Rehabilitation of IPF patients: Effects of exercise and oxidant stress

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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.