, these participants could not be reclassified into any of the GOLD stages on the basis of different race-specific equations and could only move between preserved ratio impaired spirometry (PRISm) and GOLD stage 0 groups, as described in our extended classification. As for the COPD-diagnosed participants, the different prediction equations resulted in large numbers of participants being reclassified as sicker (moving to PRISm), with the GLI Other equations (B1) having the fewest (n = 375) reclassified to PRISm; GLI Global equations had 472 participants reclassified to PRISm (B2), and race-reversed NHANES equations had 774 participants (43% of the GOLD stage 0 AA participants) reclassified to PRISm. COPDGene = Genetic Epidemiology of Chronic Obstructive Pulmonary Disease.

Figure 3.

Extended Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications for non-Hispanic White (NHW) and African American (AA) participants in COPDGene using alternative prediction equations. This provides a visual comparison of differences between AA and NHW participants using different prediction equations and emphasizes the potential impact of the fixed-ratio discrepancy for AA individuals with an inability to move into GOLD stages, as noted in the legend for Figure 2. This is characterized by the large number of PRISm-classified AA participants and fewer GOLD stage 1 participants. GLI = Global Lung Function Initiative; NHANES = National Health and Nutrition Examination Survey; PRISm = preserved ratio impaired spirometry.