Mucociliary Clearance and Its Importance

  • Deniz Tuna EdizerEmail author
  • Ozgur Yigit
  • Michael Rudenko


Nasal airway, which is exposed to a variety of noxious agents, transports tremendous amount of air into the lungs during normal respiration. Nasal cavity is lined mostly with the ciliated pseudostratified columnar epithelium, whereas the paranasal sinuses are lined with the ciliated simple columnar epithelium. Nasal mucosa is considered as the first-line defence against airborne particles through its mucosal surface which maintains intimate contact with the environment. There are many mechanisms that are acting together to protect the host: mucosal barrier function, mucociliary clearance (MCC), inherent phagocytes, and secretion of a variety of proteins. Airway surface is covered with a two-layered coating composed of periciliary layer (periciliary fluid) and mucus layer. Cilia of the epithelial cells move in a coordinated fashion in order to propel the pathogens and particles. MCC is driven by the coordinated action of the cilia. The coating of the airway surface is also called airway surface fluid (ASL) and airway epithelia are known to have a role in regulation of the volume and/or composition of the ASL. Paranasal sinuses depend solely on MCC mechanism to clear mucus, whereas nasal cavity takes the advantages of sneeze and cough reflexes in addition to MCC (Antunes MB, Cohen NA. Curr Opin Allergy Clin Immunol. 7:5–10; 2007). Cough and sneezing may become even more prominent in mucus transport in the presence of pathologic conditions. Coordinated ciliary activity of the epithelium along with intact mucus and periciliary layer production is needed for an effective MCC. Failure of the ciliary activity and/or the production of the mucus-periciliary layer lead to serious disorders.


Mucociliary clearance Nasal cavity Mucus Ciliary activity Mucosa Disorders 


  1. 1.
    Gudis DA, Cohen NA. Cilia dysfunction. Otolaryngol Clin N Am. 2010;43:461–72.Google Scholar
  2. 2.
    Antunes MB, Cohen NA. Mucociliary clearance—a critical upper airway host defense mechanism and methods of assessment. Curr Opin Allergy Clin Immunol. 2007;7:5–10.PubMedGoogle Scholar
  3. 3.
    Physiology SPLE. Mucociliary clearance and neural control. In: Kenneedy DW, Bolger WE, Zinreich SJ, editors. Diseases of the sinuses diagnosis and management. London: BC Decker; 2001.Google Scholar
  4. 4.
    Fokkens WJ, Scheeren RA. Upper airway defence mechanisms. Paediatr Respir Rev. 2000;1:336–41.PubMedGoogle Scholar
  5. 5.
    Bartlett JA, Fischer AJ, PB MC Jr. Innate immune functions of the airway epithelium. Contrib Microbiol. 2008;15:147–63.PubMedGoogle Scholar
  6. 6.
    Pallanch J, Jorissen M. Objective assessment of nasal function. In: Flint PW, Haughey BH, Lund V, Niparko JK, Robbins KT, Thomas JR, Lesperance MM, editors. Cummings otolaryngology head and neck surgery. 6th ed. Philadelphia: Elsevier Saunders; 2015.Google Scholar
  7. 7.
    Lund VJ. Nasal physiology: neurochemical receptors, nasal cycle, and ciliary action. Allergy Asthma Proc. 1996;17:179–84.PubMedGoogle Scholar
  8. 8.
    Eccles R. The nose and control of nasal airflow. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy principles and practice. 8th ed. Philadelphia: Elsevier Saunders; 2014.Google Scholar
  9. 9.
    Matsui H, Randell SH, Peretti SW, Davis CW, Boucher RC. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J Clin Invest. 1998;102:1125–31.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Sears PR, Yin WN, Ostrowski LE. Continuous mucociliary transport by primary human airway epithelial cells in vitro. Am J Physiol Lung Cell MolPhysiol. 2015;309:L99–108.Google Scholar
  11. 11.
    Hulse KE. Immune mechanisms of chronic rhinosinusitis. Curr Allergy Asthma Rep. 2016;16(1):1.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Quinton PM. Viscosity versus composition in airway pathology. Am J Respir Crit Care Med. 1994;149:6–7.PubMedGoogle Scholar
  13. 13.
    Kilburn KH. A hypothesis for pulmonary clearance and its implications. Am Rev Respir Dis. 1968;98:449–63.PubMedGoogle Scholar
  14. 14.
