Aspergillus Bronchitis in Patients with Cystic Fibrosis

Abstract

Aspergillus fumigatus frequently colonizes the airways of patients with cystic fibrosis (CF) and may cause various severe infections, such as bronchitis. Serological data, sputum dependent markers and longitudinal data of treated cases of Aspergillus bronchitis were evaluated for further description of this infection. This study, which comprises three substudies, aimed to analyze epidemiological data of Aspergillus in CF and the entity of Aspergillus bronchitis. In a first step, data of the German Cystic Fibrosis Registry were used to evaluate the frequency of Aspergillus colonization in patients with CF (n = 2599). Then a retrospective analysis of 10 cases of Aspergillus bronchitis was performed to evaluate longitudinal data for lung function and clinical presentation parameters: sputum production, cough and physical capacity. Finally, a prospective cohort study (n = 22) was conducted to investigate serological markers for Aspergillus bronchitis: total serum IgE, specific serum IgE, specific serum IgG, as well as sputum galactomannan, real-time PCR detection of Aspergillus DNA in sputum and fungal cultures. Analysis of the German CF registry revealed an Aspergillus colonization rate of 32.5% among the 2599 patients. A retrospective data analysis of 10 treated cases revealed the clinical course of Aspergillus bronchitis, including repeated positive sputum culture findings for A. fumigatus, no antibiotic treatment response, total serum IgE levels <200 kU/l, no observation of new pulmonary infiltrates and appropriate antifungal treatment response. Antifungal treatment durations of 4 ± 1.6 (2-6) weeks significantly reduced cough (P = 0.0067), sputum production (P < 0.0001) and lung function measures (P = 0.0358) but not physical capacity (P = 0.0794). From this retrospective study, a prevalence of 1.6% was calculated. In addition, two cases of Aspergillus bronchitis were identified in the prospective cohort study according to immunological, molecular and microbiological parameters. A prevalence of 9% was assessed. Aspergillus bronchitis appears to occur in a minority of colonized CF patients. Antifungal treatment may reduce respiratory symptoms and restore lung function.

Fungal Respiratory Infections in Cystic Fibrosis (CF): Recent Progress and Future Research Agenda

“…The clinical section on individual pathogens includes two articles describing Aspergillus in CF bronchiectasis and Aspergillus bronchitis [8,9]. Chotirmall and Martin-Gomez [8] summarize existing knowledge on Aspergillus colonization, allergic, chronic or invasive disease spectrum, and diagnostic and management challenges.…”

“…Chotirmall and Martin-Gomez [8] have laid out a roadmap for future research on mycobiome, biomarkers, imaging and treatment modalities that would lead to better insight into Aspergillus in the setting of bronchiectasis. Schwarz et al [9] report a retrospective analysis of patient data from the German CF Registry and prospective study of additional patients to summarize information on Aspergillus bronchitis, which is a well-defined clinical entity in CF. Their results show Aspergillus colonization in about 32.5% of 2599 patients, low prevalence of Aspergillus bronchitis (1.6-9%) and relatively good outcomes with the targeted antifungal therapy [9].…”

“…Schwarz et al [9] report a retrospective analysis of patient data from the German CF Registry and prospective study of additional patients to summarize information on Aspergillus bronchitis, which is a well-defined clinical entity in CF. Their results show Aspergillus colonization in about 32.5% of 2599 patients, low prevalence of Aspergillus bronchitis (1.6-9%) and relatively good outcomes with the targeted antifungal therapy [9]. Grenouillet et al [10] focus on the higher recovery of some fungal species, as exemplified here with Exophiala dermatitidis, from the respiratory specimens of CF patients vis-à-vis non-CF patients.…”

“…This [5,6] 2. Fungal diagnostic criteria in CF patients [6,9,12,13] 3. Antifungal therapy in CF patients [7,9,[14][15][16][17] 4.…”

“…Fungal diagnostic criteria in CF patients [6,9,12,13] 3. Antifungal therapy in CF patients [7,9,[14][15][16][17] 4. Aspergillus, Exophiala and Pneumocystis in CF patients [8][9][10][11] 5.…”