[en] [en] OBJECTIVE: To review the current literature about the epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux (LPR).
DATA SOURCES: PubMed, Cochrane Library, and Scopus.
METHODS: A comprehensive review of the literature on LPR epidemiology, clinical presentation, diagnosis, and treatment was conducted. Using the PRISMA statement, 3 authors selected relevant publications to provide a critical analysis of the literature.
CONCLUSIONS: The important heterogeneity across studies in LPR diagnosis continues to make it difficult to summarize a single body of thought. Controversies persist concerning epidemiology, clinical presentation, diagnosis, and treatment. No recent epidemiologic study exists regarding prevalence and incidence with the use of objective diagnostic tools. There is no survey that evaluates the prevalence of symptoms and signs on a large number of patients with confirmed LPR. Regarding diagnosis, an increasing number of authors used multichannel intraluminal impedance-pH monitoring, although there is no consensus regarding standardization of the diagnostic criteria. The efficiency of proton pump inhibitor (PPI) therapy remains poorly demonstrated and misevaluated by incomplete clinical tools that do not take into consideration many symptoms and extralaryngeal findings. Despite the recent advances in knowledge about nonacid LPR, treatment protocols based on PPIs do not seem to have evolved.
IMPLICATIONS FOR PRACTICE: The development of multichannel intraluminal impedance-pH monitoring and pepsin and bile salt detection should be considered for the establishment of a multiparameter diagnostic approach. LPR treatment should evolve to a more personalized regimen, including diet, PPIs, alginate, and magaldrate according to individual patient characteristics. Multicenter international studies with a standardized protocol could improve scientific knowledge about LPR.
Disciplines :
Otolaryngology
Author, co-author :
Lechien, Jerome R; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 2 Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium ; 3 Laboratory of Phonetics, Faculty of Psychology, Research Institute for Language Sciences and Technology, University of Mons, Mons, Belgium ; 4 Department of Otorhinolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Faculty of Medicine, University Libre de Bruxelles, Brussels, Belgium
Akst, Lee M; 5 Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
Hamdan, Abdul Latif; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 6 Department of Otorhinolaryngology and Head and Neck Surgery, American University of Beirut Medical Center, Beirut, Lebanon
Schindler, Antonio; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 7 Department of Biomedical and Clinical Sciences, Phoniatric Unit, L. Sacco Hospital, University of Milan, Milan, Italy
Karkos, Petros D; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 8 Department of Otorhinolaryngology and Head and Neck Surgery, Thessaloniki Medical School, Thessaloniki, Greece
Barillari, Maria Rosaria; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 9 Division of Phoniatrics and Audiology, Department of Mental and Physical Health and Preventive Medicine, University of Naples SUN, Naples, Italy
Calvo-Henriquez, Christian; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 10 Department of Otorhinolaryngology and Head and Neck Surgery, Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain
Crevier-Buchman, Lise; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 11 Department of Otorhinolaryngology and Head and Neck Surgery, Foch Hospital, Paris, France
Finck, Camille ; Université de Liège - ULiège > Département des sciences cliniques > Phoniatrie ; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 2 Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium
Eun, Young-Gyu; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 13 Department of Otorhinolaryngology and Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Korea
Saussez, Sven; 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France ; 2 Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium ; 4 Department of Otorhinolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Faculty of Medicine, University Libre de Bruxelles, Brussels, Belgium
Vaezi, Michael F; 14 Division of Gastroenterology, Hepatology, Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Language :
English
Title :
Evaluation and Management of Laryngopharyngeal Reflux Disease: State of the Art Review.
Koufman JA, Aviv JE, Casiano RR, Shaw GY., Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology—Head and Neck Surgery. Otolaryngol Head Neck Surg. 2002;127:32-35.
Amarasiri DL, Pathmeswaran A, de Silva HJ, Ranasinha CD., Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study. BMC Pulm Med. 2013;13:33.
Lechien JR, Saussez S, Schindler A. Symptoms and signs outcomes of laryngopharyngeal reflux treatment: a critical systematic review and meta-analysis. Laryngoscope. In press.
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. Laryngoscope. 1991;101(4)(pt 2, suppl 53):1-78.
Akst LM, Haque OJ, Clarke JO, Hillel AT, Best SR, Altman KW., The changing impact of gastroesophageal reflux disease in clinical practice. Ann Otol Rhinol Laryngol. 2017;126:229-235.
