Articles
Prediction of mortality in patients with chronic obstructive pulmonary disease with the new Global Initiative for Chronic Obstructive Lung Disease 2017 classification: a cohort study

https://doi.org/10.1016/S2213-2600(18)30002-XGet rights and content

Summary

Background

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 classification separates the spirometric 1–4 staging from the ABCD groups defined by symptoms and exacerbations. Little is known about how this new classification predicts mortality in patients with chronic obstructive pulmonary disease (COPD). We aimed to establish the predictive ability of the GOLD 2017 classification, compared with earlier classifications, for all-cause and respiratory mortality, both when using its main ABCD groups and when further subdividing according to spirometric 1–4 staging.

Methods

In this nationwide cohort study, we enrolled patients with COPD with data available in the Danish registry for COPD. To be included in this registry, individuals must have been outpatients in hospital-based pulmonary clinics in Denmark. Eligible patients were aged 30 years or older; had received a primary diagnosis of COPD (International Classification of Diseases [ICD]-10 J44.X) or acute respiratory failure (ICD-10 J96.X) in combination with COPD (ICD-10 J44.X) as a secondary diagnosis; and had complete data on FEV1, body-mass index, modified Medical Research Council dyspnoea scale score, and smoking status. We categorised eligible patients with complete data according to the 2007, 2011, and 2017 GOLD classifications at the first contact with an outpatient clinic. For the GOLD 2017 classification, we further subdivided the patients by spirometry into 16 subgroups (1A to 4D). We calculated adjusted hazard ratios (HRs) for all-cause and respiratory mortality and compared the predictive ability of the three GOLD classifications (2007, 2011, and 2017) using receiver operating curves.

Findings

We enrolled 33 765 patients with COPD, who were outpatients in Danish hospitals between Jan 1, 2008, and Nov 30, 2013, in the main cohort assessed for all-cause mortality. 22 621 of these patients had data available on cause-specific mortality (respiratory) and were included in a subcohort followed from Jan 1, 2008, to Dec 31, 2011. For the GOLD 2017 classification, 3 year mortality increased with increasing exacerbations and dyspnoea from group A (all-cause mortality 10·0%, respiratory mortality 3·0%) to group D (all-cause mortality 36·9%, respiratory mortality 18·0%). However, 3 year mortality was higher for group B patients (all-cause mortality 23·8%, respiratory mortality 9·7%) than for group C patients (all-cause mortality 17·4%, respiratory mortality 6·4%). Compared with group A, adjusted HRs for all-cause mortality ranged from 2·05 (95% CI 1·87–2·26) for group B, to 1·47 (1·31–1·65) for group C, and to 3·01 (2·75–3·30) for group D. Area under the curve for all-cause mortality was 0·61 (95% CI 0·60–0·61) for GOLD 2007, 0·61 (0·60–0·62) for GOLD 2011, and 0·63 (0·53–0·73) for GOLD 2017. Area under the curve for respiratory mortality was 0·64 (0·62–0·65) for GOLD 2007, 0·63 (0·62–0·64) for GOLD 2011, and 0·65 (0·53–0·78) for GOLD 2017. The GOLD 2017 classification based on ABCD groups only did not predict mortality better than the earlier 2007 and 2011 GOLD classifications. However, when 16 subgroups (1A to 4D) were defined, the new classification predicted mortality more accurately than the previous systems (p<0·0001).

Interpretation

We showed that the new GOLD 2017 ABCD classification does not predict all-cause and respiratory mortality more accurately than the previous GOLD systems from 2007 and 2011.

Funding

Danish Lung Association, Program for Clinical Research Infrastructure.

Introduction

The Global Burden of Disease study1 estimates that chronic obstructive pulmonary disease (COPD) will become the third most prevalent cause of death worldwide by 2030. Risk stratification of patients according to COPD severity is clinically important and forms the basis of therapeutic recommendations.2 Since 2007, COPD has been classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system. Because of the well established association between COPD severity and FEV1, the first GOLD classification in 20073 was based solely on patients' FEV1 thresholds compared with predicted normal values.2 Because lung function might not fully describe disease complexity, the GOLD 2011 revision4 presented an ABCD classification, combining respiratory symptoms, risk of exacerbations, and airflow limitations as indicated by FEV1. The intention was to provide improved understanding of the disease's effect on individual patients.4 The GOLD 2007 and 2011 classifications were designed to guide treatment, but also have been used widely for prognostic prediction.2, 5 Previous studies5, 6, 7, 8, 9, 10 have shown that the GOLD 2011 classification does not predict mortality or respiratory outcomes better than the GOLD 2007 classification.