    Trindade SH, de Mello JF Jr, Mion Ode G, Lorenzi-Filho G, Macchione M, Guimarães ET, Saldiva PH. Methods for studying mucociliary transport. Braz J Otorhinolaryngol. 2007;73:704–12.PubMedGoogle Scholar
  15. 15.
    Chen D, Ren J, Mei Y, Xu Y. The respiratory ciliary motion produced by dynein activity alone: a computational model of ciliary ultrastructure. Technol Health Care. 2015;23:S577–86.PubMedGoogle Scholar
  16. 16.
    Revington M, Lacroix JS, Potter EK. Sympathetic and parasympathetic interaction in vascular and secretory control of the nasal mucosa in anaesthetized dogs. J Physiol. 1997;505:823–83.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Munkholm M, Mortensen J. Mucociliary clearance: pathophysiological aspects. Clin Physiol Funct Imaging. 2014;34:171–7.Google Scholar
  18. 18.
    Shoemark A, Hogg C. Electron tomography of respiratory cilia. Thorax. 2013;68:190–1.PubMedGoogle Scholar
  19. 19.
    Ueno H, Bui KH, Ishikawa T, Imai Y, Yamaguchi T, Ishikawa T. Structure of dimericaxonemal dynein in cilia suggests an alternative mechanism of force generation. Cytoskeleton (Hoboken). 2014;71:412–22.Google Scholar
  20. 20.
    Ishikawa T. Structural biology of cytoplasmic and axonemaldyneins. J Struct Biol. 2012;179:229–34.PubMedGoogle Scholar
  21. 21.
    Chilvers MA, O'Callaghan C. Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: comparison with the photomultiplier and photodiode methods. Thorax. 2000;55:314–7.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Antunes MB, Cohen NA. Respiratory cilia: Mucociliary clearance. In: Stucker FJ, Souza CD, Kenyon GS, Lian TS, Draf W, Schick B, editors. Rhinology and facial plastic surgery. New York: Springer; 2009.Google Scholar
  23. 23.
    Gueron S, Levit-Gurevich K, Liron N, Blum JJ. Cilia internal mechanism and metachronal coordination as the result of hydrodynamical coupling. Proc Natl Acad Sci U S A. 1997;94:6001–6.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Teff Z, Priel Z, Gheber LA. The forces applied by cilia depend linearly on their frequency due to constant geometry of the effective stroke. Biophys J. 2008;94:298–305.PubMedGoogle Scholar
  25. 25.
    Satir P. The role of axonemal components in ciliary motility. Comp Biochem Physiol A Comp Physiol. 1989;94:351–7.PubMedGoogle Scholar
  26. 26.
    Keeling J, Tsiokas L, Maskey D. Cellular mechanisms of ciliary length control cells. 2016; 5(1): pii: E6.Google Scholar
  27. 27.
    Messerklinger W. On the drainage of the normal frontal sinus of man. Acta Otolaryngol. 1967;63:176–81.PubMedGoogle Scholar
  28. 28.
    Brokaw CJ. Control of flagellar bending: a new agenda based on dynein diversity. Cell Motil Cytoskeleton. 1994;28:199–204.PubMedGoogle Scholar
  29. 29.
    Satir P, Christensen ST. Overview of structure and function of mammalian cilia. Annu Rev Physiol. 2007;69:377–400.PubMedGoogle Scholar
  30. 30.
    Yeh TH, Su MC, Hsu CJ, Chen YH, Lee SY. Epithelial cells of nasal mucosa express functional gap junctions of connexin 43. Acta Otolaryngol. 2003;123:314–20.PubMedGoogle Scholar
  31. 31.
    Gheber L, Priel Z. Synchronization between beating cilia. Biophys J. 1989;55:183–91.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Sutto Z, Conner GE, Salathe M. Regulation of human airway ciliary beat frequency by intracellular pH. J Physiol. 2004;560:519–32.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Green A, Smallman LA, Logan AC, Drake-Lee AB. The effect of temperature on nasalciliary beat frequency. Clin Otolaryngol Allied Sci. 1995;20:178–80.PubMedGoogle Scholar
  34. 34.
    Wong LB, Miller IF, Yeates DB. Stimulation of ciliary beat frequency by autonomic agonists: in vivo. J Appl Physiol. 1988;65:971–81.PubMedGoogle Scholar
  35. 35.
