Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial.
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s, 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 fumigatu s, 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 fumigatu s (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).


CONCLUSIONS
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.
Faculty of Health, University of Newcastle, and the Department of Respiratory and Sleep Medicine and the Airways Infection and Immunology Research Group, John Hunter Hospital, Newcastle, Australia.
Peter Alexander Blanch
PA
Wark
Michael John
MJ
Hensley
Nicholas
N
Saltos
Michael James
MJ
Boyle
Ruth Christine
RC
Toneguzzi
Grad Dip Clin
GD
Epid
Jodie Louise
JL
Simpson
Patrick
P
McElduff
Peter Gerard
PG
Gibson
D000908:Antibodies, Fungal / Q000097:blood; D000935:Antifungal Agents / Q000627:therapeutic use*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000188:drug therapy*; D001798:Blood Proteins / Q000032:analysis; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000188:drug therapy*; D017964:Itraconazole / Q000627:therapeutic use*; D012260:Ribonucleases; D013183:Sputum / Q000737:chemistry
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007074:Immunoglobulin G; D017964:Itraconazole; D007073:Immunoglobulin E; D012260:Ribonucleases