Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
The purpose of this study is to evaluate the efficacy and safety of itraconazole monotherapy
 in patients with ABPA.
Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a complex
 hypersensitivity response to antigens released by the fungus Aspergillus fumigatus. The
 clinical entity was first described by Hinson et al in 1952, and the clinical and immunologic
 significance of Aspergillus fumigatus in the sputum were reported by Pepys and coworkers in
 1959. The prevalence of ABPA in bronchial asthma is fairly high and a recent meta-analysis
 suggested the prevalence of ABPA in asthma clinics to be as high as 13 percent. Diagnostic
 criteria for ABPA have been laid and generally include the following eight major criteria:
 (a) history of asthma; (b) transient or fixed pulmonary infiltrates; (c) immediate cutaneous
 hyperreactivity to A fumigatus antigen; (d) absolute eosinophil count > 1000/µL; (e) serum
 precipitins against A fumigatus; (f) total IgE levels > 1000 IU/mL; (g) central
 bronchiectasis on high-resolution computed tomography (HRCT); and, (h) raised A fumigatus
 specific IgE or IgG levels. However, none of these are specific for ABPA,and there is still
 no consensus on the number of criteria needed for diagnosis, and patients in different stages
 of ABPA may not fulfill all these criteria. Also, there is no established definition for
 remission of ABPA. The most widely followed criteria are clinical and radiological
 improvement with at least 35 percent decline in total serum IgE levels. However, in a recent
 study the investigators demonstrated that a 35% decline in serum IgE levels at six weeks is
 not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE
 levels < 2500 IU/mL. Moreover, the quantum decline in serum IgE levels did not predict
 clinical outcome. The disorder is highly prevalent in India. The investigators have
 previously reported our experience with screening stable outpatients with bronchial asthma
 and acute severe asthma for ABPA. The investigators have also recently reported the
 prognostic factors associated with clinical outcomes in patients with ABPA.

 Oral corticosteroids are currently the treatment of choice for ABPA associated with bronchial
 asthma. They not only suppress the immune hyperfunction but are also anti-inflammatory.
 However, there is no data to guide the dose and duration of glucocorticoids and different
 regimens of glucocorticoids have been used in literature. Itraconazole, an oral triazole with
 relatively low toxicity, is active against Aspergillus spp. in vitro and in vivo. The
 activity of itraconazole against Aspergillus spp. is more than that of ketoconazole. The
 administration of itraconazole can eliminate Aspergillus in the airways and can theoretically
 reduce the allergic responses in ABPA. The aim of this prospective randomized controlled
 trial (RCT) is to evaluate the efficacy and safety of itraconazole monotherapy in patients
 with ABPA.
Inclusion Criteria: Patients will be included in the study if they meet the criteria for
 ABPA defined by

 Presence of all the following three criteria:

 -  immediate cutaneous hyperreactivity on aspergillus skin test

 -  elevated total IgE levels > 1000 IU/mL

 -  A fumigatus specific IgE levels > 0.35 kU/L

 Two of the following criteria:

 -  presence of serum precipitating antibodies against A fumigatus

 -  fixed or transient radiographic pulmonary opacities

 -  absolute eosinophil count > 1000/µL

 -  central bronchiectasis on HRCT.

 Exclusion Criteria:

 -  if they have taken glucocorticoids for more than three weeks in the preceding six
 months

 -  failure to give informed consent

 -  enrollment in another trial of ABPA