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Background: Systemic steroids are the cornerstone of therapy in allergic bronchopulmonary aspergillosis(ABPA) but are associated with adverse effects. Itraconazole(ITZ) is proposed as an effective yet safer alternative. Aims: To evaluate the effectiveness of ITZ in comparison to systemic steroids in the management of ABPA. Methods: ABPA patients diagnosed between 2010-16 were administered oral ITZ or deflazacort(DFZ) and were followed every 3 months with serial total and specific IgE antibodies, chest x-ray; symptom control, time to remission, exacerbations and time to exacerbations were noted. Results: 172 patients were enrolled, 45 received ITZ(group A) and 106 received DFZ(group B). Both groups were homogenous with regards to their baseline characteristics (P 0.9999) achieved remissions and at a similar time (7.7±0.7 vs 7.5±0.4months respectively;P=0.77). Also, an equal number exacerbated (57.5 vs 51.7% respectively;P=0.57) within 6 months (4.4±0.7 vs 5.7±0.5 respectively;P=0.13) after stopping therapy. However patients in group A suffered more exacerbations (1.2±0.1 vs 1.05±0.03months;P=0.048) subsequently. Conclusions: ITZ and DFZ are equally effective in ABPA when administered for a similar duration to effect a disease remission. While neither drug is superior in preventing or delaying exacerbations of the disease, steroids may have the advantage of producing lesser subsequent exacerbations in comparison to ITZ.

Background: Invasive aspergillosis (IA) is now recognized in immunocompetent patients too with outbreaks known to occur in hospitals during civil work Aims: To identify characteristics and outcomes of patients who developed IA and correlate aerial spore counts and molecular types of Aspergillus isolates with possible role of civil work in nosocomial infection Methods: Patients diagnosed in 2010-16 were enrolled. Clinical data and outcome were noted. Those with nosocomial infection, defined as IA diagnosed 2days after admission served as cases. Annual incidence of IA and spore counts were calculated. Environmental and clinical Aspergillus isolates were characterized by microsatellite typing (STR) to determine possible source of infection Results: IA was observed in 50cases. Civil work was done in 2011,2014-16. Incidence of IA correlated with greater spore counts (r=0.942). COPD was commonest risk factor. None were immunocompromised. Further, 77% of those admitted required ICU care. Cases stayed longer in wards than controls(12.4±9.4vs0.8±0.8days, p=0.000) before diagnosing IA and received therapy later(7.8±7.8vs3.3±3.5days, p=0.011). 64.4% patients succumbed to IA. Both groups were similar in terms of age, sex, risk factors, serology, radiology, treatment outcomes Although no environmental A. Fumigatus isolate shared the same STR type as patient isolates, similar STR types were observed among patients suggesting common source of infection Conclusion: Civil work in augments Aspergillus spore count, increasing the incidence of IA in admitted immunocompetent patients with prolonged fungal exposure. No difference is seen in the natural history of IA with respect to source of infection.

Background Itraconazole (ITZ) is an alternative to steroids in the treatment of allergic bronchopulmonary aspergillosis (ABPA) but therapeutic drug monitoring (TDM) is warranted due to erratic absorption and early relapse. Aim To correlate serum ITZ levels with clinical outcomes in ABPA. Methods ITZ capsules 400mg/day for 6 months were administered as monotherapy to 30 consecutive patients in stage 4/5 of ABPA between Jan913 to Jun913. High-performance liquid chromatography was done on serum samples collected after 2-4 weeks to measure concentrations of ITZ and its active metabolite hydroxy-ITZ (OHITZ); ITZ levels of >2mg/L were considered adequate. Total and Aspergillus species specific IgE, leucocyte count (TLC), eosinophil count (AEC) and precipitins were recorded before and thereafter. Any relapse was noted till 2 years. Results Mean serum concentration of ITZ and OHITZ was 0.79±0.2 and 1.2±0.3mg/L respectively. Total IgE (9.9±1.4 vs 6.5±1.2×10 3 IU/mL), specific IgE (42.98±3.9 vs 34.1±4.8KUA/L), TLC (10.6±0.6 vs 9.7±0.7×10 3 cells/µL) and AEC (1.0±0.1 vs 0.6±0.09×10 3 cells/µL) reduced significantly. Remission was achieved in 64% but 52% relapsed after 3months. Serum ITZ and OHITZ levels correlated negatively with total IgE, specific IgE, TLC, AEC, relapse and time to relapse but only those between ITZ (r=0.049) and OHITZ (r=0.039) with duration to relapse were significant. Adequacy of ITZ and OHITZ significantly related with remissions(P=0.039). Conclusion ITZ monotherapy is effective in treating ABPA therefore TDM should be routinely undertaken. Adequate serum drug levels imply remissions but do not correlate well with markers of disease severity. Relapse may be prevented by prolonged drug use.

Background: Chronic pulmonary aspergillosis (CPA) is still under-diagnosed in high tuberculosis (TB) burden areas like India where similar clinical presentation and disregard for underlying risk factors lead to its misdiagnosis as the latter. Aim: To evaluate patient characteristics and treatment outcomes in CPA patients Methods: Consecutive patients with a differential diagnosis of CPA enrolled from Jan. 2012-Dec. 2013 were administered oral itraconazole (ITZ) or voriconazole. Weight, BMI, haemoglobin (Hb), total leucocyte count (TLC), specific IgG, precipitins, CRP, sputum fungus and radiology were followed till 2 years after the end of treatment. Negative specific IgG was taken as end-point of therapy. Results: CPA was diagnosed in 24(70.5%) patients including 10 CCPA, 9 CNPA, 3 CFPA and 2 simple aspergilloma. Mean age was 47.2±10.9years. Average 2.1 risk factors were present per patient; TB was the commonest risk factor (29.3%) but ABPA, sarcoidosis and diabetes mellitus were significantly associated with development of CPA. Cavitation was noted in 29% and aspergilloma in 12%. Specific IgG and serum precipitins were raised in 79% and CRP 92%. A. fumigatus was isolated in 80%. Both drugs exerted similar but significant improvements in weight (51.8±7 vs 56.3±8 Kg), BMI (18.7±3.1 vs 20.3±3.0 Kg/m 2 ), Hb (11.3±1.9 vs 12.3±1.7 g/dL), TLC (10.2±3.1 vs 7.9±2.6×10 3 /µL), precipitins and specific IgG (69.1; 26.5-84.2 vs 29.6; 0-39.3 MgA/L). Two cases on ITZ relapsed at 12 months; no deaths were reported. Conclusions: CPA should be investigated in patients with multiple risk factors. Triazole antifungals are effective in treatment. Specific IgG titers can be used to assess disease activity and response to treatment.