Research progress on diagnosis and treatment of pharyngeal reflux disease

doi:10.3760/cma.j.issn.1007-1245.2024.15.010

Abstract

Abstract:

Laryngeal reflux disease is caused by the reflux of gastroduodenal contents, the inflammatory state of the upper digestive tract and respiratory tract caused by direct or indirect behaviors. In the occurrence and development of many common diseases in children, laryngeal reflux plays a non-negligible role. Adenoidal hypertrophy, chronic sinusitis, chronic rhinitis, secretory otitis media, asthma, laryngeal disorders, etc. are closely related to pharyngeal reflux. The main diagnostic methods for pharyngeal reflux are multi-channel intracranial impedance (MII), 24-hour dynamic dual probe pH measurement, biopsy, scales, etc. Treatment for pharyngeal reflux is mainly a combination of drug, diet, and lifestyle adjustment.

Key words:

Pharyngeal reflux, Diagnosis, Treatment, Adenoidal hypertrophy, Progress

摘要：

咽喉反流性疾病是由胃十二指肠内容物反流引发直接或间接造成的上消化道、呼吸道炎性状态。在儿童许多常见疾病的发生发展中，咽喉反流均存在不可忽视的影响。腺样体肥大、慢性鼻窦炎、慢性鼻炎、分泌性中耳炎、哮喘及喉功能紊乱等疾病都与咽喉反流密切相关。咽喉反流的诊断方法主要为多通道腔内阻抗（MII）、24 h动态双探针pH测定、活检、量表等，治疗主要以药物、饮食与调节生活方式相结合的方法。

关键词:

咽喉反流, 诊断, 治疗, 腺样体肥大, 进展

Yang Yang, Yang Pei, Jing Nan.

Research progress on diagnosis and treatment of pharyngeal reflux disease [J]. International Medicine and Health Guidance News, 2024, 30(15): 2511-2518.

杨洋杨培景楠.

咽喉反流性疾病诊断及治疗方法的研究进展 [J]. 国际医药卫生导报, 2024, 30(15): 2511-2518.

