CF Fungal Disease in the Age of CFTR Modulators

Abstract

Fungi are increasingly recognised to have a significant role in the progression of lung disease in Cystic fibrosis with Aspergillus fumigatus the most common fungus isolated during respiratory sampling. The emergence of novel CFTR modulators has, however, significantly changed the outlook of disease progression in CF. In this review we discuss what impact novel CFTR modulators will have on fungal lung disease and its management in CF. We discuss how CFTR modulators affect antifungal innate immunity and consider the impact of Ivacaftor on fungal disease in individuals with gating mutations. We further review the increasing complication of drug-drug interactions with concurrent use of azole antifungal medication and highlight key unknowns that require addressing to fully understand the impact of CFTR modulators on fungal disease.

Keywords: Antifungal; Aspergillus fumigatus; Cystic fibrosis; Fungi.

Fig. 1

a Ivacaftor-treated neutrophils demonstrate: reduced reactive oxygen species (ROS) release; restored degranulation and bacterial killing; reduced expression of inflammatory proteins and retention of surface markers normally lost during neutrophil activation and normalised rates of apoptosis. Lumacaftor and Orkambi also reduce ROS release. b Ivacaftor-treated macrophages demonstrate: reduced ROS and inflammatory cytokine release; restored phagocytosis and bacterial killing and normalised rates of apoptosis. Lumacaftor reduces ROS release and restores phagocytosis and bacterial killing. Orkambi reduces ROS release and restores normal rates of apoptosis