Sandler RS, Everhart JE, Donowitz M. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122:1500-1511.
Francis DO, Rymer JA, Slaughter JC. High economic burden of caring for patients with suspected extraesophageal reflux. Am J Gastroenterol. 2013;108:905-911.
Gaynor EB., Otolaryngologic manifestations of gastroesophageal reflux. Am J Gastroenterol. 1991;86:801-808.
Connor NP, Palazzi-Churas KL, Cohen SB. Symptoms of extraesophageal reflux in a community-dwelling sample. J Voice. 2007;21:189-202.
Li J, Zhang L, Zhang C, Cheng JY, Li J, Jeff Cheng CF., Linguistic adaptation, reliability, validation, and responsivity of the Chinese version of Reflux Symptom Index. J Voice. 2016;30:104-108.
Chen XM, Li Y, Guo WL, Wang WT, Lu M., Prevalence of laryngopharyngeal reflux disease in Fuzhou region of China. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51:909-913.
Spantideas N, Drosou E, Bougea A, Assimakopoulos D., Laryngopharyngeal reflux disease in the Greek general population, prevalence and risk factors. BMC Ear Nose Throat Disord. 2015;15:7.
Kamani T, Penney S, Mitra I, Pothula V., The prevalence of laryngopharyngeal reflux in the English population. Eur Arch Otorhinolaryngol. 2012;269:2219-2225.
Eren E, Arslanoğlu S, Aktaş A. Factors confusing the diagnosis of laryngopharyngeal reflux: the role of allergic rhinitis and inter-rater variability of laryngeal findings. Eur Arch Otorhinolaryngol. 2014;271:743-747.
Randhawa PS, Mansuri S, Rubin JS., Is dysphonia due to allergic laryngitis being misdiagnosed as laryngopharyngeal reflux?Logoped Phoniatr Vocol. 2010;35:1-5.
Koufman JA, Amin MR, Panetti M., Prevalence of reflux in 113 consecutive patients with laryngeal and voice disorders. Otolaryngol Head Neck Surg. 2000;123:385-388.
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;40:234-239.
Lee YC, Kwon OE, Park JM, Eun YG., Do laryngoscopic findings reflect the characteristics of reflux in patients with laryngopharyngeal reflux?Clin Otolaryngol. 2018;43:137-143.
Borges LF, Chan WW, Carroll TL., Dual pH probes without proximal esophageal and pharyngeal impedance may be deficient in diagnosing LPR [published online August 3, 2018]. J Voice. doi:10.1016/j.jvoice.2018.03.008
Ali Mel-S, Bulmer DM, Dettmar PW, Pearson JP. Mucin gene expression in reflux laryngeal mucosa: histological and in situ hybridization observations. Int J Otolaryngol. 2014;2014:264075.
Adhami T, Goldblum JR, Richter JE, Vaezi MF., The role of gastric and duodenal agents in laryngeal injury: an experimental canine model. Am J Gastroenterol. 2004;99:2098-2106.
Lechien JR, Saussez S, Harmegnies B. Laryngopharyngeal reflux and voice disorders: a multifactorial model of etiology and pathophysiology. J Voice. 2017;31:733-752.
Wang J, Yu Z, Ren J. Effects of pepsin A on heat shock protein 70 response in laryngopharyngeal reflux patients with chronic rhinosinusitis. Acta Otolaryngol. 2017;137:1253-1259.
Gong X, Wang XY, Yang L. Detecting laryngopharyngeal reflux by immunohistochemistry of pepsin in the biopsies of vocal fold leukoplakia. J Voice. 2018;32:352-355.
Lechien JR, Finck C, Huet K. Impact of laryngopharyngeal reflux on subjective, aerodynamic, and acoustic voice assessments of responder and nonresponder patients [published online July 26, 2018]. J Voice. doi:10.1016/j.jvoice.2018.05.014
Ren JJ, Zhao Y, Wang J. PepsinA as a marker of laryngopharyngeal reflux detected in chronic rhinosinusitis patients. Otolaryngol Head Neck Surg. 2017;156:893-900.
Johnston N, Ondrey F, Rosen R. Airway reflux. Ann N Y Acad Sci. 2016;1381:5-13.