References

[1] 黄丽君,谭嘉杰,彭令仪,等. 胃蛋白酶激活巨噬细胞促进舌扁桃体肥大机制的研究[J]. 中华耳鼻咽喉头颈外科杂志,2022,57(10):1203-1211. DOI:10.3760/cma.j.cn115330-20220618-00358.
[2] Johnston N, Dettmar PW, Lively MO,et al. Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease[J]. Ann Otol Rhinol Laryngol, 2006 ,115(1):47-58.DOI: 10.1177/000348940611500108.
[3] Barrett CM, Patel D, Vaezi MF. Laryngopharyngeal reflux and atypical gastroesophageal reflux disease[J]. Gastrointest Endosc Clin N Am, 2020 ,30(2):361-376.DOI: 10.1016/j.giec.2019.12.004.
[4] Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury[J]. Laryngoscope, 1991,101(4 Pt 2 Suppl 53):1-78. DOI: 10.1002/lary.1991.101.s53.1.
[5] Bardhan KD, Strugala V, Dettmar PW. Reflux revisited: advancing the role of pepsin[J]. Int J Otolaryngol, 2012,2012:646901. DOI: 10.1155/2012/646901.
[6] Axford SE, Sharp N, Ross PE,et al. Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies[J]. Ann Otol Rhinol Laryngol, 2001,110(12):1099-1108. DOI: 10.1177/000348940111001203.
[7] Liu K, Krause A, Yadlapati R. Quality of life and laryngopharyngeal reflux[J]. Dig Dis Sci, 2023,68(9):3527-3533.DOI: 10.1007/s10620-023-08027-8.
[8] Ates F, Vaezi MF. Approach to the patient with presumed extraoesophageal GERD[J]. Best Pract Res Clin Gastroenterol, 2013 ,27(3):415-431.DOI: 10.1016/j.bpg.2013.06.009.
[9] Belafsky PC, Postma GN, Daniel E,et al. Transnasal esophagoscopy[J]. Otolaryngol Head Neck Surg, 2001,125(6):588-589. DOI: 10.1067/mhn.2001.120427.
[10] Fuchs HF, Müller DT, Berlth F,et al. Simultaneous laryngopharyngeal pH monitoring (Restech) and conventional esophageal pH monitoring-correlation using a large patient cohort of more than 100 patients with suspected gastroesophageal reflux disease[J]. Dis Esophagus, 2018,31(10).DOI: 10.1093/dote/doy018.
[11] Drinnan M, Powell J, Nikkar-Esfahani A,et al. Gastroesophageal and extraesophageal reflux symptoms: similarities and differences[J]. Laryngoscope, 2015,125(2):424-430.DOI: 10.1002/lary.24950.
[12] Nason KS, Murphy T, Schindler J,et al. A cross-sectional analysis of the prevalence of barrett esophagus in otolaryngology patients with laryngeal symptoms[J]. J Clin Gastroenterol,2013,47(9):762-768.DOI: 10.1097/MCG.0b013e318293d522.
[13] Mosli M, Alkhathlan B, Abumohssin A,et al. Prevalence and clinical predictors of LPR among patients diagnosed with GERD according to the reflux symptom index questionnaire[J]. Saudi J Gastroenterol, 2018 ,24(4):236-241.DOI: 10.4103/sjg.SJG_518_17.
[14] Lechien JR, Schindler A, Hamdan AL,et al. The development of new clinical instruments in laryngopharyngeal reflux disease: the international project of young otolaryngologists of the international federation of oto-rhino-laryngological societies[J]. Eur Ann Otorhinolaryngol Head Neck Dis, 2018 ,135(5S):S85-S91.DOI: 10.1016/j.anorl.2018.05.013.
[15] Koufman J, Sataloff RT, Toohill R. Laryngopharyngeal reflux: consensus conference report[J]. J Voice, 1996,10(3):215-216. DOI: 10.1016/s0892-1997(96)80001-4.
[16] Wiener GJ, Koufman JA, Wu WC,et al. Chronic hoarseness secondary to gastroesophageal reflux disease: documentation with 24-h ambulatory pH monitoring[J]. Am J Gastroenterol, 1989,84(12):1503-1508.
[17] Ossakow SJ, Elta G, Colturi T,et al. Esophageal reflux and dysmotility as the basis for persistent cervical symptoms[J]. Ann Otol Rhinol Laryngol, 1987,96(4):387-392.DOI: 10.1177/000348948709600408.
[18] Johnston N, Dettmar PW, Strugala V,et al. Laryngopharyngeal reflux and GERD[J]. Ann N Y Acad Sci, 2013,1300:71-79.DOI: 10.1111/nyas.12237.