    Sanderson MJ, Dirksen ER. Mechanosensitivity of cultured ciliated cells from the mammalian respiratory tract: implications for the regulation of mucociliary transport. Proc Natl Acad Sci U S A. 1986;83:7302–6.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest. 2002;109:571–7.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Tarran R, Trout L, Donaldson SH, Boucher RC. Soluble mediators, not cilia, determine airway surface liquid volume in normal and cystic fibrosis superficial airway epithelia. J Gen Physiol. 2006;127:591–604.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Lai SK, Wang YY, Wirtz D, Hanes J. Micro- and macrorheology of mucus. Adv Drug Deliv Rev. 2009;61:86–100.PubMedPubMedCentralGoogle Scholar
  39. 39.
    King M. Physiology of mucus clearance. Paediatr Respir Rev. 2006;7:S212–4.PubMedGoogle Scholar
  40. 40.
    Vallet C, Escudier E, Roudot-Thoraval F, Blanchon S, Fauroux B, Beydon N, et al. Primary ciliary dyskinesia presentation in 60 children according to ciliary ultrastructure. Eur J Pediatr. 2013;172:1053–60.PubMedGoogle Scholar
  41. 41.
    Zariwala MA, Omran H, Ferkol TW. The emerging genetics of primary ciliary dyskinesia. Proc Am Thorac Soc. 2011;8:430–3.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Haq IJ, Gray MA, Garnett JP, Ward C, Brodlie M. Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets. Thorax. 2016;71:284–7.PubMedGoogle Scholar
  43. 43.
    Uslu H, Uslu C, Varoglu E, Demirci M, Seven B. Effects of septoplasty and septal deviation on nasal mucociliary clearance. Int J Clin Pract. 2004;58:1108–11.PubMedGoogle Scholar
  44. 44.
    Ulusoy B, Arbag H, Sari O, Yöndemli F. Evaluation of the effects of nasal septal deviation and its surgery on nasal mucociliary clearance in both nasal cavities. Am J Rhinol. 2007;21:180–3.PubMedGoogle Scholar
  45. 45.
    Soane RJ, Carney AS, Jones NS, Frier M, Perkins AC, Davis SS, Illum L. The effect of the nasal cycle on mucociliary clearance. Clin Otolaryngol Allied Sci. 2001;26:9–15.PubMedGoogle Scholar
  46. 46.
    Passali D, Bellussi L, Lauriello M. Diurnal activity of the nasal mucosa. Relationship between mucociliary transport and local production of secretory immunoglobulins. Acta Otolaryngol. 1990;110:437–42.PubMedGoogle Scholar
  47. 47.
    Cohen NA. Sinonasalmucociliary clearance in health and disease. Ann Otol Rhinol Laryngol Suppl. 2006;196:20–6.PubMedGoogle Scholar
  48. 48.
    Stevens WW, Lee RJ, Schleimer RP, Cohen NA. Chronic rhinosinusitis pathogenesis. J Allergy Clin Immunol. 2015;136:1442–53.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Sun SS, Hsieh JF, Tsai SC, Ho YJ, Kao CH. The role of rhinoscintigraphy in the evaluation of nasal mucociliary clearance function in patients with sinusitis. Nucl Med Commun. 2000;21:1029–32.PubMedGoogle Scholar
  50. 50.
    Sun SS, Hsieh JF, Tsai SC, Ho YJ, Kao CH. Evaluation of nasal mucociliary clearance function in allergic rhinitis patients with technetium 99m-labeled macroaggregated albumin rhinoscintigraphy. Ann Otol Rhinol Laryngol. 2002;111:77–9.PubMedGoogle Scholar
  51. 51.
    Kirtsreesakul V, Somjareonwattana P, Ruttanaphol S. The correlation between nasal symptom and mucociliary clearance in allergic rhinitis. Laryngoscope. 2009;119:1458–62.PubMedGoogle Scholar
  52. 52.
    Randell SH, Boucher RC; University of North Carolina Virtual Lung Group Effective mucus clearance is essential for respiratory health. Am J Respir Cell Mol Biol 2006; 35:20–28.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Stannard W, O'Callaghan C. Ciliary function and the role of cilia in clearance. J Aerosol Med. 2006;19:110–5.PubMedGoogle Scholar
  54. 54.
