Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 6/2009

01-06-2009 | Review Article

Molecular pathways and genetic factors in the pathogenesis of laryngopharyngeal reflux

Authors: Alexios S. Vardouniotis, Alexander D. Karatzanis, Eleni Tzortzaki, Elias Athanasakis, Katerina D. Samara, Georgios Chalkiadakis, Nikolaos Siafakas, George A. Velegrakis

Published in: European Archives of Oto-Rhino-Laryngology | Issue 6/2009

Login to get access

Abstract

The prevalence of laryngopharyngeal reflux (LPR) has been constantly rising in the western world and affects today an alarmingly high percentage of the general population. Even though LPR and gastroesophageal reflux disease (GERD) are both the product of gastroesophageal reflux and seem to be sibling disorders, they constitute largely different pathological entities. While GERD has been for a long time identified as a source of esophageal disease, LPR has only recently been associated with head and neck disorders. Despite the high incidence of LPR and its great impact on patients’ quality of life, little is known regarding its pathogenesis. On the other hand, studying the molecular and genetic basis of a disease is of fundamental importance in medicine as it offers better insight into the pathogenesis and opens new, disease-specific therapeutic trends. The aim of this study is to enlighten any known or suspected molecular mechanisms that contribute to the pathogenesis of LPR, and to suggest new trends for future research.
Literature
1.
go back to reference Koufman JA et al (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 127:32–35PubMedCrossRef Koufman JA et al (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 127:32–35PubMedCrossRef
2.
go back to reference Koufman JA (1991) The Otolaryngologic manifestations of gastroesophageal reflux disease. Laryngoscope 101:1–78PubMed Koufman JA (1991) The Otolaryngologic manifestations of gastroesophageal reflux disease. Laryngoscope 101:1–78PubMed
3.
go back to reference Wong R, Hanson D, Waring P, Shaw G (2000) ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 95:15–22CrossRef Wong R, Hanson D, Waring P, Shaw G (2000) ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 95:15–22CrossRef
4.
go back to reference Cohen J et al (2002) Clinical manifestations of laryngopharyngeal reflux. Ear Nose Throat J 81:19–23PubMed Cohen J et al (2002) Clinical manifestations of laryngopharyngeal reflux. Ear Nose Throat J 81:19–23PubMed
5.
go back to reference 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(Suppl 53):1–78PubMed 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(Suppl 53):1–78PubMed
6.
go back to reference Richter JE, Bradley LA, DeMeester TR et al (1992) Normal 24-hour ambulatory esophageal pH values: influence of study center, pH electrode, age and gender. Dig Dis Sci 37:849–856PubMedCrossRef Richter JE, Bradley LA, DeMeester TR et al (1992) Normal 24-hour ambulatory esophageal pH values: influence of study center, pH electrode, age and gender. Dig Dis Sci 37:849–856PubMedCrossRef
7.
go back to reference Gaynor EB (1991) Otolaryngologic manifestations of gastroesophageal reflux. Am J Gastroenterol 86:801–808PubMed Gaynor EB (1991) Otolaryngologic manifestations of gastroesophageal reflux. Am J Gastroenterol 86:801–808PubMed
8.
go back to reference Fraser AG (1994) Gastro-oesophageal reflux and laryngeal symptoms. Aliment Pharmacol Ther 8:265–272PubMedCrossRef Fraser AG (1994) Gastro-oesophageal reflux and laryngeal symptoms. Aliment Pharmacol Ther 8:265–272PubMedCrossRef
9.
go back to reference Koufman JA (2002) Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease. Ear Nose Throat J 81:7–9PubMed Koufman JA (2002) Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease. Ear Nose Throat J 81:7–9PubMed
10.
go back to reference Jonaitis L, Pribuisiene R, Kupcinskas L et al (2006) Laryngeal examination is superior to endoscopy in the diagnosis of the laryngopharyngeal form of gastrooesophageal reflux disease. Scand J Gastroenterol 41:131–137PubMedCrossRef Jonaitis L, Pribuisiene R, Kupcinskas L et al (2006) Laryngeal examination is superior to endoscopy in the diagnosis of the laryngopharyngeal form of gastrooesophageal reflux disease. Scand J Gastroenterol 41:131–137PubMedCrossRef
11.
