Allergic bronchopulmonary aspergillosis

Abstract

Fungal-related lung diseases can be infective, toxic or allergic in nature. Allergic bronchopulmonary aspergillosis (ABPA) is caused by hypersensitivity to allergens of the common saprophytic filamentous fungi Aspergillus, mainly A. fumigatus. ABPA is characterized by an early allergic response and late-phase lung injury in response to repeated exposure to Aspergillus antigens, because of persistent fungal colonization of the airways. ABPA is mostly found in patients with asthma and cystic fibrosis. Patients present with respiratory symptoms including wheeze, hemoptysis, and productive cough plus other systemic symptoms, such as fever and weight loss and can suffer recurrent exacerbations. ABPA can be a cause of large airway collapse and lead to bronchiectasis. The central histological feature of ABPA is allergic eosinophilic mucin-harboring hyphae in the bronchi, for which the formation of extracellular DNA trap cell death of eosinophils induced by viable fungi is essential. When the spores contact the immune system, the A. fumigatus antigens cause a polyclonal antibody response leading to elevated levels of total IgE, A. fumigatus-IgE, and A. fumigatus-IgG antibodies. Then, eosinophilic mucus plugs containing fungal hyphae are formed in the respiratory tracts. ABPA is characterized by eosinophilic recruitment to the airways and peripheral eosinophilia. Type-2 (T2) cytokines promote eosinophil participation. The diagnosis of ABPA requires a combination of clinical, serological, and radiological findings. ABPM should be considered when peripheral blood eosinophil counts or serum IgE levels increased in patients with asthma who are sensitized to fungal antigens, or when pulmonary opacities, central bronchiectasis, or mucus plugs were accompanied by peripheral blood eosinophilia. All criteria proposed by different authors utilize the results of several investigations to aid diagnosis. These criteria represent biomarkers of the mainly involved T2 immune mechanism and of the fungi colonization of the airways. In ABPA, systemic corticosteroids are the first line of treatment. Antifungal agents are regularly added. If the patient becomes treatment dependent, alternative antifungals, pulsed methylprednisolone, nebulized amphotericin, or biologic agents against T2 asthma targets could be considered.