Allergic bronchopulmonary aspergillosis

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by immunologic reactions initiated against Aspergillus fumigatus colonizing the airways of patients with asthma and cystic fibrosis. The common manifestations include treatment-resistant asthma, transient and fleeting pulmonary opacities and bronchiectasis. It is believed that globally there are about five million cases of ABPA, with India alone accounting for about 1.4 million cases. The occurrence of ABPA among asthmatic patients in special clinics may be as high as 13 per cent. Thus, a high degree of suspicion for ABPA should be entertained while treating a patient with bronchial asthma, particularly in specialized clinics. Early diagnosis and appropriate treatment can delay (or even prevent) the onset of bronchiectasis, which suggests that all patients of bronchial asthma should be screened for ABPA, especially in chest clinics. The current review summarizes the recent advances in the pathogenesis, diagnosis and management of ABPA.

Keywords: Allergic bronchopulmonary aspergillosis; Aspergillus; allergic bronchopulmonary mycosis; asthma; azole; azole - cystic fibrosis - glucocorticoids; cystic fibrosis; glucocorticoids.

Fig. 1

Pathogenesis of allergic bronchopulmonary aspergillosis. Aspergillus conidia trapped in the airway mucus germinate into hyphae, in genetically predisposed individuals. The hyphae provide the antigenic stimulus for the allergic response, resulting in fungal sensitization. In susceptible individuals, an exaggerated T-helper 2 (Th2) immune response promotes further airway inflammation. This phase is characterized by recruitment of mast cells, increased production of immunoglobulin E (total as well as specific IgE to the fungus) and IgG antibodies to the fungi. The secreted chemokines and cytokines attract large number of eosinophils which attack the fungal hyphae, perpetuate further inflammation, finally culminating in end-organ damage and clinical manifestations. The red arrows indicate the steps where genetic predisposition plays a key role.

Fig. 2

A collage of histopathological findings in allergic bronchopulmonary aspergillosis. Gross photograph showing cystically dilated bronchi and bronchioles and lumen filled with brownish mucous plugs (panel 1A). Photomicrograph showing dilated bronchial lumen filled with allergic mucin (panel 1B; H and E, ×40). Low-power photomicrograph of allergic mucin having variegated appearance, containing mucin admixed with eosinophils, eosinophilic debris and other inflammatory cells arranged in a laminar pattern (panel 2; H and E, ×100). High-power photomicrograph of allergic mucin containing mucin admixed with eosinophils, Charcot laden crystals (thick arrow) and a few septate fungal hyphae (thin arrow) (panel 3; H and E, ×400). Photomicrographs of periodic acid-Schiff stain (panel 4A, ×400) and Grocott's stain (panel 4B, ×400) highlighting scattered fungal hyphae (arrows) within allergic mucin. Photomicrograph showing alveolar spaces filled with eosinophils indicative of eosinophilic pneumonia (panel 5; H and E, ×200). Photomicrograph of bronchocentric granulomatosis (panel 6) with occasional multinucleate giant cell (black arrow).

Fig. 3

Computed tomography chest images in a patient with allergic bronchopulmonary aspergillosis. The mediastinal window (panel A) shows the presence of high-attenuation mucus (arrow head), which is visually denser than para-spinal skeletal muscle. The lung window (panel B) shows bronchiectasis (thin arrow). Other findings discernable include centrilobular nodules, tree-in-bud opacities and mosaic attenuation.

Fig. 4

Algorithm followed in the diagnostic work-up of allergic bronchopulmonary aspergillosis (ABPA). Reproduced with permission from Ref. .

Fig. 5

Suggested treatment approach for allergic bronchopulmonary aspergillosis (ABPA).