Skip to main content
SpringerLink
Log in

Primary ciliary dyskinesia

  • Bronchiectasis (G Tino, Section Editor)
  • Published:
Current Pulmonology Reports Aims and scope Submit manuscript

Abstract

Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive disorder of motile cilia that leads to chronic respiratory disease. Current estimate for the prevalence is ∼1 in 15,000–20,000 individuals in the USA; this number is likely to change with increased awareness and improved diagnostic methods. There has been a striking increase in interest in the disease in recent years, leading to an increased understanding of the phenotype. The use of genetic testing has greatly aided the diagnosis of PCD and further helped the understanding of the pathogenesis of the disease. In parallel, the establishment of longitudinal clinical studies and the establishment of disease registries are helping to understand the natural history of the disease; all of which will help in developing clinical trials and better treatment guidelines. This review will focus on recent advances in our understanding of this interesting disease after a brief general overview.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Kartagener M. Zur pathogenese der bronkiectasien: bronkiectasien bei situs viscerum inversus. Beitr Klin Tuberk. 1933;82:489–501.

    Article  Google Scholar 

  2. Afzelius BA. A human syndrome caused by immotile cilia. Science. 1976;193:317–9.

    Article  CAS  PubMed  Google Scholar 

  3. Sleigh MA. Primary ciliary dyskinesia. Lancet. 1981;2:476.

    Article  CAS  PubMed  Google Scholar 

  4. Kobbernagel HE, Buchvald FF, Haarman EG, Casaulta C, Collins SA, Hogg C, et al. Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia. BMC Pulm Med. 2016;16(1):104.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chalmers JD, Elborn JS. Reclaiming the name ‘bronchiectasis’. Thorax. 2015;70(5):399–400. doi:10.1136/thoraxjnl-2015-206956.

  6. Shapiro AJ, Zariwala MA, Ferkol T, Davis SD, Sagel SD, Dell SD, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr Pulmonol. 2016;51(2):115–32. doi:10.1002/ppul.23304. Of major importance as an excellent up to date consensus/evidence based summary of all facets of the disease.

  7. Leigh MW, Ferkol TW, Davis SD, Lee HS, Rosenfeld M, Dell SD, et al. Clinical features and associated likelihood of primary ciliary dyskinesia in children and adolescents. Ann Am Thorac Soc. 2016;13(8):1305–13. Of major importance because the authors use good evidence to construct diagnostic criteria, and thus is very helpful to clinicians.

    Article  PubMed  Google Scholar 

  8. Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med. 2013;188(8):913–22. Of importance as a rigorous state of the art document.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lobo LJ, Zariwala MA, Noone PG. Primary ciliary dyskinesia. QJM: Mon J Assoc Physicians. 2014;107(9):691–9.

    Article  CAS  Google Scholar 

  10. Daniels ML, Noone PG. Genetics, diagnosis, and future treatment strategies for primary ciliary dyskinesia. Expert Opin Orphan Drugs. 2015;3(1):31–44.

    Article  PubMed  Google Scholar 

  11. Polineni D, Davis SD, Dell SD. Treatment recommendations in primary ciliary dyskinesia. Paediatr Respir Rev. 2016;18:39–45. Of importance as a summary of recommended treatment protocols.

    PubMed  Google Scholar 

  12. Knowles MR, Zariwala M, Leigh M. Primary ciliary dyskinesia. Clin Chest Med. 2016;37(3):449–61. Of major importance as the most recent highly rigorous state of the art document.

    Article  PubMed  Google Scholar 

  13. Noone PG, Bali D, Carson JL, Sannuti A, Gipson CL, Ostrowski LE, et al. Discordant organ laterality in monozygotic twins with primary ciliary dyskinesia. Am J Med Genet. 1999;82(2):155–60.

    Article  CAS  PubMed  Google Scholar 

  14. Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115(22):2814–21.

    Article  PubMed  Google Scholar 

  15. Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004;169(4):459–67.

    Article  PubMed  Google Scholar 

  16. Morgan LC, Birman CS. The impact of primary ciliary dyskinesia on the upper respiratory tract. Paediatr Respir Rev. 2016;18:33–8.