[19] Galli J, Meucci D, Salonna G,et al. Use of NBI for the assessment of clinical signs of rhino-pharyngo-laryngeal reflux in pediatric age: preliminary results[J]. Int J Pediatr Otorhinolaryngol, 2020 ,128:109733. DOI: 10.1016/j.ijporl.2019.109733.
[20] Lechien JR, Akst LM, Hamdan AL,et al. Evaluation and management of laryngopharyngeal reflux disease: state of the art review[J]. Otolaryngol Head Neck Surg, 2019 ,160(5):762-782.DOI: 10.1177/0194599819827488.
[21] Horvath L, Fostiropoulos K, Burri E, et al. Value of transnasal esophagoscopy in the workup of laryngo-pharyngeal reflux[J]. J Clin Med, 2021,10(14):3188.DOI: 10.3390/jcm10143188.
[22] Gill GA, Johnston N, Buda A,et al. Laryngeal epithelial defenses against laryngopharyngeal reflux: investigations of E-cadherin, carbonic anhydrase isoenzyme III, and pepsin[J]. Ann Otol Rhinol Laryngol, 2005 ,114(12):913-921. DOI: 10.1177/000348940511401204.
[23] Ciorba A, Bianchini C, Pelucchi S,et al. Gastroesophageal reflux and its possible role in the pathogenesis of upper aerodigestive tract disorders[J]. Minerva Gastroenterol Dietol,2007,53(2):171-180.
[24] Toohill RJ, Kuhn JC. Role of refluxed acid in pathogenesis of laryngeal disorders[J]. Am J Med, 1997,103(5A):100S-106S.DOI: 10.1016/s0002-9343(97)00333-1.
[25] Locke GR, Talley NJ, Fett SL,et al. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in olmsted county, minnesota[J]. Gastroenterology, 1997,112(5):1448-1456.DOI: 10.1016/s0016-5085(97)70025-8.
[26] Mariani G, Boni G, Barreca M,et al. Radionuclide gastroesophageal motor studies[J]. J Nucl Med, 2004,45(6):1004-1028.
[27] Contencin P, Narcy P. Nasopharyngeal pH monitoring in infants and children with chronic rhinopharyngitis[J]. Int J Pediatr Otorhinolaryngol, 1991,22(3):249-256. DOI: 10.1016/0165-5876(91)90079-q.
[28] Sereg-Bahar M, Jerin A, Jansa R,et al. Pepsin and bile acids in saliva in patients with laryngopharyngeal reflux - a prospective comparative study[J]. Clin Otolaryngol, 2015,40(3):234-239.DOI: 10.1111/coa.12358.
[29] Lee YC, Kwon OE, Park JM,et al. Do laryngoscopic findings reflect the characteristics of reflux in patients with laryngopharyngeal reflux?[J]. Clin Otolaryngol, 2018,43(1):137-143. DOI: 10.1111/coa.12914.
[30] Borges LF, Chan WW, Carroll TL. Dual pH probes without proximal esophageal and pharyngeal impedance may be deficient in diagnosing LPR[J]. J Voice, 2019,33(5):697-703.DOI: 10.1016/j.jvoice.2018.03.008.
[31] Gupta N, Green RW, Megwalu UC. Evaluation of a laryngopharyngeal reflux management protocol[J]. Am J Otolaryngol, 2016 ,37(3):245-250.DOI: 10.1016/j.amjoto.2016.01.008.
[32] Galli J, Cammarota G, De Corso E,et al. Biliary laryngopharyngeal reflux: a new pathological entity[J]. Curr Opin Otolaryngol Head Neck Surg, 2006,14(3):128-132.DOI: 10.1097/01.moo.0000193198.40096.be.
[33] Lee JS, Jung AR, Park JM,et al. Comparison of characteristics according to reflux type in patients with laryngopharyngeal reflux[J]. Clin Exp Otorhinolaryngol, 2018,11(2):141-145.DOI: 10.21053/ceo.2017.00577.
[34] Hoppo T, Sanz AF, Nason KS,et al. How much pharyngeal exposure is "normal"? Normative data for laryngopharyngeal reflux events using hypopharyngeal multichannel intraluminal impedance (HMII)[J]. J Gastrointest Surg, 2012,16(1):16-24.DOI: 10.1007/s11605-011-1741-1.
[35] Lechien JR, Bobin F, Dapri G,et al. Hypopharyngeal-esophageal impedance-pH monitoring profiles of laryngopharyngeal reflux patients[J]. Laryngoscope,2021,131(2):268-276.DOI: 10.1002/lary.28736.
[36] Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS)[J]. Laryngoscope, 2001,111(8):1313-1317. DOI: 10.1097/00005537-200108000-00001.