go back to reference Vaezi MF, Hicks DM, Abelson TI et al (2003) Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol 1:333–344PubMedCrossRef Vaezi MF, Hicks DM, Abelson TI et al (2003) Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol 1:333–344PubMedCrossRef
12.
go back to reference Park W, Hicks DM, Khandwala F et al (2005) Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope 115:1230–1238PubMedCrossRef Park W, Hicks DM, Khandwala F et al (2005) Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope 115:1230–1238PubMedCrossRef
13.
go back to reference Fournet J. (2003) Le reflux gastro-esophagien, Septembre 1997 et Avril Fournet J. (2003) Le reflux gastro-esophagien, Septembre 1997 et Avril
14.
go back to reference Kerkos PD, Thomas L, Temple RH et al (2005) Awareness of general practitioners towards treatment of laryngopharyngeal reflux: a British survey. Otolaryngol Head Neck Surg 133:505–508CrossRef Kerkos PD, Thomas L, Temple RH et al (2005) Awareness of general practitioners towards treatment of laryngopharyngeal reflux: a British survey. Otolaryngol Head Neck Surg 133:505–508CrossRef
15.
go back to reference Archives of the Greek Gastroenterology and Alimentation Foundation, 2006 Archives of the Greek Gastroenterology and Alimentation Foundation, 2006
16.
go back to reference Locke GR et al (1997) Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 112:1448–1456PubMedCrossRef Locke GR et al (1997) Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 112:1448–1456PubMedCrossRef
17.
go back to reference Altman KW, Stephens RM, Lyttle CS, Weiss KB (2005) Changing impact of gastroesophageal reflux in medical and otolaryngology practice. Laryngoscope 115:1145–1153PubMedCrossRef Altman KW, Stephens RM, Lyttle CS, Weiss KB (2005) Changing impact of gastroesophageal reflux in medical and otolaryngology practice. Laryngoscope 115:1145–1153PubMedCrossRef
18.
go back to reference Richter JE, Hicks DM (1997) Unresolved issues in gastroesophageal reflux-related ear, nose and throat problems. Am J Gastroenterol 92:2143–2144PubMed Richter JE, Hicks DM (1997) Unresolved issues in gastroesophageal reflux-related ear, nose and throat problems. Am J Gastroenterol 92:2143–2144PubMed
19.
go back to reference Carrau RC et al (2004) The impact of laryngopharyngeal reflux on patient-reported quality of life. Laryngoscope 114:670–674PubMedCrossRef Carrau RC et al (2004) The impact of laryngopharyngeal reflux on patient-reported quality of life. Laryngoscope 114:670–674PubMedCrossRef
20.
go back to reference Mittal RK, Shaffer HA, Parollisi S, Baggett L (1995) Influence of breathing pattern on the esophagogastric junction pressure and esophageal transit. Am J Physiol 269:G577–G583PubMed Mittal RK, Shaffer HA, Parollisi S, Baggett L (1995) Influence of breathing pattern on the esophagogastric junction pressure and esophageal transit. Am J Physiol 269:G577–G583PubMed
21.
go back to reference Yuan S, Costa M, Brookes SJH (1998) Neuronal pathways and transmission to the lower esophageal sphincter of the guinea pig. Gastroenterology 118:661–671CrossRef Yuan S, Costa M, Brookes SJH (1998) Neuronal pathways and transmission to the lower esophageal sphincter of the guinea pig. Gastroenterology 118:661–671CrossRef
22.
go back to reference Lipan M, Reidenberg J, Laitman J (2006) Anatomy of reflex: a growing health problem affecting structures of the head and neck. Anat Rec (Part B: New Anat) 289B:261–270CrossRef Lipan M, Reidenberg J, Laitman J (2006) Anatomy of reflex: a growing health problem affecting structures of the head and neck. Anat Rec (Part B: New Anat) 289B:261–270CrossRef
23.
go back to reference Holloway RH, Dent J (1990) Pathophysiology of gastroesophageal reflux: lower esophageal sphincter dysfunction in gastroesophageal reflux disease. Gastroenterol Clin North Am 19:517–535PubMed Holloway RH, Dent J (1990) Pathophysiology of gastroesophageal reflux: lower esophageal sphincter dysfunction in gastroesophageal reflux disease. Gastroenterol Clin North Am 19:517–535PubMed
24.