Kim Y, Lee YJ, Park JS. Associations between obstructive sleep apnea severity and endoscopically proven gastroesophageal reflux disease. Sleep Breath. 2018;22:85-90.
Habermann W, Schmid C, Neumann K. Reflux Symptom Index and Reflux Finding Score in otolaryngologic practice. J Voice. 2012;26:e123-e127.
Lee YS, Choi SH, Son YI, Park YH, Kim SY, Nam SY., Prospective, observational study using rabeprazole in 455 patients with laryngopharyngeal reflux disease. Eur Arch Otorhinolaryngol. 2011;268:863-869.
Chappity P, Kumar R, Deka RC, Chokkalingam V, Saraya A, Sikka K., Proton pump inhibitors versus solitary lifestyle modification in management of laryngopharyngeal reflux and evaluating who is at risk: scenario in a developing country. Clin Med Insights Ear Nose Throat. 2014;7:1-5.
Dore MP, Pedroni A, Pes GM. Effect of antisecretory therapy on atypical symptoms in gastroesophageal reflux disease. Dig Dis Sci. 2007;52:463-468.
Youssef TF, Ahmed MR., Treatment of clinically diagnosed laryngopharyngeal reflux disease. Arch Otolaryngol Head Neck Surg. 2010;136:1089-1092.
Zalvan CH, Hu S, Greenberg B, Geliebter J., A comparison of alkaline water and Mediterranean diet vs proton pump inhibition for treatment of laryngopharyngeal reflux. JAMA Otolaryngol Head Neck Surg. 2017;143:1023-1029.
Lee JS, Lee YC, Kim SW, Kwon KH, Eun YG., Changes in the quality of life of patients with laryngopharyngeal reflux after treatment. J Voice. 2014;28:487-491.
Drinnan M, Powell J, Nikkar-Esfahani A. Gastroesophageal and extraesophageal reflux symptoms: similarities and differences. Laryngoscope. 2015;125:424-430.
Vaezi MF, Richter JE, Stasney CR. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope. 2006;116:254-260.
Hanson DG, Kamel PL, Kahrilas PJ., Outcomes of antireflux therapy for the treatment of chronic laryngitis. Ann Otol Rhinol Laryngol. 1995;104:550-555.
Nunes HS, Pinto JA, Zavanela AR, Cavallini AF, Freitas GS, Garcia FE., Comparison between the Reflux Finding Score and the Reflux Symptom Index in the practice of otorhinolaryngology. Int Arch Otorhinolaryngol. 2016;20:218-221.
Andersson O, Rydén A, Ruth M, Möller RY, Finizia C., Development and validation of a laryngopharyngeal reflux questionnaire, the Pharyngeal Reflux Symptom Questionnaire. Scand J Gastroenterol. 2010;45:147-159.
Gao CK, Li YF, Wang L. Different cutoffs of the Reflux Finding Score for diagnosing laryngopharyngeal reflux disease should be used for different genders. Acta Otolaryngol. 2018;138:848-854.
Mendelsohn AH., The effects of reflux on the elderly: the problems with medications and interventions. Otolaryngol Clin North Am. 2018;51:779-787.
Lechien JR, Finck C, Huet K. Impact of age on laryngopharyngeal reflux disease presentation: a multi-center prospective study. Eur Arch Otorhinolaryngol. 2017;274:3687-3696.
Lechien JR, Huet K, Khalife M. Gender differences in the presentation of dysphonia related to laryngopharyngeal reflux disease: a case-control study. Eur Arch Otorhinolaryngol. 2018;275:1513-1524.
Belafsky PC, Postma GN, Koufman JA., The validity and reliability of the Reflux Finding Score (RFS). Laryngoscope. 2001;111:1313-1317.
Musser J, Kelchner L, Neils-Strunjas J, Montrose M., A comparison of rating scales used in the diagnosis of extraesophageal reflux. J Voice. 2011;25:293-300.
Chang BA, MacNeil SD, Morrison MD, Lee PK., The reliability of the Reflux Finding Score among general otolaryngologists. J Voice. 2015;29:572-577.
Jaspersen D, Kulig M, Labenz J. Prevalence of extra-oesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD Study. Aliment Pharmacol Ther. 2003;17:1515-1520.
Koufman JA., Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease. Ear Nose Throat J. 2002;81(9)(suppl 2):7-9.