Research in context

Evidence before this study

We searched PubMed without language restrictions for epidemiological and clinical studies published between Jan 1, 2000, and Sept 15, 2017, using the search terms “COPD”, “follow-up studies”, “diagnosis”, “mortality”, “prognosis”, “survival analysis”, “severity of illness index”, “GOLD classification”, “GOLD 2007”, “GOLD 2011”, “GOLD 2017”, and “prediction”. Searches were supplemented by review of the reference lists of the identified articles. Earlier Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications were based on either FEV1 thresholds (GOLD 2007) or a combination of spirometry, history of exacerbations, and symptoms (GOLD 2011). The GOLD 2017 classification is based on a composite of spirometry and symptoms or exacerbations and separates the spirometric 1–4 staging from the ABCD groups defined by symptoms and exacerbations. Previous studies have shown that the GOLD 2011 classification does not improve mortality prediction in patients with chronic obstructive pulmonary disease (COPD) compared with the GOLD 2007 classification. We identified only one study comparing mortality for all three GOLD classification systems in our search of the literature. That study included only 524 patients with COPD and did not assess predictive accuracies. We identified no previous large-scale studies examining how well the new GOLD 2017 classification predicts all-cause and respiratory mortality in patients with COPD.

Added value of this study

We prospectively enrolled a cohort of 33 765 patients with COPD with data in the Danish registry for COPD. All patients had attended hospital outpatient clinics in Denmark. We categorised each patient according to the ABCD groups in the GOLD 2017 classification. We further subcategorised by spirometry 1–4 staging, resulting in 16 subgroups (1A to 4D). After adjustment for confounders, we found that 3 year all-cause and respiratory mortality increased from group A to group D. All-cause and respiratory mortality were higher in group B than in group C. Cardiovascular disease-related mortality was high in group B and was similar to cardiovascular disease-related mortality in group D. Receiver operating curve analyses showed that the GOLD 2017 classification based on symptoms and exacerbation risk (ABCD groups) only did not predict all-cause and respiratory mortality more accurately than the older classification systems (GOLD 2007 and 2011). When spirometry results were added to the GOLD 2017 ABCD groups and 16 subgroups were created, we found that 3 year mortality increased successively from subgroup 1A (all-cause mortality 5·4%) to subgroup 4D (all-cause mortality 42·5%) and that the 16 subgroups predicted all-cause and respiratory mortality more accurately than either of the previous GOLD classification systems.

Implications of all the available evidence

This cohort study is the first large-scale study to show that the new GOLD 2017 classification does not predict all-cause and respiratory mortality more accurately than the older GOLD systems, unless the spirometric stages 1–4 and ABCD groups based on symptoms and exacerbations are combined into 16 subgroups.

The new GOLD 2017 classification is based on a composite of spirometry and symptoms and exacerbations, separating the spirometric 1–4 staging from the ABCD groups.2 To our knowledge, no previous studies have examined the association between the GOLD 2017 classification and mortality or established how well the new classification predicts mortality compared with the earlier 2007 and 2011 GOLD classifications. Therefore, we aimed to establish the predictive ability of the GOLD 2017 classification, compared with earlier classifications, for all-cause and respiratory mortality, both when using its main ABCD groups and when further subdividing according to spirometric 1–4 staging.

Section snippets

Study population

In this nationwide cohort study, we enrolled patients with data in the Danish registry for COPD.11 This registry was established in 2008 after Danish health-care authorities began to monitor evidence-based care of patients with COPD in all hospitals in Denmark.11 The Danish registry for COPD draws on patient-level medical data from the Danish National Patient Registry, which covers all hospitals in Denmark and contains computerised discharge records for all hospital admissions since 1977 and

Results

Of the 53 374 patients with COPD who visited a hospital outpatient clinic between Jan 1, 2008, and Nov 30, 2013, 33 765 (63%) were aged 30 years or older and had complete data on FEV1, BMI, modified MRC dyspnoea scale score, and smoking status, and could thus be classified according to GOLD 2017 (figure 1). These patients, prospectively enrolled in the Danish registry for COPD, were then followed from the index date until death, migration, or Nov 30, 2013, whichever came first.

Table 1 shows the

Discussion

To the best of our knowledge, this cohort study is the first large-scale, nationwide study to examine the association between the GOLD 2017 classification and all-cause and respiratory mortality in patients with COPD, and the ability of this new classification to predict these outcomes. We found that the GOLD 2017 ABCD classification (based on symptoms or exacerbations alone) was not able to better predict all-cause or respiratory mortality than either of the GOLD 2007 and GOLD 2011

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