Pathophysiological mechanisms of mucociliary clearance function in patients with respiratory and olfactory disorders of functional-mechanical and viral origin
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Keywords

otorhinolaryngology
ciliary epithelium
nasal obstruction
olfactory dysfunction
COVID-19
rhinomanometry

How to Cite

Bondarenko, Y., Shushliapina, N., Kalashnyk-Vakulenko, Y., & Yashchenko, M. (2025). Pathophysiological mechanisms of mucociliary clearance function in patients with respiratory and olfactory disorders of functional-mechanical and viral origin. Inter Collegas, 12(4). https://doi.org/10.35339/ic.2025.12.4.bsk

Abstract

In press

Background. MucoCiliary Clearance (MCC) is the primary protective mechanism of the upper respiratory tract. Differentiating between extracellular (functional-mechanical) and intracellular (viral cytopathic) mechanisms of MCC impairment has been studied insufficiently but critical for selecting adequate therapeutic strategies.

Aim. To investigate the pathophysiological mechanisms of MCC in patients with respiratory and olfactory disorders depending on the duration and degree of nasal obstruction, and in patients post-Coronavirus Disease 2019.

Materials and Methods. A prospective observational study included 196 patients (mean age [37.4±13.1] years) with nasal obstruction and impaired respiratory/olfactory functions (disease duration from 1 month to 5 years). Patients were divided into four groups: Group 1 (n=53) – pronounced chronic nasal obstruction ([3–5] years); Group 2 (n=48) – partial obstruction (up to 6 months); Group 3 (n=44) – pronounced obstruction (up to 1 month); Group 4 (n=51) – acute post-viral rhinosinusitis after Severe Acute Respiratory Syndrome Coronavirus 2. Two pathogenetic profiles were evaluated: functional-mechanical (groups 1–3) and viral cytopathic (Group 4). Assessment included rhinomanometry, Saccharin Transit Time (STT), olfactometry (Sniffin’ Sticks), and high-speed video microscopy of ciliary epithelium (×100, 120 frames/s) analyzed in ImageJ/ciliaFA. Statistical processing of the data was performed using one-way analysis of variance (ANOVA) with post hoc Student’s test and Bonferroni correction and Pearson correlation with Excel 2022 (Microsoft, USA). The article is a part of scientific research with state registration number 0125U001264.

Research Ethics. The study complied with the World Medical Association Declaration of Helsinki (1964–2024) and relevant Ministry of Health of Ukraine orders. All participants provided written informed consent.

Results. In Group 1, aerodynamic resistance was [3.1±0.4] kPa·s/L, STT was [24.5±3.1] min, and ciliary beat frequency (CBF) was [7.3±1.4] Hz; metachronal wave was absent in 100% of cases, with hyposmia in 100% ([4.1±1.3] points). In Group 2, STT was [18.0±2.4] min, CBF was [7.6±3.1] Hz; in Group 3, STT was [34.7±3.3] min, CBF was [6.8±2.2] Hz. In Group 4, resistance was [1.9±0.4] kPa·s/L, STT was [17.0±1.9] min, and CBF was [8.1±1.4] Hz. Here, anosmia was present in 31.6% ([0.9±0.5] points) and hyposmia in 68.4% ([4.1±0.9] points).

Conclusions. Two fundamentally different pathophysiological profiles of MCC dysfunction were identified: functional-mechanical origin(groups 1–3) and viral cytopathic origin (Group 4), requiring diametrically opposite therapeutic strategies.

Keywords: otorhinolaryngology, ciliary epithelium, nasal obstruction, olfactory dysfunction, COVID-19, rhinomanometry.

https://doi.org/10.35339/ic.2025.12.4.bsk
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References

Comba A, Atan D. Evaluation of nasal mucociliary clearance time in children with celiac disease. Int J Pediatr Otorhinolaryngol. 2020;133:109936. DOI: 10.1016/j.ijporl.2020.109936. PMID: 32088546.

Cohen NA. Sinonasal mucociliary clearance in health and disease. Ann Otol Rhinol Laryngol Suppl. 2006;196:20-6. DOI: 10.1177/00034894061150s904. PMID: 17040014.

Svitlychna YV, Shushliapina NO, Lupyr AV, Bondarenko YD. Analysis of the relationship between nasal mucosa mucociliary clearance parameters and the duration and severity of nasal obstruction. Medicine Today and Tomorrow. 2025;94(3):10p. DOI: 10.35339/msz.2025.94.3.ssl.

