Application of the European Respiratory Society/American Thoracic Society Spirometry Standards and Race-Neutral Equations in the COPDGene Study

Abstract

Rationale: For spirometry interpretation, the European Respiratory Society (ERS) and American Thoracic Society (ATS) recommend using z-scores, and the ATS has recommended using Global Lung Initiative (GLI) "Global" race-neutral reference equations. However, these recommendations have been variably implemented, and the impact has not been widely assessed in clinical or research settings. Objectives: To evaluate the ERS/ATS classification of airflow obstruction severity. Methods: In COPDGene (Genetic Epidemiology of COPD Study) (N = 10,108), airflow obstruction has been defined by an FEV₁/FVC ratio <0.70, with spirometric severity graded from class 1 to class 4 based on race-specific percent predicted (pp) FEV₁ cutoff points as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the GOLD approach, using National Health and Nutrition Examination Survey III race-specific equations, versus the application of GLI Global equations using the ERS/ATS definition of airflow obstruction as an FEV₁/FVC ratio below the lower limit of normal and z-score-based FEV₁ cutoff points of -1.645, -2.5, and -4 ("zGLI Global"). We tested the four-tier severity scheme for association with chronic obstructive pulmonary disease outcomes. Measurements and Main Results: The lowest agreement between ERS/ATS with zGLI Global and the GOLD classification was observed in individuals with milder disease (56.9% and 42.5% in GOLD stages 1 and 2, respectively), and race was a major determinant of redistribution. After adjustment for relevant covariates, zGLI Global distinguished all-cause mortality risk between normal spirometry and the first grade of chronic obstructive pulmonary disease (hazard ratio, 1.23; 95% confidence interval, 1.04-1.44; P = 0.014) and showed a linear increase in exacerbation rates with increasing disease severity in comparison with GOLD. Conclusions: The zGLI Global severity classification outperformed the GOLD criteria in the discrimination of survival, exacerbations, and imaging characteristics.

Keywords: COPD; ethnicity; pulmonary function tests; survival analysis.