Clin Exp Otorhinolaryngol.  2023 Aug;16(3):259-274. 10.21053/ceo.2023.00409.

Predictors of Early and Late Response to Esomezol and Lifestyle Modification in Adults With Laryngopharyngeal Reflux Disease: A Prospective, Multicenter, Open-Label Cohort Study

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
  • 2Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea
  • 3Department of Otolaryngology-Head and Neck Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
  • 4Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 5Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 6Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
  • 7Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Suwon, Korea
  • 8Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
  • 9Department of Otorhinolaryngology-Head and Neck Surgery, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea


. This study aimed to assess predictors of the response to varying durations of proton pump inhibitor (PPI) use and lifestyle modification treatment for laryngopharyngeal reflux disease (LPRD).
. Between October 2014 and June 2016, a prospective, multicenter, open-label, single-cohort, intention-to-treat, observational study was conducted at eight referral hospitals across the Republic of Korea to examine predictors of early and late response to treatment in adult patients (age ≥19 years) with LPRD. Participants underwent standard treatment (PPI [Esomezol] and lifestyle modification) for 3 months. Response to treatment was defined as greater than 50% improvement in reflux symptom index score. The primary outcome was potential predictors of treatment response at 1 and 3 months. The secondary outcome was potential predictors distinguishing early from late responders.
. In total, 394 patients were enrolled. Improved sleep habits was a positive predictor (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.06–3.007; P=0.029), while initial alcohol consumption (OR, 0.587; 95% CI, 0.355–0.969; P=0.037) and past medication history (OR, 0.438; 95% CI, 0.215–0.891; P=0.005) were negative predictors of response after 1 month of treatment. High pre-reflux finding score was a positive predictor (OR, 1.187; 95% CI, 1.049– 1.344; P=0.007), while male sex (OR, 0.516; 95% CI, 0.269–0.987; P=0.046), higher depression score (OR, 0.867; 95% CI, 0.784–0.958; P=0.005), and past thyroid hormone medication history (OR, 0.161; 95% CI, 0.033–0.788; P=0.024) were negative predictors of response after 3 months of treatment. Past medication history (OR, 0.438; 95% CI, 0.215–0.891; P=0.023) was the only negative predictor for early responders compared to late responders.
. Adult patients with LPRD and a history of prior medication use may require longer treatment durations to achieve a therapeutic response. Future research should explore the incorporation of diverse treatment approaches to improve treatment outcomes for patients exhibiting negative prognostic indicators.


Laryngopharyngeal Reflux; Proton Pump Inhibitors; Life Style Modification; Predictive Factor; Patient Compliance; Patient Medical History; Medication History


  • Fig. 1. Detailed information on recruitment and participant flow. During the study period, 394 participants were enrolled. However, 106 participants had dropped out by the 1-month follow-up, and an additional 51 participants had dropped out by the 3-month follow-up. Therefore, data on 288 participants were utilized for predictor analysis of early response to treatment after 1 month, and data on 237 participants were utilized for predictor analysis of overall response to treatment after 3 months, as well as for predicting early responders compared to late responders. LPRD, laryngopharyngeal reflux disease.


