Skip to main content
Erschienen in: European Archives of Oto-Rhino-Laryngology 1/2009

01.01.2009 | Review Article

Pathophysiological mechanisms of extraesophageal reflux in otolaryngeal disorders

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

Abstract

As more than 40% of adults experience symptoms of the gastroesophageal reflux (GER) and 26% are affected by the extraesophageal reflux (EER), the aim of this article was to review the literature concerning pathophysiological mechanisms contributing to these common diseases. Reflux symptoms are ascribable for nearly one-third of otolaryngeal disorders. In contrast to patients solely affected by GERD, patients with otolaryngeal disorders attributable to extraesophageal reflux have a relatively good esophageal acid clearance but for unknown reasons increased amounts of laryngeal reflux. Transient upper esophageal sphincter relaxations are discussed as the pathophysiological mechanism, as the resting tone of the upper esophageal sphincter is not affected. When exposed to gastroduodenal contents, the ciliated epithelium of otolaryngeal structures is more susceptible to damage, and thereby even a few reflux episodes are suggested to cause extraesophageal reflux disease (EERD). Particularly active pepsin contributes to laryngeal lesions and eustachian tube dysfunction. Despite the importance of EER in laryngeal diseases, the causative role in other otolaryngeal disorders like sinusitis and otitis media with effusion remains unresolved.
Literatur
2.
Zurück zum Zitat Bluestone CD (1985) Current concepts in eustachian tube function as related to otitis media. Auris Nasus Larynx 12(Suppl 1):S1–S4PubMed Bluestone CD (1985) Current concepts in eustachian tube function as related to otitis media. Auris Nasus Larynx 12(Suppl 1):S1–S4PubMed
4.
Zurück zum Zitat Borkowski G, Gurr A, Stark T, Philippou S, Sudhoff H (2000) Functional and morphological defects of the mucociliary system in secretory otitis media. Laryngorhinootologie 79:135–138. doi:10.1055/s-2000-285 PubMedCrossRef Borkowski G, Gurr A, Stark T, Philippou S, Sudhoff H (2000) Functional and morphological defects of the mucociliary system in secretory otitis media. Laryngorhinootologie 79:135–138. doi:10.​1055/​s-2000-285 PubMedCrossRef
7.
Zurück zum Zitat Champion G, Richter JE, Vaezi MF, Singh S, Alexander R (1994) Duodenogastroesophageal reflux: relationship to pH and importance in Barrett’s esophagus. Gastroenterology 107:747–754PubMed Champion G, Richter JE, Vaezi MF, Singh S, Alexander R (1994) Duodenogastroesophageal reflux: relationship to pH and importance in Barrett’s esophagus. Gastroenterology 107:747–754PubMed
9.
Zurück zum Zitat Collman PI, Tremblay L, Diamant NE (1993) The central vagal efferent supply to the esophagus and lower esophageal sphincter of the cat. Gastroenterology 104:1430–1438PubMed Collman PI, Tremblay L, Diamant NE (1993) The central vagal efferent supply to the esophagus and lower esophageal sphincter of the cat. Gastroenterology 104:1430–1438PubMed
11.
Zurück zum Zitat Dent J, Dodds WJ, Friedman RH, Sekiguchi T, Hogan WJ, Arndorfer RC et al (1980) Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest 65:256–267. doi:10.1172/JCI109667 PubMedCrossRef Dent J, Dodds WJ, Friedman RH, Sekiguchi T, Hogan WJ, Arndorfer RC et al (1980) Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest 65:256–267. doi:10.​1172/​JCI109667 PubMedCrossRef
16.
Zurück zum Zitat Franchi A, Brogelli B, Massi D, Santucci M, De CE, Gallo O (2007) Dilation of intercellular spaces is associated with laryngo-pharyngeal reflux: an ultrastructural morphometric analysis of laryngeal epithelium. Eur Arch Otorhinolaryngol 264:907–911. doi:10.1007/s00405-007-0295-z PubMedCrossRef Franchi A, Brogelli B, Massi D, Santucci M, De CE, Gallo O (2007) Dilation of intercellular spaces is associated with laryngo-pharyngeal reflux: an ultrastructural morphometric analysis of laryngeal epithelium. Eur Arch Otorhinolaryngol 264:907–911. doi:10.​1007/​s00405-007-0295-z PubMedCrossRef
19.
Zurück zum Zitat Gold BD (2004) Gastroesophageal reflux disease: could intervention in childhood reduce the risk of later complications? Am J Med 117(Suppl 5A):23S–29SPubMed Gold BD (2004) Gastroesophageal reflux disease: could intervention in childhood reduce the risk of later complications? Am J Med 117(Suppl 5A):23S–29SPubMed
20.
Zurück zum Zitat Goldberg HI, Dodds WJ, Gee S, Montgomery C, Zboralske FF (1969) Role of acid and pepsin in acute experimental esophagitis. Gastroenterology 56:223–230PubMed Goldberg HI, Dodds WJ, Gee S, Montgomery C, Zboralske FF (1969) Role of acid and pepsin in acute experimental esophagitis. Gastroenterology 56:223–230PubMed
25.
26.
Zurück zum Zitat Helm JF, Dodds WJ, Hogan WJ, Soergel KH, Egide MS, Wood CM (1982) Acid neutralizing capacity of human saliva. Gastroenterology 83:69–74PubMed Helm JF, Dodds WJ, Hogan WJ, Soergel KH, Egide MS, Wood CM (1982) Acid neutralizing capacity of human saliva. Gastroenterology 83:69–74PubMed
27.
Zurück zum Zitat Helm JF, Dodds WJ, Pelc LR, Palmer DW, Hogan WJ, Teeter BC (1984) Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med 310:284–288PubMed Helm JF, Dodds WJ, Pelc LR, Palmer DW, Hogan WJ, Teeter BC (1984) Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med 310:284–288PubMed
28.
Zurück zum Zitat Holloway RH, Hongo M, Berger K, McCallum RW (1985) Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 89:779–784PubMed Holloway RH, Hongo M, Berger K, McCallum RW (1985) Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 89:779–784PubMed
29.
Zurück zum Zitat Holloway RH, Kocyan P, Dent J (1991) Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux. Dig Dis Sci 36:1034–1039. doi:10.1007/BF01297443 PubMedCrossRef Holloway RH, Kocyan P, Dent J (1991) Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux. Dig Dis Sci 36:1034–1039. doi:10.​1007/​BF01297443 PubMedCrossRef
31.
Zurück zum Zitat Jacob P, Kahrilas PJ, Herzon G (1991) Proximal esophageal pH-metry in patients with ‘reflux laryngitis’. Gastroenterology 100:305–310PubMed Jacob P, Kahrilas PJ, Herzon G (1991) Proximal esophageal pH-metry in patients with ‘reflux laryngitis’. Gastroenterology 100:305–310PubMed
32.
Zurück zum Zitat Johnson LF, DeMeester TR (1974) Twenty-four-hour pH monitoring of the distal esophagus. A quantitative measure of gastroesophageal reflux. Am J Gastroenterol 62:325–332PubMed Johnson LF, DeMeester TR (1974) Twenty-four-hour pH monitoring of the distal esophagus. A quantitative measure of gastroesophageal reflux. Am J Gastroenterol 62:325–332PubMed
33.
Zurück zum Zitat Johnston N, Bulmer D, Gill GA, Panetti M, Ross PE, Pearson JP et al (2003) Cell biology of laryngeal epithelial defenses in health and disease: further studies. Ann Otol Rhinol Laryngol 112:481–491PubMed Johnston N, Bulmer D, Gill GA, Panetti M, Ross PE, Pearson JP et al (2003) Cell biology of laryngeal epithelial defenses in health and disease: further studies. Ann Otol Rhinol Laryngol 112:481–491PubMed
38.
Zurück zum Zitat Kinoshita M, Kume E, Igarashi S, Saito N, Narita H (1999) Role of salivary mucin in the protection of rat esophageal mucosa from acid and pepsin-induced injury. Am J Physiol 277:G796–G800PubMed Kinoshita M, Kume E, Igarashi S, Saito N, Narita H (1999) Role of salivary mucin in the protection of rat esophageal mucosa from acid and pepsin-induced injury. Am J Physiol 277:G796–G800PubMed
39.
Zurück zum Zitat Koufman JA (1991) 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 101:1–78PubMedCrossRef Koufman JA (1991) 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 101:1–78PubMedCrossRef
40.
Zurück zum Zitat Koufman JA, Aviv JE, Casiano RR, Shaw GY (2002) 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 127:32–35. doi:10.1067/mhn.2002.125760 PubMedCrossRef Koufman JA, Aviv JE, Casiano RR, Shaw GY (2002) 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 127:32–35. doi:10.​1067/​mhn.​2002.​125760 PubMedCrossRef