Patel D, Vaezi MF., Normal esophageal physiology and laryngopharyngeal reflux. Otolaryngol Clin N Am. 2013;46:1023-1041.
Perry KA, Enestvedt CK, Lorenzo CS. The integrity of esophagogastric junction anatomy in patients with isolated laryngopharyngeal reflux symptoms. J Gastrointest Surg. 2008;12:1880-1887.
Vaezi MF, Hicks DM, Abelson TI, Richter JE., Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol. 2003;1:333-344.
Hoppo T, Sanz AF, Nason KS. How much pharyngeal exposure is “normal”? Normative data for laryngopharyngeal reflux events using hypopharyngeal multichannel intraluminal impedance (HMII). J Gastrointest Surg. 2012;16:16-24.
Zelenik K, Kajzrlikova IM, Vitek P, Urban O, Hanousek M, Kominek P., There is no correlation between signs of reflux laryngitis and reflux oesophagitis in patients with gastro-oesophageal reflux disease symptoms. Acta Otorhinolaryngol Ital. 2017;37:401-405.
Reichel O, Issing WJ., Should patients with pH-documented laryngopharyngeal reflux routinely undergo oesophagogastroduodenoscopy? A retrospective analysis. J Laryngol Otol. 2007;121:1165-1169.
Lai YC, Wang PC, Lin JC., Laryngopharyngeal reflux in patients with reflux esophagitis. World J Gastroenterol. 2008;14:4523-4528.
Groome M, Cotton JP, Borland M, McLeod S, Johnston DA, Dillon JF., Prevalence of laryngopharyngeal reflux in a population with gastroesophageal reflux. Laryngoscope. 2007;117:1424-1428.
Nason KS, Murphy T, Schindler J,; Barrett’s Esophagus Risk Consortium. A cross-sectional analysis of the prevalence of Barrett esophagus in otolaryngology patients with laryngeal symptoms. J Clin Gastroenterol. 2013;47:762-768.
Lechien JR, Schindler A, De Marrez LG. Instruments evaluating the clinical findings of laryngopharyngeal reflux: a systematic review [published online October 6, 2018]. Laryngoscope. doi:10.1002/lary.27537
Belafsky PC, Postma GN, Koufman JA., Validity and reliability of the Reflux Symptom Index (RSI). J Voice. 2002;16:274-277.
Wilson JA, Deary IJ, Maran AG., The persistence of symptoms in patients with globus pharyngis. Clin Otolaryngol Allied Sci. 1991;16:202-205.
Deary IJ, Wilson JA, Harris MB, MacDougall G., Globus pharyngis: development of a symptom assessment scale. J Psychosom Res. 1995;39:203-213.
Carrau RL, Khidr A, Gold KF. Validation of a quality-of-life instrument for laryngopharyngeal reflux. Arch Otolaryngol Head Neck Surg. 2005;131:315-320.
Dauer E, Thompson D, Zinsmeister AR. Supraesophageal reflux: validation of a symptom questionnaire. Otolaryngol Head Neck Surg. 2006;134:73-80.
Papakonstantinou L, Leslie P, Gray J, Chadwick T, Hudson M, Wilson JA., Laryngopharyngeal reflux: a prospective analysis of a 34 item symptom questionnaire. Clin Otolaryngol. 2009;34:455-459.
Hicks DM, Ours TM, Abelson TI, Vaezi MF, Richter JE., The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice. 2002;16:564-579.
Beaver ME, Stasney CR, Weitzel E. Diagnosis of laryngopharyngeal reflux disease with digital imaging. Otolaryngol Head Neck Surg. 2003;128:103-108.
Williams RB, Szczesniak MM, Maclean JC, Brake HM, Cole IE, Cook IJ., Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis. Am J Gastroenterol. 2004;99:777-785.
Steward DL, Wilson KM, Kelly DH. Proton pump inhibitor therapy for chronic laryngo-pharyngitis: a randomized placebo-control trial. Otolaryngol Head Neck Surg. 2004;131:342-350.
Vaezi MF, Richter JE, Stasney CR. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope. 2006;116:254-260.
Schindler A, Mozzanica F, Ginocchio D, Peri A, Bottero A, Ottaviani F., Reliability and clinical validity of the Italian Reflux Symptom Index. J Voice. 2010;24:354-358.
Lechien JR, Huet K, Finck C. Validity and reliability of a French version of Reflux Symptom Index. J Voice. 2017;31:512.e1-e7.