1. Ford CN. Evaluation and management of laryngopharyngeal reflux. JAMA. 2005; Sep. 294(12):1534–40.
2. Lee SH, Huh SH. Recent trends of laryngopharyngeal reflux disease. Korean J Otorhinolaryngol Head Neck Surg. 2011; Aug. 54(8):519–25.
3. 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; Apr. 101(4 Pt 2 Suppl 53):1–78.
4. Connor NP, Palazzi-Churas KL, Cohen SB, Leverson GE, Bless DM. Symptoms of extraesophageal reflux in a community-dwelling sample. J Voice. 2007; Mar. 21(2):189–202.
5. 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; Dec. 15:7.
6. Kamani T, Penney S, Mitra I, Pothula V. The prevalence of laryngopharyngeal reflux in the English population. Eur Arch Otorhinolaryngol. 2012; Oct. 269(10):2219–25.
7. Guo H, Ma H, Wang J. Proton pump inhibitor therapy for the treatment of laryngopharyngeal reflux: a meta-analysis of randomized controlled trials. J Clin Gastroenterol. 2016; Apr. 50(4):295–300.
8. Reichel O, Dressel H, Wiederanders K, Issing WJ. Double-blind, placebo-controlled trial with esomeprazole for symptoms and signs associated with laryngopharyngeal reflux. Otolaryngol Head Neck Surg. 2008; Sep. 139(3):414–20.
9. Lam PK, Ng ML, Cheung TK, Wong BY, Tan VP, Fong DY, et al. Rabeprazole is effective in treating laryngopharyngeal reflux in a randomized placebo-controlled trial. Clin Gastroenterol Hepatol. 2010; Sep. 8(9):770–6.
10. Gupta N, Green RW, Megwalu UC. Evaluation of a laryngopharyngeal reflux management protocol. Am J Otolaryngol. 2016; May-Jun. 37(3):245–50.
11. Dulery C, Lechot A, Roman S, Bastier PL, Stoll D, de Gabory L, et al. A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors. Neurogastroenterol Motil. 2017; Jan. 29(1):e12909.
12. Spantideas N, Drosou E, Bougea A, AlAbdulwahed R. Proton pump inhibitors for the treatment of laryngopharyngeal reflux. A systematic review. J Voice. 2020; Nov. 34(6):918–29.
13. Yang J, Dehom S, Sanders S, Murry T, Krishna P, Crawley BK. Treating laryngopharyngeal reflux: evaluation of an anti-reflux program with comparison to medications. Am J Otolaryngol. 2018; Jan-Feb. 39(1):50–5.
14. 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; Oct. 143(10):1023–9.
15. Shin MH, Nam SY, Park YH, Son YI. Open-label observational study for evaluating the short-term benefits of rabeprazole medication on laryngopharyngeal reflux. Clin Exp Otorhinolaryngol. 2012; Mar. 5(1):28–33.
16. Park W, Hicks DM, Khandwala F, Richter JE, Abelson TI, Milstein C, et al. Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope. 2005; Jul. 115(7):1230–8.
17. Williams RB, Szczesniak MM, Maclean JC, Brake HM, Cole IE, Cook IJ. Predictors of outcome in an open label, therapeutic trial of highdose omeprazole in laryngitis. Am J Gastroenterol. 2004; May. 99(5):777–85.
18. Siupsinskiene N, Adamonis K, Toohill RJ, Sereika R. Predictors of response to short-term proton pump inhibitor treatment in laryngopharyngeal reflux patients. J Laryngol Otol. 2008; Nov. 122(11):1206–12.
19. Massawe WA, Nkya A, Abraham ZS, Babu KM, Moshi N, Kahinga AA, et al. Laryngopharyngeal reflux disease, prevalence and clinical characteristics in ENT department of a tertiary hospital Tanzania. World J Otorhinolaryngol Head Neck Surg. 2020; Aug. 7(1):28–33.
20. Chen T, Lu M, Wang X, Yang Y, Zhang J, Jin L, et al. Prevalence and risk factors of gastroesophageal reflux symptoms in a Chinese retiree cohort. BMC Gastroenterol. 2012; Nov. 12:161.
21. Lechien JR, Saussez S, Schindler A, Karkos PD, Hamdan AL, Harmegnies B, et al. Clinical outcomes of laryngopharyngeal reflux treatment: a systematic review and meta-analysis. Laryngoscope. 2019; May. 129(5):1174–87.
22. Wang AJ, Liang MJ, Jiang AY, Lin JK, Xiao YL, Peng S, et al. Predictors of acid suppression success in patients with chronic laryngitis. Neurogastroenterol Motil. 2012; May. 24(5):432–7. e210.
23. Lee YC, Lee JS, Kim SW, Kwon KH, Eun YG. Influence of age on treatment with proton pump inhibitors in patients with laryngopharyngeal reflux disease: a prospective multicenter study. JAMA Otolaryngol Head Neck Surg. 2013; Dec. 139(12):1291–5.
24. Wong MW, Bair MJ, Chang WC, Hsu CS, Hung JS, Liu TT, et al. Clinical and psychological characteristics in gastroesophageal reflux disease patients overlapping with laryngopharyngeal reflux symptoms. J Gastroenterol Hepatol. 2019; Oct. 34(10):1720–6.
25. Joo YH, Song YS, Pae CU. Relationship between depression and laryngopharyngeal reflux. Psychiatry Investig. 2017; Mar. 14(2):226–9.
26. Belafsky PC, Postma GN. The laryngeal and esophageal manifestations of Sjogren’s syndrome. Curr Rheumatol Rep. 2003; Aug. 5(4):297–303.
27. Cusimano A, Macaione I, Fiorentino E. How uncomplicated total thyroidectomy could aggravate the laryngopharyngeal reflux disease. Eur Arch Otorhinolaryngol. 2016; Jan. 273(1):197–202.
28. Cipolla C, Macaione I, Vieni S, Latteri M, Vullo A, Graceffa G, et al. Laryngopharyngeal reflux as a potential cause of persistent local neck symptoms after total thyroidectomy. Eur Arch Otorhinolaryngol. 2021; May. 278(5):1577–83.
29. Hamdan AL, Jabbour J, Barazi R, Korban Z, Azar ST. Prevalence of laryngopharyngeal reflux disease in patients with diabetes mellitus. J Voice. 2013; Jul. 27(4):495–9.
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