[37] Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI)[J]. J Voice,2002,16(2):274-277.DOI: 10.1016/s0892-1997(02)00097-8.
[38] Luo HN, Yang QM, Sheng Y,et al. Role of pepsin and pepsinogen: linking laryngopharyngeal reflux with otitis media with effusion in children[J]. Laryngoscope, 2014,124(7):E294-300.DOI: 10.1002/lary.24538.
[39] May JG, Shah P, Lemonnier L,et al. Systematic review of endoscopic airway findings in children with gastroesophageal reflux disease[J]. Ann Otol Rhinol Laryngol,2011,120(2):116-122. DOI: 10.1177/000348941112000208.
[40] Lechien JR, Saussez S, Schindler A,et al. Clinical outcomes of laryngopharyngeal reflux treatment: a systematic review and meta-analysis[J]. Laryngoscope,2019,129(5):1174-1187.DOI: 10.1002/lary.27591.
[41] Han H, Lv Q. Characteristics of laryngopharyngeal reflux in patients with chronic otitis media[J]. Am J Otolaryngol, 2018 ,39(5):493-496.DOI: 10.1016/j.amjoto.2018.05.010.
[42] Avincsal MO, Altundag A, Ulusoy S,et al. Halitosis associated volatile sulphur compound levels in patients with laryngopharyngeal reflux[J]. Eur Arch Otorhinolaryngol,2016,273(6):1515-1520.DOI: 10.1007/s00405-016-3961-1.
[43] Altundag A, Cayonu M, Salihoglu M,et al. Laryngopharyngeal reflux Has negative effects on taste and smell functions[J]. Otolaryngol Head Neck Surg, 2016,155(1):117-121.DOI: 10.1177/0194599816640249.
[44] Musser J, Kelchner L, Neils-Strunjas J,et al. A comparison of rating scales used in the diagnosis of extraesophageal reflux[J]. J Voice, 2011,25(3):293-300. DOI: 10.1016/j.jvoice.2009.11.009.
[45] Chang BA, MacNeil SD, Morrison MD,et al. The reliability of the reflux finding score among general otolaryngologists[J]. J Voice, 2015 ,29(5):572-577. DOI: 10.1016/j.jvoice.2014.10.009.
[46] Jetté ME, Gaumnitz EA, Birchall MA,et al. Correlation between reflux and multichannel intraluminal impedance pH monitoring in untreated volunteers[J]. Laryngoscope, 2014,124(10):2345-2351. DOI: 10.1002/lary.24737.
[47] van der Pol RJ, Singendonk MM, König AM,et al. Development of the reflux finding score for infants and its observer agreement[J]. J Pediatr,2014,165(3):479-484.DOI: 10.1016/j.jpeds.2014.05.022.
[48] Włodarczyk E, Jetka T, Miaśkiewicz B,et al. Validation and reliability of polish version of the reflux symptoms index and reflux finding score[J]. Healthcare (Basel), 2022,10(8):1411. DOI: 10.3390/healthcare10081411.
[49] 腺样体肥大与胃内容物反流的相关性研究[D].银川:宁夏医科大学,2019.
[50] Lechien JR, Schindler A, De Marrez LG,et al. Instruments evaluating the clinical findings of laryngopharyngeal reflux: a systematic review[J]. Laryngoscope, 2019,129(3):720-736.DOI: 10.1002/lary.27537.
[51] Lechien JR, Rodriguez Ruiz A, Dequanter D,et al. Validity and reliability of the reflux sign assessment[J]. Ann Otol Rhinol Laryngol, 2020,129(4):313-325.DOI: 10.1177/0003489419888947.
[52] Lechien JR, Bobin F, Muls V,et al. Validity and reliability of the reflux symptom score[J]. Laryngoscope, 2020,130(3):E98-E107.DOI: 10.1002/lary.28017.
[53] Zerbib F, Roman S, Bruley Des Varannes S, et al. Normal values of pharyngeal and esophageal 24-hour pH impedance in individuals on and off therapy and interobserver reproducibility[J]. Clin Gastroenterol Hepatol, 2013,11(4):366-372.DOI: 10.1016/j.cgh.2012.10.041.
[54] Falk GL, Beattie J, Ing A,et al. Scintigraphy in laryngopharyngeal and gastroesophageal reflux disease: a definitive diagnostic test?[J]. World J Gastroenterol, 2015,21(12):3619-3627. DOI: 10.3748/wjg.v21.i12.3619.
