Skip to main content

Cystic Fibrosis: an Update on Disease Pathophysiology, Management, and Novel Modalities of Therapy

Abstract

Purpose of review

To explain the underlying pathophysiology of cystic fibrosis and to describe current treatment modalities for disease manifestations, including an introduction to novel therapies known as CFTR modulator drugs, which are now available to over 50% of people with cystic fibrosis.

Recent findings

CFTR modulator drugs, aimed at restoring CFTR protein function, have been shown to improve lung function and reduce pulmonary exacerbations, improve BMI and QOL, and are a new added treatment to the traditional therapies for cystic fibrosis.

Summary

With the current modalities of treatment available to patient with cystic fibrosis, the quality of life and the life expectancy continues to improve. Future directions for research include looking at novel anti-inflammatory agents, antimicrobial agents, mucociliary clearance agents, and newer generation CFTR modulator drugs/drugs that restore CFTR function.

This is a preview of subscription content, access via your institution.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • 2017 Patient Registry Annual Data Report, CF Foundation. https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2017-Patient-Registry-Annual-Data-Report.pdf. This is the most recent CF Foundation registry annual data report.

  2. Konstan MW, Hilliard KA, Norvell TM, Berger M. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am J Respir Crit Care Med. 1994;150(2):448–54. https://doi.org/10.1164/ajrccm.150.2.8049828.

    CAS  Article  PubMed  Google Scholar 

  3. Chaaban MR, Kejner A, Rowe SM, Woodworth BA. Cystic fibrosis chronic rhinosinusitis: a comprehensive review. Am J Rhinol Allergy. 2013;27:387–95.

    Article  Google Scholar 

  4. Robertson JM, Friedman EM, Rubin BK. Nasal and sinus disease in cystic fibrosis. Paediatr Respir Rev. 2008;9:213–9.

    Article  Google Scholar 

  5. Nicollas R, Facon F, Sudre-Levillain I, et al. Pediatric paranasal sinus mucoceles: etiologic factors, management and outcome. Int J Pediatr Otorhinolaryngol. 2006;70:905–8.

    CAS  Article  Google Scholar 

  6. Walkowiak J, Lisowska A, Blaszczynski M. The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype. Eur J Gastroenterol Hepatol. 2008;20:157–60.

    Article  Google Scholar 

  7. Colombo C, Russo MC, Zazzeron L, et al. Liver disease in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2006;43(Suppl 1):S49–55.

    Article  Google Scholar 

  8. Flume PA, O’Sullivan BP, Robinson KA, et al. Cystic fibrosis guidelines: chronic medications for lung health. Am J Respir Crit Care Med. 2007;176(10):957–69.

    CAS  Article  Google Scholar 

  9. Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: chronic medications for lung health. Am J Respir Care Med. 2013;187(7):680–9.

    Article  Google Scholar 

  10. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006;354:229–40.

    CAS  Article  Google Scholar 

  11. Halfhide C, Evans HJ, Couriel J. Inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev:4, CD003428.

  12. Balfour-Lynn IM, Welch K. Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev. 2009;(1):CD001915.

  13. Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995;332:848–54.

    CAS  Article  Google Scholar 

  14. Southern KW, Barker PM, Solis-Moya A, Patel L. Macrolide antibiotics for cystic fibrosis. Cochrane Database Syst Rev. 2012;11:CD002203

  15. Saiman L, Anstead M, Mayer-Hamblett N, et al. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010;303:1707–15.

    CAS  Article  Google Scholar 

  16. Ryan G, Singh M, Dwan K. Inhaled antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev. 2011;16(3):CD001021.

    Google Scholar 

  17. • Le C, McCray HC, Chang E. Cystic fibrosis sinusitis. Adv Otorhinolaryngol. 2016;79:29–37. This is a nice review of CF-related sinus disease.

    PubMed  Google Scholar 

  18. • Gallant J, Mitchell MB, Virgin FW. Update on sinus disease in children with cystic fibrosis: advances in treatment modalities, microbiology and health-related quality-of-life instruments. Curr Opin Otolaryngol Head Neck Surg. 2018;26(6):417–20. This is an update on sinus disease and advances in treatment.

    Article  Google Scholar 

  19. Stallings VA, Stark LJ, Robinson KA, et al. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008;108:832–9.

    Article  Google Scholar 

  20. Colombo C, Ellemunter H, Houwen R, et al. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros. 2011;10(Suppl 2):S24–8.

    Article  Google Scholar 

  21. • Ooi CY, Durie PR. Cystic fibrosis from the gastroenterologist’s perspective. Nat Rev Gastroenterol Hepatol. 2016;13(3):175–85. This is a nice review of GI manifestations of CF.

    CAS  Article  Google Scholar 

  22. Ramsey BW, Davies J, McElvaney NG, Tullis E, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation: VX08-770-102 Study Group. N Engl J Med. 2011;365(18):1663–72.

    CAS  Article  Google Scholar 

  23. • Wainwright CE, Elborn JS, Ramsey BW, Boyle MP, et al. TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373(3):220–31. https://doi.org/10.1056/NEJMoa1409547. This article shows data for the first approved CFTR modulator combination drug.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. •• Taylor-Cousar JL, Munck A, McKone EF, Elborn JS, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med. 2017;377(21):2013–23. This is the data for the most recently approved CFTR modulator drug.

    CAS  Article  Google Scholar 

  25. •• Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, et al. VX-445-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. N Engl J Med. 2018;379(17):1612–20. This shows recent phase 2 data for a triple CFTR modulator drug.

    CAS  Article  Google Scholar 

  26. •• Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, et al. VX16-659-101 Study Group. VX-659-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. N Engl J Med. 2018;379(17):1599–611. This shows recent phase 2 data for a triple CFTR modulator drug.

    CAS  Article  Google Scholar 

  27. • Bessonova L, Volkova N, Higgins M, Bengtsson L, Tian S, Simard C, et al. Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor. Thorax. 2018;73(8):731–40. This article demonstrates the longer term effects of CFTR modulator ivacaftor based on registry data.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Patricia H. Eshaghian.

Ethics declarations

Conflict of Interest

Timothy Young, Douglas Li, and Patricia Eshaghian have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Pediatric Allergy

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Young, T.J., Li, D.A. & Eshaghian, P.H. Cystic Fibrosis: an Update on Disease Pathophysiology, Management, and Novel Modalities of Therapy. Curr Treat Options Allergy 6, 226–237 (2019). https://doi.org/10.1007/s40521-019-00211-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-019-00211-4

Keywords

  • Cystic fibrosis
  • Bronchiectasis
  • Nasal polyps
  • Chronic rhinosinusitis
  • Pancreatic insufficiency
  • CFTR modulator