Kumar L, Belaldavar BP, Bannur H. Influence of deviated nasal septum on nasal epithelium: an analysis. Head Neck Pathol. 2017;11(4):501-5. DOI: 10.1007/s12105-017-0819-9. PMID: 28474294.

Babchenko NV. The condition of mucociliary clearance in patients with nasal septum deviation and postnasal drip syndrome. Clin Prev Med. 2023;9(26):53-6. DOI: 10.31612/2616-4868.4(26).2023.08.

Hu B, Gong M, Xiang Y, Qu S, Zhu H, Ye D. Mechanism and treatment of olfactory dysfunction caused by coronavirus disease 2019. J Transl Med. 2023;21(1):829. DOI: 10.1186/s12967-023-04719-x. PMID: 37978386.

Bondarenko Y, Kochnieva O, Kotsar O, Kauk O, Pionova O, Tsyhanenko O, et al. CRISPR-edited commensals of the nasopharynx as platform for developing next-generation microbial probiotics. Proceeding of the Shevchenko Scientific Society. Medical Sciences. 2025;77(2). doi: 10.25040/ntsh2025.02.16.

Avrunin OG, Tymkovych MYu, Abdelhamid IY, Shushliapina NO, Nosova YV, Semenets VV. Features of image segmentation of the upper respiratory tract for planning of rhinosurgical surgery. Proc ELNANO. 2019:485-8. doi: 10.1109/ELNANO.2019.8783739.

Doty RL, Mishra A. Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis. Laryngoscope. 2001;111(3):409-23. DOI: 10.1097/00005537-200103000-00008. PMID: 11224769.

Zhao K, Scherer PW, Hajiloo SA, Dalton P. Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction. Chem Senses. 2004;29(5):365-79. DOI: 10.1093/chemse/bjh033. PMID: 15201204.

Li C, Jiang J, Kim K, Otto BA, Farag AA, Cowart BJ, et al. Nasal structural and aerodynamic features that may benefit normal olfactory sensitivity. Chem Senses. 2018;43(4):229-37. DOI: 10.1093/chemse/bjy013. PMID: 29555355.

Shushliapina N, Kalashnyk-Vakulenko Y, Bondarenko Y. Symptomatic treatment of dysosmia in rhinological pathology of functional and viral (SARS-CoV-2) origin. Inter Collegas. 2025;12(3):7р. DOI: 10.35339/ic.2025.12.3.skb.

Grabosky A, Mackers P, Langdon C, Alobid I. Change in olfactory function after septoplasty. A systematic review and meta-analysis. Rhinology. 2021;59(2):144-50. DOI: 10.4193/Rhin20.252. PMID: 33320116.

Rumeau C, Nguyen DT, Jankowski R. How to assess olfactory performance with the Sniffin' Sticks test®. Eur Ann Otorhinolaryngol Head Neck Dis. 2016;133(3):203-6. DOI: 10.1016/j.anorl.2015.08.004. PMID: 26344139.

Rutland J, Cole PJ. Nasal mucociliary clearance and ciliary beat frequency in cystic fibrosis compared with sinusitis and bronchiectasis. Thorax. 1981;36(9):654-8. DOI: 10.1136/thx.36.9.654. PMID: 7314040.

Deborah S, Prathibha KM. Measurement of nasal mucociliary clearance. Clin Res Pulmonol. 2014;2(2):14-9. DOI: 10.47739/2333-6625/1019.

Churchill SE, Shackelford LL, Georgi JN, Black MT. Morphological variation and airflow dynamics in the human nose. Am J Hum Biol. 2004;16(6):625-38. DOI: 10.1002/ajhb.20074. PMID: 15495232.

Wang DY, Lee HP, Gordon BR. Impacts of fluid dynamics simulation in study of nasal airflow physiology and pathophysiology in realistic human three-dimensional nose models. Clin Exp Otorhinolaryngol. 2012;5(4):181-7. DOI: 10.3342/ceo.2012.5.4.181. PMID: 23275797.

Bustamante-Marin XM, Ostrowski LE. Cilia and mucociliary clearance. Cold Spring Harb Perspect Biol. 2017;9(4):a028241. DOI: 10.1101/cshperspect.a028241. PMID: 27815315.

Button B, Cai LH, Ehre C, Kesimer M, Hill DB, Sheehan JK, et al. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science. 2012;337(6097):937-41. DOI: 10.1126/science.1223012. PMID: 22923584.

