Application of the ERS/ATS spirometry standards and race-neutral equations in the COPDGene Study

<bold>Rationale:</bold> The European Respiratory Society (ERS) and the American Thoracic Society (ATS) recommend using z-scores and Global Lung Initiative (GLI) “Global” race-neutral reference equations for spirometry interpretation. However, the impact of those recommendations has not been widely implemented nor assessed, both in clinical and research settings. <bold>Objectives:</bold> We evaluated the ERS/ATS airflow obstruction severity classification. <bold>Methods:</bold> In the COPDGene Study (n = 10,108), airflow obstruction has been defined as a forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio <0.70, with spirometry severity graded from class 1 to 4 based on race-specific percent predicted (pp) FEV1 cut-points as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared this approach to the application of GLI Global equations with airflow obstruction by FEV1/FVC< lower limit of normal and z-FEV1 cut-points of –1.645, –2.5, and –4. We tested the four-tier severity scheme for association with COPD outcomes. <bold>Measurements and Main Results:</bold> The lowest agreement between GLI Global and GOLD classification was observed in individuals with milder disease (56.9% and 42.5% in GOLD 1 and 2) and race was a major determinant of redistribution. After adjustment for relevant covariates, only GLI Global distinguished all-cause mortality risk between normal spirometry and the first grade of COPD (HR 1.23, 95% CI 1.04-1.44, p=0.014) and showed a linear increase in exacerbation rates with increasing disease severity, compared to GOLD. <bold>Conclusion:</bold> The GLI Global severity classification outperformed GOLD in the discrimination of survival, exacerbations and imaging characteristics.