The role of laryngopharyngeal reflux in the development of nasopharyngeal manifestations of GERD in preschoolers
DOI:
https://doi.org/10.12775/JEHS.2022.12.04.011Keywords
gastroesophageal reflux disease (GERD), laryngopharyngeal reflux (LFR), 25(ОН)D3, 1,25(ОН)2D, αdefensins 1–3, cathelicidins, Haemophilus influenza, childrenAbstract
Purpose. To study the level of vitamin D and the levels of antimicrobial peptides in the blood of children suffering from gastroesophageal reflux disease with nasopharyngeal symptoms, to find out how they depend on the composition of refluxate in LFR and how they affect microbial colonization in the nasopharynx.
Materials and methods. The clinical study was conducted on the basis of the ENT and the Gastroenterology Departments of the Municipal Non-Commercial Enterprise “City Children's Hospital no. 5" of Zaporizhia City Council. By clinical examination and pH monitoring in the esophagus, the following groups of children 3 to 6 years were established: the 1st group of 22 children with gastroesophageal reflux disease with nasopharyngeal signs, the 2nd group of 22 children with gastroesophageal reflux disease without nasopharyngeal signs. Children were assigned to 1st group on the basis of the presence of clinical manifestations that indicated like a high GER. For children with nasopharyngeal manifestations of GERD, there are not only complaints specific to GERD, as well as symptoms that may indicate LFR: cough after eating and morning hoarseness, redness of the larynx and swelling of the vocal cords.The control group (the 3rd group) consisted of 22 children without pathology from the gastrointestinal tract and ENT systems. The children were tested for the levels of 25(ОН)D3, 1,25(ОН)2D, vitamin D binding protein (DBP), αdefensins 1–3 and cathelicidins. Microbial contamination of the mucous membrane of the nasopharyngeal zone was carried out. As far as the distribution differed from normal one (p<0.05), the data are presented as median and inter-quartile ranges Me (Q25; Q75). The results were processed in Microsoft Excelfor Windows 4.0 and Statistica 6.0.
Results. Vitamin D deficiency was revealed in all children of the 1st group (with GERD with LFR). Also, the level of 25(OH)D3 was statistically significantly lower than in children with GERD without LFR and in children of the control group. So, in children of the 1st group, the level 25(ОН)D3 was equel to 13.3 (11.6; 14.9) ng / ml, while in the children of 2nd group it was equal to 21.6 (20.3; 22.9) ng / ml at p < 0.0001 and in children of the control group it was equal to 24.6 (22.8; 28.2) ng / ml at p < 0.0001. The study of the level of antimicrobial peptides showed their significant decrease in children with LFR: the level of αdefensins 1–3 was equel to 2535.0 (1950.0; 3120.0) pg / ml and cathelicidins was equel to 17.9 (5.8; 33.3) ng / ml, which showed a significant statistical difference at p <0.01 compared to other groups. It was noted that in children with acidic and mixed LFR, the level of cathelicidins is lower than in children with alkaline reflux. Thus, in most children with LFR, Haemophilus influenza was detected in nasopharyngeal cultures. Haemophilus influenza in the nose was sown only in children with mixed and acid reflux (30.0% and 80.0%, respectively). This is not typical of children with alkaline reflux. Also, more than two microorganisms were found in half of children with mixed and acid reflux, which was also not registered in children with alkaline reflux (p = 0.05). It was determined that in children with nasopharyngeal manifestations of GERD with Haemophilus influenza in the throat and nose at the same time higher parameters of the total number of acid reflux (180.0 (91.0; 310.0)), the number of prolonged acid reflux (8.0 (4.0; 12.0)) and the percentage of acid reflux per day (20.0 (11.0; 37.6)), which is significant at р˂0,05 than in children when the pathogen was detected only in the throat and in children who do not detected this microorganism Thus, the data obtained confirm that pathological manifestations from the ENT organs are a consequence of the LFR due to GERD.
Conclusions. Our study indicates the aggressive effect of acid reflux on the nasopharyngeal mucosa in children suffering from gastroesophageal reflux disease with LFR. Thus, the lack of anti-inflammatory action of cathelicidins due to their increased utilization and reduced formation in conditions of vitamin D deficiency, leads to significant colonization by gram-negative flora, which can contribute to severe disease.
References
Shaprins'kii Є. V. Stan mіkroflori porozhnini rotoglotki ta stravokhodu u khvorikh na stenozuyuchі zakhvoryuvannya stravokhodu. Aktual'nі problemi suchasnoї meditsini. 2016. T. 16, Vol. 4 (1). P. 223–226.
The role of vitamin D in children with recurrent tonsillopharyngitis / I. Yildiz, et al. Ital. J.Pediatr. 2012. Vol. 38. Article 25.
Vitamin D levels in children with recurrent tonsilliti / S. Aydın et al. J. Pediatr. Otorhinolaryngol. 2011. Vol. 75. P. 364–367.
Zabolotnyi D. I., Mitin Yu. Yu., Bezshaposhnyi S. B. Otolaringologiya : uchebnik. 3-e izd. K. : Meditsina, 2017. 472 s.
Bereznyuk V. V., Molochek Yu. A. Sovremennye podkhody k lecheniyu infektsionno-vospalitel'nykh zabolevanii LOR-organov. Otolaringologіya. Oglyad. 2015. Vol. 23. P. 22–24.
Bomar L., Brugger S. D., Lemon K. P. Bacterial microbiota of the nasal passages across the span of human life. Curr. Opin. Microbiol. 2018. Vol. 41. P. 8–14. DOI : 10.1016/j.mib.2017.10.023.
Siqueira J. F. Jr., Rôças I. N. The Oral Microbiota in Health and Disease: An Overview of Molecular Findings. Methods Mol. Biol. 2017. Vol. 1537. P. 127–138. DOI : 10.1007/978-1-4939-6685-1_7.
