Pathophysiology and immunology of allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis (ABPA) is a complication of persistent asthma and cystic fibrosis (CF), diseases in part characterized by excessive viscous mucus and compromised mucociliary clearance. Inhaled conidia of Aspergillus fumigatus are able to persist and germinate, releasing exoproteases and other fungal products that further compromise clearance, breach the epithelium, and activate immune responses. Chemotactic cytokines (e.g. IL-8, RANTES, eotaxin) in particular have been implicated in murine models. Chemokine-mediated recruitment of CD4+TH2 lymphocytes specific for A. fumigatus is a crucial feature of ABPA. Susceptibility also appears to involve immunogenetic factors including atopy and defined major histocompatibility complex-restricted allelic expression on antigen-presenting cells that are permissive for a TH2-predominant immune response. Certain A. fumigatus allergens appear more associated with ABPA rather than simple A. fumigatus allergy. ABPA is characterized by marked local and systemic eosinophilia, an adaptive immune response with elevated levels of A. fumigatus-specific IgG, IgA and IgE antibodies, and a profound nonspecific IL-4-dependent elevation in total IgE. Clinically, ABPA manifests with recurring episodes of asthma, pulmonary infiltrates, and central bronchiectasis that may progress to fibrosis. It is treated with systemic glucocorticoids and azoles. Monitoring clinical, radiographic and serologic responses (especially total IgE) is essential for successful management.
Moss
R B
RB
Department of Pediatrics, Division of Pulmonary Medicine, Stanford University, Palo Alto, CA 94304-5786, USA. rmoss@stanford.edu
D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology* / Q000503:physiopathology*; D001232:Aspergillus fumigatus / Q000472:pathogenicity; D001249:Asthma / Q000150:complications; D001987:Bronchiectasis / Q000382:microbiology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000150:complications; D006801:Humans