go back to reference Mittal RK, Holloway RH, Penagini R, Blackshaw LA, Dent J (1995) Transient lower esophageal sphincter relaxation. Gastroenterology 109:601–610PubMedCrossRef Mittal RK, Holloway RH, Penagini R, Blackshaw LA, Dent J (1995) Transient lower esophageal sphincter relaxation. Gastroenterology 109:601–610PubMedCrossRef
25.
go back to reference Trudgill NJ, Riley SA (2001) Transient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers. Am J Gastroenterol 96:2569–2574PubMedCrossRef Trudgill NJ, Riley SA (2001) Transient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers. Am J Gastroenterol 96:2569–2574PubMedCrossRef
26.
go back to reference Kahrilas PJ (1998) GERD revisited: advances in pathogenesis. Hepatogastroenterology 45:1301–1307PubMed Kahrilas PJ (1998) GERD revisited: advances in pathogenesis. Hepatogastroenterology 45:1301–1307PubMed
27.
go back to reference Sifrim D, Holloway R (2001) Transient lower esophageal sphincter relaxations: how many or how harmful? Am J Gastroenterol 96:2529–2532PubMedCrossRef Sifrim D, Holloway R (2001) Transient lower esophageal sphincter relaxations: how many or how harmful? Am J Gastroenterol 96:2529–2532PubMedCrossRef
28.
go back to reference Grossi L, Ciccaglione AF, Marzio L (2001) Transient lower oesophageal sphincter relaxations play an insignificant role in gastro-oesophageal reflux to the proximal oesophagus. Neurogastroenterol Motil 13:503–509PubMedCrossRef Grossi L, Ciccaglione AF, Marzio L (2001) Transient lower oesophageal sphincter relaxations play an insignificant role in gastro-oesophageal reflux to the proximal oesophagus. Neurogastroenterol Motil 13:503–509PubMedCrossRef
29.
go back to reference Shaker R, Milbrath M, Ren J et al (1995) Esophagopharyngeal distribution of refluxed gastric acid in patients with reflux laryngitis. Gastroenterology 109:1575–1582PubMedCrossRef Shaker R, Milbrath M, Ren J et al (1995) Esophagopharyngeal distribution of refluxed gastric acid in patients with reflux laryngitis. Gastroenterology 109:1575–1582PubMedCrossRef
30.
go back to reference Hornby PJ, Abrahams TP (2000) Central control of lower esophageal sphincter relaxation. Am J Med 108(Suppl 4A):90S–98SPubMedCrossRef Hornby PJ, Abrahams TP (2000) Central control of lower esophageal sphincter relaxation. Am J Med 108(Suppl 4A):90S–98SPubMedCrossRef
31.
go back to reference Clerc N, Condamin M (1987) Selective labeling of vagal sensory nerve fibers in the lower esophageal sphincter with anterogradely transported WGA-HRP. Brain Res 424:216–224PubMedCrossRef Clerc N, Condamin M (1987) Selective labeling of vagal sensory nerve fibers in the lower esophageal sphincter with anterogradely transported WGA-HRP. Brain Res 424:216–224PubMedCrossRef
32.
go back to reference Blackshaw LA, Dent J (1997) Lower oesophageal sphincter responses to noxious oesophageal chemical stimuli in the ferret: involvement of tachykinin receptors. J Auton Nerv Syst 66:189–200PubMedCrossRef Blackshaw LA, Dent J (1997) Lower oesophageal sphincter responses to noxious oesophageal chemical stimuli in the ferret: involvement of tachykinin receptors. J Auton Nerv Syst 66:189–200PubMedCrossRef
33.
go back to reference Abounader R, Villemure JG, Hamel E (1995) Characterization of neuropeptide Y (NPY) receptors in human cerebral arteries with selective agonists and the new Y1 antagonist BIBP 3226. Br J Pharmacol 116:2245–2250PubMed Abounader R, Villemure JG, Hamel E (1995) Characterization of neuropeptide Y (NPY) receptors in human cerebral arteries with selective agonists and the new Y1 antagonist BIBP 3226. Br J Pharmacol 116:2245–2250PubMed
34.
