The AIDS syndrome often manifests itself clinically as Pneumocystis carinii pneumonia. At the time of presentation, patients are short of breath, with evidence of gas exchange and radiologic abnormalities. Treatment usually involves hospitalization and parenteral therapy. While the infection is confined to the lung, therapy is often unsuccessful because of systemic toxicity and, we suspect, inadequate drug delivery to the lung. The goal of this proposal, in conjunction with Pulmonary Function section of this Clinical Studies Group project, is to detect patients with P. carinii infection at the earliest possible time and establish the optimal mode of therapy. This project has the following specific aims: (1) To quantitate the delivery of aerosolized pentamidine to patients with AIDS-related Pneumocystis pneumonia. (2) To determine the effectiveness of aerosolized pentamidine in hospitalized and ambulatory patients. (3) To relate the clinical response of intravenous and aerosolized pentamidine to dose, pulmonary fluid, and blood levels. (4) To study the effects of intravenous and aerosolized pentamidine on islet cell function. Using radiolabeled aerosols and nuclear medicine techniques, we will optimize the aerosolized delivery of pentamidine in patients with P. carinii pneumonia. In addition to the usual hospitalized patients presenting with clinical signs and symptoms, we will attempt to define, using pulmonary function testing (PFTs), a clinically asymptomatic patient population with early infection. With an optimized aerosol system and HPLC determined blood, pulmonary lavage fluid, and pulmonary macrophage levels of pentamidine, the effectiveness of aerosolized and intravenous therapy will be compared in ambulatory and hospitalized patients. All patients will be followed clinically and with serial PFTs and broncho-alveolar lavage. These data, combined with measurement of pancreatic hormone function during therapy could lead to an improved clinical response, reduced drug toxicity, and shortened hospitalization.
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