    PubMed  Google Scholar 

  17. Yiallouros PK, Kouis P, Middleton N, Nearchou M, Adamidi T, Georgiou A, et al. Clinical features of primary ciliary dyskinesia in Cyprus with emphasis on lobectomized patients. Respir Med. 2015;109(3):347–56.

    Article  PubMed  Google Scholar 

  18. Davis SD, Ferkol TW, Rosenfeld M, Lee HS, Dell SD, Sagel SD, et al. Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. Am J Respir Crit Care Med. 2015;191(3):316–24. doi:10.1164/rccm.201409-1672OC. Of importance as highlighting emerging evidence for a genotype—phenotype relationship in PCD.

  19. Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S. Primary ciliary dyskinesia and neonatal respiratory distress. Pediatrics. 2014;134(6):1160–6.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Brown DE, Pittman JE, Leigh MW, Fordham L, Davis SD. Early lung disease in young children with primary ciliary dyskinesia. Pediatr Pulmonol. 2008;43(5):514–6.

    Article  PubMed  Google Scholar 

  21. Leigh MW, Hazucha MJ, Chawla KK, Baker BR, Shapiro AJ, Brown DE, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc. 2013;10(6):574–81. Of importance as setting standards for a simple non-invasive reliable test for PCD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. El Khouri E, Thomas L, Jeanson L, Bequignon E, Vallette B, Duquesnoy P, et al. Mutations in DNAJB13, encoding an HSP40 family member, cause primary ciliary dyskinesia and male infertility. Am J Hum Genet. 2016;99(2):489–500.

    Article  CAS  PubMed  Google Scholar 

  23. Wallmeier J, Shiratori H, Dougherty GW, Edelbusch C, Hjeij R, Loges NT, et al. TTC25 deficiency results in defects of the outer dynein arm docking machinery and primary ciliary dyskinesia with left-right body asymmetry randomization. Am J Hum Genet. 2016;99(2):460–9.

    Article  CAS  PubMed  Google Scholar 

  24. Ellerman A, Bisgaard H. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. Eur Respir J. 1997;10(10):2376–9.

    Article  CAS  PubMed  Google Scholar 

  25. Kennedy MP, Noone PG, Leigh MW, Zariwala MA, Minnix SL, Knowles MR, et al. High-resolution CT of patients with primary ciliary dyskinesia. AJR Am J Roentgenol. 2007;188(5):1232–8.

    Article  PubMed  Google Scholar 

  26. Magnin ML, Cros P, Beydon N, Mahloul M, Tamalet A, Escudier E, et al. Longitudinal lung function and structural changes in children with primary ciliary dyskinesia. Pediatr Pulmonol. 2012;47(8):816–25.

    Article  PubMed  Google Scholar 

  27. Marthin JK, Petersen N, Skovgaard LT, Nielsen KG. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med. 2010;181(11):1262–8.

    Article  PubMed  Google Scholar 

  28. Shah A, Shoemark A, MacNeill SJ, Bhaludin B, Rogers A, Bilton D, et al. A longitudinal study characterising a large adult primary ciliary dyskinesia population. Eur Respir J. 2016;48(2):441–50. doi: 10.1183/13993003.00209-2016. Of importance as a good study of a large number of patients tracking clinical outcomes.

  29. Sunther M, Bush A, Hogg C, McCann L, Carr SB. Recovery of baseline lung function after pulmonary exacerbation in children with primary ciliary dyskinesia. Pediatr Pulmonol. 2016. doi:10.1002/ppul.2347910.1002/ppul.23479.

  30. Frija-Masson J, Bassinet L, Honoré I, Dufeu N, Housset B, Coste A, et al. Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia. Thorax. 2016. doi:10.1136/thoraxjnl-2015-207891.

  31. Knapp EA, Fink AK, Goss CH, Sewall A, Ostrenga J, Dowd C, et al. The cystic fibrosis foundation patient registry. Design and methods of a national observational disease registry. Ann Am Thorac Soc. 2016;13(7):1173–9.

    Article  PubMed  Google Scholar 

  32. Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, et al. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med. 2014;189(5):576–85.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Noone PG, Bennett WD, Regnis JA, Zeman KL, Carson JL, King M, et al. Effect of aerosolized uridine-5′-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia. Am J Respir Crit Care Med. 1999;160(1):144–9.