go back to reference Paterson WG, Anderson MA, Anand N (1992) Pharmacological characterization of lower esophageal sphincter relaxation induced by swallowing, vagal efferent nerve stimulation, and esophageal distention. Can J Physiol Pharmacol 70:1011–1015PubMed Paterson WG, Anderson MA, Anand N (1992) Pharmacological characterization of lower esophageal sphincter relaxation induced by swallowing, vagal efferent nerve stimulation, and esophageal distention. Can J Physiol Pharmacol 70:1011–1015PubMed
35.
go back to reference Kawahara H, Blackshaw LA, Lehmann A, Dent J (1997) Responses of the rat lower oesophageal sphincter (LOS) to vagal efferent activation. Neurogastroenterol Motil 9:85–97PubMedCrossRef Kawahara H, Blackshaw LA, Lehmann A, Dent J (1997) Responses of the rat lower oesophageal sphincter (LOS) to vagal efferent activation. Neurogastroenterol Motil 9:85–97PubMedCrossRef
36.
go back to reference Rattan S (1986) The non-adrenergic non-cholinergic innervation of the esophagus and the lower esophageal sphincter. Arch Int Pharmacodyn Ther 280:62–83PubMed Rattan S (1986) The non-adrenergic non-cholinergic innervation of the esophagus and the lower esophageal sphincter. Arch Int Pharmacodyn Ther 280:62–83PubMed
37.
go back to reference Sivarao DV, Goyal RK (2000) Functional anatomy and physiology of the upper esophageal sphincter. Am J Med 108(4A):27S–37SPubMedCrossRef Sivarao DV, Goyal RK (2000) Functional anatomy and physiology of the upper esophageal sphincter. Am J Med 108(4A):27S–37SPubMedCrossRef
38.
go back to reference Asoh R, Goyal RK (1978) Manometry and electromyography of the upper esophageal sphincter in the opossum. Gastroenterology 74:514–520PubMed Asoh R, Goyal RK (1978) Manometry and electromyography of the upper esophageal sphincter in the opossum. Gastroenterology 74:514–520PubMed
39.
go back to reference Kahrilas PJ (1997) Upper esophageal sphincter function during antegrade and retrograde transit. Am J Med 103:56S–60SPubMedCrossRef Kahrilas PJ (1997) Upper esophageal sphincter function during antegrade and retrograde transit. Am J Med 103:56S–60SPubMedCrossRef
40.
go back to reference Kahrilas PJ, Dodds WJ, Dent J, Haeberle B, Hogan WJ, Arndorfer RC (1987) Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology 92:466–471PubMed Kahrilas PJ, Dodds WJ, Dent J, Haeberle B, Hogan WJ, Arndorfer RC (1987) Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology 92:466–471PubMed
41.
go back to reference Vakil NB, Kahrilas PJ, Dodds WJ, Vanagunas A (1989) Absence of an upper esophageal sphincter response to acid reflux. Am J Gastroenterol 84:606–610PubMed Vakil NB, Kahrilas PJ, Dodds WJ, Vanagunas A (1989) Absence of an upper esophageal sphincter response to acid reflux. Am J Gastroenterol 84:606–610PubMed
42.
go back to reference Torrico S, Kern M, Aslam M 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 et al (2000) Upper esophageal sphincter function during gastroesophageal reflux events revisited. Am J Physiol Gastrointest Liver Physiol 279:G262–G267PubMed
43.
go back to reference Lang IM, Shaker R (1997) Anatomy and physiology of the upper esophageal sphincter. Am J Med 103:50S–55SPubMedCrossRef Lang IM, Shaker R (1997) Anatomy and physiology of the upper esophageal sphincter. Am J Med 103:50S–55SPubMedCrossRef
44.
go back to reference Mu L, Sanders I (1996) The innervation of the human upper esophageal sphincter. Dysphagia 11:234–238PubMedCrossRef Mu L, Sanders I (1996) The innervation of the human upper esophageal sphincter. Dysphagia 11:234–238PubMedCrossRef
45.
