“The ABC of GOLD A-B-C-D”

Chronic obstructive pulmonary disease (COPD) is the cause of considerable morbidity and mortality with the global burden of disease projected to increase even further in forthcoming years [1]. Although significant advances have been made in our understanding, assessment and management of COPD in the past decade, the heterogeneity of clinical features and variability in disease course continue to be only partially explained by currently available metrics. Hence, COPD subtype determination remains challenging.

Until the late 1990s, COPD was defined by abnormal expiratory airflow [2, 3]. Although there was no consensus about a universal staging system, forced expiratory volume in 1 s (FEV₁) alone was generally used to define disease severity [3]. FEV₁ does capture many facets of disease severity and hence algorithms were proposed for the management of COPD, based on the reduction in FEV₁ [3]. However, this approach is problematic in that not all aspects of the disease are adequately captured by FEV₁. Furthermore, such algorithms were not globally implemented [2] and attention from the healthcare community, scientific societies and government officials for COPD was generally low.

In 1997 the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was launched in order to raise worldwide awareness of COPD and improve prevention and treatment of the disease. In the first GOLD workshop summary report [4], COPD was defined as “a disease state characterized by airflow limitation that is not fully reversible and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases”. Furthermore, it stated that “symptoms, functional abnormalities and complications of COPD can all be explained on the basis of this underlying inflammation and the resulting pathology” [4]. A unidimensional classification of disease severity was proposed: GOLD 0: “at risk” but with normal spirometry; GOLD I: FEV₁≥80% predicted; GOLD II: 30% pred≤FEV₁<80% pred; GOLD III: FEV₁<30% pred or FEV₁<50% pred plus respiratory failure or signs of right heart failure [4]. Given the wide range of FEV₁ values in GOLD stage II, this category was further subdivided into segments IIA (50% pred≤FEV₁<80% pred) and IIB (30% pred≤FEV₁<50% pred) for the purpose of management. However, it was recognised that this staging should be regarded as a very general indication of the approach to management [4]. Inspired by the GOLD document, multiple initiatives were subsequently introduced to study the pathophysiology of the disease, predict and modify its natural course and improve its management by pharmacological and nonpharmacological interventions.

10 years after the launch of GOLD, the first revision was released [5]. It was acknowledged that the disease has “some significant extrapulmonary effects that may contribute to the severity in individual patients” and it was emphasised that FEV₁ should be considered for spirometric classification of COPD instead of as a marker for disease severity [5]. However, recommendations for pharmacological and nonpharmacological management of COPD were still largely based on the degree of airflow limitation, as measured by FEV₁. However, in the past decade it has become evident that the correlation between FEV₁ and symptoms is imperfect [6]. Large heterogeneity also exists within the COPD population with respect to clinical course and the efficacy of interventions that are not completely explained by FEV₁. Moreover, exacerbations are independently associated with poor health status [7], lung function decline [8] and increased mortality risk [9].

With the second GOLD revision in 2011 [10], exacerbations and comorbidities were introduced to the definition of COPD as they contribute to disease severity in individual patients. A new multidimensional system for assessment and management of the disease was introduced. For the first time in GOLD, it was recommended that factors beyond FEV₁ should be included in the assessment of COPD. The proposed approach, consisting of a combination of the degree of airflow limitation, the impact of disease as perceived by the patient and the exacerbation frequency, better reflects the complexity of COPD than the old unidimensional analysis. In fact, this was the first attempt to phenotype individuals with COPD. Although the new staging system was an important step towards personalised medicine in COPD, it was also acknowledged that this is an empirical staging, requiring real-life validation. Since the introduction of this new COPD assessment, healthcare professionals, policy makers and investigators have been actively discussing the potential strengths and limitations of this system and its implications for clinical practice. In this issue of the European Respiratory Journal, Agusti et al. [11] review the results of several recent studies that have applied the GOLD 2011 multidimensional staging system to existing COPD cohorts. Although the four studies [12–15] included in this review were not designed for this purpose, these analyses have significantly increased our understanding of the distribution, characteristics, stability over time and relationship with long-term outcomes of the new GOLD A, B, C and D categories.

