Adequate Patient Characterization in COPD: Reasons to Go Beyond GOLD Classification

INTRODUCTION

The GOLD classification for chronic obstructive pulmonary disease (COPD) has been introduced in order to facilitate comparability of clinical studies, by stratifying patients according to severity of airflow limitation, measured as forced expiratory volume in 1 second as percentage of predicted (FEV₁%) [1,2]. Severity classes of COPD can be used to tailor diagnostic and therapeutic interventions in the management of this large patient group.

Clearly, airflow obstruction is only one aspect of COPD. Other key pathophysiological aspects include hyperinflation, diminished exercise capacity, malnourishment, and decreased muscle strength. In addition, there are clinical manifestations such as dyspnoea, functional impairment in daily life, and quality of life. All these aspects are key components of health status (HS) [3-5].

It is unclear to what extent GOLD stages discriminate in aspects of health status, other than airflow obstruction. One study showed a statistically significant difference only in St. George’s Respiratory Questionnaire (SGRQ) section impact and total score between GOLD 2 and 3 (previously designated as stages 2a and 2b), but not in the sections symptoms and activities [6]. Another study found higher exacerbation rates with increasing COPD severity stage (0-IV), but the correlation was weak (r=0.29) [7]. Other relationships between GOLD stages and aspects of health status have not been reported.

In studies on the relationship between health status and GOLD staging, to date, only few aspects of health status were measured. The SGRQ is most frequently used, but as this instrument contains only three sections, at best three aspects of health status are measured. In a previous study we have developed and validated a conceptual framework of health status, the Nijmegen Integral Assessment Framework (NIAF) [8]. This framework provides a much more detailed definition of health status, and is much more formulated in terms of empirical observations than definitions found in the literature. The NIAF covers the following main domains of health status: Physiological Functioning, Complaints, Functional Impairment, and Quality of Life. These four main domains were found to be subdivided into 15 more concrete and relatively independent sub-domains. In addition, the NIAF provides an integration of many existing tests and instruments, by indicating which aspect of health status is measured by each instrument.

The purpose of the present study was to evaluate the relevance of the GOLD classification in COPD to a broad spectrum of aspects of health status, as measured by the NIAF. We focused on GOLD stages 2 and 3, as these stages make up the major part of patients seen in primary and secondary care, and because previous studies have shown that GOLD stages discriminated in aspects of health status between these two stages, and not between other consecutive stages.

METHODS

Study Design and Recruitment of Patients

Cross-sectional data were collected from a prospective cohort of patients with COPD, who visited three outpatient pulmonary clinics for respiratory complaints. The clinics consisted of one University Hospital (Radboud University Nijmegen Medical Centre, location Dekkerswald), a non-academic teaching hospital (Rijnstate Hospital), and a smaller city-hospital (Maas Hospital). Patients were seen by pulmonologists, whether for reasons of follow-up or new referrals. All patients with an established diagnosis of COPD within GOLD stages 2 and 3 (FEV₁ post-bronchodilation between 30-80% predicted), and in a stable condition, were selected by examination of the medical records by one of the authors (JM). Exclusion criteria were: co-morbidity (e.g. cardial, neurological, oncological, or diabetes mellitus), acute exacerbation of COPD within six weeks before enrolment, participation in a pulmonary rehabilitation program within the last six months, or inability to speak Dutch.

The recruitment procedure resulted in 361 eligible patients (Fig. 1). Of them, 316 (88%) gave permission for a telephone call by one of the investigators (LD). One-hundred-and-forty-eight patients did not consent with the study protocol for a variety of reasons, e.g. refusing cycle ergometry, travel problems, being too busy at work or at home, feeling too old. Of the remaining 168 patients, all of whom had given written informed consent, 156 belonged to GOLD stages 2 and 3. Twelve patients had to be classified into GOLD 1 or 4 on the basis of their baseline post-bronchodilator spirometry (shortly after enrolment), which differed slightly from spirometric values observed during the recruitment procedure. Finally, 21 non-smokers, all with a clear history of asthma extending from childhood, were excluded, resulting in 135 smoking-related COPD patients. Subgroup analysis of these never smoking chronic asthmatics revealed neither significant differences in scores of the sub-domains of health status, nor in demographic variables, as compared to the total group (results not shown).

