Exercise Training in Patients With Mild COPD

Peripheral muscle mass and function can be impaired in patients with mild chronic obstructive pulmonary disease (COPD). Quadriceps cross-sectional area is reduced in these patients compared to controls [1], particularly in those with dyspnea as compared to non-dyspneic counterparts and smoker controls [2]. Reduced physical activity is closely related to peripheral muscle mass in mild COPD [1], suggesting that early therapeutic interventions are needed in this group of patients. In addition, reduced quadriceps mass is strongly associated to quadriceps weakness [3,4] and a substantial proportion of patients with mild COPD (28%) had quadriceps weakness [5]. Reduced muscle mass and resultant muscle weakness contribute to limiting exercise in COPD [6-8] and to reduce physical activity, particularly in mild disease [1].

Exercise training (ET) is widely used in patients with moderate-to-very-severe COPD to improve peripheral muscle function and thus exercise capacity and quality of life [9]. Unfortunately, the effects of ET in mild COPD are currently unclear. A recent systematic review identified three low-quality studies with different designs (retrospective, one group pre-posttest, and one randomized controlled trial) [10]. The authors found significant improvements in exercise capacity (effect size 0.87-1.82) and quality of life (effect size 0.24-0.86) after comparing pretest-posttest data and ET with usual care. Although these results are inconclusive and indicate that additional and more robust studies should be conducted [10], current recommendations to initiate ET include even mild disease if dyspnea or exercise limitation are present [11]. Since peripheral muscle mass and function improve with ET [9], the investigators hypothesize that this statement is correct and consequently ET will increase exercise capacity in dyspneic patients with mild COPD in comparison to usual care.

Patients will enter an 8-week ET program of 3 days per week supervised exercise training at the Rehabilitation Physiotherapy Gymnasium. Exercise training will include high-intensity endurance training at 60-80% of baseline peak work rate and strength training of upper and lower limbs with 3 sets of 6 repetitions at 50% of one repetition maximum [12,13]. Each session will be 60 min duration, 30 min dedicated to cycle exercise. The UC group will receive usual outpatient care and follow-up.

The study will require 30 patients per arm to detect an effect size of 0.88 [10] at the 5% significance level and with 80% power, allowing a dropout rate of 30%.

Inclusion criteria

• male or female subjects, aged 45-80 years
• baseline post-bronchodilator forced expiratory volume at one second (FEV1) ≥80% of predicted normal and baseline (post-bronchodilator) FEV1/forced vital capacity (FVC) ≤70%
• current or ex-smokers with a smoking history of at least 10 pack-years
• dyspnea during activities of daily life, defined as modified Medical Research Council (mMRC) scale [0-4 points] ≥1 point

Exclusion criteria

• history of asthma or other chronic lung disease (e.g.: interstitial lung disease; sarcoidosis; tuberculosis; cystic fibrosis; bronchiectasis; previous lung resection)
• comorbidities that would prevent the patient from performing an exercise test (including psychological or cognitive disorders): chronic congestive heart failure; recent myocardial infarction [6 months or less]; cardiac arrhythmia requiring drug therapy; neuromuscular and peripheral vascular diseases
• the presence of usual co-morbidities, such as essential hypertension, diabetes, osteoporosis, hypothyroidism, under proper medical control, and obesity, excluding extreme obesity, will not be considered an exclusion criterion.