    Corbo GM, Foresi A, Bonfitto P, Mugnano A, Agabiti N, Cole PJ. Measurement of nasalmucociliary clearance. Arch Dis Child. 1989;64:546–50.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Andersen I, Lundqvist GR, Proctor DF. Human nasal mucosal. Arch Environ Health. 1971;23:408–20.PubMedGoogle Scholar
  56. 56.
    Deitmer T. A modification of the saccharine test for nasal mucociliaryclearance. Rhinology. 1986;24:237–40.PubMedGoogle Scholar
  57. 57.
    Dostbil Z, Polat C, Uysal IÖ, Bakır S, Karakuş A, Altındağ S. Evaluation of nasal Mucociliary transport rate by Tc-macroaggregated albumin Rhinoscintigraphy in woodworkers. Int J Mol Imaging. 2011:620482.Google Scholar
  58. 58.
    De Boeck K, Proesmans M, Mortelmans L, Van Billoen B, Willems T, Jorissen M. Mucociliary transport using 99mTc-albumin colloid: a reliable screening test for primary ciliary dyskinesia. Thorax. 2005;60:414–7.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Rizzo JA, Medeiros D, Silva AR, Sarinho E. Benzalkonium chloride and nasal mucociliary clearance: a randomized, placebo-controlled, crossover, double-blind trial. Am J Rhinol. 2006;20:243–7.PubMedGoogle Scholar
  60. 60.
    Dostbil Z, Dag Y, Cetinkaya O, Akdag M, Tasdemir B. Assessment of technetium-99m labeled macroaggregated albumin rhinoscintigraphy for the measurement of nasal mucociliary transport rate: intratest, interobserver, and intraobserver reproducibility. Scientifica (Cairo) 2014: 982515, 2014, 1.Google Scholar
  61. 61.
    Di Giuda D, Galli J, Calcagni ML, Corina L, Paludetti G, Ottaviani F, De Rossi G. Rhinoscintigraphy: a simple radioisotope technique to study the mucociliary system. Clin Nucl Med. 2000;25:127–30.PubMedGoogle Scholar
  62. 62.
    Chilvers MA, Rutman A, O'Callaghan C. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J Allergy Clin Immunol. 2003;112:518–24.PubMedGoogle Scholar
  63. 63.
    Schipor I, Palmer JN, Cohen AS, Cohen NA. Quantification of ciliary beat frequency in sinonasal epithelial cells using differential interference contrast microscopy and high-speed digital video imaging. Am J Rhinol. 2006;20:124–7.PubMedGoogle Scholar
  64. 64.
    Clare DK, Magescas J, Piolot T, Dumoux M, Vesque C, Pichard E, et al. Basal foot MTOC organizes pillar MTs required for coordination of beating cilia. Nat Commun. 2014;12(5):4888.Google Scholar
  65. 65.
    Gamarra F, Bergner A, Stauss E, Stocker I, Grundler S, Huber RM. Rotation frequency of human bronchial and nasal epithelial spheroids as an indicator of mucociliary function. Respiration. 2006;73:664–72.PubMedGoogle Scholar
  66. 66.
    Tsang KW, Tipoe GL, Mak JC, Sun J, Wong M, Leung R, et al. Ciliary central microtubular orientation is of no clinical significance in bronchiectasis. Respir Med. 2005;99:290–7.PubMedGoogle Scholar
  67. 67.
    O'Brien DW, Morris MI, Ding J, Zayas JG, Tai S, King M. A mechanism of airway injury in an epithelial model of mucociliary clearance. Respir Res. 2004;5:10.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Zayas JG, O'Brien DW, Tai S, Ding J, Lim L, King M. Adaptation of an amphibian mucociliary clearance model to evaluate early effects of tobacco smoke exposure. Respir Res. 2004;5(9)Google Scholar
  69. 69.
    Macchione M, Lorenzi-Filho G, Guimarães ET, Junqueira VB, Saldiva PH. The use of the frog palate preparation to assess the effects of oxidants on ciliated epithelium. Free Radic Biol Med. 1998;24:714–21.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Deniz Tuna Edizer
    • 1
    Email author
  • Ozgur Yigit
    • 1
  • Michael Rudenko
    • 2
  1. 1.Department of OtorhinolaryngologyUniversity of Health Sciences, Istanbul Training and Research HospitalIstanbulTurkey
  2. 2.The London Allergy and Immunology CentreLondonUK

Personalised recommendations