title: New drug developments in the management of cystic fibrosis lung disease.
abstract: BACKGROUND
  Therapies for cystic fibrosis (CF) pulmonary disease have, until recently, all targeted downstream manifestations rather than the root cause of the disease. A step-change in our approach has been achieved in the last few years, with novel small-molecule CFTR modulating drugs entering the clinic.
  
  
  METHODS
  In this article, we will discuss the field of drug development for CF lung disease. The case will be made for the potential benefits of basic defect-targeted strategies, which will be described in detail. Novel therapies directed at the downstream pulmonary manifestations of CF - infection, inflammation, and mucus impaction - will be reviewed. Finally, we will speculate on future directions and challenges.
  
  
  CONCLUSIONS
  CF drug development is in an exciting phase, catalysed by the impressive results seen in patients with ivacaftor-responsive CFTR mutations. The research field is active with trials of novel therapies targeting the basic defect, alongside drugs targeting downstream effects. In order to detect potentially small improvements due to novel therapies, especially in the context of treating young patients with early disease, sensitive outcome measures and the coordinated efforts of collaborative research networks are crucial.
authors.affiliation: a National Heart and Lung Institute, Imperial College , London , UK.|b Department of Paediatric Respiratory Medicine , Royal Brompton and Harefield NHS Foundation Trust , London , UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Turnbull
authors.affiliation: a National Heart and Lung Institute, Imperial College , London , UK.|b Department of Paediatric Respiratory Medicine , Royal Brompton and Harefield NHS Foundation Trust , London , UK.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
mesh_terms: D003550:Cystic Fibrosis / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans
keywords: CFTR modulators; Cystic fibrosis; antibiotics; correctors; gene therapy; potentiators