Calvo-Henríquez C, Ruano-Ravina A, Vaamonde P. Translation and validation of the Reflux Symptom Index to Spanish [published online July 31, 2018]. J Voice. doi:10.1016/j.jvoice.2018.04.019
Lapeña JFF, Jr Ambrocio GMC, Carrillo RJD., Validity and reliability of the Filipino Reflux Symptom Index. J Voice. 2017;31:387.e11-e16.
Farahat M, Malki KH, Mesallam TA., Development of the Arabic version of Reflux Symptom Index. J Voice. 2012;26:814.e15-e19.
Printza A, Kyrgidis A, Oikonomidou E, Triaridis S., Assessing laryngopharyngeal reflux symptoms with the Reflux Symptom Index: validation and prevalence in the Greek population. Otolaryngol Head Neck Surg. 2011;145:974-980.
Karkos PD, Wilson JA., Empiric treatment of laryngopharyngeal reflux with proton pump inhibitors: a systematic review. Laryngoscope. 2006;116:144-148.
Chen M, Hou C, Chen T. Reflux Symptom Index and Reflux Finding Score in 91 asymptomatic volunteers. Acta Otolaryngol. 2018;138:659-663.
Han H, Lv Q., Characteristics of laryngopharyngeal reflux in patients with chronic otitis media. Am J Otolaryngol. 2018;39:493-496.
Avincsal MO, Altundag A, Ulusoy S. Halitosis associated volatile sulphur compound levels in patients with laryngopharyngeal reflux. Eur Arch Otorhinolaryngol. 2016;273:1515-1520.
Lechien JR, Schindler A, Hamdan 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. Eur Ann Otorhinolaryngol Head Neck Dis. 2018;135(5S):S85-S91.
Milstein CF, Charbel S, Hicks DM, Abelson TI, Richter JE, Vaezi MF., Prevalence of laryngeal irritation signs associated with reflux in asymptomatic volunteers: impact of endoscopic technique (rigid vs flexible laryngoscope). Laryngoscope. 2005;115:2256-2261.
Altundag A, Cayonu M, Salihoglu M. Laryngopharyngeal reflux has negative effects on taste and smell functions. Otolaryngol Head Neck Surg. 2016;155:117-121.
Jetté ME, Gaumnitz EA, Birchall MA, Welham NV, Thibeault SL., Correlation between reflux and multichannel intraluminal impedance pH monitoring in untreated volunteers. Laryngoscope. 2014;124:2345-2351.
Witt DR, Chen H, Mielens JD. Detection of chronic laryngitis due to laryngopharyngeal reflux using color and texture analysis of laryngoscopic images. J Voice. 2014;28:98-105.
Ozturan O, Dogan R, Yenigun A, Veyseller B, Yildirim YS., Photographic objective alterations for laryngopharyngeal reflux diagnosis. J Voice. 2017;31:78-85.
Nayak A, Kumar S, Arora R, Singh GB., Image analysis of interarytenoid area to detect cases of laryngopharyngeal reflux: an objective method. Am J Otolaryngol. 2018;39:171-174.
Merati AL, Lim HJ, Ulualp SO, Toohill RJ., Meta-analysis of upper probe measurements in normal subjects and patients with laryngopharyngeal reflux. Ann Otol Rhinol Laryngol. 2005;114:177-182.
Lee JS, Jung AR, Park JM, Park MJ, Lee YC, Eun YG., Comparison of characteristics according to reflux type in patients with laryngopharyngeal reflux. Clin Exp Otorhinolaryngol. 2018;11:141-145.
Galli J, Cammarota G, De Corso E. Biliary laryngopharyngeal reflux: a new pathological entity. Curr Opin Otolaryngol Head Neck Surg. 2006;14:128-132.
Becker V, Graf S, Schlag C. First agreement analysis and day-to-day comparison of pharyngeal pH monitoring with pH/impedance monitoring in patients with suspected laryngopharyngeal reflux. J Gastrointest Surg. 2012;16:1096-1101.
Gupta R, Sataloff RT., Laryngopharyngeal reflux: current concepts and questions. Curr Opin Otolaryngol Head Neck Surg. 2009;17:143-148.
Chander B, Hanley-Williams N, Deng Y, Sheth A., 24 versus 48-hour bravo pH monitoring. J Clin Gastroenterol. 2012;46:197-200.
