Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: a pooled analysis of individual patient data

Summary

Background

There is no universal consensus on the best staging system for chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2007) have traditionally used forced expiratory volume in 1 s (FEV₁) for staging, clinical parameters have been added to some guidelines (eg, GOLD 2011) to improve patient management. As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aimed to investigate how individual patients were categorised by GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents for mortality.

Methods

We searched reports published from Jan 1, 2008, to Dec 31, 2014. Using data from cohorts that agreed to participate and had a minimum amount of information needed for GOLD 2007 and 2011, we did a patient-based pooled analysis of existing data. With use of raw data, we recalculated all participant assignments to GOLD 2007 I–IV classes, and GOLD 2011 A–D stages. We used survival analysis, C statistics, and non-parametric regression to model time-to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict mortality.

Findings

We collected individual data for 15 632 patients from 22 COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the patients was 63·9 years (SD 10·1); 10 751 (69%) were men. Based on FEV₁ alone (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346 (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660 patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity distribution to more severe categories. There were nearly three times more COPD patients in stage D than in former stage IV (p<0·05). The predictive capacity for survival up to 10 years was significant for both systems (p<0·01) but area under the curves were only 0·623 (GOLD 2007) and 0·634 (GOLD 2011), and GOLD 2007 and 2011 did not differ significantly. We identified the percent predicted FEV₁ thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality, which are similar to the ones used previously.

Interpretation

Neither GOLD COPD classification schemes have sufficient discriminatory power to be used clinically for risk classification at the individual level to predict total mortality for 3 years of follow-up and onwards. Increasing intensity of treatment of patients with COPD due to their GOLD 2011 reclassification is not known to improve health outcomes. Evidence-based thresholds should be searched when exploring the prognostic ability of current and new COPD multicomponent indices.

Funding

None.

Introduction

Chronic obstructive pulmonary disease (COPD) affects about 328 million people worldwide and accounts for 4 million deaths every year.¹ To address the growing global burden of COPD, efforts have been made to increase awareness and to standardise treatment models. The most influential effort has been the Global Initiative for Chronic Obstructive Lung Disease (GOLD), which was launched in 1997 as a joint effort between the US National Institutes of Health and WHO.² Traditionally, GOLD and other similar initiatives have classified patients' COPD severity through thresholds of forced expiratory volume in 1 sec (FEV₁). However, in 2011 the GOLD committee added clinical parameters (ie, a history of exacerbation and respiratory symptoms) to FEV₁ to improve clinical management of patients with COPD.³ Although the GOLD staging system was designed to guide therapy, it is commonly used for prognostication.4, 5 The usefulness of both the 2007 and 2011 GOLD staging systems to predict mortality of patients with COPD is debated, with small, partial studies giving largely inconclusive results. To resolve this important issue, we obtained and pooled individual data for 15 632 patients from 22 COPD cohorts from seven countries and compared the prognostic power of the 2011 versus 2007 GOLD classification schemes to predict mortality.⁶

Research in context

Evidence before this study

COPD affects many people worldwide, but its definition and staging remain controversial. Before 2011, the GOLD classification scheme was based exclusively on forced expiratory volume in 1 s (FEV₁) thresholds. The 2011 GOLD document proposed a new classification scheme based on spirometry, the history of exacerbations, and symptoms. Since the publication of that document, several reports have compared it with the old 2007 grading, with somewhat conflicting results.

Added value of this study

We obtained and pooled individualised data from 22 published COPD cohorts, totalling 15 632 patients that contributed 70 184 person-years of follow-up to the study. The most important finding was that the 2011 GOLD classification scheme did not improve the prediction of mortality, as compared to the 2007 classification. Through the large size of the sample, we were able to overcome many of the limitations of individual studies, and had a large statistical power for most subanalyses. Therefore, we conclude that the more complicated GOLD 2011 classification scheme is no better than the simpler previous one based on spirometry only. The use of the 2011 staging system resulted in many more patients with the most severe disease (more in GOLD D than in GOLD IV), making them seem more ill. Further, GOLD class C might be superfluous because patients in this category have a similar mortality as those in class B and treatment strategies do not differ between the two groups.

Implications of all the available evidence

Neither GOLD COPD classification schemes had sufficient discriminatory power to be used clinically for risk-classification at the individual level to predict total mortality for 3 years of follow-up and up to 10 years. It is yet to be established if an increased intensity of treatment of patients with COPD by their GOLD 2011 reclassification improves their health outcomes.