Skeletal Muscle Adaptations to Exercise in COPD

Cardiopulmonary Physical Therapy Journal, Dec 2003 by Mathur, Sunita

ABSTRACT

Contrary to original findings that attributed improvements in exercise capacity solely to psychological adaptations, physiologic adaptations to exercise have also keen shown in patients with mild to severe COPD. Skeletal muscle is an adaptable tissue and shows a response to training in these patients similar to that of healthy individuals. Whole body endurance training studies demonstrate reductions in lactic acidosis with exercise, improvements in oxidative enzymes and metabolism of muscle, and improvements in muscle strength of the lower extremity. Although few resistance training studies are available, preliminary findings show an increase in upper and lower body muscle strength, muscle cross-sectional area, and an added benefit to aerobic training. Future studies on skeletal muscle adaptation should use training protocols that vary in intensity and duration to target the specific abnormalities found in skeletal muscle of patients with COPD.

INTRODUCTION

Exercise training is a key component in the rehabilitation of patients with chronic obstructive pulmonary disease (COPD) and has been associated with increased functional capacity and improvements in quality of life.1 The mechanism by which tolerance for exercise is increased through training is multifactorial and includes both psychological and physiological factors.2 Early studies on exercise training in COPD used low intensity training programs and concluded that patients with COPD were unable to exercise to an adequate intensity to induce a physiologic training effect. They concluded that any observed increase in exercise tolerance was due to psychological factors such as desensitization to dyspnea, increased motivation, reduced anxiety, and also to improved efficiency of movement. This was further substantiated by the fact that exercise training did not result in any changes in pulmonary function (eg, airflow limitation) which was thought to be the only physiologic limitation to exercise in this population.3

Further studies have demonstrated that dyspnea may not be the sole limitation to exercise in patients with COPD. Leg fatigue has been reported as a common symptom limiting exercise in these patients with up to 30%-40% of patients with moderate to severe disease reporting it as the main limiting factor to maximal cycle exercise.4,5 The presence of contractile fatigue of the quadriceps has been demonstrated in 60% of patients with COPD following maximal cycle exercise.6 Further support for skeletal muscle function as a limitation to exercise comes from correlational studies where isometric strength of the quadriceps has been correlated to maximal exercise capacity on a cycle ergometer (r = 0.65) and to the distance covered during a Six Minute Walk Test (r = 0.61) in this patient population.7

A growing body of evidence suggests that the skeletal muscle of patients with COPD demonstrates abnormalities in comparison to healthy age- and weight-matched control subjects. The limb muscles of these patients show a reduced oxidative capacity demonstrated by a reduced proportion of Type I fibers, smaller cross-sectional area of Type I and IIa fibers, reduced concentration of oxidative enzymes, and a lower capillary density.8 In addition, the muscle cross-sectional area measured using CT also is significantly reduced in comparison to healthy controls.9 A number of contributing factors have been identified including inactivity, altered blood gases, nutritional depletion, electrolyte imbalance, systemic inflammation, and oxidative stress.8,10

Exercise training is an intervention that can reverse many of the changes seen in muscle of patients with COPD. In healthy young and older adults, endurance training can result in muscle adaptations such as increased mitochondrial density and concentration of oxidative enzymes, improved capillary density, and transformation of Type IIb to Type Ha fibers.11 Resistance training can result in increased muscle strength and increases in muscle cross-sectional area.12 The purpose of this paper is to review the literature on skeletal muscle adaptation as a result of whole body endurance training and resistance training programs in patients with COPD. Skeletal muscle in this paper refers only to muscles of the upper and lower extremity and not to muscles of respiration.

WHOLE BODY ENDURANCE TRAINING

Evidence for skeletal muscle adaptations to whole body endurance exercise can be grouped as follows: indirect evidence including reductions in lactic acidosis with exercise and direct evidence including changes in oxidative enzymes, muscle bioenergetics, and improvements in measures of skeletal muscle performance (eg, strength, endurance, and fatigue). Evidence from each of these 3 areas will be discussed. Table 1 provides details on subject characteristics and training protocols for these studies.

Indirect Evidence: Reductions in Lactic Acidosis

The lactate threshold, also called the anaerobic threshold (AT), is associated with a disproportionate increase in concentration of serum lactate during incremental exercise. The AT is the result of an increasingly greater dependence on anaerobic metabolism by the working muscle and generally occurs at high levels of exercise intensity; approximately 80% to 85% of VO^sub 2^max in healthy individuals.11 It was previously thought that individuals with COPD were unable to exercise to an adequate intensity to reach their AT. However, a study by Sue et al13 reliably detected the onset of the AT at low levels of incremental exercise in two-thirds of patients with moderate to severe COPD. This suggests an increased reliance on anaerobic metabolism in patients with COPD and is in keeping with the histochemical and morphological changes seen in (heir skeletal muscle. This finding led to further investigation to determine whether increases in lactate concentration with exercise could be attenuated with high intensity exercise training. A reduction in the concentration of lactate could be indicative of skeletal muscle adaptation (ie, improved oxidative capacity of muscle). Two well-designed studies have been done in this area and are discussed below.