TY - JOUR
T1 - Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: A randomized controlled trial
AU - Mcelduff, Patrick
AU - Wark, P. A B
AU - Hensley, Michael John
AU - Saltos, Nicholas
AU - Boyle, Michael James
AU - Toneguzzi, Ruth Christine
AU - Simpson, Jodie Louise
AU - McElduff, Patrick
AU - Gibson, Peter Gerard
N1 - UI - 22628010DA - 20030513IS - 0091-6749LA - engPT - Clinical TrialPT - Journal ArticlePT - Randomized Controlled TrialRN - 0 (Antibodies, Fungal)RN - 0 (Antifungal Agents)RN - 0 (Blood Proteins)RN - 0 (Immunoglobulin G)RN - 0 (eosinophil basic protein)RN - 37341-29-0 (Immunoglobulin E)RN - 84625-61-6 (Itraconazole)SB - AIMSB - IM
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Background: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatus, causing an intense systemic immune response and progressive lung damage. Objective: We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA. Methods: A randomized, double-blind, placebo-controlled trial was performed in stable subjects with ABPA (n = 29). Subjects received 400 mg of itraconazole per day (n = 15) or placebo (n = 14) for 16 weeks. All subjects were reviewed monthly with history, spirometry, and sputum induction to measure airway inflammation, serum total IgE and IgG levels to A fumigatus, and blood eosinophil counts. Results: By using regression analysis in a random-effects model, subjects receiving itraconazole had a decrease in sputum eosinophils of 35% per week, with no decrease seen in the placebo arm (P <.01). Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42% per week compared with 23% in the placebo group (P <.01). Itraconazole reduced systemic immune activation, leading to a decrease in serum IgE levels (310 IU/mL) compared with levels seen in the placebo group (increase of 18 IU/mL, P <.01) and a decrease in IgG levels to A fumigatus (15.4 IU/mL) compared with levels seen in the placebo group (increase of 3.7 IU/mL, P = .03). There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group (P = .03). Conclusion: Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation, systemic immune activation, and exacerbations. These results imply that itraconazole is a potential adjunctive treatment for ABPA.
AB - Background: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatus, causing an intense systemic immune response and progressive lung damage. Objective: We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA. Methods: A randomized, double-blind, placebo-controlled trial was performed in stable subjects with ABPA (n = 29). Subjects received 400 mg of itraconazole per day (n = 15) or placebo (n = 14) for 16 weeks. All subjects were reviewed monthly with history, spirometry, and sputum induction to measure airway inflammation, serum total IgE and IgG levels to A fumigatus, and blood eosinophil counts. Results: By using regression analysis in a random-effects model, subjects receiving itraconazole had a decrease in sputum eosinophils of 35% per week, with no decrease seen in the placebo arm (P <.01). Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42% per week compared with 23% in the placebo group (P <.01). Itraconazole reduced systemic immune activation, leading to a decrease in serum IgE levels (310 IU/mL) compared with levels seen in the placebo group (increase of 18 IU/mL, P <.01) and a decrease in IgG levels to A fumigatus (15.4 IU/mL) compared with levels seen in the placebo group (increase of 3.7 IU/mL, P = .03). There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group (P = .03). Conclusion: Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation, systemic immune activation, and exacerbations. These results imply that itraconazole is a potential adjunctive treatment for ABPA.
KW - Airway inflammation
KW - Allergic bronchopulmonary aspergillosis
KW - Asthma
KW - Induced sputum
KW - Itraconazole
U2 - 10.1067/mai.2003.1388
DO - 10.1067/mai.2003.1388
M3 - Article
SN - 0091-6749
VL - 111
SP - 952
EP - 957
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -