Determination of mucociliary clearance in patients with laryngopharyngeal refl ux symptoms – preliminary results

Czech version

Authors: Diana Vážanová ¹; Martin Ďuriček ¹; Dáša Oppová ²; Patrícia Čelková ²; Júlia Kvaššayová ²; Alena Varády ³; Tatiana Haličková ^4,5; Peter Lipták ¹; Peter Bánovčin ¹
Published in: Gastroent Hepatol 2024; 78(4): 328-334
Category: Clinical and Experimental Gastroenterology: Review Article
doi: https://doi.org/10.48095/ccgh2024328

Overview

Introduction: Mucociliary clearance represents an important protective mechanism of the respiratory tract. Results of multiple studies indicate that gastroesophageal reflux can participate in worsening mucociliary clearance leading to laryngopharyngeal reflux symptoms including recurrent upper respiratory tract infections. Thereby, we decided to provide ciliary beat frequency of the upper respiratory tract epithelium in patients with laryngopharyngeal reflux. Materials and methods: We enrolled 23 patients with laryngopharyngeal reflux symptoms. Control group consisted of 9 healthy volunteers. Patients were enrolled upon a positive questionnaire reflux symptom index (RSI >13 points), with no proton pump inhibitor treatment. We obtained a nasopharyngeal swab and evaluated ciliary beat frequency of the respiratory epithelium using highspeed videomicroscopy and special sofware Ciliary Analysis. We compared the values of ciliary beat frequency with values from healthy volunteers. Results: We provided median, minimal and maximum values of ciliary beat frequency. Median ciliary beat frequency in healthy volunteers was significantly higher than in patients with laryngopharyngeal reflux symptomatology (10.86 ± 1.67 vs. 6.6 ± 2.2; P <0.001). Maximum ciliary beat frequency was also significantly higher in healthy volunteers than in patients with LPR (17.9 ± 0.95 vs. 15.3 ± 2.39; P <0.001). Minimal value had no significant difference. Correlation analysis showed an inverse correlation between median ciliary beat frequency of the respiratory epithelium and LPR symptoms (RSI value) (P <0.04). Conclusion: Patients with laryngopharyngeal reflux symptoms had lower ciliary beat frequency compared to healthy volunteers. The degree of frequency defect correlates with the degree of their laryngopharyngeal symptoms. More studies are needed to confirm direct evidence of gastroesophageal reflux etiology in mucociliary clearance worsening.

Keywords:

mucociliary clearance – laryngopharyngeal reflux – cilia

Sources

1. Wong IWY, Rees G, Greiff L et al. Gastroesophageal reflux dis ease and chronic sinusitis: in search of an esophageal-nasal reflex. Am J Rhinol Allergy 2010; 24 (4): 255–259. doi: 10.2500/ajra.2010.24.3490.

2. Loehrl TA, Smith TL, Darling RJ et al. Autonomic dysfunction, vasomotor rhinitis, and extra esophageal manifestations of gastroesophageal reflux. Otolaryngol Head Neck Surg 2002; 126 (4): 382–387. doi: 10.1067/mhn.2002.123857.

3. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice 2002; 16 (2): 274–277. doi: 10.1016/s0892-1997 (02) 00097-8.

4. Lechien JR, Vaezi MF, Chan WW et al. The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus. Laryngoscope 2024; 134 (4): 1614–1624. doi: 10.1002/lary.31134.

5. Ďuriček M, Péčová R, Lipták P et al. Increased sensitivity of cough reflex is not the mechanism of cough attributed to laryngopharyngeal reflux. J Voice 2023; S0892-1997 (23) 00075-9. doi: 10.1016/j.jvoice.2023.02.019.

6. Herregods TVK, Pauwels A, Jafari J et al. Determinants of reflux-induced chronic cough. Gut 2017; 66 (12): 2057–2062. doi: 10.1136/gutjnl-2017-313721.

7. Rosen R, Amirault J, Giligan E et al. Intraesophageal pressure recording improves the detection of cough during multichannel intraluminal impedance testing in children. J Pediatr Gastroenterol Nutr 2014; 58 (1): 22–26. doi: 10.1097/MPG.0b013e3182a80059.

8. Phipps CD, Wood WE, Gibson WS et al. Gastroesophageal reflux contributing to chronic sinus dis ease in children: a prospective analysis. Arch Otolaryngol Head Neck Surg 2000; 126 (7): 831–836. doi: 10.1001/archotol.126.7.831.

9. DiBaise JK, Olusola BF, Huerter JV et al. Role of GERD in chronic resistant sinusitis: a prospective, open label, pilot trial. Am J Gastroenterol 2002; 97 (4): 843–850. doi: 10.1111/j.1572-0241.2002.05598.x.

10. Delehaye E, Dore MP, Bozzo C et al. Correlation between nasal mucociliary clearance time and gastroesophageal reflux dis ease: our experience on 50 patients. Auris Nasus Larynx 2009; 36 (2): 157–161. doi: 10.1016/j.anl.2008.06.004.

11. Hait EJ, McDonald DR. Impact of gastroesophageal reflux dis ease on mucosal immunity and atopic disorders. Clin Rev Allergy Immunol 2019; 57 (2): 213–225. doi: 10.1007/s120 16-018-8701-4.

12. Hargaš L, Koniar D, Štofan S. Advanced methodology for frequency description of bio mechanical systems. Proc Eng 2012; 48: 205–212. doi: 10.1016/j.proeng.2012.09.506.

13. Munkholm M, Mortensen J. Mucociliary clearance: pathophysiological aspects. Clin Physiol Funct Imaging 2014; 34 (3): 171–177. doi: 10.1111/cpf.12085.

14. Stein MR. Possible mechanisms of influence of esophageal acid on airway hyperresponsiveness. Am J Med 2003; 115 (Suppl 3): 55S–59S. doi: 10.1016/s0002-9343 (03) 00194-3.

15. Marusiakova L, Durdik P, Jesenak M et al. Ciliary beat frequency in children with adenoid hypertrophy. Pediatr Pulmonol 2020; 55 (3): 666–673. doi: 10.1002/ppul.24622.

16. Vasu PK, Gopalankutty NV, Somayaji G. Does laryngopharyngeal reflux dis ease impair nasal mucociliary transport? A case control prospective study. Int J Otorhinolaryngol Head Neck Surg 2020; 6 (4): 633. doi: 10.18203/issn.2454-5929.ijohns20201022.

17. Andersen I, Camner P, Jensen PL et al. A comparison of nasal and tracheobronchial clearance. Arch Environ Health 1974; 29 (5): 290–293. doi: 10.1080/00039896.1974.10666589.

18. Lechien JR. Treating and managing laryngopharyngeal reflux dis ease in the over 65s: evidence to date. Clin Interv Aging 2022; 17: 1625–1633. doi: 10.2147/CIA.S371992.

19. Duricek M, Banovcin P, Halickova T et al. Acidic Pharyngeal Reflux Does Not Correlate with Symptoms and Laryngeal Injury Attributed to Laryngopharyngeal Reflux. Dig Dis Sci 2019; 64 (5): 1270–1280. doi: 10.1007/s10620-018-5372-1.

20. Duricek M, Banovcin P, Halickova T et al. Comprehensive analysis of acidic pharyngeal reflux before and after proton pump inhibitor treatment in patients with suspected laryngopharyngeal reflux. Eur J Gastroenterol Hepatol 2020; 32 (2): 166–174. doi: 10.1097/MEG.0000000000001584.

21. Jorissen M, Willems T, Van Der Schueren B. Nasal ciliary beat frequency is age independent. Laryngoscope 1998; 108 (7): 1042–1047. doi: 10.1097/00005537-199807000-00017.

22. Ho JC, Chan KN, Hu WH et al. The Effect of Aging on Nasal Mucociliary Clearance, Beat Frequency, and Ultrastructure of Respiratory Cilia. Am J Respir Crit Care Med 2001; 163 (4): 983–988. doi: 10.1164/ajrccm.163.4.9909121.

23. Green A, Smallman LA, Logan ACM et al. The effect of temperature on nasal ciliary beat frequency. Clin Otolaryngol Allied Sci 1995; 20 (2): 178–180. doi: 10.1111/j.1365-2273.1995.tb00040.x.

24. Bor S, Capanoglu D, Vardar R et al. Validation of PeptestTM in patients with gastro-esophageal reflux dis ease and laryngopharyngeal reflux undergoing impedance testing. J Gastrointestin Liver Dis 2019; 28 (4): 383–387. doi: 10.15403/jgld-335.

25. Johnston N, Dettmar PW, Ondrey FG et al. Pepsin: bio marker, mediator, and therapeutic target for reflux and aspiration. Ann N Y Acad Sci 2018; 1434 (1): 282–289. doi: 10.1111/nyas.13729.

26. Na SY, Kwon OE, Lee YC et al. Optimal timing of saliva collection to detect pepsin in patients with laryngopharyngeal reflux. Laryngoscope 2016; 126 (12): 2770–2773. doi: 10.1002/lary.26018.

27. Lechien JR, Allen JE, Barillari MR et al. Management of laryngopharyngeal reflux around the world: an international study. Laryngoscope 2021; 131 (5): E1589–E1597. doi: 10.1002/lary.29270.

28. Kim B, Lee HJ, Im NR et al. Effect of matrix metalloproteinase inhibitor on disrupted E-cadherin after acid exposure in the human nasal epithelium. Laryngoscope 2018; 128 (1): E1–E7. doi: 10.1002/lary.26932.

29. Hunt EB, Sullivan A, Galvin J et al. Gastric aspiration and its role in airway inflammation. Open Respir Med J 2018; 12 (1): 1–10. doi: 10.2174/1874306401812010001.

30. Marik PE. Pulmonary aspiration syndromes. Curr Opin Pulm Med 2011; 17 (3): 148–154. doi: 10.1097/MCP.0b013e32834397d6.

31. De Corso E, Baroni S, Salonna G et al. Impact of bile acids on the severity of laryngo‐pharyngeal reflux. Clin Otolaryngol 2021; 46 (1): 189–195. doi: 10.1111/coa.13643.

32. Aldhahrani A, Powell J, Ladak S et al. The potential role of bile acids in acquired laryngotracheal stenosis: bile acids and laryngotracheal stenosis. Laryngoscope 2018; 128 (9): 2029–2033. doi: 10.1002/lary.27105.

ORCID autorov

D. Vážanová 0009-0008-9606-117X,

M. Ďuriček 0000-0002-0754-4532,

D. Oppová 0000-0003-1041-6520,

P. Čelková 0009-0003-3585-1091,

T. Haličková 0000-0001-5793-4187,

P. Lipták 0000-0001-8257-8567,

P. Bánovčin 0000-0001-6694-9364.

Doručené/Submitted: 26. 6. 2024

Prijaté/Accepted: 22. 7. 2024

Korešpondenčná autorka

MUDr. Diana Vážanová