When should a physician consider ciliary dysfunction?

Česká verzia

Authors: V. Martinů ¹; P. Dvořáková ^1,2; J. Uhlík ²; Ž. Varényiová ¹; L. Bořek-Dohalská ¹; P. Pohunek ¹
Authors place of work: Pediatrická klinika 2. LF UK a FN Motol, Praha ¹; Ústav histologie a embryologie 2. LF UK, Praha ²
Published in the journal: Čes-slov Pediat 2020; 75 (7): 401-409.
Category:

Summary

Primary ciliary dyskinesia (PCD) is a rare genetic diseases with diverse clinical symptoms. Clinicians should think of PCD in the differential diagnostic process in both children and adults who suffer from recurrent or chronic upper and lower respiratory tract symptoms frequently accompanied by hearing impairment.

The first manifestations of PCD often occur very early in life and might present as an acute respiratory distress syndrome of a newborn or neonatal rhinitis. During the whole life the patients suffer from chronic wet cough and recurrent airway and lung inflammations, which can result in bronchiectasis. Situs viscerum inversus, other laterality defects and fertility disorders are other common symptoms in PCD. Early diagnosis and complex therapy play a key role in the prognosis of PCD patients, as deterioration of lung functions and lung tissue destruction may occur at an early age in some phenotypes.

Keywords:

diagnosis – situs viscerum inversus – therapy – primary ciliary dyskinesia – symptoms

Zdroje

1. Lucas JS, Burgess A, Mitchison HM, et al. National PCD Service, UK, 2014. Diagnosis and management of primary ciliary dyskinesia. Arch Dis Child 2014; 99: 850–856. https://doi.org/10.1136/archdischild-2013-304831.

2. Lucas JS, Davis SD, Omran H, Shoemark A. Primary ciliary dyskinesia in the genomics age. Lancet Respir Med 2020; 8: 202–216. https://doi.org/10.1016/S2213-2600(19)30374-1.

3. Kuehni CE, Frischer T, Strippoli M-PF, et al., ERS Task Force on Primary Ciliary Dyskinesia in Children. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J 2010; 36: 1248–1258. https://doi.org/10.1183/09031936.00001010

4. O’Callaghan C, Chetcuti P, Moya E. High prevalence of primary ciliary dyskinesia in a British Asian population. Arch Dis Child 2010; 95: 51–52. https://doi.org/10.1136/adc.2009.158493.

5. Halbeisen FS, Goutaki M, Spycher BD, et al. Lung function in patients with primary ciliary dyskinesia: an iPCD Cohort study. Eur Respir J 2018 Aug; 52 (2). https://doi.org/10.1183/13993003.01040-2018.

6. Lucas JS, Behan L, Dunn Galvin A, et al. A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD. Eur Respir J 2015; 46: 375–383. https://doi.org/10.1183/09031936.00216214.

7. Behan L, Leigh MW, Dell SD, et al. Validation of a health-related quality of life instrument for primary ciliary dyskinesia (QOL-PCD). Thorax 2017; 72: 832–839. https://doi.org/10.1136/thoraxjnl-2016-209356.

8. 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: 1262–1268. https://doi.org/10.1164/rccm.200811-1731OC.

9. Conraads VM, Galdermans DI, Kockx MM, et al. Ultrastructurally normal and motile spermatozoa in a fertile man with Kartagener’s syndrome. Chest 1992; 102: 1616–1618. https://doi.org/10.1378/chest.102.5.1616.

10. Kennedy MP, Omran H, Leigh MW, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation 2007; 115: 2814–2821. https://doi.org/10.1161/CIRCULATIONAHA.2007; 106.649038.

11. Shapiro AJ, Davis SD, Ferkol T, et al., Genetic Disorders of Mucociliary Clearance Consortium. Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy. Chest 2014; 146: 1176–1186. https://doi.org/10.1378/chest.13-1704.

12. Goutaki M, Meier AB, Halbeisen FS, et al. Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J 2016; 48: 1081–1095. https://doi.org/10.1183/13993003.00736-2016.

