Immunopathogenesis of allergic bronchopulmonary aspergillosis and airway remodeling

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease clinically characterized by manifestation of wheezing, pulmonary infiltrates and bronchiectasis and fibrosis which afflicts asthmatic and cystic fibrosis (CF) patients. The pathophysiologic mechanisms are mediated by a first and direct interaction of Aspergillus fumigatus (Af) antigens with airway epithelial cells, followed by an immunologic/allergic inflammatory response to Af antigens. In the first phase, Af proteases directly activate epithelial cells by damaging the epithelial integrity and by a direct interaction with epithelial cells, resulting in a rapid wave of pro-inflammatory cytokines and chemokines that initiates an inflammatory response. During the second phase, this fungus induces a strong Th2-type immunological response with markedly elevated Aspergillus-specific and total serum IgE levels and a strong eosinophilic inflammatory response. It is proposed that strong repair reactions, similar to that described for asthmatic patients, are induced by fungal proteinases followed by concurrent release of epithelial derived growth factors. Furthermore, Th2-type cytokines e.g. IL-4 and IL-13 and proteases from inflammatory cells and mast cells, will also promote the release of growth factors from airway epithelial cells driving a strong and irreversible remodeling reactions in airways of patient with ABPA, resulting in bronchiectatic lesions and fibrosis.