bile; biomarker; cholesterol; elastase; enzyme; gastroesophageal reflux; laryngopharyngeal reflux; lipase; pepsin; saliva; Bile Acids and Salts; Biomarkers; Cholesterol; Adult; Female; Humans; Male; Middle Aged; Bile Acids and Salts/metabolism; Bile Acids and Salts/analysis; Case-Control Studies; Cholesterol/metabolism; Cholesterol/analysis; Esophageal pH Monitoring; Hydrogen-Ion Concentration; Prospective Studies; Aged; Biomarkers/analysis; Biomarkers/metabolism; Laryngopharyngeal Reflux/metabolism; Laryngopharyngeal Reflux/diagnosis; Saliva/chemistry; Saliva/metabolism; Surgery; Otorhinolaryngology
Abstract :
[en] [en] OBJECTIVE: To investigate the digestive enzymes and biomarkers in the saliva of patients with laryngopharyngeal reflux (LPR) and asymptomatic individuals.
STUDY DESIGN: Prospective controlled study.
SETTING: Multicenter study.
METHODS: Patients with LPR at the hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) and asymptomatic individuals were consecutively recruited from January 2020 to April 2023 from 2 University Hospitals. The saliva of patients (off PPIs) and asymptomatic individuals was collected to measure pH, elastase, bile salts, cholesterol, gastric, and pancreatic lipases. Anxiety, symptoms, and findings were studied through perceived stress scale (PSS), reflux symptom score (RSS), and reflux sign assessment (RSA).
RESULTS: Sixty-seven LPR patients and 57 asymptomatic individuals completed the evaluations. LPR patients reported higher PSS, RSS, and RSA than asymptomatic individuals. The mean saliva pH was more alkaline in LPR patients (7.23: 95% confidence interval [CI]: 7.08, 7.38) compared to controls (6.13; 95% CI: 5.95, 6.31; P = .001). The mean concentration of elastase was higher in patients (51.65 µg/mL; 95% CI: 44.47, 58.83 µg/mL) versus asymptomatic individuals (25.18 µg/mL; 95% CI: 21.64, 28.72 µg/mL; P = .001). The saliva cholesterol reported higher concentration in healthy individuals (3.43 mg/dL; 95% CI: 3.21, 3.65 mg/dL) compared to patients (1.16 mg/dL; 95% CI: 1.05, 1.27 mg/dL; P = .001). The saliva pH, and elastase concentration were significantly associated with the baseline RSS, while saliva cholesterol was negatively associated with the severity of RSS and RSA.
CONCLUSION: Cholesterol, bile salts, and elastase are biomarkers of LPR and should be considered to develop future non-invasive saliva device for the detection of LPR.
Disciplines :
Otolaryngology
Author, co-author :
Lechien, Jerome R; Division of Laryngology and Broncho-esophagology, Department of Otolaryngology-Head Neck Surgery, EpiCURA Hospital, Baudour, Belgium ; Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium ; Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, School of Medicine, Paris Saclay University, Phonetics and Phonology Laboratory, (UMR 7018 CNRS, Université Sorbonne Nouvelle/Paris 3), Paris, France ; Department of Otolaryngology-Head and Neck Surgery, CHU Saint-Pierre, Brussels, Belgium ; Polyclinique Elsan de Poitiers, Poitiers, France
De Marrez, Lisa G; Department of Otorhinolaryngology-Head and Neck Surgery, CHU Brugmann, Brussels, Belgium
Hans, Stephane; Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, School of Medicine, Paris Saclay University, Phonetics and Phonology Laboratory, (UMR 7018 CNRS, Université Sorbonne Nouvelle/Paris 3), Paris, France
Muls, Vinciane; Department of Gastroenterology, CHU Saint-Pierre, Brussels, Belgium
Spinato, Linda; Department of Otorhinolaryngology-Head and Neck Surgery, CHU Brugmann, Brussels, Belgium
Briganti, Giovanni ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Médecine computationnelle et Neuropsychiatrie ; Department of Psychiatry, CHU Brugmann, Brussels, Belgium
Saussez, Sven ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service d'Anatomie humaine et Oncologie expérimentale ; Division of Laryngology and Broncho-esophagology, Department of Otolaryngology-Head Neck Surgery, EpiCURA Hospital, Baudour, Belgium ; Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, School of Medicine, Paris Saclay University, Phonetics and Phonology Laboratory, (UMR 7018 CNRS, Université Sorbonne Nouvelle/Paris 3), Paris, France
De Vos, Nathalie; Department of Clinical Chemistry, LHUB-ULB, Brussels, Belgium
Language :
English
Title :
Digestive Biomarkers of Laryngopharyngeal Reflux: A Preliminary Prospective Controlled Study.
