The Effect of N-Acetyl Cysteine on Laryngopharyngeal Reflux

  • Payman Dabirmoghaddam Otorhinolaryngology Research Center, Department of Otorhinolaryngology, Tehran University of Medical Sciences, Tehran, Iran.
  • Amin Amali Mail Otorhinolaryngology Research Center, Department of Otorhinolaryngology, Tehran University of Medical Sciences, Tehran, Iran.
  • Maziar Motiee Langroudi Otorhinolaryngology Research Center, Department of Otorhinolaryngology, Tehran University of Medical Sciences, Tehran, Iran.
  • Mohammad Reza Samavati Fard Otorhinolaryngology Research Center, Department of Otorhinolaryngology, Tehran University of Medical Sciences, Tehran, Iran.
  • Mona Hejazi Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
  • Masoud Sharifian Razavi Department of Gastroenterology, Mashhad University of Medical Sciences, Mashhad, Iran.
Keywords:
Laryngopharyngeal reflux, N-acetyl Cysteine, Omeprazole

Abstract

Laryngopharyngeal reflux (LPR) is a variant of gastroesophageal reflux disease (GERD) in which the stomach contents go up into the pharynx and then down into the larynx. LPR causes a wide spectrum of manifestations mainly related to the upper and the lower respiratory system such as laryngitis, asthma, chronic obstructive pulmonary disease, cough, hoarseness, postnasal drip disease, sinusitis, otitis media, recurrent pneumonia, laryngeal cancer and etc. The object of this study was to examine the effect of N-acetyl Cysteine (NAC) with and without Omeprazole on laryngitis and LPR. Ninety patients with laryngitis or its symptoms were referred and randomly assigned into three groups. The first group was treated by Omeprazole and NAC. The second group was treated by Omeprazole and placebo and the last group was treated by NAC and placebo. Duration of treatment was 3 months and all patients were evaluated at the beginning of study, one month and three month after treatment of sign and symptoms, based on reflux symptom index (RSI) and reflex finding score (RFS). Based on the results of this study, despite therapeutic efficacy of all treatment protocols, the RSI before and after 3 months treatment had significant difference in (NAS+ Omeprazole) and (Omeprazole+ placebo) group (P<0.001 in the first group, P<0.001 in the second group and P=0.35 in the third group). Whereas RFS before and after 3 month treatment had significant difference in all groups. (P<0.001 in each group in comparison with itself) but this results had not significant difference after 1 month treatment. Our results showed that the combination therapy with Omeprazole and NAC treatment had the most effect on both subjective and objective questionnaire at least after 3 months treatment. Based on the results of the present study, it seems that the use objective tools are more accurate than subjective tools in evaluation of therapeutic effects in patients with GERD-related laryngitis.

References

Farrokhi F, Vaezi MF. Extra-esophageal manifestations of gastroesophageal reflux. Oral Dis 2007;13(4):349-59.

Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006;10(8)1:1900–20.

Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD). A clinical investigation of 225 patients using ambulatory 24-hour 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.

Kamel PL, Hanson D, Kharilas PJ. Omeprazole for the treatment of posterior laryngitis. Am J Med 1994;96(4):321–6.

Wetscher GJ, Gadenstaetter M, Klingler PJ, Weiss H, Obrist P, Wykypiel H, Klaus A, Profanter C. Efficacy of medical therapy and antireflux surgery to prevent Barrett’s metaplasia in patients with gastroesophageal reflux disease. Ann Surg 2001;234(5):627-32.

Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis 1976;21(11):953–6.

Kahrilas PJ, Shaheen NJ, Vaezi MF; American Gastroenterological Association Institute; Clinical Practice and Quality Management Committee. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterol 2008;135(4):1392–413.

Jonaitis L, Pribuisiene R, Kupcinskas L, Uloza V. Laryngeal examination is superior to endoscopy in the diagnosis of the laryngopharyngeal form of gastroesophageal reflux disease. Scand J Gastroenterol 2006;41(2):131–7.

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(5):333-44.

Jaspersen D, Kulig M, Labenz J, Leodolter A, Lind T, Meyer-Sabellek W, Vieth M, Willich SN, Lindner D, Stolte M, Malfertheiner P. Prevalence of extraoesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD study. Aliment Pharmacol Ther 2003;17(12):1515–20.

Karkos PD, Benton J, Leong SC, Karkanevatos A, Badran K, Srinivasan VR, Temple RH, Issing WJ. Trends in laryngopharyngeal reflux: a British ENT survey. Eur Arch Otorhinolaryngol 2007;264(5):513–17.

Ford CN. Evaluation and Managementof Laryngopharyngeal Reflux. JAMA 2005;294(12):1534-40.

Barry DW, Vaezi MF. Laryngopharyngeal reflux: More questions than answers. Cleve Clin J Med 2010;77(5):327- 34.

Saritas Y, Vaezi M. Extraesophageal manifestations of gastroe sophageal reflux disease: cough, asthma, laryngitis, chest pain. Swiss Med Wkly 2012;142:ww13544.

Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux symptom index (RSI). J Voice 2002;16(2):274–7.

Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux findings score (RFS). Laryngoscope 2001;111(8):1313–7.

Darely FL. Diagnostic methods in speech pathology. 2nd ed. New York: Harper, Aow Joanna Cotler Books; 1978.

Issing WJ, Gross M, Tauber S. Manifestationsof gastroesophageal reflux inotorhinolarygology tract. Laryngorhinootologie 2001;80(8):464-9.

Pribuisiene R, Uloza V, Kupcinskas L, Jonaitis L. Perceptual and acousticcharacteristics of voice changes in refluxlaryngitis patients. J Voice 2006;20(1):128-36.

Mohammed I, Nightingale P, Trudgill NJ.Risk factors for gastro-oesophageal refluxdisease symptoms: a community study. Aliment Pharmacol Ther 2005;21(7):821-7.

Sataloff RT. Clinical assessment of voice. San Diego: Plural Publishing; 2005.

El-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in UnitedStates Veterans. Gastroenterol 1997;113(3):755–60.

Chung JH, Tae K, Lee YS, Jeong JH, Cho SH, Kim KR, Park CW, Han DS. The significance of laryngopharyngeal reflux in benign vocal mucosal lesions. Otolaryngol Head Neck Surg 2009;141(3):369-73.

Richter JE. Extraesophageal presentations of gastroesophageal reflux disease. Semin Gastrointest Dis 1997;8(2):75–89.

Wright RA, Miller SA, Corsello BF. Acid-induced esophagobronchial-cardiac reflexes in humans. Gastroenterol 1990;99(1):71-3.

Field SK, Evans JA, Price LM. The effects of acid perfusion of the esophagus on ventilation and respiratory sensation. Am J Respir Crit Care Med 1998;157(4 Pt1):1058–62.

Ing AJ, Ngu MC, Breslin AB. Pathogenesis of chronic persistent cough associated with gastro-esophageal reflux. Am J Respir Crit Care Med 1994;149(1):160-7.

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(11):2098–106.

Tuchman DN, Boyle JT, Pack AI, Scwartz J, Kokonos M, Spitzer AR, Cohen S. Comparison of airway responses following tracheal or esophageal acidification in the cat. Gastroenterol 1984;87(4):872–81.

Vaezi MF, Schroeder PL, Richter JE. Reproducibility ofproximal pH parameters in 24-hour ambulatory esophageal pH monitoring. Am J Gastroenterol 1997;92(5):825–9.

Richter JE, Hicks DM. Unresolved issues in gastroesophageal reflux-related ear, nose, and throat problems. Am J Gastroenterol 1997;92(12):2143– 4.

Schenk BE, Kuipers EJ, Klinkenberg-Knol EC, Festen HP, Jansen EH, Tuynman HA, Schrijver M, Dieleman LA, Meuwissen SG.. Omeprazole as a diagnostic tool in gastroesophageal reflux disease. Am J Gastroenterol 1997;92(11):1997–2000.

Fass R, Ofman JJ, Gralnek IM, Johnson C, Camargo E, Sampliner RE, Fennerty MB. Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease. Arch Intern Med 1999;159(18):2161– 8.

Wo JM, Grist WJ, Gussack G, Delgaudio JM, Waring JP.. Empiric trial of high-dose omeprazole in patients with posterior laryngitis: A prospective study. Am J Gastroenterol 1997;92(12):2160–5.

Fass R, Fennerty MB, Ofman JJ, Gralnek IM, Johnson C, Camargo E, Sampliner RE.. The clinical and economic value of a short course of omeprazole in patients withnoncardiac chest pain. Gastroenterol 1998;115(1):42–9.

Hershcovici T, Achem SR, Jha LK, Fass R. Systematic review: the treatment of noncardiac chest pain. Aliment Pharmacol Ther 2012;35(1):5-14.

Ours TM, Kavuru MS, Schilz RJ, Richter JE. A prospective evaluation of esophageal testing and a doubleblind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol 1999;94(11):3131–8.

Irwin RS, Madison JM. Anatomic diagnostic protocol in evaluating chronic cough with specific reference to gastroesophageal reflux disease. Am J Med 2000;108 Suppl 4a:126S-30S.

Ulualp SO, Toohill RJ, Shaker R. Outcomes of Acid Suppressive Therapy in Patients with Posterior Laryngitis. Otolaryngol Head Neck Surg 2001;124(1):16-22.

RogersD.Airwaymucus hypersecretion in asthma: anund valued pathology? Curr Opin Pharmacol 2004;4(3):241e50.

Bruce K R. Mucolytics, Expectorants, and Mucokinetic Medications. Respiratory Care 2007;52(7):11–4.

Hopkins C, Yousaf U, Pedersen M. Acid reflux treatment for hoarseness. Cochrane Database Syst Rev 2006;25(1):CD005054.

How to Cite
1.
Dabirmoghaddam P, Amali A, Motiee Langroudi M, Samavati Fard MR, Hejazi M, Sharifian Razavi M. The Effect of N-Acetyl Cysteine on Laryngopharyngeal Reflux. Acta Med Iran. 51(11):757-764.
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