Cystic Fibrosis: The Dawn of a New Therapeutic Era

Clinical outcomes and management of cystic fibrosis (CF) have undergone startling and dramatic advances in the last two decades. These improvements can be linked to the advances in CF basic science starting with the identification of the disease-causing gene defect (the gene producing cystic fibrosis transmembrane conductance regulator protein [CFTR]) to more recent animal models such as the CF pig, that have led to an improved understanding of the early pathophysiologic events leading to lung disease (1). By developing a robust clinical trial network (the CF Foundation Therapeutics Development Network in the United States and Clinical Trials Network in Europe), advances in the laboratory have been translated into the repurposing of existing therapeutics and the development of novel therapeutics, with 11 medications approved specifically for CF in either Europe or the United States. CF basic and clinical research has led the way in demonstrating how advances in the laboratory can lead to advances in clinical care and outcomes. Therapeutics in CF have evolved from treating downstream events such as chronic lower airway infection to addressing the primary defect in CF by modifying mutant CFTR protein with the approval of both ivacaftor and ivacaftor–lumacaftor by the U.S. Food and Drug Administration (2, 3). The CF community is now challenged with how to continue to advance the science in CF to ensure that every patient with CF can live a full and normal life free of disease. In this Perspective, we highlight the changing demographics of the CF population, in addition to advances in therapeutics and challenges we face in continuing to improve the outcomes of our patients.