go back to reference Mu L, Sanders I (1998) Neuromuscular organization of the human upper esophageal sphincter. Ann Otol Rhinol Laryngol 107:370–377PubMed Mu L, Sanders I (1998) Neuromuscular organization of the human upper esophageal sphincter. Ann Otol Rhinol Laryngol 107:370–377PubMed
46.
go back to reference Kobler JB, Datta S, Goyal RK, Benecchi EJ (1994) Innervation of the larynx, pharynx, and upper esophageal sphincter of the rat. J Comp Neurol 349:129–147PubMedCrossRef Kobler JB, Datta S, Goyal RK, Benecchi EJ (1994) Innervation of the larynx, pharynx, and upper esophageal sphincter of the rat. J Comp Neurol 349:129–147PubMedCrossRef
47.
go back to reference Hammond CS, Davenport PW, Hutchison A, Otto RA (1997) Motor innervation of the cricopharyngeus muscle by the recurrent laryngeal nerve. J Appl Physiol 83:89–94PubMed Hammond CS, Davenport PW, Hutchison A, Otto RA (1997) Motor innervation of the cricopharyngeus muscle by the recurrent laryngeal nerve. J Appl Physiol 83:89–94PubMed
48.
go back to reference Hyodo M, Aibara R, Kawakita S, Yumoto E (1998) Histochemical study of the canine inferior pharyngeal constrictor muscle: implications for its function. Acta Otol Laryngol 118:272–279CrossRef Hyodo M, Aibara R, Kawakita S, Yumoto E (1998) Histochemical study of the canine inferior pharyngeal constrictor muscle: implications for its function. Acta Otol Laryngol 118:272–279CrossRef
49.
go back to reference Malmberg L, Ekberg O, Ekstrom J (1991) Effects of drugs and electrical field stimulation on isolated muscle strips from rabbit pharyngoesophageal segment. Dysphagia 6:203–208PubMedCrossRef Malmberg L, Ekberg O, Ekstrom J (1991) Effects of drugs and electrical field stimulation on isolated muscle strips from rabbit pharyngoesophageal segment. Dysphagia 6:203–208PubMedCrossRef
50.
go back to reference Hisa Y, Tadaki N, Uno T, Okamura H, Taguchi J, Ibata Y (1994) Calcitonin gene-related peptide-like immunoreactive motoneurons innervating the canine inferior pharyngeal constrictor muscle. Acta Otolaryngol 114:560–564PubMedCrossRef Hisa Y, Tadaki N, Uno T, Okamura H, Taguchi J, Ibata Y (1994) Calcitonin gene-related peptide-like immunoreactive motoneurons innervating the canine inferior pharyngeal constrictor muscle. Acta Otolaryngol 114:560–564PubMedCrossRef
51.
go back to reference Tadaki N, Hisa Y, Uno T, Koike S, Okamura H, Ibata Y (1995) Neurotransmitters for the canine inferior pharyngeal constrictor muscle. Otolaryngol Head Neck Surg 113:755–759PubMedCrossRef Tadaki N, Hisa Y, Uno T, Koike S, Okamura H, Ibata Y (1995) Neurotransmitters for the canine inferior pharyngeal constrictor muscle. Otolaryngol Head Neck Surg 113:755–759PubMedCrossRef
52.
go back to reference Shaker R, Hogan W (2000) Reflex-mediated enhancement of airway protective mechanisms. Am J Med 108(4A):8–14CrossRef Shaker R, Hogan W (2000) Reflex-mediated enhancement of airway protective mechanisms. Am J Med 108(4A):8–14CrossRef
53.
go back to reference Medda BK, Lang IM, Layman R, Hogan WJ, Dodds WJ, Shaker R (1994) Characterization and quantification of a pharyngo–UES contractile reflex in cats. Am J Physiol 167(Gastrointest Liver Physiol, 30):G972–G983 Medda BK, Lang IM, Layman R, Hogan WJ, Dodds WJ, Shaker R (1994) Characterization and quantification of a pharyngo–UES contractile reflex in cats. Am J Physiol 167(Gastrointest Liver Physiol, 30):G972–G983
54.
go back to reference Shaker R, Ren J, Xie P, Lang IM, Bardan E, Sui Z (1997) Characterization of the pharyngo–UES contractile reflex in humans. Am J Physiol 273(Gastrointest Liver Physiol, 36):854–858 Shaker R, Ren J, Xie P, Lang IM, Bardan E, Sui Z (1997) Characterization of the pharyngo–UES contractile reflex in humans. Am J Physiol 273(Gastrointest Liver Physiol, 36):854–858
55.
