Maximal Exercise Capacity in Chronic Obstructive Pulmonary Disease: A Limited Indicator of the Health Status

Background: Dyspnoea and diminished functional status are pivotal features of the health status (HS) in chronic obstructive pulmonary disease (COPD). However, it is still not fully understood how pulmonary function tests and cardiopulmonary exercise testing relate to these aspects. This may be due to incomplete assessment and/or deficient definitions of HS. Especially regarding peak oxygen consumption, inconsistent results have been reported. Objectives: To determine the value of maximal cycle ergometry in relation to a broad spectrum of HS aspects. Methods: 129 patients with COPD, stage II and III according to the GOLD classification, performed a cardiopulmonary exercise test. Sixteen independent sub-domains of HS were assessed according to the Nijmegen Integral Assessment Framework, covering physiological functioning, complaints, functional impairments and quality of life as main domains. V ̇ O 2 max and HS sub-domains were correlated by bivariate analysis. Results: Weak correlations of V ̇ O 2 max with most sub-domains were found, Received: June 26, 2009 Accepted after revision: November 24, 2009 Published online: March 11, 2010 J. Vercoulen, MSc, PhD Radboud University Nijmegen Medical Centre PO Box 9101 NL–6500 HB Nijmegen (The Netherlands) Tel. +31 24 685 9554, Fax +31 24 685 9290, E-Mail j.vercoulen @ mps.umcn.nl © 2010 S. Karger AG, Basel 0025–7931/10/0806–0453$26.00/0 Accessible online at: www.karger.com/res Verhage/Vercoulen/van Helvoort/Peters/ Molema/Dekhuijzen/Heijdra Respiration 2010;80:453–462 454 Our recent study [4] confirmed this theoretical definition of HS empirically. In that study, we developed and validated a conceptual framework of HS in COPD, the Nijmegen Integral Assessment Framework (NIAF), which shows that these 4 main domains are conceptually distinct. Moreover, we found that these main domains were subdivided into 15 relatively independent sub-domains, each representing a unique aspect of HS. In another, yet unpublished study, the sub-domain fatigue was added, thus resulting in 16 sub-domains. The definition of HS provided by the NIAF is both detailed and based on empirical observations, far more than the definitions found in the literature. With respect to airflow limitation, we showed in a previous paper that the severity of airflow limitation classified according to the Global Initiative for Chronic Obstructive Lung Diseases (GOLD) hardly relates to complaints, functional impairment or QoL [5] . Several previous studies already provided substantial evidence for such a conclusion [6–17] , yielding weak correlations between forced expiratory volume in 1 s (FEV 1 ) and components of the other 3 domains of HS. With respect to CPET, it is unclear whether physiological impairments are reflected by functional impairments in daily life or other aspects of HS. Similar to the correlations with airflow, exercise capacity and HS aspects correlate weakly [6–17] . Moreover, the corresponding literature lacks clear definitions of HS, QoL and health-related QoL. As a consequence, these terms are frequently used interchangeably, which is a setback in comparing the results between studies. Also, most of these studies were restricted to only one or a few aspects of HS. Only two studies in COPD evaluated exercise capacity in relation to a greater number of HS aspects, using a range of questionnaires [12, 13] . However, both studies selected different instruments, thus hampering comparability. Also, the way of exercise testing differed in both reports. One study reported a wide range of strengths of correlation of the 6-minutes walk distance (6-MWD) with various HS aspects: dyspnoea (r = 0.35), measures of functional status and selfefficacy walking (r = 0.34 and 0.68, respectively) [12] . The correlation between 6-MWD and the Chronic Respiratory Questionnaire total score was weak (r = 0.28). The other study used the disease-specific questionnaire (St. George’s Respiratory Questionnaire, SGRQ) and the generic SF-36 [13] . Exercise capacity measured as peak oxygen consumption (V̇ O 2 max ) on treadmill was found to correlate rather strongly with the SGRQ total score (r = 0.58) and less with some domains of the SF-36 (general health: r = 0.48; social functioning: r = 0.58, and mental health: r = 0.53). Common to all these studies is the paucity and variability in HS aspects that were measured. Starting from the NIAF as a much more detailed and comprehensive assessment of HS, we hypothesized that maximal exercise capacity would show less strong correlations with other physiological aspects of COPD than generally reported, and low or non-significant correlations with the other sub-domains of HS. Therefore, this study explored correlations between maximal exercise capacity performed on a cycle ergometer and the 16 subdomains composing the NIAF HS assessment. Besides V̇ O 2 max , different types of exercise limitations were also evaluated with respect to HS. Materials and Methods Study Design A cross-sectional cohort of patients with COPD was selected from the outpatient departments of three different hospitals. The inclusion and exclusion criteria were published elsewhere [3] . In brief, patients were included if their COPD fell within GOLD stages II and III (FEV 1 /forced vital capacity was ! 70 and FEV 1 between 30 and 80% after bronchodilation), they were current or ex-smokers, were in stable clinical condition without exacerbation in the last 6 weeks before enrolment, and did not participate in a pulmonary rehabilitation program within the last 6 months, and asthma was excluded (defined as a long history of dyspnoea attacks and reversible airflow obstruction dating from childhood, with persistent airflow obstruction later on). The study was approved by the local ethics committee. Methods Health Status HS was assessed by NIAF, which provides an empirical definition of HS and covers the domains physiological functioning, complaints, functional impairment and QoL. These 4 domains of HS were found to be subdivided into 16 distinct sub-domains. In this process, factor analyses were used to identify underlying concepts in the data. The sub-domains were measured by different existing tests and instruments, and for each sub-domain, a subdomain total score (STS) was calculated. Higher scores indicate a worse clinical condition. A detailed description of the validation of the NIAF and the calculation of the STS is reported elsewhere [4] . The Appendix provides details on instruments for each subdomain. Physiological Functioning CPET. All subjects performed an incremental maximal CPET on a bicycle, according to the criteria of the American Thoracic Society on CPET [18] . Subjects cycled on an electrically braked cycle ergometer (Masterlab , Jaeger, Würzburg, Germany) at a pedaling rate of 60 rotations min –1 breathing room air. After unloaded pedaling for 3 min, the workload was increased every minute by 5–20 W. During exercise, ventilation (V̇ E ), V̇ O 2 and carbon dioxide production (V̇ CO 2 ) were measured breath by breath