Pathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis: current understanding and future directions

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disease characterized clinically by wheezing, pulmonary infiltrates, bronchiectasis, and fibrosis that affects patients with asthma and cystic fibrosis (CF). Although this disease has been characterized by a Th2 immune response to Aspergillus, the disease has some features such as central bronchiectasis which is not seen in other Th2 driven lung diseases such as atopic asthma. Here we will review the current pathophysiology of ABPA in CF and highlight new molecules that may affect immune responses against Aspergillus and ABPA disease pathogenesis.

Blood basophils from cystic fibrosis patients with allergic bronchopulmonary aspergillosis are primed and hyper-responsive to stimulation by aspergillus allergens

“…In others, ABPA occurs, which severely impacts lung function [11]. The reasons underlying the progression from CF-AC to CF-ABPA are unknown but host genetic factors are likely to be involved [12,13]. Over the last two decades, cases of CF-AC and CF-ABPA have become increasingly prevalent [5,7,14].…”

Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

“…Importantly, not all CF patients with ABPA have growth of Aspergillus species from their respiratory cultures (209,411). The pathogenesis of ABPA is complex (484), but individuals with CF appear to be especially predisposed to this hypersensitivity reaction to Aspergillus. For this reason, ABPA may suggest undiagnosed CF (627) or heterozygosity for a CFTR mutation (403).…”

Coevolution of TH1, TH2, and TH17 Responses during Repeated Pulmonary Exposure toAspergillus fumigatusConidia

“…Allergic bronchopulmonary aspergillosis (ABPA) is characterized by early allergic and late-phase lung injury in response to repeated exposures to Aspergillus antigens, which are the consequence of persistent fungal colonization of the lungs (47,60). The disease occurs primarily in patients who have skewed pulmonary immune responses, such as those found in atopic asthma or cystic fibrosis.…”

“…The underlying mechanism(s) by which Aspergillus induces T H 2 responses in some patients, but not others, is presently unknown. If undiagnosed, ABPA can result in progressive lung damage, pulmonary fibrosis, and death (47,60).…”