Phenotypic Variability of Cystic Fibrosis: New Challenges

Cystic Fibrosis (CF) is a severe, chronic and progressive disease that affects approximately 70,000 people worldwide and around 1,000 new cases are diagnosed each year. CF is a paradigm of how a monogenic disease can be associated with an extraordinary large phenotypic variability that results from heritable (genetic) and non-heritable (environmental) factors. Together CFTR mutations, polymorphisms at modifier genes, the epigenome and interactions with the environment generate the unique phenotype of each patient. The complex relationship between all these factors is not clearly elucidated.

Loss of lung function progresses at different rates, even among people with CF (PWCF), who share the same CFTR mutations. Therapeutic advances have dramatically increased life expectancy for PWCF, and precision therapies capable of modulating the CFTR defect represent the most significant therapeutic advances in CF to date. 

However, CFTR modulators do not treat the underlying disease-shaping immune defect, leaving PWCF with unresolved and chronically activated immune responses. Likely, lung and gut microbiota and their metabolites mediate and shape the immune and inflammatory responses.

Although a great success, the increased life expectancy brings new challenges; about 50% of adult PWCF develop diabetes and comorbidities are now a major clinical issue, emphasizing the importance of addressing CF as a multisystem disease.

In this Special Issue, we welcome reviews and original articles addressing molecular, cellular and physiological mechanisms responsible for the phenotypic variability seen in PWCF. We are interested in genomic, transcriptomic, epigenomic, proteomic, metabolomic analyses, not excluding studies that focus on specific genes, proteins or pathways. We also encourage the publication of articles proposing microbiota manipulation and host directed therapies.

Dr. Albertina De Sario
Dr. Bettina Schock
Guest Editors

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