42.
Zurück zum Zitat Little AG, DeMeester TR, Skinner DB (1979) Combined gastric and esophageal 24-hour pH monitoring in patients with gastroesophageal reflux. Surg Forum 30:351–352PubMed Little AG, DeMeester TR, Skinner DB (1979) Combined gastric and esophageal 24-hour pH monitoring in patients with gastroesophageal reflux. Surg Forum 30:351–352PubMed
43.
Zurück zum Zitat Little JP, Matthews BL, Glock MS, Koufman JA, Reboussin DM, Loughlin CJ et al (1997) Extraesophageal pediatric reflux: 24-hour double-probe pH monitoring of 222 children. Ann Otol Rhinol Laryngol Suppl 169:1–16PubMed Little JP, Matthews BL, Glock MS, Koufman JA, Reboussin DM, Loughlin CJ et al (1997) Extraesophageal pediatric reflux: 24-hour double-probe pH monitoring of 222 children. Ann Otol Rhinol Laryngol Suppl 169:1–16PubMed
44.
Zurück zum Zitat Lopez-Alonso M, Moya MJ, Cabo JA, Ribas J, del Carmen MM, Silny J et al (2006) Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux. Pediatrics 118:e299–e308. doi:10.1542/peds.2005-3140 PubMedCrossRef Lopez-Alonso M, Moya MJ, Cabo JA, Ribas J, del Carmen MM, Silny J et al (2006) Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux. Pediatrics 118:e299–e308. doi:10.​1542/​peds.​2005-3140 PubMedCrossRef
45.
46.
Zurück zum Zitat Masclee AA, de Best AC, de GR, Cluysenaer OJ, Jansen JB (1990) Ambulatory 24-hour pH-metry in the diagnosis of gastroesophageal reflux disease. Determination of criteria and relation to endoscopy. Scand J Gastroenterol 25:225–230 Masclee AA, de Best AC, de GR, Cluysenaer OJ, Jansen JB (1990) Ambulatory 24-hour pH-metry in the diagnosis of gastroesophageal reflux disease. Determination of criteria and relation to endoscopy. Scand J Gastroenterol 25:225–230
48.
Zurück zum Zitat Mitchell DJ, McClure BG, Tubman TR (2001) Simultaneous monitoring of gastric and oesophageal pH reveals limitations of conventional oesophageal pH monitoring in milk fed infants. Arch Dis Child 84:273–276. doi:10.1136/adc.84.3.273 PubMedCrossRef Mitchell DJ, McClure BG, Tubman TR (2001) Simultaneous monitoring of gastric and oesophageal pH reveals limitations of conventional oesophageal pH monitoring in milk fed infants. Arch Dis Child 84:273–276. doi:10.​1136/​adc.​84.​3.​273 PubMedCrossRef
51.
Zurück zum Zitat Nelson SP, Chen EH, Syniar GM, Christoffel KK (1997) Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 151:569–572PubMed Nelson SP, Chen EH, Syniar GM, Christoffel KK (1997) Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 151:569–572PubMed
55.
Zurück zum Zitat Paradise JL (1980) Otitis media in infants and children. Pediatrics 65:917–943PubMed Paradise JL (1980) Otitis media in infants and children. Pediatrics 65:917–943PubMed
56.
Zurück zum Zitat Paradise JL, Rockette HE, Colborn DK, Bernard BS, Smith CG, Kurs-Lasky M et al (1997) Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics 99:318–333. doi:10.1542/peds.99.3.318 PubMedCrossRef Paradise JL, Rockette HE, Colborn DK, Bernard BS, Smith CG, Kurs-Lasky M et al (1997) Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics 99:318–333. doi:10.​1542/​peds.​99.​3.​318 PubMedCrossRef
57.
Zurück zum Zitat Postma GN, Tomek MS, Belafsky PC, Koufman JA (2001) Esophageal motor function in laryngopharyngeal reflux is superior to that in classic gastroesophageal reflux disease. Ann Otol Rhinol Laryngol 110:1114–1116PubMed Postma GN, Tomek MS, Belafsky PC, Koufman JA (2001) Esophageal motor function in laryngopharyngeal reflux is superior to that in classic gastroesophageal reflux disease. Ann Otol Rhinol Laryngol 110:1114–1116PubMed
59.
Zurück zum Zitat Quigley EM, Turnberg LA (1992) Studies of luminal and mucosal pH in reflux esophagitis and antral gastritis. Dig Dis 10:134–143PubMedCrossRef Quigley EM, Turnberg LA (1992) Studies of luminal and mucosal pH in reflux esophagitis and antral gastritis. Dig Dis 10:134–143PubMedCrossRef