Publication date :
May 2024
Journal title :
Otolaryngology - Head and Neck Surgery
ISSN :
0194-5998
eISSN :
1097-6817
Publisher :
John Wiley and Sons Inc, England
Volume :
170
Issue :
5
Pages :
1364 - 1371
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
M121 - Service de Médecine computationnelle et Neuropsychiatrie
Research institute :
Santé
Funding text :
Vesale Grant & IRIS‐Recherche Grant (Foundation Roi Baudouin). The study is funded by the Groupement de Coopération Sanitaire ELSAN, 58 bis rue de la Boétie, 75008 Paris, France. Pr. Giovanni Briganti for the sample size analyzes. B. Johnson for the proofread.
Lechien JR, Akst LM, Hamdan AL, et al. Evaluation and management of laryngopharyngeal reflux disease: state of the art review. Otolaryngol Head Neck Surg. 2019;160(5):762-782. doi:10.1177/0194599819827488
Johnston N, Wells CW, Samuels TL, Blumin JH. Pepsin in nonacidic refluxate can damage hypopharyngeal epithelial cells. Ann Otol, Rhinol, Laryngol. 2009;118(9):677-685. doi:10.1177/000348940911800913
Klimara MJ, Randall DR, Allen J, Figueredo E, Johnston N. Proximal reflux: biochemical mediators, markers, therapeutic targets, and clinical correlations. Ann NY Acad Sci. 2020;1481(1):127-138. doi:10.1111/nyas.14366
Lechien JR, Vaezi MK, Chan WW, et al. The Dubai definition and diagnostic criteria of laryngopharyngeal reflux: the IFOS consensus. Laryngoscope. 2023. doi:10.1002/lary.31134
Gourcerol G, Verin E, Leroi AM, Ducrotté P. Can multichannel intraluminal pH-impedance monitoring be limited to 3 hours? Comparison between ambulatory 24-hour and post-prandial 3-hour recording: three-hour pH-impedance monitoring. Dis Esophagus. 2014;27(8):732-736. doi:10.1111/dote.12161
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
Calvo-Henríquez C, Ruano-Ravina A, Vaamonde P, Martínez-Capoccioni G, Martín-Martín C. Is pepsin a reliable marker of laryngopharyngeal reflux? A systematic review. Otolaryngol Head Neck Surg. 2017;157(3):385-391. doi:10.1177/0194599817709430
Le Huerou-Luron I, Guilloteau P, Wicker-Planquart C, et al. Gastric and pancreatic enzyme activities and their relationship with some gut regulatory peptides during postnatal development and weaning in calves. J Nutr. 1992;122(7):1434-1445. doi:10.1093/jn/122.7.1434
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
Sereg-Bahar M, Jerin A, Jansa R, Stabuc B, Hocevar-Boltezar I. Pepsin and bile acids in saliva in patients with laryngopharyngeal reflux—a prospective comparative study. Clin Otolaryngol. 2015;40(3):234-239. doi:10.1111/coa.12358
Lechien JR, Bobin F, Muls V, et al. Validity and reliability of the reflux symptom score. Laryngoscope. 2020;130(3):E98-E107. doi:10.1002/lary.28017
Lechien JR, Rodriguez Ruiz A, Dequanter D, et al. Validity and reliability of the reflux sign assessment. Ann Otol, Rhinol, Laryngol. 2019;129:313-325. doi:10.1177/0003489419888947
Lechien JR, Chan WW, Akst LM, et al. Normative Ambulatory reflux monitoring metrics for laryngopharyngeal reflux: a systematic review of 720 healthy individuals. Otolaryngol Head Neck Surg. 2022;166(5):802-819. doi:10.1177/01945998211029831
Gyawali CP, Kahrilas PJ, Savarino E, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67(7):1351-1362. doi:10.1136/gutjnl-2017-314722
Lechien JR, Lisan Q, Eckley CA, et al. Acute, recurrent, and chronic laryngopharyngeal reflux: the IFOS classification. Laryngoscope. 2023;133(5):1073-1080. doi:10.1002/lary.30322
Lesage FX, Berjot S, Deschamps F. Psychometric properties of the French versions of the Perceived Stress Scale. Int J Occup Med Environ Health. 2012;25(2):178-184.