[55] Park JS, Khoma O, Burton L,et al. A new diagnostic paradigm for laryngopharyngeal reflux disease: correlation of impedance-pH monitoring and digital reflux scintigraphy results[J]. Eur Arch Otorhinolaryngol,2021 ,278(6):1917-1926.DOI: 10.1007/s00405-021- 06658-z.
[56] Vaezi MF, Katzka D, Zerbib F. Extraesophageal symptoms and diseases attributed to GERD: where is the pendulum swinging now?[J]. Clin Gastroenterol Hepatol, 2018,6(7):1018-1029.DOI: 10.1016/j.cgh.2018.02.001.
[57] Nostrant TT. Gastroesophageal reflux and laryngitis: a skeptic's view[J]. Am J Med, 2000,8 Suppl 4a:149S-152S.DOI: 10.1016/s0002-9343(99)00355-1.
[58] Kang JW, Lee YC, Ko SG,et al. The key timing of pharyngeal reflux in patients with laryngopharyngeal reflux[J]. Auris Nasus Larynx,2023 ,50(4):565-570.DOI: 10.1016/j.anl.2022.11.002.
[59] Zalvan CH, Hu S, Greenberg B,et al. A comparison of alkaline water and mediterranean diet vs proton pump inhibition for treatment of laryngopharyngeal reflux[J]. JAMA Otolaryngol Head Neck Surg, 2017,143(10):1023-1029.DOI: 10.1001/jamaoto.2017.1454.
[60] Lechien JR, Huet K, Khalife M,et al. Alkaline, protein, low-fat and low-acid diet in laryngopharyngeal reflux disease: our experience on 65 patients[J]. Clin Otolaryngol, 2019,44(3):379-384.DOI: 10.1111/coa.13269.
[61] 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[J]. Eur Arch Otorhinolaryngol,2020 ,277(2):511-520.DOI: 10.1007/s00405-019-05711-2.
[62] Krause AJ, Walsh EH, Weissbrod PA,et al. An update on current treatment strategies for laryngopharyngeal reflux symptoms[J]. Ann N Y Acad Sci, 2022,1510(1):5-17. DOI: 10.1111/nyas.14728.
[63] Lechien JR, Finck C, Huet K,et al. Impact of age on laryngopharyngeal reflux disease presentation: a multi-center prospective study[J]. Eur Arch Otorhinolaryngol, 2017,274(10):3687-3696.DOI: 10.1007/s00405-017-4671-z.
[64] Rohof WO, Bennink RJ, Smout AJ,et al. An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease[J]. Clin Gastroenterol Hepatol,2013,11(12):1585-1591.DOI: 10.1016/j.cgh.2013.04.046.
[65] Hampson FC, Jolliffe IG, Bakhtyari A,et al. Alginate-antacid combinations: raft formation and gastric retention studies[J]. Drug Dev Ind Pharm, 2010,36(5):614-623.DOI: 10.3109/03639040903388290.
[66] Kwiatek MA, Roman S, Fareeduddin A,et al. An alginate-antacid formulation (gaviscon double action liquid) can eliminate or displace the postprandial 'acid pocket' in symptomatic GERD patients[J]. Aliment Pharmacol Ther,2011,34(1):59-66.DOI: 10.1111/j.1365-2036.2011.04678.x.
[67] Malmud LS, Charkes ND, Littlefield J,et al. The mode of action alginic acid compound in the reduction of gastroesophageal reflux[J]. J Nucl Med,1979,20(10):1023-1028.
[68] Bytzer P. What makes individuals with gastroesophageal reflux disease dissatisfied with their treatment?[J].Clin Gastroenterol Hepatol,2009,7(8):816-822.DOI: 10.1016/j.cgh.2009.03.006.
[69] Reimer C, Lødrup AB, Smith G,et al. Randomised clinical trial: alginate (gaviscon advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor[J]. Aliment Pharmacol Ther, 2016,43(8):899-909.DOI: 10.1111/apt.13567.
[70] Lee YC, Jung AR, Kwon OE,et al. The effect of baclofen combined with a proton pump inhibitor in patients with refractory laryngopharyngeal reflux: a prospective, open-label study in thirty-two patients[J]. Clin Otolaryngol, 2019,44(3):431-434.DOI: 10.1111/coa.13297.
[71] Li S, Shi S, Chen F,et al. The effects of baclofen for the treatment of gastroesophageal reflux disease: a meta-analysis of randomized controlled trials[J]. Gastroenterol Res Pract, 2014,2014:307805.DOI: 10.1155/2014/307805.
