ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

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It is recognized that the lung functions as an immunologic organ. Allergic Mronchopulmonary Aspergillosis (ABPA) may serve as a very important model of how the pulmonary immune system responds. The proposed investigations will include analysis of bronchoalveolar lavage (BAL) from known ABPA and suspected ABPA subjects, will extend currently available immunoassays to study aspects of ABPA and cystic fibrosis (CF), and will attempt to develop new assays that may provide insight into the immunopathogenesis of ABPA. Investigations are planned to explain mechanisms of lung damage in ABPA, to identify prognostic factors in ABPA, to guide prednisone therapy more precisely, and to confirm a diagnosis earlier in suspect cases. The pathogenesis of ABPA is unclear but is likely related to the array of immunologic abnormalities including 1) elevation of total serum IgE, not all of which is directed to Af, 2) elevated serum IgE-Af IgG-AF, and IgA-Af, 3) precipitating antibodies to Af, 4) hyperreactivity of peripheral blood basophils to Af and other fungi, and 5) sensitized lymphocytes. Progressively earlier diagnosis of ABPA is possible through immunoassays. The main hypothesis to be tested is that the local immune response (antibodies, immune complexes, cells) occurring in ABPA results in lung injury which produces proximal bronchiectasis, bronchiolitis obliterans, or mixed interstitial intraalveolar lesions in ABPA. Logical questions that follow are: 1) can analysis of BAL and peripheral blood explain mechanisms of lung damage? and 2) does measurement of local antibody production permit an earlier diagnosis of ABPA in suspect cases or serve as a guide to prednisone therapy in established patients? The hypothesis regarding the evaluation of ABPA in patients with CF is that when ABPA complicates CF, progressive lung destruction results from an intense immune response to organisms that colonize the bronchi. A critical question may be whether there are increased levels of isotypic antibodies (IgE, IgG, IgA) to mucoid producing Pseudomonas aeruginosa in sera of patients with ABPA and CF compared to sera of patients ?with CF alone.