Lechien JR, Bobin F, Muls V, et al. Saliva pepsin concentration of laryngopharyngeal reflux patients is influenced by meals consumed before the samples. Laryngoscope. 2021;131(2):350-359. doi:10.1002/lary.28756
Lechien JR, Bobin F, Muls V, et al. Patients with acid, high-fat and low-protein diet have higher laryngopharyngeal reflux episodes at the impedance-pH monitoring. Eur Arch Otrhinolaryngol. 2020;277(2):511-520. doi:10.1007/s00405-019-05711-2
Lechien JR, Saussez S, Muls V, et al. Laryngopharyngeal reflux: evolution and predictive value of symptoms and pH-impedance features on clinical evolution. Otolaryngol Head Neck Surg. 2022;167(5):852-859. doi:10.1177/01945998221075009
Sacco O, Silvestri M, Sabatini F, et al. IL-8 and airway neutrophilia in children with gastroesophageal reflux and asthma-like symptoms. Respir Med. 2006;100(2):307-315. doi:10.1016/j.rmed.2005.05.011
Sasaki CT, Doukas SG, Costa J, Vageli DP. Biliary reflux as a causal factor in hypopharyngeal carcinoma: new clinical evidence and implications. Cancer. 2019;125(20):3554-3565. doi:10.1002/cncr.32369
Ville E, Carrière F, Renou C, Laugier R. Physiological study of pH stability and sensitivity to pepsin of human gastric lipase. Digestion. 2002;65(2):73-81. doi:10.1159/000057708
Lechien JR, Saussez S, Harmegnies B, Finck C, Burns JA. Laryngopharyngeal reflux and voice disorders: a multifactorial model of etiology and pathophysiology. J Voice. 2017;31(6):733-752. doi:10.1016/j.jvoice.2017.03.015
Wood JM, Hussey DJ, Woods CM, Watson DI, Carney AS. Biomarkers and laryngopharyngeal reflux. J Laryngol Otol. 2011;125(12):1218-1224. doi:10.1017/S0022215111002234
Eckley CA, Costa HO. Comparative study of salivary pH and volume in adults with chronic laryngopharyngitis by gastroesophageal reflux disease before and after treatment. Braz J Otorhinolaryngol. 2006;72(1):55-60. doi:10.1016/s1808-8694(15)30035-5
Axford SE, Sharp N, Dettmar PW, et al. Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies. Ann Otol, Rhinol, Laryngol. 2001;110:1099-1108.
Min HJ, Hong SC, Yang HS, Mun SK, Lee SY. Expression of CAIII and Hsp70 is increased the mucous membrane of the posterior commissure in laryngopharyngeal reflux disease. Yonsei Med J. 2016;57:469-474.
Crowther JR. The ELISA Guidebook. 2nd ed. Springer Edition; 2009.
Lechien JR, Saussez S, Nacci A, et al. Association between laryngopharyngeal reflux and benign vocal folds lesions: a systematic review. Laryngoscope. 2019;129(9):E329-E341. doi:10.1002/lary.27932
Kamargiannis N, Gouveris H, Katsinelos P, et al. Chronic pharyngitis is associated with severe acidic laryngopharyngeal refluxin patients with Reinke's edema. Ann Otol, Rhinol, Laryngol. 2011;120(11):722-726. doi:10.1177/000348941112001105
Lechien JR, Saussez S, Hopkins C. Association between laryngopharyngeal reflux, gastroesophageal reflux and recalcitrant chronic rhinosinusitis: a systematic review. Clin Otolaryngol. 2023;48(4):501-514. doi:10.1111/coa.14047
Samuels TL, Khampang P, Espahbodi M, et al. Association of pepsin with inflammatory signaling and effusion viscosity in pediatric otitis media. Laryngoscope. 2022;132(2):470-477. doi:10.1002/lary.29749
Bergeron JM, Parsel SM, Do TM, Unis GD, McCoul ED. Association of a standardized measure of nasopharyngeal inflammation with Eustachian tube dysfunction questionnaire score. Int Forum Allergy Rhinol. 2021;11(8):1177-1186. doi:10.1002/alr.22771
Lechien JR, Hans S, De Marrez LG, et al. Prevalence and features of laryngopharyngeal reflux in patients with primary burning mouth syndrome. Laryngoscope. 2021;131(10):E2627-E2633. doi:10.1002/lary.29604