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Allergic bronchopulmonary aspergillosis
A rare immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, clinically manifesting with poorly controlled asthma and recurrent pulmonary infiltrates.
ORPHA:1164Classification level: Disorder
The prevalence of ABPA in the general population is unknown.
ABPA is most commonly diagnosed in adults although it is increasingly being diagnosed in children. Although affected individuals can occasionally be asymptomatic, most of them present with wheezing, bronchial hyperreactivity, hemoptysis, productive cough, low-grade fever, malaise, weight loss, and/or worsening symptoms of asthma and cystic fibrosis (see this term), the two underlying diseases of most of the ABPA patients (about 2% of patients with asthma and 1 to 15% of patients with cystic fibrosis develop ABPA).
ABPA is an immunologic disorder due to a predominant T-helper 2 lymphocyte response to Aspergillus fumigatus infection without tissue invasion. The resulting lung inflammation induces mucus production, airway hyperactivity and, finally, bronchiectasis. Its increased frequency in patients with asthma or cystic fibrosis is consistent with a genetic susceptibility to ABPA.
Diagnostic findings of ABPA include immediate cutaneous hyperreactivity to A. fumigatus antigen, elevated A. fumigatus specific IgE levels and total serum IgE levels over 1,000 IU/mL. High levels of A. fumigatus-specific IgG antibodies and eosinophils can also be observed. Chest radiographs and thoracic high-resolution computed tomography (HRCT) can reveal fleeting pulmonary parenchymal opacities, central bronchiectasis, high attenuation mucus, air trapping and centrilobular nodules. Pulmonary function tests may detect airflow obstruction. According to laboratory and imaging findings, five stages of the disease have been defined: acute, remission, recurrent exacerbation (with presence of pulmonary infiltrates, elevation of total serum IgE), corticosteroid-dependent asthma (severe wheezing resulting from discontinuation of the treatment) and fibrotic (irreversible pulmonary function abnormalities). However, the disease usually does not progress through these successive stages.
Differential diagnosis includes severe asthma with fungal sensitization, newly diagnosed cystic fibrosis, tuberculosis, infectious pneumonia (especially during exacerbations) and other causes of eosinophilic pneumonia like Churg-Strauss syndrome (see this term), and bronchocentric granulomatosis.
Management and treatment
The best treatment approach is not currently established. Therapeutic options include oral corticosteroids (e.g: prednisolone, prednisone) and antifungal agents (like itraconazole, voriconazole or posaconazole). Other treatments that have been tried include pulse doses of methylprednisolone, and nebulized amphotericin B and omalizumab (antifungal agents). The duration of corticosteroid therapy ranges from several weeks to several months after an acute episode but corticosteroid-dependent asthma patients are very difficult to wean off steroids. The duration of the antifungal therapy has yet to be established. However, if tolerated, it can be used for years.
The clinical course of ABPA is variable. Many ABPA patients can be stabilized for long periods when treated. However, long-lasting remissions are seen in only 50% of patients and many patients require recurrent courses of therapy. Central bronchiectasis, high-attenuation mucus and concomitant aspergilloma at diagnosis identify a patient with a propensity for recurrent relapses and chronicity, which requires close monitoring.