go back to reference Ulualp SO, Toohill RJ, Kern M, Shaker R (1998) Pharyngo–UES contractile reflex in patients with posterior laryngitis. Laryngoscope 108:1354–1357PubMedCrossRef Ulualp SO, Toohill RJ, Kern M, Shaker R (1998) Pharyngo–UES contractile reflex in patients with posterior laryngitis. Laryngoscope 108:1354–1357PubMedCrossRef
56.
go back to reference Aviv JE, Liu H, Parides M, Kaplan ST, Close LG (2000) Laryngopharyngeal sensory deficits in patients with laryngopharyngeal reflux and dysphagia. Ann Otol Rhinol Laryngol 109:1000–1006PubMed Aviv JE, Liu H, Parides M, Kaplan ST, Close LG (2000) Laryngopharyngeal sensory deficits in patients with laryngopharyngeal reflux and dysphagia. Ann Otol Rhinol Laryngol 109:1000–1006PubMed
57.
go back to reference Phua SY, McGarvey LP, Ngu MC, Ing AJ (2005) Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity. Thorax 60:488–491PubMedCrossRef Phua SY, McGarvey LP, Ngu MC, Ing AJ (2005) Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity. Thorax 60:488–491PubMedCrossRef
58.
go back to reference Vaezi MF, Singh S, Richter JE (1995) Role of acid and duodenogastric reflux in esophageal mucosal injury: a review of animal and human studies. Gastroenterology 108:1897–1907PubMedCrossRef Vaezi MF, Singh S, Richter JE (1995) Role of acid and duodenogastric reflux in esophageal mucosal injury: a review of animal and human studies. Gastroenterology 108:1897–1907PubMedCrossRef
59.
go back to reference Marshall REK, Anggiansah A, Owen WA, Owen WJ (1997) The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease. Gut 40:182–187PubMed Marshall REK, Anggiansah A, Owen WA, Owen WJ (1997) The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease. Gut 40:182–187PubMed
60.
go back to reference Axford SE, Sharp N, Ross PE et al (2001) Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies. Ann Otol Rhinol Laryngol 110:1099–1108PubMed Axford SE, Sharp N, Ross PE et al (2001) Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies. Ann Otol Rhinol Laryngol 110:1099–1108PubMed
61.
go back to reference Lillemoe KD, Johnson LF, Harmon JW (1982) Role of the components of the gastroduodenal contents in experimental acid esophagitis. Surgery 92:276–284PubMed Lillemoe KD, Johnson LF, Harmon JW (1982) Role of the components of the gastroduodenal contents in experimental acid esophagitis. Surgery 92:276–284PubMed
62.
go back to reference Bremner RM, Crookes PP, DeMeester TR, Peters JH, Stein HJ (1992) Concentration of refluxed acid and esophageal mucosal injury. Am J Surg 164:522–527PubMedCrossRef Bremner RM, Crookes PP, DeMeester TR, Peters JH, Stein HJ (1992) Concentration of refluxed acid and esophageal mucosal injury. Am J Surg 164:522–527PubMedCrossRef
63.
go back to reference Feldman M, Friedman LS, Sleisenger MH (eds) (2002) Sleisenger and Fordtran’s gastrointestinal and liver disease, 7th edn edn. Saunders, Philadelphia, pp 715–731 Feldman M, Friedman LS, Sleisenger MH (eds) (2002) Sleisenger and Fordtran’s gastrointestinal and liver disease, 7th edn edn. Saunders, Philadelphia, pp 715–731
64.
go back to reference 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
65.
go back to reference Knight RE, Wells JR, Parrish RS (2000) Esophageal dysmotility as an important co-factor in extraesophageal manifestations of gastroesophageal reflux. Laryngoscope 110:1462–1466PubMedCrossRef Knight RE, Wells JR, Parrish RS (2000) Esophageal dysmotility as an important co-factor in extraesophageal manifestations of gastroesophageal reflux. Laryngoscope 110:1462–1466PubMedCrossRef
66.
