A High-Intensity versus Moderate-Intensity exercise training program 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 programs with different training intensities.

Methods: 30 patients with AATD (genotype PiZZ) and COPD III-IV were randomly assigned either to high-intensity (HIT) or moderate-intensity training (MIT), each consisting of endurance, strength and a squat training for a duration of 3 weeks. 6-minute walk distance (6MWD) was used as the primary outcome.

Results: 25 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±43m vs. +32±28m, p=0.741), 1-minute sit-to-stand test (5.6±4.9 repetitions vs. 5.6±4.5 repetitions, p=0.766), exercise-induced BORG dyspnoea (-1.4±1.7pts vs. -1.5±2.4pts, 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 to 7.5]) or depression symptoms (-5.0 pts, 95% CI [2.8 to 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.