<em>Aspergillus fumigatus</em> in the cystic fibrosis lung: pros and cons of azole therapy

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.

Culture-Based Methods and Molecular Tools for Azole-Resistant Aspergillus fumigatus Detection in a Belgian University Hospital

“…Indeed, other studies in cystic fibrosis patients have shown prevalences of azole resistance in A. fumigatus varying between 0 and 20%, depending on previous azole exposure. Nevertheless, a prevalence of approximately 5% is the most common in this population (28)(29)(30)(31)(32). In the present study, TR 34 /L98H was the most frequent mutation observed, as has been observed in other studies (4,(23)(24)(25)31).…”

“…A recently published international expert opinion on the management of infection due to azole-resistant A. fumigatus recommends reconsidering azole monotherapy in regions where azole resistance rates exceed 10% (42). However, some authors consider that before making decisions on therapeutics, a harmonization of surveillance approaches in terms of mycological procedures and/or the use of an appropriate denominator is required (27,28).…”

The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal Airways

“…ABPA affects approximately 5 million people worldwide, causing serious recurrent respiratory impairment in immune-compromised individuals and significant exacerbations in asthma and cystic fibrosis patients (Burgel et al, 2016).…”

The diagnosis and management of respiratory tract fungal infection in cystic fibrosis: A UK survey of current practice

“…Aspergillus sensitisation is defined as a positive skin prick test to Aspergillus antigens or an elevated serum Aspergillus IgE level. 1,8 An observational study over two years described a decline in FEV 1 and an increase in IV antibiotic days for patients sensitised to Aspergillus. 29 Aspergillus bronchitis is a clinical deterioration associated with positive Aspergillus cultures but low or minimally elevated markers of sensitisation.…”

“…Aspergillus fumigatus is the most common fungal species found in the sputum of PWCF, with an estimated prevalence of 6-57%. [1][2][3][4] Allergic bronchopulmonary aspergillosis (ABPA) is the main clinical manifestation. However, asymptomatic colonisation, Aspergillus bronchitis and Aspergillus sensitisation are also recognized as part of the disease spectrum.…”