The survival of patients with idiopathic pulmonary fibrosis (IPF) is short, their quality of life is poor, and spontaneous progression of their disease is almost universal. We propose to collaborate with like-minded institutions to increase the pace of investigation into treatment options with a goal of prolonging survival, improving quality of life, and increasing functional capacity in these patients. The overall objective in this proposal is to evaluate, in a multicentered clinical research network, the efficacy of one multi-drug (N-acetyl cysteine [NAC], clarithromycin, and pravastatin) and a novel therapy (prostaglandin 12 [PG12], prostacyclin or its analogues) in the treatment of IPF. Our primary endpoint will be to determine if one or both of these approaches delays the time to death or decline in FVC. Our secondary endpoints will be to determine if these approaches improve quality of life, increase functional status, or delay loss of lung function. Exploratory endpoints will be to determine in these therapies decrease in unplanned clinic visits or hospitalizations and favorably alter proposed biologic markers of disease activity. Our hypothesis is that NAC, clarithromycin, and paravastatin will have favorable biologic and clinical effects on three sites of disease activity, abnormal alveolar epithelium, lymphoplasmacytic inflammation, and persistence of interstitial myofibroblasts. We hypothesize that PG12 will block the differentiation of fibroblasts into myofibroblasts thereby delaying or preventing the progression of fibrosis. A secondary objective will be to determine if the ability of bronchoalveolar lavage fluid to convert fibroblasts to myofibroblasts can be used as a bioassay to monitor biologic disease activity. Our hypothesis is that active TGF-beta in BAL fluid is responsible for this activity and can be favorably altered by PG12 therapy.
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