It has become clear that the frequency distribution of the different GOLD categories depends on the study population, that classification can actually change over time and that comorbidities are predominantly present in the “high symptom” groups B and D [11]. Moreover, the results of these recent studies clearly indicate that the new A–D categorisation does not necessarily reflect a linear increase in disease severity, in that the risk of hospitalisation and mortality are similar in groups B (high symptoms, low risk) and C (low symptoms, high risk) [11]. Also, the GOLD groups did not differ in the rate of lung function decline, suggesting that this system does not predict disease activity. It is worth mentioning that none of the analysed COPD cohorts used the COPD Assessment Test (CAT) [16] to measure current symptoms. However, a discrepancy in patient-related outcomes between the two proposed symptom measures (modified Medical Research Council dyspnoea score and CAT) was previously reported [17].

From a historical perspective, it becomes clear that the GOLD initiative is a constant “work in progress”. Definition, assessment and management of COPD have been refined as our understanding of the disease advances and new tools for assessment and treatment options become available. Therefore, it is obvious that the updated GOLD strategy is not a definitive one. In fact, minor changes to the assessment were recently proposed, including the use of an alternative symptom cut-off point [17], the use of one hospitalised exacerbation in the past year as a marker for high risk status and the use of the clinical COPD questionnaire [18] as an alternative measure for current symptoms [11]. Like the previous updates, these changes will also require validation. Although the adverse impact of comorbidities, including cardiovascular disease, diabetes and hypertension [19], on morbidity and mortality in COPD is well established, these were not incorporated into the current staging system. However, management of co-occurring chronic conditions in individual patients is probably an essential component of personalised treatment of the disease. Furthermore, one could argue that, in the future of GOLD, the use of FEV₁ could be limited to establishing the diagnosis of COPD, instead of being incorporated into an index for disease severity or management.

Based on current knowledge about the GOLD 2011 COPD assessment, it is probably safe to conclude that the clinical presentation and course of COPD are too heterogeneous to be captured by a limited number of variables in two dimensions. Indeed, it was recently shown that considerable heterogeneity exists within a population of group D patients [20]. One possible explanation for this observation is the fact that the vast majority of patients classified as “high risk” (groups C and D) are in these groups because of a severely reduced FEV₁ and not because of a high number of exacerbations. In fact, the “frequent exacerbator” phenotype [21] of patients within groups C and D might require a separate classification [12]. From the perspective of an optimal assessment of integrated health status in COPD, the list of variables to be included is probably endless, including not only additional clinical outcomes (such as hyperinflation, exercise capacity, body mass index and comorbidities), but also lifestyle factors (including smoking, physical activity level and diet), and supplemental biological and genetic markers. However, it must be kept in mind that GOLD is indeed a global initiative and that the less developed regions of the world may not benefit from more complex disease staging approaches. Thus, any COPD staging system must strike a balance between ease of implementation and adequate capture of disease complexity.

Although Agusti et al. [11] discuss the “top 11” questions about the GOLD 2011 staging system, additional questions still need to be answered. Do the GOLD A-B-C-D groups respond differently to treatment? What is the optimal care for each of these groups? Is there a different treatment response and prognosis for subgroups within GOLD C and D? Do the groups tell us anything about disease activity? What is the impact of the recently added variables “history of hospitalisation” and clinical COPD questionnaire? What is the optimal instrument to assess current symptoms? Keeping in mind that COPD staging is a continually evolving process, instead of focusing on the obvious limitations of the proposed multidimensional system, it is time to look ahead towards improved understanding of this disease. Ultimately, this will result in improved management of this disabling and heterogeneous condition.

• Received June 24, 2013.
• Accepted June 29, 2013.

• ©ERS 2013