[72] Xu XH, Yang ZM, Chen Q,et al. Therapeutic efficacy of baclofen in refractory gastroesophageal reflux-induced chronic cough[J]. World J Gastroenterol, 2013,19(27):4386-4392.DOI: 10.3748/wjg.v19.i27.4386.
[73] Hoppo T, Komatsu Y, Nieponice A,et al. Toward an improved understanding of isolated upright reflux: positional effects on the lower esophageal sphincter in patients with symptoms of gastroesophageal reflux[J]. World J Surg,2012,36(7):1623-1631.DOI: 10.1007/s00268-012-1537-9.
[74] Saritas Yuksel E, Hong SK, Strugala V,et al. Rapid salivary pepsin test: blinded assessment of test performance in gastroesophageal reflux disease[J]. Laryngoscope,2012,122(6):1312-1316.DOI: 10.1002/lary.23252.
[75] Yadlapati R, Pandolfino JE, Greytak M,et al. Upper esophageal sphincter compression device as an adjunct to proton pump inhibition for laryngopharyngeal reflux[J]. Dig Dis Sci, 2022 ,67(7):3045-3054.DOI: 10.1007/s10620-021-07172-2.
[76] Hicks DM, Ours TM, Abelson TI,et al. The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers[J]. J Voice, 2002,16(4):564-579.DOI: 10.1016/s0892-1997(02)00132-7.
[77] Ates F, Yuksel ES, Higginbotham T,et al. Mucosal impedance discriminates GERD from non-GERD conditions[J]. Gastroenterology,2015 ,148(2):334-343. DOI: 10.1053/j.gastro.2014.10.010.
[78] Spyridoulias A, Lillie S, Vyas A,et al. Detecting laryngopharyngeal reflux in patients with upper airways symptoms: symptoms, signs or salivary pepsin?[J]. Respir Med, 2015,109(8):963-969.DOI: 10.1016/j.rmed.2015.05.019.
[79] Lechien JR, Dapri G, Dequanter D,et al. Surgical treatment for laryngopharyngeal reflux disease: a systematic review[J]. JAMA Otolaryngol Head Neck Surg,2019,145(7):655-666.DOI: 10.1001/jamaoto.2019.0315.
[80] Ward MA, Ebrahim A, Kopita J,et al. Magnetic sphincter augmentation is an effective treatment for atypical symptoms caused by gastroesophageal reflux disease[J]. Surg Endosc, 2020 ,34(11):4909-4915. DOI: 10.1007/s00464-019-07278-9.
[81] Saki N, Samarbaf Zadeh AR, Sheikhpour Jonaky R,et al. The prevalence rate of helicobacter pylori infection in, chronic otitis media with effusion patients[J]. Jundishapur J Microbiol,2014,7(3):e15694.DOI: 10.5812/jjm.15694.
[82] Dowsett SA, Kowolik MJ. Oral helicobacter pylori: can we stomach it?[J].Crit Rev Oral Biol Med,2003,14(3):226-233.DOI: 10.1177/154411130301400307.
[83] Katra R, Kabelka Z, Jurovcik M,et al. Pilot study: association between helicobacter pylori in adenoid hyperplasia and reflux episodes detected by multiple intraluminal impedance in children[J]. Int J Pediatr Otorhinolaryngol,2014 ,78(8):1243-1249.DOI: 10.1016/j.ijporl.2014.04.040.
[84] Ali MS, Parikh S, Chater P,et al. Bile acids in laryngopharyngeal refluxate: will they enhance or attenuate the action of pepsin?[J]. Laryngoscope,2013,123(2):434-439.DOI: 10.1002/lary.23619.
[85] 黄俣栋,谭嘉杰,韩晓燕,等. 儿童腺样体肥大与咽喉反流的相关性研究[J]. 临床耳鼻咽喉头颈外科杂志,2018,32(12):899-904. DOI:10.13201/j.issn.1001-1781.2018.12.005.
[86] 刘伟清,季永红,张国华. 腺样体肥大患者的临床特征及咽喉反流与病情严重程度的相关性分析[J]. 系统医学,2023,8(3):167-170,193. DOI:10.19368/j.cnki.2096- 1782. 2023.03.167.
[87] Wilkinson J, Wade A, Thomas SJ,et al. Randomized clinical trial: a double-blind, placebo-controlled study to assess the clinical efficacy and safety of alginate-antacid (gaviscon double action) chewable tablets in patients with gastro-oesophageal reflux disease[J]. Eur J Gastroenterol Hepatol, 2019,31(1):86-93.DOI: 10.1097/MEG.0000000000001258.
[88] 林枫,赵晶,陆颖霞,等. 儿童腺样体肥大伴咽喉反流的临床特征分析[J]. 中华耳鼻咽喉头颈外科杂志,2024,59(2):140-146. DOI:10.3760/cma.j.cn115330-20231221- 00318.