RESULTS

DISCUSSION

This is the first study that evaluated the relevance of the GOLD classification in relation to a broad range of aspects of health status in COPD. In the present study it was shown that the GOLD classification has no clinical relevance in aspects of health status other than airway obstruction.

The relevance of GOLD stages with respect to different aspects of health status (HS) was evaluated using the recently developed Nijmegen Integral Assessment Framework (NIAF) of health status in COPD [8]. Most existing instruments contain only three to five subscales, and thus measure only few aspects of HS. An integral assessment of HS therefore requires the use of multiple instruments. However, an evidence-based integration of existing instruments is lacking [17]. The NIAF covers the main domains Physiological Functioning, Complaints, Functional Impairment, and Quality of Life. We found that these four main domains were conceptually distinct, and were shown to be further subdivided into 15 more concrete and homogeneous sub-domains. The NIAF has four key characteristics. First, it covers a broad range of aspects of health status relevant to COPD. Second, it integrates existing instruments by indicating which instruments measure the same sub-domain of HS, and it provides information on the validity of these instruments by indicating which sub-domain is actually measured. Third, all 15 sub-domains were shown to be relatively independent, which means that each sub-domain represents a unique aspect of the patient’s health status. Fourth, the sub-domains are measured by existing tests and instruments and for each sub-domain a single score is calculated. Taken together, the NIAF provides an empirical and detailed definition of health status, and allows a valid and integral assessment of 15 relatively unrelated and therefore unique aspects of health status in COPD, expressed in only 15 scores.

We found significant differences between GOLD stage 2 and stage 3 in only five of 15 sub-domains, other than airway obstruction. These were Static lung volumes, Exercise Capacity, Subjective Pulmonary Complaints, Subjective Impairment, and Health-Related QoL. Considering the large overlap in the scores of these five sub-domains between both stages, the clinical relevance of these differences is small. With respect to the sub-domain Exercise Capacity, significant but minor correlations with FEV₁% predicted were reported by several authors, based mostly on maximal oxygen consumption (V_O2max), varying between .22 and .44 [18-20]. In the present study the sub-domain Exercise Capacity contained three other factors in addition to V_O2max, but we found a similar correlation with FEV₁% predicted (r= .38). Hyperinflation commonly occurs in conjunction with decreasing FEV₁, but empirical studies on this issue are lacking. The correlation of the sub-domains Static Lung Volumes and FEV₁% predicted was low (r=-.22) and not statistically significant, indicating low shared variance. With respect to the main domain Complaints, there was a significant difference between both stages in sub-domain Subjective Pulmonary Complaints, but not in the sub-domains Dyspnoea Emotions and Dyspnoea Expected. With respect to the main domain Functional Impairment, GOLD discriminated in the sub-domain Subjective Impairment, but not in the sub-domains Behavioural Impairment and Actual Physical Activity. Concerning the main domain Quality of Life, GOLD stages discriminated only in the sub-domain Health-Related QoL.

Poor associations between airflow obstruction and other pathophysiological parameters, complaints, functional impairment, and quality of life have been reported by many studies [17, 20-27], but little research has been done on the clinical relevance of the GOLD classification system in relation to these different aspects of health status. A low correlation (r=0.29) was reported between GOLD staging and number of hospital readmissions for exacerbations [7]. Antonelli-Incalzi et al. [6] found significant differences between GOLD stages regarding the St. George’s Respiratory Questionnaire (SGRQ). However, no significant differences were found for the 6-minute walk distance, quality of sleep, and cognitive and affective status. Also, the differences in the SGRQ scores were only found for some subscales of the SGRQ, and only between stages 2 and 3 (previously stages 2a and 2b). Similar to the present study, the authors found large variability within all GOLD stages, resulting in major overlap in scores between consecutive stages. Strikingly, this study also demonstrated substantial problems in health status in patients with COPD with GOLD stage 0 and stage 1. The authors concluded that health status cannot be inferred from GOLD stage.

