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Aspergillus Bronchitis in Patients with Cystic Fibrosis

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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.

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Acknowledgements

This work was supported by the Gilead–Aspergillosis Project (IN-DE-205-3955). We would like to thank all patients and all the members of the Cystic Fibrosis Center Berlin and of the German Cystic Fibrosis Benchmarking Group.

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Authors and Affiliations

  1. Department of Pediatric Pneumology and Immunology, Cystic Fibrosis Center, Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Claudia Brandt, Jobst Roehmel & Carsten Schwarz

  2. FG16, Robert Koch Institute Berlin, Seestraße 10, 13353, Berlin, Germany

    Volker Rickerts

  3. Department of Pediatrics, Universitätsmedizin Erlangen, Loschgestraße 15, 91054, Erlangen, Germany

    Volker Melichar

  4. Zentrum für Qualität und Management im Gesundheitswesen, Einrichtung der Ärztekammer Niedersachsen, Berliner Allee 20, 30175, Hannover, Germany

    Nadja Niemann

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  1. Claudia Brandt
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  2. Jobst Roehmel
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  3. Volker Rickerts
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  4. Volker Melichar
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  5. Nadja Niemann
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  6. Carsten Schwarz
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Contributions

CB, JR, VR, VM, NN, CS were involved in study design. CB, JR, VR, VM, NN CS collected the data. CB, VM, NN, CS analyzed the data. CB, JR, VM, NN, CS wrote the paper.

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Correspondence to Carsten Schwarz.

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None of the authors has any potential financial or non-financial conflict of interests related to this manuscript. There was no research involving human participants or animals.

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Brandt, C., Roehmel, J., Rickerts, V. et al. Aspergillus Bronchitis in Patients with Cystic Fibrosis. Mycopathologia 183, 61–69 (2018). https://doi.org/10.1007/s11046-017-0190-0

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  • DOI: https://doi.org/10.1007/s11046-017-0190-0

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