Use of the Spirometric "Fixed-Ratio" Underdiagnoses COPD in African-Americans in a Longitudinal Cohort Study

Abstract

Background: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV₁/FVC < 0.7. African-Americans are less often diagnosed with COPD.

Objective: Compare COPD diagnosis by fixed-ratio with findings and outcomes by race.

Design: Genetic Epidemiology of COPD (COPDGene) (2007-present), cross-sectional comparing non-Hispanic white (NHW) and African-American (AA) participants for COPD diagnosis, manifestations, and outcomes.

Setting: Multicenter, longitudinal US cohort study.

Participants: Current or former smokers with ≥ 10-pack-year smoking history enrolled at 21 clinical centers including over-sampling of participants with known COPD and AA. Exclusions were pre-existing non-COPD lung disease, except for a history of asthma.

Measurements: Subject diagnosis by conventional criteria. Mortality, imaging, respiratory symptoms, function, and socioeconomic characteristics, including area deprivation index (ADI). Matched analysis (age, sex, and smoking status) of AA vs. NHW within participants without diagnosed COPD (GOLD 0; FEV₁ ≥ 80% predicted and FEV₁/FVC ≥ 0.7).

Results: Using the fixed ratio, 70% of AA (n = 3366) were classified as non-COPD, versus 49% of NHW (n = 6766). AA smokers were younger (55 vs. 62 years), more often current smoking (80% vs. 39%), with fewer pack-years but similar 12-year mortality. Density distribution plots for FEV₁ and FVC raw spirometry values showed disproportionate reductions in FVC relative to FEV₁ in AA that systematically led to higher ratios. The matched analysis demonstrated GOLD 0 AA had greater symptoms, worse D_LCO, spirometry, BODE scores (1.03 vs 0.54, p < 0.0001), and greater deprivation than NHW.

Limitations: Lack of an alternative diagnostic metric for comparison.

Conclusions: The fixed-ratio spirometric criteria for COPD underdiagnosed potential COPD in AA participants when compared to broader diagnostic criteria. Disproportionate reductions in FVC relative to FEV₁ leading to higher FEV₁/FVC were identified in these participants and associated with deprivation. Broader diagnostic criteria for COPD are needed to identify the disease across all populations.

Keywords: COPD; deprivation; diagnosis; fixed ratio; spirometry.

Figure 1

Characterization of COPDGene participants: COPD diagnosis and severity, self-reported race and socioeconomic measures (A–D). Ever-smoking participants were classified at enrollment using Hankinson race-specific prediction equations and the “fixed ratio” criteria FEV₁/FVC < 0.7 for COPD. A “Modified GOLD stage” distribution of phase 1 COPDGene subjects by race. The distribution of the cohort is shown by race using a combination of the GOLD classification system for COPD (GOLD 1–4) with two additional groups (PRISm (FEV₁/FVC > 0.7, and FEV₁ < 80% predicted) and GOLD 0 (FEV₁/FVC > 0.7, and FEV₁ > 80% predicted). Seventy percent (70%) of the AA enrolled in COPDGene were categorized as PRISm or GOLD 0, while 50% of the NHW participants were categorized as PRISm or GOLD 0. B Self-reported annual income by race. Self-reported income data was collected at Phase 2 visit approximately five years after enrollment (n = 4407 NHW and 1836 AA participants). C Educational level reported by race. The percent distribution of educational levels by self-reported race in the enrollment data collection. D Distribution of Area Deprivation Index (ADI) in non-Hispanic White and African-American participants. Bars represent the number of subjects with specific deciles of index values derived from the 2018 ADI national dataset and geo-coded address information for the participants. The range for ADI is 0–100 and higher values are associated with worse deprivation characteristics. (n = 4368 NHW, 1776 AA for geo-coded data).

Figure 2

Race and spirometry issues in the COPDGene participants Parts A–C. A, B, C Density plots of FEV₁, FVC, and the ratio by race in the GOLD 0 only group. Distributions of FEV₁, FVC, and FEV₁/FVC distributions in COPDGene GOLD 0 subjects with non-Hispanic white (blue line) and African-American (red line) participants depicted. Extensive overlap is seen between the two groups in values with small differences in mean values for both FEV₁ and FVC (A and B). FEV₁Mean: NHW 2.96 (0.69) liters, AA 2.79 (0.65) liters, [mean (SD)]. Difference between group means = 170 mL. FVC Mean: NHW 3.82 (0.90) liters, AA 3.51 (0.84) liters, [mean (SD)], Difference between group means = 310 mL.

Figure 3

Persistent symptomatology in African-American participants within the matched analysis of the non-COPD GOLD 0 group. Key disease-related findings that remained significantly more frequent in African-American participants in the GOLD 0 group after matching for age, gender, and smoking status include: worse (greater) SGRQ values for activity, impact, and total scales, higher MMRC dyspnea score, and reduced DLCO percent predicted values. (p values for all comparisons are < 0.0001 except for SGRQ Symptom which is non-significant.) In addition, the raw spirometry values are significantly lower (p < 0.0001) in the AA participants compared to the NHW, while the percent predicted values for AA using NHANES race-specific equations are significantly higher (p < 0.0001).