The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis.

Mahasin Al Shakirchi,Peter Bergman,Kimmo Sorjonen,Lena Klingspor,Isabelle De Monestrol,Lena Hjelte

doi:10.3390/jof7110944

Mahasin Al Shakirchi, Peter Bergman + Show 4 more

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https://doi.org/10.3390/jof7110944

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Abstract

Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent predicted forced expiratory volume in the first second (ppFEV1), decline before and after the first colonization with A. fumigatus. Further, in the same individual, the ratios of lung function when patients were colonized with A. fumigatus and when they were not were calculated. The impact of eradication, with antifungal treatment or spontaneously, was assessed. The annual ppFEV1 was significantly lower after the first colonization with A. fumigatus. Furthermore, within the same individual, colonization with A. fumigatus for two and three years in a row was associated with 4.3% and 7.9% lower ppFEV1, respectively, compared to when not colonized. Finally, patients who eradicated A. fumigatus the following two years after colonization exhibited 9.9% and 14.5% higher ppFEV1 compared to patients who continued to produce cultures with A. fumigatus for two and three years. Our study demonstrated that A. fumigatus colonization was associated with a negative impact on lung function in the long term and eradication, spontaneously or with treatment, was associated with a better pulmonary outcome.

Highlights

Cystic fibrosis (CF) is the most common lethal hereditary disease in the Caucasian population
Pancreatic insufficiency, allergic bronchopulmonary aspergillosis (ABPA) diagnosed according to minimal ABPA criteria [22], chronic and intermittent colonization with P. aeruginosa and the presence of C. albicans were more common in the colonizer group compared to the non-colonizer group
We aimed to study the impact of A. fumigatus colonization and eradication on lung function

Summary

Introduction

Cystic fibrosis (CF) is the most common lethal hereditary disease in the Caucasian population. Novel experiments have demonstrated an impaired mucociliary transport and an inadequate innate and adaptive antifungal immune response resulting in reduced ability to clear A. fumigatus in CF [3]. An exaggerated antifungal inflammatory response to A. fumigatus is reported in animal CF models [4,5,6]. In a CF murine model, A. fumigatus infection resulted in increased levels of interleukin (IL)-1 α, IL-1 β and IL-9, leading to an uncontrolled detrimental inflammatory response [4,6,7]. The first to address the antifungal immune response in CF in humans, has shown that the level of reactive oxygen species (ROS) produced by phagocytes in response to A. fumigatus were significantly higher than in healthy controls and that ROS-levels were correlated to CF disease severity [8]

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