A High-Intensity versus Moderate-Intensity Exercise Training Programme in Alpha-1 Antitrypsin Deficiency-Related COPD (IMAC): A Randomized, Controlled Trial

Introduction: Training-induced adaptations of the oxidative capacity have been shown to be blunted in alpha-1 antitrypsin deficiency (AATD)-related chronic obstructive pulmonary disease (COPD). To improve training outcomes in AATD, this study was aimed to compare the effects of two exercise training programmes with different training intensities.

Methods: Thirty patients with AATD (genotype PiZZ) and COPD III-IV were randomly assigned to either high-intensity (HIT) or moderate-intensity training (MIT), each consisting of endurance, strength, and squat training for a duration of 3 weeks. 6-Min walk distance (6MWD) was used as the primary outcome.

Results: Twenty-five subjects augmented with alpha-1 antitrypsin (HIT: n = 12, FEV1 41.3 ± 17.4%pred., MIT: n = 13, FEV1 45.9 ± 15.5%pred.) completed the study. In HIT and MIT, 6MWD (+37 ± 43 m vs. +32 ± 28 m, p = 0.741), 1-min sit-to-stand test (5.6 ± 4.9 repetitions vs. 5.6 ± 4.5 repetitions, p = 0.766), exercise-induced BORG dyspnoea (-1.4 ± 1.7 pts vs. -1.5 ± 2.4 pts, p = 0.952), and all CRQ domains have improved after training without between-group differences. When considering only subgroups of (probably) anxious or depressive patients (Hospital Anxiety and Depression Scale [HADS] ≥8 pts), only HIT induced a significant reduction of anxiety (-4.8 pts, 95% CI [2.1-7.5]) or depression symptoms (-5.0 pts, 95% CI [2.8-7.3]).

Conclusion: Although HIT and MIT were equally effective by improving exercise capacity, quality of life, and dyspnoea in homozygous AATD, HIT may show advantages over MIT, if anxiety or depression symptoms were present. The goal should be personalized training based on the patient's personal preference in order to achieve long-term adherence.