The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 revision of the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (COPD) consensus report defined COPD as “a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases” (1). The GOLD 2011 report required spirometry to diagnose COPD and the postbronchodilator FEV₁/FVC fixed ratio of <0.70 as the spirometric criterion for airflow limitation. The GOLD 2007 publication (GOLD 2006 revision) similarly defined and graded (stages 1, 2, 3, and 4) expiratory airflow obstruction (Table 1) (2). Spirometric stages/grades 3 and 4 indicate high risk and stages/grades 1 and 2 indicate nonhigh risk. Because the FEV₁ does not reliably predict the degree of breathlessness, exercise limitation, and health status impairment in patients with COPD, the GOLD 2011 report added symptoms and exacerbation risk to the airflow obstruction grading to help define risk groups and a severity staging system (Figure 1, categories A, B, C, and D).

Figure 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 classification system. Reproduced from Reference 1 by permission from GOLD. When assessing exacerbation risk, choose the highest risk according to GOLD airflow limitation classification (Table 1) or exacerbation history. GOLD 1: FEV₁ ≥ 80% predicted. GOLD 2: FEV₁ 50 to 79% predicted. GOLD 3: FEV₁ 30 to 49% predicted. GOLD 4: FEV₁ < 30% predicted. CAT = chronic obstructive pulmonary disease assessment test; mMRC = modified Medical Research Council dyspnea scale.

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Although many validated respiratory questionnaires exist, the GOLD 2011 report recommended the modified British Medical Research Council (mMRC) questionnaire (scaled 0 to 4) or the COPD Assessment Test (CAT) (scaled 0 to 40) for symptom assessment. The GOLD authors chose questionnaire scoring cut-offs to separate patients with a higher symptom burden (mMRC dyspnea scale score of ≥2 or a CAT score of ≥10) from those with a lower burden.

The GOLD 2011 report defined a COPD exacerbation as “an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.” Two or more “mild” (respiratory symptoms requiring change of inhaled treatment) or “moderate” (respiratory symptoms requiring medical intervention including a short course of antibiotic and/or oral steroids) exacerbations or a COPD exacerbation-related hospitalization (“severe exacerbation”) in the preceding year indicate high risk for recurrent exacerbations.

The GOLD 2011 report recommended spirometric and exacerbation history classification to place patients into a risk category. If these criteria produce a discrepancy in risk assignment, the report recommends assignment to the higher risk category.

The revised GOLD COPD classification created controversy. Some stakeholders felt that they did not have adequate input (3). The revision generated many questions about choice of symptom measurement tool and cut-offs for the high/low symptom assessment and exacerbation history. Questions about the degree of and the results of validation and reliability testing before and after the revision’s publication have arisen. For example, does the 2011 classification have better predictive characteristics than the 2007 classification, and does its use change management that leads to better outcomes? Recent studies that evaluated and compared the GOLD 2007 and GOLD 2011 classification schemas in different patients and settings have produced interesting and sometimes conflicting results. The studies have also identified some issues that may lead to future criteria revisions.

Han and colleagues (4) assessed the influence of symptom instrument choice (e.g., CAT vs. mMRC) on GOLD 2011 patient category assignment and COPD exacerbation risk. In their retrospective analysis of data from the prospective longitudinal cohort COPDGene study of 4,484 patients with COPD, they assessed exacerbation severity and event rates during a minimum of 6 months (mean, 20 mo) of follow-up. They used the required data for GOLD 2011 categorization with the exception of the CAT. Instead, they used the St. George’s Respiratory Questionnaire (SGRQ) (scaled 0 to 100; high risk score ≥ 25, low risk score < 25) as a surrogate for the CAT (high risk score ≥ 10, low risk score < 10). To further refine the GOLD classification, they analyzed data from subgroups defined by combinations of GOLD 2011 airflow limitation and exacerbation history. They found that the symptom measure (MRC vs. SGRQ) influenced the GOLD category assignment. Regarding unadjusted outcomes analyses, the category C (low symptom + high exacerbation history) group did not have a significantly different exacerbation rate than the category B (high symptom + low exacerbation history) group. Category C had a relatively small number of patients. The authors did detect a difference in exacerbation rates within the high-risk category D subgroups. Thus, the study showed that the mechanism for assigning patients to a risk group significantly affected the outcomes; some risk groups did not have different outcomes, and group D subcategories had differential outcomes.

Soriano and colleagues (5) conducted a retrospective analysis of predictor and survival outcomes data from 3,633 patients who came from 11 cohorts in the Spanish COCOMICS (Collaborative Cohorts to Assess Multicomponent Indices of COPD in Spain) study. The study used the mMRC for symptom assessment. For exacerbation history, it only captured events associated with hospitalization (severe category). The cohorts had great risk group categorization heterogeneity. Using unadjusted analyses, the GOLD 2011 group A had the best survival, group D had the worst, and groups B and C fell between groups A and D. The GOLD 2007 and GOLD 2011 risk group comparison did not show a difference in mortality at 1, 3, and 10 years of follow-up. Similar to the Han and colleagues study, the COCOMICS study showed heterogeneity of outcomes among the GOLD 2011 group D subcategories.

Lange and colleagues (6) conducted a retrospective study of two similar Danish population studies that included 6,628 patients with COPD based on prebronchodilator pulmonary function values. Using unadjusted analyses, they assessed COPD exacerbation and survival outcomes during an average follow-up of 4.3 years. The GOLD 2011 group stratification performed well in identifying individuals at risk for exacerbations. In comparison to the GOLD 2007 FEV₁ stage 1 to 4 classification, the GOLD 2011 multidimensional A to D classification had better separation for the prediction of exacerbations. Unlike the Soriano and colleagues study results, GOLD 2011 group B had worse survival than group C, even though group B had better lung function. Similar to the results from the Han and colleagues (4) and the Soriano and colleagues (5) studies, the GOLD 2011 subcategories of groups C and D showed great outcomes heterogeneity, and these differences became most apparent over longer-term follow-up.

In this issue of the Journal, Johannessen and colleagues (pp. 51–59) described the results of their attempts to validate the GOLD 2011 categorization of patients with COPD and compared its ability to predict mortality and hospitalization to the GOLD 2007 classification using adjusted analyses (7). The study used the Norwegian GenKOLS case-control study data set of 954 patients diagnosed with COPD who had up to 8 years of follow-up regarding hospitalization (all-cause and respiratory-specific) and mortality (all-cause, respiratory-specific, and cardiovascular-specific). The study did not include patients that had mild airflow obstruction. The study further validated the GOLD 2011 classification’s ability to identify groups of patients with different risks for severe COPD exacerbations and mortality. However, the GOLD 2007 and GOLD 2011 classifications had similar predictive ability for these outcomes. Similar to the Han and colleagues study, GOLD 2011 category C had a relatively small number of patients.

The GOLD 2011 classification system attempted to take a bold step forward from the 2007 classification system by adding symptom and exacerbation history to the severity grading of airflow limitation. The revised classification system emphasizes the heterogeneity among patients with COPD. The increased complexity of the GOLD 2011 COPD assessment tool has generated new issues and concerns. Multiple pathways exist for assignment to GOLD 2011 categories A to D, and category C and D subgroups appear to have different risks of adverse outcomes. Thus, studies that use the GOLD 2011 categories should address these subgroups in their study design and data presentation. Future revisions of the GOLD classification schema should address existing and anticipate future controversies and questions.

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