go back to reference 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
67.
go back to reference Sarosiek J, McCallum RW (1995) Do salivary organic components play a protective role in health and disease of the esophageal mucosa? Digestion 56(Suppl 1):32–37PubMedCrossRef Sarosiek J, McCallum RW (1995) Do salivary organic components play a protective role in health and disease of the esophageal mucosa? Digestion 56(Suppl 1):32–37PubMedCrossRef
68.
go back to reference Rourk RM, Namiot Z, Sarosiek J et al (1994) Impairment of salivary epidermal growth factor secretory response to esophageal mechanical and chemical stimulation in patients with reflux esophagitis. Am J Gastroenterol 89:237–244PubMed Rourk RM, Namiot Z, Sarosiek J et al (1994) Impairment of salivary epidermal growth factor secretory response to esophageal mechanical and chemical stimulation in patients with reflux esophagitis. Am J Gastroenterol 89:237–244PubMed
69.
go back to reference Eckley CA, Michelsohn N, Rizzo LV, Tadokoro CE, Costa HO (2004) Salivary epidermal growth factor concentration in adults with reflux laryngitis. Otolaryngol Head Neck Surg 131:401–406PubMedCrossRef Eckley CA, Michelsohn N, Rizzo LV, Tadokoro CE, Costa HO (2004) Salivary epidermal growth factor concentration in adults with reflux laryngitis. Otolaryngol Head Neck Surg 131:401–406PubMedCrossRef
70.
go back to reference Ino M, Ushiro K, Ino C et al. (1993) Kinetics of epidermal growth factor in saliva. Acta Otolaryngol (Stockh) Suppl 500:126–130 Ino M, Ushiro K, Ino C et al. (1993) Kinetics of epidermal growth factor in saliva. Acta Otolaryngol (Stockh) Suppl 500:126–130
71.
go back to reference Tobey NA, Powell DW et al (1989) Serosal bicarbonate protects against acid injury to rabbit esophagus. Gastroenterology 96:1466–1477PubMed Tobey NA, Powell DW et al (1989) Serosal bicarbonate protects against acid injury to rabbit esophagus. Gastroenterology 96:1466–1477PubMed
72.
go back to reference Christie KN, Thomson C, Xue L et al (1997) Carbonic anhydrase isoenzymes I, II, III and IV are present in human esophageal epithelium. J Histochem Cytochem 45:35–40PubMed Christie KN, Thomson C, Xue L et al (1997) Carbonic anhydrase isoenzymes I, II, III and IV are present in human esophageal epithelium. J Histochem Cytochem 45:35–40PubMed
73.
go back to reference Hopwood D, Reynolds N et al (1998) Carbonic anhydrase isoenzymes in oesophagitis and Barrett’s mucosa. J Pathol 184(Suppl S):18A Hopwood D, Reynolds N et al (1998) Carbonic anhydrase isoenzymes in oesophagitis and Barrett’s mucosa. J Pathol 184(Suppl S):18A
74.
go back to reference Johnston N, Knight J, Dettmar PW, Lively MO, Koufman J (2004) Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope 114:2129–2134PubMedCrossRef Johnston N, Knight J, Dettmar PW, Lively MO, Koufman J (2004) Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope 114:2129–2134PubMedCrossRef
75.
go back to reference Naito Y, Kuroda M, Uchiyama K et al (2006) Inflammatory response of esophageal epithelium in combined-type esophagitis in rats: a transcriptome analysis. Int J Mol Med 18:821–828PubMed Naito Y, Kuroda M, Uchiyama K et al (2006) Inflammatory response of esophageal epithelium in combined-type esophagitis in rats: a transcriptome analysis. Int J Mol Med 18:821–828PubMed
76.
go back to reference Dvorakova K, Payne CM, Ramsey L et al (2004) Increased expression and secretion of interleukin-6 in patients with Barrett’s esophagus. Clin Cancer Res 10:2020–2028PubMedCrossRef Dvorakova K, Payne CM, Ramsey L et al (2004) Increased expression and secretion of interleukin-6 in patients with Barrett’s esophagus. Clin Cancer Res 10:2020–2028PubMedCrossRef
77.
