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In this review, we have selected several outstanding studies from the American Journal of Respiratory and Critical Care Medicine (AJRCCM), the American Journal of Respiratory Cell and Molecular Biology (AJRCMB), and the Annals of the American Thoracic Society (AnnalsATS) in 2018 to provide readers with an overview of the important contributions to the rapidly evolving literature in the field of cystic fibrosis (CF) published in these three journals. The featured studies focus on advances in five major themes central to the understanding of the pathogenesis and treatment of CF: 1) therapies directed at the underlying defect, 2) early intervention strategies to delay disease progression, 3) respiratory tract infections, 4) inflammation, and 5) epidemiology and outcome measures. Because of word limitations, we regret that not every original contribution could be included.
Advances in Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapies
Over the past decade, management of CF has been transformed with the approval of several small molecules, termed CFTR (cystic fibrosis transmembrane conductance regulator) modulators, used alone or in combination. These modulators consist of two classes of drugs: potentiators that augment opening of the CFTR channel function at the apical membrane of epithelial cells and correctors that assist in transport of nascent protein to the cell surface. These oral therapies have been able to restore CFTR function across a range of CFTR mutations. Ivacaftor (potentiator), used in treating patients with at least one copy of G551D and other ivacaftorresponsive mutations, was approved by the Food and Drug Administration in January 2012 with extended approval to children aged 12 months and older in 2018. Lumacaftor (corrector)/ivacaftor combination for treatment of patients homozygous for the F580del mutation received Food and Drug Administration approval in July 2015 and since August 2018 is approved for use in patients aged 2 years and older. Tezacaftor (corrector)/ivacaftor combination was approved in February 2018 for the homozygous F508del populations aged 12 years and older, as well as for some F580del heterozygotes with a residual function mutation on the other allele. Together, these three drug combinations provide therapies for approximately 50% of individuals with CF. All these therapies were approved on the basis of phase 2 and 3 trial efficacy data demonstrating significant improvement in multiple clinical outcomes: percent predicted FEV1 (ppFEV1), improved body...