Supplementary Material for: 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.

研究背景：已有研究证实，α1-抗胰蛋白酶缺乏症（alpha-1 antitrypsin deficiency, AATD）相关慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）患者的氧化能力训练适应性会受到抑制。为改善AATD患者的运动训练获益，本研究旨在对比两种不同运动强度的运动训练方案的干预效果。
方法：将30例携带PiZZ基因型的AATD合并Ⅲ~Ⅳ级COPD患者随机分为高强度间歇训练（high-intensity training, HIT）组与中等强度训练（moderate-intensity training, MIT）组，两组训练均包含耐力训练、力量训练及深蹲训练，干预周期均为3周。以6分钟步行距离（6-minute walk distance, 6MWD）作为本研究的主要结局指标。
结果：最终25例接受α1-抗胰蛋白酶补充治疗的患者完成本研究：其中HIT组12例，第1秒用力呼气容积占预计值百分比（FEV1%pred）为41.3±17.4%；MIT组13例，FEV1%pred为45.9±15.5%。训练后，两组患者的6分钟步行距离（HIT组：较基线增加37±43m，MIT组：较基线增加32±28m，p=0.741）、1分钟坐站试验重复次数（5.6±4.9次 vs 5.6±4.5次，p=0.766）、运动诱发的BORG呼吸困难评分（较基线降低1.4±1.7分 vs 较基线降低1.5±2.4分，p=0.952）及所有慢性呼吸疾病问卷（Chronic Respiratory Questionnaire, CRQ）维度均得到改善，且组间差异无统计学意义。仅针对（疑似）合并焦虑或抑郁症状的亚组（医院焦虑抑郁量表[Hospital Anxiety and Depression Scale, HADS]评分≥8分）进行分析时发现，仅HIT组可显著降低患者的焦虑症状评分（较基线降低4.8分，95%置信区间[2.1, 7.5]）与抑郁症状评分（较基线降低5.0分，95%置信区间[2.8, 7.3]）。
结论：尽管高强度间歇训练与中等强度训练在改善纯合子型AATD患者的运动能力、生活质量及呼吸困难症状方面疗效相当，但当患者合并焦虑或抑郁症状时，高强度间歇训练可能展现出优于中等强度训练的优势。临床实践中应基于患者个体偏好制定个性化训练方案，以提升长期治疗依从性。