Aspergillus hypersensitivity (AH) is defined by the presence of an immediate-type cutaneous hypersensitivity to A fumigatus antigens, and it is the first step in the development of ABPA. Only a minority of patients with AH develop the complete clinical picture of ABPA. The population prevalence of ABPA in asthma, generally referred to as 1 to 2%, is based on the inference of only three studies (one peer-reviewed and two non-peer-reviewed studies). In the only peer-reviewed study, 14 patients with allergic bronchopulmonary mycosis were identified from a total of 1,390 new referrals in a catchment area population of half a million, estimating a period prevalence of just above 1%. The other two non-peer-reviewed questionnaire-based studies suggested a maximum prevalence of ABPA of 1% in the United States. In a recent metaanalysis, we demonstrated a prevalence of AH and ABPA in asthma of 28% and 12.9%, respectively. The limitation noted in this review was that all the studies were performed in specialized clinics and may not be representative of the general population. Thus the exact population prevalence of ABPA remains speculative but is likely to be fairly

806 high in patients attending asthma clinics. Table 1 summarizes the prevalence of ABPA in patients with asthma reported in various studies over the last two decades. The prevalence of ABPA in patients admitted with acute severe asthma is even higher. In a recent study of 57 patients with acute severe asthma admitted in the respiratory ICUs, we demonstrated the prevalence of AH and ABPA to be around 51% and 39%, respectively. The occurrence of AH and ABPA was significantly higher in patients with acute asthma compared to the outpatient bronchial asthma (around 39% and 21%, respectively).

Pathogenesis of ABPA

The susceptibility of asthmatic patients to develop ABPA is not fully understood (Fig 1). Some authors have reported that exposure to large concentrations of spores of A fumigatus may cause ABPA.

Most present with low-grade fever, wheezing, bronchial hyperreactivity, hemoptysis, or productive cough. Expectoration of brownish black mucus plugs is seen in 31 to 69% of patients. The symptoms of hemoptysis, expectoration of brownish black mucus plugs, and history of pulmonary opacities in an asthmatic patient suggests ABPA. Patients can occasionally be asymptomatic, and the disorder is diagnosed on routine screening of asthmatic pa-tients. Physical examination can be normal or may reveal polyphonic wheeze. Clubbing is rare, seen in only 16% of patients. On auscultation, coarse crackles can be heard in 15% of patients. Physical examination can also detect complications such as pulmonary hypertension and/or respiratory failure. During exacerbations of ABPA, localized findings of consolidation and atelectasis can occur that needs to be differentiated from other conditions.

Aspergillus Skin Test: The Aspergillus skin test is performed using an A fumigatus antigen, either commercial (eg, Aspergillin; Hollister-Stier Laboratories; Spokane, WA) or locally prepared. The test is read every 15 min for 1 h, and then after 6 to 8 h. The reactions are classified as type I if a wheal and erythema developed within 1 min, reaches a maximum after 10 to 20 min, and resolves within 1 to 2 h. A type III reaction is read after 6 h, and any amount of subcutaneous edema is considered a positive result. An immediate cutaneous hypersensitivity to A fumigatus antigens is a characteristic finding of ABPA and represents the presence A fumigatus-specific IgE antibodies, whereas a type III skin reaction probably represents the immune complex hypersensitivity reaction, although its exact significance remains unclear. The test can be performed using either a skin-prick test or intradermal injection with the latter being more sensitive. A skin-prick test should be performed for Aspergillus skin testing, and if the results are negative should be confirmed by an intradermal test. There is no difference on the outcome of the test and the type of antigen (locally prepared or commercial) used for performance of the test.

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