    Article  CAS  PubMed  Google Scholar 

  34. Quittner AL, Marciel KK, Salathe MA, O’Donnell AE, Gotfried MH, Ilowite JS, et al. A preliminary quality of life questionnaire-bronchiectasis: a patient-reported outcome measure for bronchiectasis. Chest. 2014;146(2):437–48.

    Article  PubMed  Google Scholar 

  35. Lucas JS, Behan L, Dunn Galvin A, Alpern A, Morris AM, Carroll MP, et al. A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD. Eur Respir J. 2015;46(2):375–83. Of major importance as the first PCD specific quality of life measure that will greatly help in clinical trial design.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, et al. Primary ciliary dyskinesia: first health-related quality-of-life measures for pediatric patients. Ann Am Thorac Soc. 2016;13(10):1726–1735.

  37. Loukides S, Kharitonov S, Wodehouse T, Cole PJ, Barnes PJ. Effect of arginine on mucociliary function in primary ciliary dyskinesia. Lancet. 1998;352(9125):371–2.

    CAS  PubMed  Google Scholar 

  38. Welsh EJ, Evans DJ, Fowler SJ, Spencer S. Interventions for bronchiectasis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2015;7, CD010337.

    Google Scholar 

  39. Barbato A, Frischer T, Kuehni CE, Snijders D, Azevedo I, Baktai G, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J. 2009;34(6):1264–76.

    Article  CAS  PubMed  Google Scholar 

  40. Bradley JM, Moran FM, Elborn JS. Evidence for physical therapies (airway clearance and physical training) in cystic fibrosis: an overview of five Cochrane systematic reviews. Respir Med. 2006;100(2):191–201.

    Article  PubMed  Google Scholar 

  41. Lee AL, Burge AT, Holland AE. Airway clearance techniques for bronchiectasis. Cochrane Database Syst Rev. 2015;11, CD008351.

    Google Scholar 

  42. Lee AL, Hill CJ, Cecins N, Jenkins S, McDonald CF, Burge AT, et al. The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis—a randomised controlled trial. Respir Res. 2014;15:44.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Madsen A, Green K, Buchvald F, Hanel B, Nielsen KG. Aerobic fitness in children and young adults with primary ciliary dyskinesia. PLoS One. 2013;8(8), e71409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Donnell AE O, Barker AE, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase. Chest. 1998;113:1329–34.

    Article  Google Scholar 

  45. Hart A, Sugumar K, Milan SJ, Fowler SJ, Crossingham I. Inhaled hyperosmolar agents for bronchiectasis. Cochrane Database Syst Rev. 2014;5, CD002996.

    Google Scholar 

  46. Wong C, Jayaram L, Karalus N, Eaton T, Tong C, Hockey H, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):660–7.

    Article  CAS  PubMed  Google Scholar 

  47. Serisier DJ, Martin ML, McGuckin MA, Lourie R, Chen AC, Brain B, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA. 2013;309(12):1260–7.

    Article  CAS  PubMed  Google Scholar 

  48. Altenburg J, de Graaff CS, Stienstra Y, Sloos JH, van Haren EH, Koppers RJ, et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013;309(12):1251–9.

    Article  CAS  PubMed  Google Scholar 

  49. Pasteur MC, Bilton D, Hill AT. British Thoracic Society guidelines for non-CF bronchiectasis. Thorax. 2010;65 Suppl 1:i1–i58.

    Article  PubMed  Google Scholar 

  50. Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, et al. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2011;183(4):491–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The UNC Center for Bronchiectasis Care, Pulmonary Division, Department of Medicine, The University of North Carolina at Chapel Hill, CB 7020, Bioinformatics Building UNC, Chapel Hill, NC, 27599, USA

    Mary Leigh-Anne Daniels, Sohini Ghosh & Peadar G. Noone

Authors
  1. Mary Leigh-Anne Daniels
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sohini Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peadar G. Noone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peadar G. Noone.

Ethics declarations

Conflict of interest

Peadar Noone, Sohini Ghosh, and M. Leigh Anne Daniels declare no conflict 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

This article is part of the Topical Collection on Bronchiectasis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Daniels, M.LA., Ghosh, S. & Noone, P.G. Primary ciliary dyskinesia. Curr Pulmonol Rep 5, 191–198 (2016). https://doi.org/10.1007/s13665-016-0158-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13665-016-0158-4

Keywords

Search

Navigation