13. Mullowney T, Manson D, Kim R, et al. Primary ciliary dyskinesia and neonatal respiratory distress. Pediatrics 2014; 134: 1160–1166. https://doi.org/10.1542/peds.2014-0808.

14. Kreicher KL, Schopper HK, Naik AN, et al. Hearing loss in children with primary ciliary dyskinesia. Int J Pediatr Otorhinolaryngol 2018; 104: 161–165. https://doi.org/10.1016/j.ijporl.2017.11.005.

15. Knowles MR, Daniels LA, Davis SD, et al. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med 2013; 188: 913–922. https://doi.org/10.1164/rccm.201301-0059CI.

16. Lucas JS, Barbato A, Collins SA, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J 2017 Jan 4; 49 (1). https://doi.org/10.1183/13993003.01090-2016.

17. Behan L, Dimitrov BD, Kuehni CE, et al. PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia. Eur Respir J 2016; 47: 1103–1112. https://doi.org/10.1183/13993003.01551-2015.

18. Djakow J, Svobodová T, Pohunek P. Primární ciliární dyskineze. Pediatr praxi 2013; 14 (6): 368–371.

19. Walker WT, Jackson CL, Lackie PM, et al. Nitric oxide in primary ciliary dyskinesia. Eur Respir J 2012; 40: 1024–1032. https://doi.org/10.1183/09031936.00176111.

20. ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am J Respir Crit Care Med 2005; 171: 912–930. https://doi.org/10.1164/rccm.200406-710ST.

21. Chilvers MA, Rutman A, O’Callaghan C. Functional analysis of cilia and ciliated epithelial ultrastructure in healthy children and young adults. Thorax 2003; 58: 333–338. https://doi.org/10.1136/thorax.58.4.333.

22. Dvořáková P, Uhlík J, Svobodová T, et al. Diagnostika primární ciliární dyskineze. Čes-slov Pediat 2016; 71: 104–110.

23. Fitzgerald DA, Shapiro AJ. When to suspect primary ciliary dyskinesia in children. Paediatr Respir Rev 2016; 18: 3–7. https://doi.org/10.1016/j.prrv.2015.11.006.

24. Davis SD, Ferkol TW, Rosenfeld M, et al. Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. Am J Respir Crit Care Med 2015; 191: 316–324. https://doi.org/10.1164//rccm.201409-1672OC.

25. Davis SD, Rosenfeld M, Lee H-S, et al. Primary ciliary dyskinesia: Longitudinal study of lung disease by ultrastructure defect and genotype. Am J Respir Crit Care Med 2019; 199: 190–198. https://doi.org/10.1164/rccm.201803-0548OC.

26. Fassad MR, Shoemark A, Legendre M, et al. Mutations in outer dynein arm heavy Chain DNAH9 cause motile cilia defects and situs inversus. Am J Hum Genet 2018; 103 (6): 984–994. https://doi.org/10.1016/j.ajhg.2018.10.016.

27. Shapiro AJ, Zariwala MA, Ferkol T, et al., Genetic Disorders of Mucociliary Clearance Consortium. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr Pulmonol 2016; 51: 115–132. https://doi.org/10.1002/ppul.23304.

28. Rubbo B, Lucas JS. Clinical care for primary ciliary dyskinesia: current challenges and future directions. Eur Respir Rev 2017; 26. https://doi.org/10.1183/16000617.0023-2017.

29. Kobbernagel HE, Buchvald FF, Haarman EG, 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 Jul; 16. https://doi.org/10.1186/s12890-016-0261-x.

30. Kobbernagel HE, Buchvald FF, Haarman EG, et al. Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2020; 8: 493–505. https://doi.org/10.1016/S2213-2600(20)30058-8.

31. Knowles M, Zariwala M, Leigh M. Primary ciliary dyskinesia. Clin Chest Med 2016; 37: 449–461. https://doi.org/10.1016/j.ccm.2016.04.008.

32. Řasinky.cz [www document], n.d. URL. https://rasinky.cz/ (accessed 6.22.20).