Smit CF, Mathus-Vliegen LM, Devriese PP, van Leeuwen JA, Semin A., Monitoring of laryngopharyngeal reflux: influence of meals and beverages. Ann Otol Rhinol Laryngol. 2003;112:109-112.
Maldonado A, Diederich L, Castell DO, Gideon RM, Katz PO., Laryngopharyngeal reflux identified using a new catheter design: defining normal values and excluding artifacts. Laryngoscope. 2003;113:349-355.
Harrell SP, Koopman J, Woosley S, Wo JM., Exclusion of pH artifacts is essential for hypopharyngeal pH monitoring. Laryngoscope. 2007;117:470-474.
Nennstiel S, Andrea M, Abdelhafez M. pH/multichannel impedance monitoring in patients with laryngo-pharyngeal reflux symptoms—prediction of therapy response in long-term follow-up. Arab J Gastroenterol. 2016;17:113-116.
Francis DO, Goutte M, Slaughter JC. Traditional reflux parameters and not impedance monitoring predict outcome after fundoplication in extraesophageal reflux. Laryngoscope. 2011;121:1902-1909.
Wang AJ, Liang MJ, Jiang AY. Predictors of acid suppression success in patients with chronic laryngitis. Neurogastroenterol Motil. 2012;24:432-437, e210.
Park JO, Shim MR, Hwang YS. Combination of voice therapy and antireflux therapy rapidly recovers voice-related symptoms in laryngopharyngeal reflux patients. Otolaryngol Head Neck Surg. 2012;146:92-97.
Jiang A, Liang M, Su Z. Immunohistochemical detection of pepsin in laryngeal mucosa for diagnosing laryngopharyngeal reflux. Laryngoscope. 2011;121:1426-1430.
Wang AJ, Liang MJ, Jiang AY. Gastroesophageal and laryngopharyngeal reflux detected by 24-h combined impedance and pH monitoring in Chinese healthy volunteers. J Dig Dis. 2011;12:173-180.
Wang AJ, Liang MJ, Jiang AY. Comparison of patients of chronic laryngitis with and without troublesome reflux symptoms. J Gastroenterol Hepatol. 2012;27:579-585.
de Bortoli N, Nacci A, Savarino E. How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related? World J Gastroenterol. 2012;18:4363-4370.
Xiao YL, Liu FQ, Li J. Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance–pH monitoring. Neurogastroenterol Motil. 2012;24:e258-e265.
Wang AJ, Liang MJ, Jiang AY. Gastroesophageal and laryngopharyngeal reflux detected by 24-hour combined impedance and pH monitoring in healthy Chinese volunteers. J Dig Dis. 2011;12:173-180.
Wan Y, Yan Y, Ma F. LPR: how different diagnostic tools shape the outcomes of treatment. J Voice. 2014;28:362-368.
Mazzoleni G, Vailati C, Lisma DG, Testoni PA, Passaretti S., Correlation between oropharyngeal pH-monitoring and esophageal pH-impedance monitoring in patients with suspected GERD-related extra-esophageal symptoms. Neurogastroenterol Motil. 2014;26:1557-1564.
Falk M, Van der Wall H, Falk GL., Differences between scintigraphic reflux studies in gastrointestinal reflux disease and laryngopharyngeal reflux disease and correlation with symptoms. Nucl Med Commun. 2015;36:625-630.
Na SY, Kwon OE, Lee YC, Eun YG., Optimal timing of saliva collection to detect pepsin in patients with laryngopharyngeal reflux. Laryngoscope. 2016;126:2770-2773.
Cumpston EC, Blumin JH, Bock JM., Dual pH with multichannel intraluminal impedance testing in the evaluation of subjective laryngopharyngeal reflux symptoms. Otolaryngol Head Neck Surg. 2016;155:1014-1020.
Jung AR, Kwon OE, Park JM. Association between pepsin in the saliva and the subjective symptoms in patients with laryngopharyngeal reflux [published online November 24, 2017]. J Voice. doi:10.1016/j.jvoice.2017.10.015
Formánek M, Jančatová D, Komínek P, Tomanová R, Zeleník K., Comparison of impedance and pepsin detection in the laryngeal mucosa to determine impedance values that indicate pathological laryngopharyngeal reflux. Clin Transl Gastroenterol. 2017;8:e123.
