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。虽然慢性阻塞性肺病（COPD）是最突出的，但以特发性肺纤维化（IPF）为代表的纤维化肺病明显增加。我们在一项血管扩张剂治疗的随机对照临床试验中，对VA特发性肺纤维化（IPF）人群积累了丰富的经验。 根据目前的文献和我们在IPF患者中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）将导致IPF患者的改善的结果，可证明为：a.通过6分钟步行测试（MWT）距离量化的运动耐量增加; B.通过博格呼吸困难量表量化的运动后呼吸困难减少;以及c.通过圣乔治呼吸问卷量化的生活质量总体主观改善。2.改善的运动耐量和降低的呼吸困难的代谢和生理机制将包括：通过最大O2摄取（VO 2 max）证明更有效的氧代谢; B.通过运动后异前列腺素和血浆总抗氧化能力（TAC）证明的运动后氧化应激降低;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。将评估以下重要终点以检验肺康复改善运动能力并减轻呼吸困难的工作假设：6-MWT距离; B.呼吸困难指数;以及，c.生活质量（圣乔治呼吸问卷[SGRQ]）。2.为了评估由肺康复引起的氧摄取、氧化剂应激标志物和肺功能的变化，为了测试改善的结果与更有效的O2利用、降低的氧化剂应激标志物和维持的努力依赖性肺功能相关的工作假设，将测量以下变量：最大摄氧量（VO 2 max）; B.氧化应激的标志物，包括血浆和尿异前列腺素和血浆总抗氧化能力;以及c.最大吸气和呼气压力（PInmax和PExmax）。 这些具体目标的完成将使我们的研究小组能够在此定义的人群和有发生肺纤维化风险的人群中进行以下研究：1）运动限制的机制和2）抗氧化治疗。因此，该应用的长期影响是基于对氧代谢和氧化应激的潜在变化的了解，为IPF患者制定有效的肺康复策略。

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.