GOLD 2011 disease severity classification in COPDGene: a prospective cohort study

Summary

Background

The 2011 GOLD (Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease [COPD]) consensus report uses symptoms, exacerbation history, and forced expiratory volume (FEV₁)% to categorise patients according to disease severity and guide treatment. We aimed to assess both the influence of symptom instrument choice on patient category assignment and prospective exacerbation risk by category.

Methods

Patients were recruited from 21 centres in the USA, as part of the COPDGene study. Eligible patients were aged 45–80 years, had smoked for 10 pack-years or more, and had an FEV₁/forced vital capacity (FVC) <0·7. Categories were defined with the modified Medical Research Council (mMRC) dyspnoea scale (score 0–1 vs ≥2) and the St George's Respiratory Questionnaire (SGRQ; ≥25 vs <25 as a surrogate for the COPD Assessment Test [CAT] ≥10 vs <10) in addition to COPD exacerbations in the previous year (<2 vs ≥ 2), and lung function (FEV₁% predicted ≥50 vs <50). Statistical comparisons were done with k-sample permutation tests. This study cohort is registered with ClinicalTrials.gov, number NCT00608764.

Findings

4484 patients with COPD were included in this analysis. Category assignment using the mMRC scale versus SGRQ were similar but not identical. On the basis of the mMRC scale, 1507 (33·6%) patients were assigned to category A, 919 (20·5%) to category B, 355 (7·9%) to category C, and 1703 (38·0%) to category D; on the basis of the SGRQ, 1317 (29·4%) patients were assigned to category A, 1109 (24·7%) to category B, 221 (4·9%) to category C, and 1837 (41·0%) to category D (κ coefficient for agreement, 0·77). Significant heterogeneity in prospective exacerbation rates (exacerbations/person-years) were seen, especially in the D subcategories, depending on the risk factor that determined category assignment (lung function only [0·89, 95% CI 0·78–1·00]), previous exacerbation history only [1·34, 1·0–1·6], or both [1·86, 1·6–2·1; p<0·0001]).

Interpretation

The GOLD classification emphasises the importance of symptoms and exacerbation risk when assessing COPD severity. The choice of symptom measure influences category assignment. The relative number of patients with low symptoms and high risk for exacerbations (category C) is low. Differences in exacerbation rates for patients in the highest risk category D were seen depending on whether risk was based on lung function, exacerbation history, or both.

Funding

National Heart, Lung, and Blood Institute, and the COPD Foundation through contributions from AstraZeneca, Boehringer Ingelheim, Novartis, and Sepracor.

Introduction

The development of a disease staging system in Chronic Obstructive Pulmonary Disease (COPD) to assess severity and determine treatment algorithms has proven challenging. The Global initiative for chronic Obstructive Lung Disease (GOLD) 2006 staging system used forced expiratory volume (FEV₁) to determine disease severity.¹ In large population studies, lung function correlated reasonably well with many disease outcomes but was poorly predictive of dyspnoea, quality of life, and exacerbation frequency.2, 3 Lung function alone does not completely capture the heterogeneity that exists among patients with COPD.⁴ Hence, the GOLD 2011 consensus report proposed a new classification system for COPD to more comprehensively assess disease severity,⁵ incorporating symptoms with either a dyspnoea measure (the modified Medical Research Council [mMRC] dyspnoea score) or a health status measure (the COPD Assessment Test [CAT] score) in addition to COPD exacerbation history and airflow limitation measured by FEV₁ (figure 1). We aimed to use the COPDGene cohort to establish whether the choice of a symptom versus health-status measure significantly influences baseline category assignment and whether the categories differ, especially with respect to exacerbation risk.