Rehabilitation of IPF patients: Effects of exercise and oxidant stress

描述(由申请人提供)： 慢性肺病在退伍军人中很常见。虽然慢性阻塞性肺疾病(COPD)是最突出的，但以特发性肺纤维化(IPF)为代表的纤维性肺疾病明显增加。在血管扩张剂治疗的随机对照临床试验的背景下，我们在VA特发性肺纤维化(IPF)人群中积累了广泛的经验。根据目前的文献和我们对IPF患者进行运动试验的初步经验，我们假设：1.正式的肺康复(即有氧运动计划)将改善IPF患者的预后，表现为：a.通过6分钟步行试验(MWT)距离量化的运动耐量增加；b.运动后呼吸困难的减少(Borg呼吸困难量表量化)；c.圣乔治呼吸问卷量化的生活质量的总体主观改善。2.改善运动耐力和减少呼吸困难的代谢和生理机制包括：a.通过最大吸氧量(VO2max)证明更有效的氧代谢；b.减少运动后氧化应激，表现为运动后异前列腺素和血浆总抗氧化能力(TAC)；以及c.维持最大吸气和呼气压力(PInmax和PExmax)。我们的具体目标是：1.为了调查IPF患者的正规肺康复和运动耐量，将评估以下重要终点，以检验肺康复可以提高运动能力和减少呼吸困难的工作假设：a.6-MWT距离；b.呼吸困难指数；c.生活质量(圣乔治呼吸问卷[SGRQ])。2.为了评估肺康复引起的摄氧量、氧化应激标志物和肺功能的变化，以检验以下变量：a.最大摄氧量(VO2max)；b.氧化应激标志物，包括血浆和尿异前列腺素以及血浆总抗氧化能力；以及，c.最大吸气压和呼气压(PInmax和PExmax)，以验证改善的结果与更有效地利用氧气、减少氧化剂应激标志物和维持努力依赖的肺功能有关。完成这些具体目标将使我们的研究小组能够对1)运动限制的机制和2)抗氧化疗法进行未来的研究，无论是在这一确定的人群中，还是在那些有发展成肺纤维化的风险的人群中。因此，这种应用的长期影响是根据对氧代谢和氧化应激的潜在变化的知识，为IPF患者开发有效的肺康复策略。

DESCRIPTION (provided by applicant): Chronic lung disease is common in the veteran population. While chronic obstructive pulmonary disease (COPD) is most prominent, fibrotic lung diseases, typified by idiopathic pulmonary fibrosis (IPF), are clearly increasing. We have developed extensive experience with a VA idiopathic pulmonary fibrosis (IPF) population in the context of a randomized, controlled clinical trial of vasodilator therapy. Based on the current literature and our preliminary experience with exercise testing in IPF patients, we hypothesize that: 1. Formal pulmonary rehabilitation (i.e., an aerobic exercise program) will result in improved outcomes for IPF patients, demonstrable as an: a. Increase in exercise tolerance as quantified by 6-minute walk test (MWT) distance; b. Decrease in post-exercise dyspnea as quantified by the Borg dyspnea scale; and an c. Overall subjective improvement in quality of life as quantified by Saint George's Respiratory Questionnaire. 2. Metabolic and physiologic mechanisms of improved exercise tolerance and decreased dyspnea will include: a. More efficient oxygen metabolism demonstrated by maximum O2 uptake (VO2max); b. Decreased post-exercise oxidant stress demonstrated by post-exercise isoprostanes and plasma total antioxidant capacity (TAC); and, c. Maintenance of maximum inspiratory and expiratory pressures (PInmax and PExmax). Our Specific Objectives are: 1. To investigate formal pulmonary rehabilitation and exercise tolerance in IPF patients The following important endpoints will be assessed to test the working hypothesis that pulmonary rehabilitation improves exercise capacity and lessens dyspnea: a. 6-MWT distance; b. Dyspnea index; and, c. Quality of life (Saint George's Respiratory Questionnaire [SGRQ]). 2. To assess changes in oxygen uptake, markers of oxidant stress and pulmonary function resulting from pulmonary rehabilitation To test the working hypothesis that improved outcomes are associated with more efficient O2 utilization, decreased markers of oxidant stress and maintained effort dependent pulmonary function, the following variables will be measured: a. Maximum oxygen uptake (VO2max); b. Markers of oxidant stress, including plasma and urine isoprostanes and plasma total antioxidant capacity; and, c. Maximum inspiratory and expiratory pressures (PInmax and PExmax). Completion of these Specific Objectives will position our research group to conduct future studies of 1) mechanisms of exercise limitation and 2) antioxidant therapies, both in this defined population and those who are at risk of developing pulmonary fibrosis. The long term impact of this application is thus to develop effective pulmonary rehabilitation strategies for IPF patients, based on knowledge of underlying changes in oxygen metabolism and oxidant stress.