60.
Zurück zum Zitat Reiner CE, Pulec JL (1969) Experimental production of serous otitis media. Ann Otol Rhinol Laryngol 78:880–887PubMed Reiner CE, Pulec JL (1969) Experimental production of serous otitis media. Ann Otol Rhinol Laryngol 78:880–887PubMed
62.
Zurück zum Zitat Sondheimer JM (1983) Upper esophageal sphincter and pharyngoesophageal motor function in infants with and without gastroesophageal reflux. Gastroenterology 85:301–305PubMed Sondheimer JM (1983) Upper esophageal sphincter and pharyngoesophageal motor function in infants with and without gastroesophageal reflux. Gastroenterology 85:301–305PubMed
65.
Zurück zum Zitat Sung MW, Roh JL, Park BJ, Park SW, Kwon TK, Lee SJ et al (2003) Bile acid induces cyclo-oxygenase-2 expression in cultured human pharyngeal cells: a possible mechanism of carcinogenesis in the upper aerodigestive tract by laryngopharyngeal reflux. Laryngoscope 113:1059–1063. doi:10.1097/00005537-200306000-00027 PubMedCrossRef Sung MW, Roh JL, Park BJ, Park SW, Kwon TK, Lee SJ et al (2003) Bile acid induces cyclo-oxygenase-2 expression in cultured human pharyngeal cells: a possible mechanism of carcinogenesis in the upper aerodigestive tract by laryngopharyngeal reflux. Laryngoscope 113:1059–1063. doi:10.​1097/​00005537-200306000-00027 PubMedCrossRef
66.
Zurück zum Zitat Sutphen JL, Dillard VL (1986) Effects of maturation and gastric acidity on gastroesophageal reflux in infants. Am J Dis Child 140:1062–1064PubMed Sutphen JL, Dillard VL (1986) Effects of maturation and gastric acidity on gastroesophageal reflux in infants. Am J Dis Child 140:1062–1064PubMed
69.
Zurück zum Zitat Torrico S, Kern M, Aslam M, Narayanan S, Kannappan A, Ren J et al (2000) Upper esophageal sphincter function during gastroesophageal reflux events revisited. Am J Physiol Gastrointest Liver Physiol 279:G262–G267PubMed Torrico S, Kern M, Aslam M, Narayanan S, Kannappan A, Ren J et al (2000) Upper esophageal sphincter function during gastroesophageal reflux events revisited. Am J Physiol Gastrointest Liver Physiol 279:G262–G267PubMed
71.
Zurück zum Zitat Tselepis C, Morris CD, Wakelin D, Hardy R, Perry I, Luong QT et al (2003) Upregulation of the oncogene c-myc in Barrett’s adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Gut 52:174–180. doi:10.1136/gut.52.2.174 PubMedCrossRef Tselepis C, Morris CD, Wakelin D, Hardy R, Perry I, Luong QT et al (2003) Upregulation of the oncogene c-myc in Barrett’s adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Gut 52:174–180. doi:10.​1136/​gut.​52.​2.​174 PubMedCrossRef
74.
Zurück zum Zitat Wallin L, Boesby S, Madsen T (1978) The effect of HCl infusion in the lower part of the oesophagus on the pharyngo-oesophageal sphincter pressure in normal subjects. Scand J Gastroenterol 13:821–826PubMedCrossRef Wallin L, Boesby S, Madsen T (1978) The effect of HCl infusion in the lower part of the oesophagus on the pharyngo-oesophageal sphincter pressure in normal subjects. Scand J Gastroenterol 13:821–826PubMedCrossRef
76.
77.
Zurück zum Zitat Winkelstein A (1935) Peptic esophagitis. JAMA 104:906–909 Winkelstein A (1935) Peptic esophagitis. JAMA 104:906–909
80.
Zurück zum Zitat Zoumalan R, Maddalozzo J, Holinger LD (2007) Etiology of stridor in infants. Ann Otol Rhinol Laryngol 116:329–334PubMed Zoumalan R, Maddalozzo J, Holinger LD (2007) Etiology of stridor in infants. Ann Otol Rhinol Laryngol 116:329–334PubMed
Metadaten
Titel
Pathophysiological mechanisms of extraesophageal reflux in otolaryngeal disorders
Publikationsdatum
01.01.2009
Erschienen in
European Archives of Oto-Rhino-Laryngology / Ausgabe 1/2009
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-008-0770-1

Weitere Artikel der Ausgabe 1/2009

European Archives of Oto-Rhino-Laryngology 1/2009 Zur Ausgabe

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.