INTRODUCTION
Aspergillus spp . can cause different diseases, depending on the host immune system status. Invasive pulmonary aspergillosis (IPA) is a serious disease affecting patients with prolonged neutropenia, transplantat recipients and those receiving long-term treatment with high doses of corticosteroids, among others (1). Even antifungal prophylaxis is indicated in vulnerable patients, an increase of fungal infections prevalence and severity has been observed. Lung transplant (LT) recipients are especially vulnerable to IPA (2), a prevalence of 6.5% and mortality rate of 52% has been reported in this population (3). Other non-immunosuppressed patients, such as those with cystic fibrosis (CF), can be affected by Aspergillus spp. ; it has been reported that more than 50% of respiratory cultures from CF patients in a year were positive and about 10% of the patients developed allergic bronchopulmonary aspergillosis, related to airway damage and respiratory function alterations (4,5). Even if azole treatment has shown positive results in CF, treating Aspergillus spp . colonization in this population remains controversial due to the need of long treatments related to drug interactions, toxicity and the emergence of antifungal resistance.
Voriconazole is the primary treatment for IPA; it is available in oral and intravenous pharmaceutical forms. Other antifungal drugs such as amphotericin, itraconazole, posaconazole and echinocandines can be added to the treatment or used as alternatives in case of treatment failure (6). IPA management usually involves long systemic antifungal treatments that lead to high rates of adverse events including liver, kidney and medullar toxicities; moreover, these therapies are usually involved in major drug-drug interactions with clinical implications and their pharmacokinetic profile is difficult to predict due to pharmacogenetic diversity among the population (7,8). Finally, treatment efficacy depends on the drug distribution to the lung and the epithelial lining fluid that coats the bronchoalveolar epithelium; however, it has been observed that the distribution of antifungal drugs to the biophase might be limited by their physicochemical properties in some cases (9).
In this context, antifungal administration through the pulmonary route has been suggested in order to ensure therapeutic concentrations of drug in the biophase and increase treatment efficacy, avoid adverse events and prevent drug-drug interactions. Even if there are not commercial antifungal pharmaceutical presentations for pulmonary administration currently, vials of liposomal amphotericin B and amphotericin B deoxycholate for intravenous administration have been widely used for nebulization in prophylaxis and treatment of pulmonary aspergillosis; this approach has been proved to be a safe and effective (10).
There is little evidence about voriconazole administration via nebulization. The goal of this study is to characterize the compounded voriconazole solution for nebulization and describe the use of nebulized voriconazole in our center.