Lung failure due to chronic bacterial infections and exaggerated inflammatory responses is the main cause of morbidity and mortality in individuals with cystic fibrosis (CF). The increased susceptibility to bacterial infections in CF has been ascribed to the lack of a functional Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in epithelial cells leading to altered ions transport and impaired mucociliary clearance.
For a long time, all available CF therapies targeted symptoms and the consequences of CFTR dysfunction. More recently, the development of small molecule drugs, termed CFTR modulators targeting CFTR itself aims to restore the channel activity. In particular, very recently a triple modulator combination, named Trikafta, has been developed to treat Cystic fibrosis patients carrying the Phe508del mutation which is the most frequent CFTR mutation.
At present, the effects of CFTR modulators have primary focused on pulmonary function, pulmonary exacerbation (PEx), and quality of life measures, while few studies have evaluated the effect of CFTR modulators on inflammation and immune cells. However, since innate immune cells, especially monocytes/macrophages are important contributors of cystic fibrosis lung disease progression, in this proposal we intend to evaluate the effect of Trikafta treatment on the phagocytic activity of monocytes and on the inflammatory response of CF patients. This will improve our understanding of the mechanism of action of this new CF treatment and of the role of immune cells in the disease progression.
