Pulmonary function impairment was related to a broad array of physical functional limitations among patients with COPD, including lower extremity functioning, exercise performance, skeletal muscle strength, and self-reported limitation in basic physical actions. These findings are consistent with the theory that the central pulmonary function impairment of COPD translates into diverse impacts on body systems that ultimately compromise physical functioning.
Although knowledge about functional limitation in COPD has been limited, cohort studies of older, community-living adults without lung disease indicate that limitation of lower extremity function is a key determinant of subsequent disability (34
). In a general population sample of 1,122 older adults, lower extremity function was measured using the Short Physical Performance Battery (33
). During 4-year follow-up, reduced baseline lower extremity function was associated with a greater risk of developing incident disability in activities of daily living. Decreased lower extremity function was also related to all-cause mortality, with a gradient of risk across the entire functional spectrum (35
). Our finding that pulmonary function impairment is related to poorer lower extremity function in COPD may translate into a greater risk of disability during longitudinal follow-up.
Respiratory muscle weakness, especially of the diaphragm, has long been considered to be an important determinant of dyspnea and decreased exercise tolerance in COPD (51
). Emerging evidence suggests that peripheral skeletal muscle strength is also reduced in COPD (52
). Although some studies indicate that lower extremity strength is more affected than upper extremity strength in COPD, other investigators have found significant upper extremity involvement, suggesting a generalized myopathy (41
). Our findings suggest that greater pulmonary function impairment may result in both upper and lower extremity muscle weakness in COPD, consistent with systemic involvement from the disease. Skeletal muscle weakness, in turn, could mediate COPD-related disability. Prospective follow-up will be necessary to determine the impact of this key functional limitation on the disablement process in COPD.
The etiology of peripheral muscle dysfunction in COPD remains unclear. Skeletal muscle metabolism appears to be altered, with reduced oxidative metabolism (59
). Specific effects of the disease, such as hypoxemia or acidosis, may impair muscle function (60
). Deconditioning from inactivity, malnutrition, oxidative stress, and chronic inflammation are other explanations (52
). “Sarcopenia,” or reduced muscle mass, may occur (52
). Treatment with corticosteroids may also reduce skeletal and respiratory muscle strength (42
In our analysis, reduced lower extremity function and muscle strength contributed to decreased exercise performance, an integrative functional limitation that may contribute to the development of COPD-related disability. The negative effect of COPD on exercise performance has been demonstrated for both submaximal and maximal exercise performance (31
). Submaximal exercise performance, such as the distance walked in 6 minutes, may have a greater impact on the risk of developing COPD-related disability than maximal exercise. This is because daily activities and work usually require sustained lower level exertion, rather than briefer periods of maximum exercise. Our finding that greater pulmonary function impairment is linked with poorer exercise performance among COPD patients may have longer term significance for the disablement process.
Pulmonary rehabilitation programs have become an important management strategy for improving quality of life in patients with COPD (67
). Our findings suggest that rehabilitation programs aimed at increasing lower extremity strength, in particular, may improve walking and other activities that involve submaximal exercise capacity. Future longitudinal follow-up of the FLOW cohort should elaborate the impact of functional limitation on the risk of disability, which would also have important implications for pulmonary rehabilitation.
A notable study strength is the large sample of COPD patients who have a broad spectrum of disease severity, ranging from mild to severe. Our study is, to our knowledge, the largest prospective COPD cohort study to systematically evaluate a broad range of functional limitations, such as lower extremity function and skeletal muscle strength. Recruitment from a large health plan should also help to ensure generalizability to patients who are being treated for COPD in clinical practice. Availability of interview data, pulmonary function tests, and extensive physical characterization allows robust conclusions about physical functioning.
Our study is also subject to several limitations. Although the inclusion criteria required health-care utilization for COPD, misclassification of asthma could have occurred. Our COPD definition required concomitant treatment with COPD medications to increase the specificity of the definition. In addition, all patients had a physician diagnosis of COPD and reported having the condition. The observed lifetime smoking prevalence was similar to that in other population-based epidemiologic studies of COPD, supporting the diagnosis of COPD rather than asthma (1
). We also previously demonstrated the validity of our approach using medical record review (18
). Nonetheless, we cannot exclude the possibility that some subjects, especially those with GOLD stage 0, may have conditions other than COPD. When we excluded GOLD stage 0 from key analyses, however, the results were not substantively affected (data not shown). For the present analysis, we would expect any misclassification to have a conservative effect (i.e., reducing the impact of pulmonary function on functional limitation).
Because our ultimate focus is on disability prevention, we intentionally sampled younger adults with COPD. Therefore, these results may underestimate the impact of pulmonary function impairment among older patients with COPD. In addition, Kaiser Permanente members, because they have health-care access, may also be different from the general population of adults with COPD. Mitigating these limitations, the sociodemographic characteristics of Northern California Kaiser Permanente members are similar to those of the regional population, with some underrepresentation of income extremes (16
). Moreover, selection bias could have been introduced by nonparticipation in the study. There were some differences among subjects who did and did not participate in the interviews and clinic visits, but they were modest in scope and not likely to affect the relation between pulmonary function and functional limitation. In addition, when we repeated the main analysis weighted to account for nonparticipation, there were no substantive differences in the results (data not shown). Nonetheless, we acknowledge the potential for selection bias as a limitation of our study.
Our analysis is guided by a specific theoretical model about how pulmonary function impairment leads to subsequent functional limitations and disability. This is based on the earlier work of Verbrugge and Jette (15
). We acknowledge, however, that there could be areas in which the causal pathway has not yet been fully elucidated.
We measured muscle strength with a hand-held dynamometer rather than a computerized isokinetic dynamometer, such as the Cybex II (Lumex, Inc., New York, New York). Although isokinetic dynamometers can provide better isolation of muscle groups and more information about muscle dynamics, they are expensive and require specialized training to use. In contrast, hand-held dynamometers are more feasible, in terms of both cost (about $1,000) and ease of use. Hand-held dynamometers provide reliable and valid results, correlating strongly with isokinetic dynamometer results (69
). In particular, hand-held dynamometers have been used to measure knee extension strength in studies of COPD (41
). In epidemiologic studies, hand-held dynamometer measurements of knee extensor strength and grip strength have been associated with disability of mobility tasks, supporting the construct validity of this testing approach (69
). We minimized measurement variability by having the same experienced physical therapist train the examiners in a standardized fashion and ensuring adequate interrater reliability.
In sum, greater pulmonary function impairment was associated with physical functional limitation among COPD patients. Longitudinal follow-up will determine the impact of these functional limitations on the risk of disability. Preventive strategies may ultimately be designed to target loss of physical function to attenuate the disablement process.