Weitzendorfer M, Pfandner R, Antoniou SA. Role of pepsin and oropharyngeal pH-monitoring to assess the postoperative outcome of patients with laryngopharyngeal reflux: results of a pilot trial. J Laparoendosc Adv Surg Tech A. 2017;27:937-943.
Kim SI, Kwon OE, Na SY, Lee YC, Park JM, Eun YG., Association between 24-hour combined multichannel intraluminal impedance–pH monitoring and symptoms or quality of life in patients with laryngopharyngeal reflux. Clin Otolaryngol. 2017;42:584-591.
Du C, Al-Ramahi J, Liu Q, Yan Y, Jiang J., Validation of the laryngopharyngeal reflux color and texture recognition compared to pH-probe monitoring. Laryngoscope. 2017;127:665-670.
Dulery C, Lechot A, Roman S. A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors. Neurogastroenterol Motil. 2017;29(1). doi:10.1111/nmo.12909
Wang L, Tan JJ, Wu T. Association between laryngeal pepsin levels and the presence of vocal fold polyps. Otolaryngol Head Neck Surg. 2017;156:144-151.
Tseng WH, Tseng PH, Wu JF. Double-blind, placebo-controlled study with alginate suspension for laryngopharyngeal reflux disease. Laryngoscope. 2018;128:2252-2260.
Suzuki T, Seki Y, Okamoto Y, Hoppo T., Hypopharyngeal multichannel intraluminal impedance leads to the promising outcome of antireflux surgery in Japanese population with laryngopharyngeal reflux symptoms. Surg Endosc. 2018;32:2409-2419.
Chiou E, Rosen R, Jiang H, Nurko S., Diagnosis of supra-esophageal gastric reflux: correlation of oropharyngeal pH with esophageal impedance monitoring for gastro-esophageal reflux. Neurogastroenterol Motil. 2011;23:717-e326.
Ummarino D, Vandermeulen L, Roosens B, Urbain D, Hauser B, Vandenplas Y., Gastroesophageal reflux evaluation in patients affected by chronic cough: restech versus multichannel intraluminal impedance/pH metry. Laryngoscope. 2013;123:980-984.
Fuchs HF, Müller DT, Berlth F. 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. Dis Esophagus. 2018;31(10). doi:10.1093/dote/doy018
Ayazi S, Lipham JC, Hagen JA. A new technique for measurement of pharyngeal pH: normal values and discriminating pH threshold. J Gastrointest Surg. 2009;13:1422-1429.
Wiener GJ, Tsukashima R, Kelly C. Oropharyngeal pH monitoring for the detection of liquid and aerosolized supraesophageal gastric reflux. J Voice. 2009;23:498-504.
Vailati C, Mazzoleni G, Bondi S, Bussi M, Testoni PA, Passaretti S., Oropharyngeal pH monitoring for laryngopharyngeal reflux: is it a reliable test before therapy?J Voice. 2013;27:84-89.
Feng G, Wang J, Zhang L, Liu Y., A study to draw a normative database of laryngopharynx pH profile in Chinese. J Neurogastroenterol Motil. 2014;20:347-351.
Yuksel ES, Slaughter JC, Mukhtar N. An oropharyngeal pH monitoring device to evaluate patients with chronic laryngitis. Neurogastroenterol Motil. 2013;25:e315-e323.
Chheda NN, Seybt MW, Schade RR, Postma GN., Normal values for pharyngeal pH monitoring. Ann Otol Rhinol Laryngol. 2009;118:166-171.
Sun G, Muddana S, Slaughter JC. A new pH catheter for laryngopharyngeal reflux: normal values. Laryngoscope. 2009;119:1639-1643.
Ford CN., Evaluation and management of laryngopharyngeal reflux. JAMA. 2005;294:1534-1540.
Gupta N, Green RW, Megwalu UC., Evaluation of a laryngopharyngeal reflux management protocol. Am J Otolaryngol. 2016;37:245-250.
Lien HC, Wang CC, Lee SW. Responder definition of a patient-reported outcome instrument for laryngopharyngeal reflux based on the US FDA guidance. Value Health. 2015;18:396-403.