ChanW.-Y., Cohen J. M., Brown J. S. The new first-line defense: the potential of nasopharyngeal colonization in vaccine strategies. Vaccine: Develop. Ther. 2016. Vol.6. Р. 47–57. DOI : https://doi.org/10.2147/VDT.S89026.
Control of Pathogens and Pathobionts by the Gut Microbiota / N. Kamada, G. Y. Chen, N. Inohara, G. Núñez. Nat. Immunol. 2013. Vol. 14 (7). P. 685–690. DOI : https://doi.org/10.1038/ni.2608.
The developing hypopharyngeal microbiota in early life / M. S. Mortensen et al. Microbiome. 2016. Vol. 4 (1). P. 1–12. DOI :https://doi.org/10.1186/s40168-016-0215-9.
Oropharyngeal Microbiota in Frail Older Patients Unaffected by Time in Hospital / V. C. Ewan et al. Front. Cell. Infect. Microbiol. 2018. Vol. 8. P. 1–9. DOI : https://doi.org/10.3389/fcimb.2018.00042.
Iwasaki A., Foxman E. F., Molony R. D. Early local immune defences in the respiratory tract. Nat. Rev. Immunol. 2016. Vol. 17 (1). P. 7–20. DOI : https://doi.org/10.1038/nri.2016.117.
Man W. H., de Steenhuijsen P. W. A. A., Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat. Rev. Microbiol. 2017. Vol. 15 (5). P. 259–270. DOI : 10.1038/nrmicro.2017.14.
Hom C., Vaezi M. F. Extraesophageal Manifestations of Gastroesophageal Reflux Disease. Gastroenterol. Clin. North Am. 2013. Vol. 42 (1). Р. 71–91. DOI : https://doi.org/10.1016/j.gtc.2012.11.004.
Relation between chronic rhinosinusitis and gastroesophageal reflux in adults: systematic review / G. C. P. Sella, E. Tamashiro, W. T. Anselmo-Lima, F. C. P.Valera. Brazil. J. Otorhinolaryngol. 2017. Vol. 83 (3). Р. 356–363. DOI : https://doi.org/10.1016/j.bjorl.2016.05.012.
Pepsin and Carbonic Anhydrase Isoenzyme III as Diagnostic Markers for Laryngopharyngeal Reflux Disease / N. Johnston et al. Laryngoscope. 2004. Vol. 114 (12). Р. 2129–2134. DOI : https://doi.org/10.1097/01.mlg.0000149445.07146.03.
Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells / N. Johnston, J. C. Yan, C. R. Hoekzema et al. Laryngoscope. 2012. Vol. 122. P. 1317–1325.
Holick, M.F., Binkley, N.C., Heike, A., et al. “Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline.” J Clin Endocrinol Metab, 96(7) (2011):1911-30.
K. Waterhouse, A. Katta, J. Teckman, T. Foy, J. Derdoy, A. Jain, A. Knutsen, B. Becker Vitamin D Levels In Children With Eosinophilic Esophagitis and Gastroesophageal Reflux / The Journal of Allergy and Clinical Immunology , 2011Volume 127, Issue 2, Supplement, Page AB107
Rubenstein JH1,2,3, McConnell D4, Beer DG5, Chak A6, Metko V2, Clines G3,7. Association of Vitamin D and Parathyroid Hormone With Barrett's Esophagus. J Clin Gastroenterol. 2018 Sep 1. doi: 10.1097/MCG.0000000000001124. [Epub ahead of print]
Yurenko E. A. Optimizatsiya lecheniya patsientov s polipami i granulemami gortani, na fone laringofaringeal'nogo reflyuksa : dissertation for the degree of PhD, Kiev, 2016. 159 p.
An association of serum vitamin D concentrations < 40 nmol/l with acute respiratory tract infection in young Finnish men / I. Laaksi et al. Am. J. Clin. Nutr. 2007. Vol. 86 (3). P. 714–717.
Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers / G. Karatekin et al. Eur. J. Clin. Nutr. 2009. Vol. 63 (4). P. 473–477.
Vitamin D and airway infections: a European perspective / A. Zittermann, S. Pilz, H. Hoffmann, W. März. Eur. J. Med. Res. 2016. Vol. 21. Article 14. DOI : 10.1186/s40001-016-0208-y.
Human Oral Defensins Antimicrobial Peptides: A Future Promising Antimicrobial Drug / Z. Khurshid et al. Curr. Pharm. Des. 2018. Vol. 24 (10). P. 1130–1137. DOI : 10.2174/1381612824666180403114615.
Lezhenko G. O., Pashkova O. Є., Krainya G. V. Mіstse endogennikh antimіkrobnikh peptidіv v patogenetichnikh mekhanіzmakh rozvitku pnevmonії, viklikanoї Streptococcus pneumoniae, u dіtei rann'ogo vіku. Zdorov'e rebenka. 2017. Vol. 12 (4). P. 459–464.
Tulupov D. A., Karpova E. P. O roli bakterial'noi mikroflory v etiologii khronicheskogo adenoidita u detei. Voprosy sovremennoi pediatrii. 2014. Vol. 13 (1). P. 172–175.
Vzaimosvyaz' urovnya rN slizistoi obolochki rotoglotki i nalichiya gribkovoi flory u bol'nykh GERB / E. V. Khrustaleva, V. V. Pedder, N. M. Shishkina, T. G. Lubyanskaya. Meditsinskie nauki. 2013. Vol. 6. URL : https://cyberleninka.ru/article/n/vzaimosvyaz-urovnya-rn-slizistoy-obolochki-rotoglotki-i-nalichiya-gribkovoy-flory-u-bolnyh-gerb.
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