Two studies used criteria for disease staging similar to GOLD. Ferrer and colleagues [28] found low to moderate correlations of the SGRQ subscales with COPD stages according to the American Thoracic Society (ATS) guidelines (r=.27 to .51). This relationship was stronger in patients without co-morbidity, as compared to patients with co-morbidity (r=.68 versus .40, respectively). These authors also reported a large overlap in scores between the ATS stages and substantial health status problems in patients with mild disease severity. Hajiro et al. used British Thoracic Society (BTS) staging criteria [29]. They found significant differences between moderate and severe COPD on all subscales of the SGRQ and V_O2max. Between mild and moderate COPD they only found significant differences on the subscale activity and the total score of the SGRQ. Several pulmonary function parameters, dyspnoea, anxiety, and depression were not significantly different between any stage.

Results of the present study and previous studies show that a classification system based on the severity of airflow obstruction has no relevance with respect to aspects of health status other than airflow obstruction. In only a few aspects of health status significant relationships were found, but considering the major overlap in scores between consecutive stages these differences have little clinical relevance. We explicitly would discard staging systems based on only one aspect of health status in favour of assessment incorporating multiple aspects of health status.

This conclusion is not surprising, because many studies have shown that airflow obstruction (the parameter on which the GOLD stages are based) is poorly related to other pathophysiological processes, functional impairment, complaints, and quality of life. In addition, previously, we found that the 15 sub-domains of HS represented by the NIAF are relatively independent [8]. This means that scores on a particular sub-domain, such as airflow, do not predict scores on other sub-domains.

Some methodological considerations should be discussed. First, we focused on patients with GOLD stages 2 and 3, as these patients constitute the most part of patients seen in medical care, and because in a previous study it was shown that GOLD stages discriminated in aspects of health status between these stages, and not between other consecutive stages [6]. Second, we excluded primary co-morbidity to exclude its confounding effect, which was reported in a study on the relationship between ATS classification and health status [28]. In that study, also a relationship between disease stage and the SGRQ was found. This relationship was most pronounced in patients without co-morbidity. Thus, if any differences between GOLD stages are present, these would have been found in the present sample where co-morbidity was excluded.

The present findings have important implications for clinical practice and research. The GOLD classification was designed to create more homogeneous subgroups for research purposes, and it was expected that this classification could guide diagnosis and treatment of COPD [1, 2]. Our findings show that GOLD staging is only clinically meaningful with respect to airway obstruction, but not to any other aspect of health status, such as other physiological processes, complaints, functional impairment in daily life, and quality of life. The relative independence of the different sub-domains of health status implies that treatment directed at only one aspect of HS, for example airflow obstruction, does not result in improvement in other aspects. Integral diagnosis, treatment, and management of COPD therefore should go beyond staging and management of airway obstruction alone, and should include additional and specific interventions aimed at improving other aspects of health status as well. In order to tailor treatment to the needs of an individual patient, GOLD staging proves to be inadequate. What is needed is an integral assessment of all aspects of health status.

The key characteristic of the NIAF is that multiple, and relatively unique aspects of health status are integrated, which produces a more complete picture of the patient with COPD. The recently developed BODE index also is an approach in which different aspects of COPD are combined to yield a more complete picture of the patient. The BODE index (Body Mass Index, airway obstruction, dyspnoea, and exercise capacity) significantly better predicted mortality [30] and hospitalization [31], as compared to FEV₁ alone. The difference between the BODE index and the NIAF is, that the former combines the different aspects into a single parameter. The NIAF, in contrast, produces 15 different scores. In clinical practice, this has the advantage of obtaining a detailed picture of an individual patient, with respect to which aspects of health status are problematic, and which aspects are not. This enables the clinician to fine-tune treatment to the needs of an individual patient.

In conclusion, GOLD staging only has clinical relevance with respect to airflow obstruction, and not to any other sub-domain of HS. Therefore, the GOLD classification system is not useful in guiding treatment and management of COPD. Integral assessment of different aspects of health status is needed. The NIAF provides clinicians with a detailed picture of the patient’s health status, and therefore a guide to tailor treatment to the needs of the individual patient.

REFERENCES