Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy

Pierre-Régis Burgel,1,2 André Paugam,2,3 Dominique Hubert,1,2 Clémence Martin1,2 1Department of Respiratory Medicine, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, 2Université Paris Descartes, Sorbonne Paris Cité, 3Parasitology-Mycology Laboratory, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France Abstract: Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy. Keywords: itraconazole, voriconazole, posaconazole, azole resistance, allergic bronchopulmonary aspergillosis