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Allergic bronchopulmonary aspergillosis

INTRODUCTION

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis (CF), that occurs when bronchi become colonized by Aspergillus species [1-4]. Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to bronchiectasis, fibrosis, and respiratory compromise [5].

The pathophysiology, diagnosis, and treatment of ABPA will be reviewed here. General issues related to bronchiectasis are discussed separately. (See "Clinical manifestations and diagnosis of bronchiectasis in adults" and "Treatment of bronchiectasis in adults".)

PATHOPHYSIOLOGY

The pathogenesis of ABPA remains incompletely understood [5,6]. There is no relation between the intensity of exposure to airborne Aspergillus spores and rates of sensitization to the fungus as measured by skin testing [7]. Although all spores that are inhaled in sufficient quantities can behave as allergens, the normally low level of IgG against fungal antigens in the circulation and the low anti-fungal secretory IgA in bronchoalveolar fluid suggest that healthy individuals are able to effectively eliminate fungal spores [8,9]. In contrast, exposure of atopic individuals to fungal spores or mycelial fragments results in the formation of IgE and IgG antibodies.

T cells also play an important role in ABPA. There are increases in Th2 CD4+ cell responses to Aspergillus antigens both in the bronchoalveolar lymphoid tissue and systemically [5]. Aspergillus-responsive T cells generate cytokines interleukin (IL)-4, IL-5, and IL-13, which in turn account for the increases in eosinophilia and IgE in ABPA. In one study, T cell clones specific to the Asp f 1 antigen of A. fumigatus were established from the peripheral blood of three patients with ABPA [10]. The majority of these clones were CD4+ cells of the Th2 phenotype, which produce interleukin (IL)-4 and IL-5 [10]. The response to the Asp f 1 antigen was HLA restricted, being mediated exclusively by either HLA-DR2 or HLA-DR5 and was restricted to specific T cell receptor V-beta chains [10]. In addition, there is increased sensitivity of B cells, T cells, NK cells, and eosinophils to IL-4 [5].

In another study, the costimulatory molecule OX40 ligand was crucial for driving Th2 responses to A. fumigatus in the CD4+ cells of patients with CF and ABPA [11]. Heightened Th2 reactivity in these patients correlated with lower mean serum vitamin D levels.

                        

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Literature review current through: Mar 2014. | This topic last updated: Oct 15, 2012.
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