Allergic Bronchopulmonary Aspergillosis: Diagnostic and Treatment Challenges

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder, occurring mostly in asthmatic and\ud cystic fibrosis patients, caused by an abnormal T-helper 2 lymphocyte response of the host to Aspergillus fumigatus\ud antigens. ABPA diagnosis is defined by clinical, laboratory and radiological criteria including active asthma, immediate\ud skin reactivity to A. fumigatus antigens, total serum IgE levels>1000 IU/mL, fleeting pulmonary parenchymal\ud opacities and central bronchiectases that represent an irreversible complication of ABPA. Despite advances in our\ud understanding of the role of the allergic response in the pathophysiology of ABPA, pathogenesis of the disease is still\ud not completely clear. In addition, the absence of consensus regarding its prevalence, diagnostic criteria and staging\ud limits the possibility of diagnosing the disease at early stages. This may delay the administration of a therapy that can\ud potentially prevent permanent lung damage. Long-term management is still poorly studied. Present primary therapies,\ud based on clinical experience, are not yet standardized. These consist in oral corticosteroids, which control acute\ud symptoms by mitigating the allergic inflammatory response, azoles and, more recently, anti-IgE antibodies. The latter\ud two are used as a steroid-sparing agent to prolong the remission stage of the disease. Anti-IgE antibodies also have\ud immunomodulatory properties. At present, the only way to bypass these limits and allow for an early diagnosis, is\ud to assume ABPA in all patients with difficult-to-control asthma or cystic fibrosis. They should then be screened for\ud sensitization to A. fumigatus antigens and, if positive, monitored more closely. Future controlled studies are needed\ud to standardize present therapy, standardize cut-off values of various investigations, define the role of different novel\ud immunomodulatory therapies, define the role of novel assays (such as recombinant A. fumigatus antigens and CCL17)\ud and confirm new diagnostic and staging criteria