Ueda T, Hoshikawa M, Shibata Y, Kumamoto N, Ugawa S. Basal cells express functional TRPV4 channels in the mouse nasal epithelium. Biochem Biophys Rep. 2015;4:169-74. DOI: 10.1016/j.bbrep.2015.09.008. PMID: 29124151.

Kim YJ, Cho HJ, Shin WC, Song HA, Yoon JH, Kim CH. Hypoxia-mediated mechanism of MUC5AC production in human nasal epithelia and its implication in rhinosinusitis. PLoS One. 2014;9(5):e98136. DOI: 10.1371/journal.pone.0098136. PMID: 24853033.

Park JA, Tschumperlin DJ. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am J Respir Cell Mol Biol. 2009;41(4):459-66. DOI: 10.1165/rcmb.2008-0195OC. PMID: 19168703.

Deinhardt-Emmer S, Böttcher S, Häring C, Giebeler L, Henke A, Zell R, et al. SARS-CoV-2 causes severe epithelial inflammation and barrier dysfunction. J Virol. 2021;95(10):e00110-21. DOI: 10.1128/JVI.00110-21. PMID: 33692203.

Bilinska K, Jakubowska P, Von Bartheld CS, Butowt R. Expression of the SARS-CoV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and trends with age. ACS Chem Neurosci. 2020;11(11):1555-62. DOI: 10.1021/acschemneuro.0c00210. PMID: 32371031.

Pliss A, Kuzmin AN, Prasad PN, Mahajan SD. Mitochondrial dysfunction: a prelude to neuropathogenesis of SARS-CoV-2. ACS Chem Neurosci. 2022;13(3):308-12. DOI: 10.1021/acschemneuro.1c00675. PMID: 35041416.

Oliveira BR, Nehlmeier I, Kempf AM, Venugopalan V, Rehders M, Ceniza MEP, et al. Cytoskeletal β-tubulin and cysteine cathepsin L deregulation by SARS-CoV-2 spike protein interaction with the neuronal model cell line SH-SY5Y. Biochimie. 2024;226:49-61. DOI: 10.1016/j.biochi.2024.02.006. PMID: 38387807.

Aminpour M, Hameroff S, Tuszynski JA. How COVID-19 hijacks the cytoskeleton: therapeutic implications. Life (Basel). 2022;12(6):814. DOI: 10.3390/life12060814. PMID: 35743845.

Schreiner T, Allnoch L, Beythien G, Marek K, Becker K, Schaudien D, et al. SARS-CoV-2 infection dysregulates cilia and basal cell homeostasis in the respiratory epithelium of hamsters. Int J Mol Sci. 2022;23(9):5124. DOI: 10.3390/ijms23095124. PMID: 35563515.

Shi D, Komatsu K, Hirao M, Toyooka Y, Koyama H, Tissir F, et al. Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct. Development. 2014;141(23):4558-68. DOI: 10.1242/dev.115659. PMID: 25406397.

Boutin C, Labedan P, Dimidschstein J, Richard F, Cremer H, André P, et al. A dual role for planar cell polarity genes in ciliated cells. Proc Natl Acad Sci USA. 2014;111(30):E3129-38. DOI: 10.1073/pnas.1404988111. PMID: 25024228.

Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, et al. Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. J Clin Invest. 2011;121(7):2662-7. DOI: 10.1172/JCI43639. PMID: 21633168.

Rao VG, Subramanianbalachandar VA, Magaj MM, Redemann S, Kulkarni SS. Mechanisms of cilia regeneration in Xenopus multiciliated epithelium in vivo. EMBO Rep. 2025;26(8):2192-220. DOI: 10.1038/s44319-025-00414-8. PMID: 40087471.

Jang YJ, Myong NH, Park KH, Koo TW, Kim HG. Mucociliary transport and histologic characteristics of the mucosa of deviated nasal septum. Arch Otolaryngol Head Neck Surg. 2002;128(4):421-4. DOI: 10.1001/archotol.128.4.421. PMID: 11926916.

Pavlov SV, Avrunin OG, Zlepko SM, Bodyanskyi YeV. Intelligent Technologies in Medical Diagnosis, Treatment, and Rehabilitation: Monograph. Vinnytsia: PP TD "Edelweiss & K"; 2019. 260 р. [In Ukrainian].

Ismail HF, Abu E, Osman A, Omari A, Avrunin O, Bin S. The role of paranasal sinuses in the aerodynamics of the nasal cavities. Int J Life Sci Med Res. 2012;2(3):52-5. DOI: 10.5963/lsmr0203004.

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