Cystic fibrosis

Abstract

Cystic fibrosis is an autosomal recessive, monogenetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene defect was first described 25 years ago and much progress has been made since then in our understanding of how CFTR mutations cause disease and how this can be addressed therapeutically. CFTR is a transmembrane protein that transports ions across the surface of epithelial cells. CFTR dysfunction affects many organs; however, lung disease is responsible for the vast majority of morbidity and mortality in patients with cystic fibrosis. Prenatal diagnostics, newborn screening and new treatment algorithms are changing the incidence and the prevalence of the disease. Until recently, the standard of care in cystic fibrosis treatment focused on preventing and treating complications of the disease; now, novel treatment strategies directly targeting the ion channel abnormality are becoming available and it will be important to evaluate how these treatments affect disease progression and the quality of life of patients. In this Primer, we summarize the current knowledge, and provide an outlook on how cystic fibrosis clinical care and research will be affected by new knowledge and therapeutic options in the near future. For an illustrated summary of this Primer, visit: http://go.nature.com/4VrefN

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Figure 1: Cystic fibrosis in the United States.
Figure 2: Structure of CFTR.
Figure 3: The mucociliary transport defect in cystic fibrosis.
Figure 4: Diagnosing cystic fibrosis: nasal potential difference measurement.
Figure 5: Currently available therapies to treat patients with cystic fibrosis.
Figure 6: Emerging approaches to address the ion channel abnormalities in cystic fibrosis.

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Affiliations

Authors

Contributions

Introduction (F.R.); Epidemiology (C.H.G.), Mechanisms/pathophysiology (S.M.R. and S.C.B.); Diagnosis, screening and prevention (A.B., F.R. and S.M.R.); Management (S.C.B. and F.R.); Quality of life (A.L.Q.); Outlook (F.R. and A.B.); overview of the Primer (F.R.).

Corresponding author

Correspondence to Felix Ratjen.

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Competing interests

S.M.R. has received grants and/or non-financial support from: Cystic Fibrosis Foundation Therapeutics, the US National Institutes of Health (NIH), Vertex Pharmaceuticals, PTC Therapeutics, Novartis, Forest Research Institute, Bayer Healthcare and Galapagos. C.H.G. has received grant funding and/or honoraria from: the NIH (grants P30 DK089507, R01HL103965, R01AI101307 and UM1HL119073), Food and Drug Administration (grant R01FD003704), the Cystic Fibrosis Foundation, Vertex Pharmaceuticals, Transave Inc., L. Hoffmann-La Roche Ltd, Johns Hopkins University, the European Cystic Fibrosis Society, Medscape and Gilead Sciences. He has also participated in Advisory Boards for KaloBios Pharmaceuticals and Transave Inc. A.L.Q. has received grants and/or consulting income from: NIH (grant R01 DC04797), European Union Health Commission (BESTCILIA), National Health and Medical Research Council of Australia, Cystic Fibrosis Foundation Clinical Research Grant, Novartis, Abbott Pharmaceuticals, Vertex Pharmaceuticals and Gilead Sciences. F.R. has received grants and/or consulting fees from: the Canadian Institutes of Health Research, National Heart, Lung, and Blood Institute, the Cystic Fibrosis Foundation, Genentech, Vertex Pharmaceuticals, Novartis, Gilead Sciences, Boehringer Ingelheim and Roche. S.C.B. has received grants, personal fees, speaker's fees and/or non-financial support from the National Health and Medical Research Council of Australia, the Cystic Fibrosis Foundation, the Office of Health and Medical Research, Queensland Health, the Queensland Children's Foundation, Vertex Pharmaceuticals, Novartis and Gilead. He has served on advisory boards for Vertex Pharmaceuticals, Novartis and Rempex and as a site principal investigator in several clinical trials sponsored by Vertex Pharmaceuticals. A.B. is supported by the UK National Institute of Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London.

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Ratjen, F., Bell, S., Rowe, S. et al. Cystic fibrosis. Nat Rev Dis Primers 1, 15010 (2015). https://doi.org/10.1038/nrdp.2015.10

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