Sustainability of Rehabilitation Gains in COPD

描述（由申请人提供）： 原理：动态过度充气的发展是慢性阻塞性肺疾病（COPD）运动耐量的主要限制因素。为了减少动态过度充气的发展，并提高COPD患者的运动耐量，我们开发了一种呼吸再训练技术，用于肺康复期间。这种呼吸再训练技术旨在降低呼吸频率并延长呼气时间。我们证明，在短期内，呼吸再训练加运动训练比单独运动训练更能改善过度充气和运动持续时间。由于肺康复的一个关键方面是在长期内维持其短期受益，我们现在建议测试呼吸再训练加运动的短期受益以及随后的依从性干预计划在长期内是否可持续主要假设：（H1）COPD患者，在12周的呼吸再训练加运动后，在恒定负荷跑步机测试中运动持续时间的改善将更大，训练后进行42周的依从性干预计划（1年，总的来说）比单独运动训练12周后进行42周的坚持干预计划（1年）。共计）。次要假设：随机分组后一年，呼吸再训练加运动训练组在恒定负荷平板试验期间运动诱导的动态过度充气将比单独运动组更少（H2），6分钟步行距离将更长（H3），对呼吸的掌握将比单独运动组更大（H4）。最后（探索性目标），我们将评估 患者生理、心理和临床表型对肺康复短期和长期反应性的影响。方法：拟开展的研究是一项随机、对照的临床试验，将纳入250例中重度COPD患者。预计这些患者中有140例有资格随机分为呼吸再训练加运动训练组或单纯运动训练组。患者将根据分组接受12周的监督培训（每周三次），然后进行依从性干预计划（每周电话激励访谈，家庭锻炼计划和每月实验室助推器会议）。将在12周、6个月和12个月时完成随访试验。测试将包括肺功能测试、递增负荷和恒定负荷跑步机测试、6分钟步行测试、呼吸困难测量、呼吸和股四头肌肌力和耐力评估以及股四头肌超声检查。分析：在主要结果指标（运动持续时间; H1）的主要分析中，我们将使用双样本t检验（双尾t = 0.05）比较运动持续时间（恒定功率跑步机试验）从基线到研究结束的变化。主要分析将基于意向治疗原则。对于缺失12个月测量值的研究受试者，将使用多重插补。该插补模型将基于研究受试者的基线特征。将对主要结局指标进行几项次要分析（H2-H4）。将使用线性回归确定在调整基线协变量和治疗依从性指标后观察到的治疗获益是否持续。由于将对每例患者进行多次测量，因此将使用混合模型分析来比较两组之间恒定负荷跑步机测试随时间的变化。

DESCRIPTION (provided by applicant): Rationale: Development of dynamic hyperinflation is a primary limiting factor of exercise tolerance in chronic obstructive pulmonary disease (COPD). To lessen the development of dynamic hyperinflation, and to improve exercise tolerance in COPD patients, we have developed a breathing- retraining technique to be used during pulmonary rehabilitation. This breathing-retraining technique is designed to decrease respiratory rate and prolong exhalation. We demonstrated that, in the short- term, hyperinflation and exercise duration improved more with breathing-retraining plus exercise- training than with exercise-training alone. Because a crucial aspect of pulmonary rehabilitation is the maintenance its short-term benefits over the long-term, we now propose to test whether short- term benefits of breathing-retraining plus exercise followed by an adherence-intervention program are sustainable over the long-term Primary Hypothesis: (H1) In COPD patients, improvements in exercise duration on a constant- load treadmill test will be greater after 12 weeks of breathing- retraining plus exercise-training followed by a 42-week adherence-intervention program (1 yr. total) than after 12 weeks of exercise-training alone followed by a 42-week adherence-intervention program (1 yr. total). Secondary Hypotheses: One year after randomization, exercise-induced dynamic hyperinflation will be less during a constant-load treadmill test (H2), 6-minute walking distance will be longer (H3), and mastery over breathing will be greater (H4) in the breathing- retraining plus exercise-training group than in the exercise-alone group. Lastly (exploratory objective), we will assess the effect of the patient's physiologic, psychologic and clinical phenotype on short-term and long-term responsiveness to pulmonary rehabilitation. Methods: The proposed study is a randomized, controlled clinical trial in which 250 patients with moderate-to-severe COPD will be enrolled. One hundred forty of these patients are expected to qualify for randomization into the breathing-retraining plus exercise-training group or the exercise-training alone group. Patients will receive 12-weeks of supervised training according to group assignment (three times weekly) followed by an adherence-intervention program (weekly phone motivational interviews, home-exercise program, and monthly laboratory booster sessions). Follow-up testing will be completed at 12 weeks, and at 6 and 12 months. Testing will include pulmonary function test, incremental-load and constant-load treadmill tests, 6-minute walk test, measurements of dyspnea, assessment of respiratory and quadriceps muscle strength and endurance and quadriceps ultrasonography. Analysis: In the principal analysis of the primary outcome measure (exercise duration; H1) we will compare changes in exercise duration (constant work-rate treadmill test) from baseline to end of study using 2-sample t-test (two-tailed �=.05). The primary analysis will be based on intention-to-treat principles. Multiple imputation will be used for study subjects missing the 12-month measurement. This imputation model will be based on baseline characteristics of study participants. Several secondary analyses of the primary outcome measure will be performed (H2-H4). Linear regression will be used to determine whether the observed treatment benefits persist after adjustment for baseline covariates and measures of adherence to treatment. Since several measurements will be taken on each patient, mixed-models analysis will be used to compare the changes on the constant- load treadmill test over time between the two groups.