Lechien JR, Finck C, Huet K. Voice quality as therapeutic outcome in laryngopharyngeal reflux disease: a prospective cohort study [published online September 13, 2018]. J Voice. doi:10.1016/j.jvoice.2018.08.018
Lechien JR, Finck C, Khalife M. Change of signs, symptoms and voice quality evaluations throughout a 3- to 6-month empirical treatment for laryngopharyngeal reflux disease. Clin Otolaryngol. 2018;43:1273-1282.
Lechien JR, Huet K, Khalife M. Impact of laryngopharyngeal reflux on subjective and objective voice assessments: a prospective study. J Otolaryngol Head Neck Surg. 2016;45:59.
Brauer DL, Tse KY, Lin JC, Schatz MX, Simon RA., The utility of the Reflux Symptom Index for diagnosis of laryngopharyngeal reflux in an allergy patient population. J Allergy Clin Immunol Pract. 2018;6:132-138.e1.
Qadeer MA, Phillips CO, Lopez AR. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006;101:2646-2654.
Ross JA, Noordzji JP, Woo P., Voice disorders in patients with suspected laryngo-pharyngeal reflux disease. J Voice. 1998;12:84-88.
Saritas Yuksel E, Hong SK, Strugala V. Rapid salivary pepsin test: blinded assessment of test performance in gastroesophageal reflux disease. Laryngoscope. 2012;122:1312-1316.
Wang J, Zhao Y, Ren J, Xu Y., Pepsin in saliva as a diagnostic biomarker in laryngopharyngeal reflux: a meta-analysis. Eur Arch Otorhinolaryngol. 2018;275:671-678.
Calvo-Henríquez C, Ruano-Ravina A, Vaamonde P. Is pepsin a reliable marker of laryngopharyngeal reflux? A systematic review. Otolaryngol Head Neck Surg. 2017;157:385-391.
Altman KW, Stephens RM, Lyttle CS, Weiss KB., Changing impact of gastroesophageal reflux in medical and otolaryngology practice. Laryngoscope. 2005;115:1145-1153.
Lechien JR, Huet K, Khalife M. Alkaline, protein and low fat diet in laryngopharyngeal reflux disease: our experience on 65 patients [published online December 11, 2018]. Clin Otolaryngol. doi:10.1111/coa.13269
Koufman JA., Low-acid diet for recalcitrant laryngopharyngeal reflux: therapeutic benefits and their implications. Ann Otol Rhinol Laryngol. 2011;120:281-287.
Lechien JR, Saussez S, Karkos PD., Laryngopharyngeal reflux disease: clinical presentation, diagnosis and therapeutic challenges in 2018. Curr Opin Otolaryngol Head Neck Surg. 2018;26:392-402.
Wilkie MD, Fraser HM, Raja H., Gaviscon® Advance alone versus co-prescription of Gaviscon® Advance and proton pump inhibitors in the treatment of laryngopharyngeal reflux. Eur Arch Otorhinolaryngol. 2018;275:2515-2521.
Kroch DA, Madanick RD., Medical treatment of gastroesophageal reflux disease. World J Surg. 2017;41:1678-1684.
Park W, Hicks DM, Khandwala F. Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope. 2005;115:1230-1238.
Pisegna JM, Yang S, Purcell A, Rubio A., A mixed-methods study of patient views on reflux symptoms and medication routines. J Voice. 2017;31:381.e15-e25.
Patel DA, Sharda R, Choksi YA. Model to select on-therapy vs off-therapy tests for patients with refractory esophageal or extra-esophageal symptoms. Gastroenterology. 2018;155:1729-1740.e1.
Bucca CB, Bugiani M, Culla B. Chronic cough and irritable larynx. J Allergy Clin Immunol. 2011;127:412-419.
Stachler RJ, Francis DO, Schwartz SR. Clinical practice guideline: hoarseness (dysphonia) (update). Otolaryngol Head Neck Surg. 2018;158(1):S1-S42.
Nam IC, Park YH., Pharyngolaryngeal symptoms associated with thyroid disease. Curr Opin Otolaryngol Head Neck Surg. 2017;25:469-474.
Jaume Bauza G, Tomas Barberan M, Epprecth Gonzalez P. The diagnosis and management of globus: a perspective from Spain. Curr Opin Otolaryngol Head Neck Surg. 2008;16:507-510.
Oridate N, Nishizawa N, Fukuda S., The diagnosis and management of globus: a perspective from Japan. Curr Opin Otolaryngol Head Neck Surg. 2008;16:498-502.