go back to reference Yoshida N, Uchiyama K, Kuroda M, Sakuma K, Kokura S, Ichikawa H, Naito Y, Takemura T, Yoshikawa T, Okanoue T (2004) Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease. Scand J Gastroenterol 39:9816–9822CrossRef Yoshida N, Uchiyama K, Kuroda M, Sakuma K, Kokura S, Ichikawa H, Naito Y, Takemura T, Yoshikawa T, Okanoue T (2004) Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease. Scand J Gastroenterol 39:9816–9822CrossRef
78.
go back to reference Berardi RR (2000) A critical evaluation of proton-pump inhibitors in the treatment of gastroesophageal reflux disease. Am J Manag Care 6:S491–S505PubMed Berardi RR (2000) A critical evaluation of proton-pump inhibitors in the treatment of gastroesophageal reflux disease. Am J Manag Care 6:S491–S505PubMed
79.
go back to reference Hom DB (1994) Growth factors and wound healing in otolaryngology. Otolaryngol Head Neck Surg 110:560–564PubMed Hom DB (1994) Growth factors and wound healing in otolaryngology. Otolaryngol Head Neck Surg 110:560–564PubMed
80.
go back to reference Fujiwara Y, Higuchi K, Takashima T et al (2002) Increased expresion of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats. Aliment Pharmacol Ther 16(suppl 2):52–58PubMedCrossRef Fujiwara Y, Higuchi K, Takashima T et al (2002) Increased expresion of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats. Aliment Pharmacol Ther 16(suppl 2):52–58PubMedCrossRef
81.
go back to reference Lord LVN, Park JM, Wickramasinghe K et al (2003) Vascular endothelial growth factor and basic fibroblast growth factor expression in eosophageal carcinoma and Barret esophagus. J Thorac Cardiovasc Surg 125:246–253PubMedCrossRef Lord LVN, Park JM, Wickramasinghe K et al (2003) Vascular endothelial growth factor and basic fibroblast growth factor expression in eosophageal carcinoma and Barret esophagus. J Thorac Cardiovasc Surg 125:246–253PubMedCrossRef
82.
go back to reference Sarosiek J, Jensen RT, Maton PN et al (2000) Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential. Am J Gastroenterol 95:1158–1165PubMedCrossRef Sarosiek J, Jensen RT, Maton PN et al (2000) Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential. Am J Gastroenterol 95:1158–1165PubMedCrossRef
83.
go back to reference Grotendorst GR (1997) Connective tissue growth factor: a mediator of TGF-β action on fibroblasts. Cytokine Growth Factor Rev 8:171–179PubMedCrossRef Grotendorst GR (1997) Connective tissue growth factor: a mediator of TGF-β action on fibroblasts. Cytokine Growth Factor Rev 8:171–179PubMedCrossRef
84.
go back to reference Ylitalo R et al (2004) Effect of acid and pepsin on gene expression in laryngeal fibroblasts. Ann Otol Rhinol Laryngol 113:866–871PubMed Ylitalo R et al (2004) Effect of acid and pepsin on gene expression in laryngeal fibroblasts. Ann Otol Rhinol Laryngol 113:866–871PubMed
85.
go back to reference Thibeault S et al (2007) Gene expression changes of inflammatory mediators in posterior laryngitis due to laryngopharyngeal reflux and evolution with PPI treatment: A preliminary study. The Larygoscope 117:2050–2056CrossRef Thibeault S et al (2007) Gene expression changes of inflammatory mediators in posterior laryngitis due to laryngopharyngeal reflux and evolution with PPI treatment: A preliminary study. The Larygoscope 117:2050–2056CrossRef
86.
go back to reference Hu FZ et al (2000) Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14. JAMA 284:325–334PubMedCrossRef Hu FZ et al (2000) Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14. JAMA 284:325–334PubMedCrossRef
87.
go back to reference Hu FZ et al (2004) Fine mapping a gene for pediatric gastroesophageal reflux on human chromosome 13q14. Hum Genet 114:562–572PubMedCrossRef Hu FZ et al (2004) Fine mapping a gene for pediatric gastroesophageal reflux on human chromosome 13q14. Hum Genet 114:562–572PubMedCrossRef
88.
go back to reference Johnston N, Bulmer D, Gill GA 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 et al (2003) Cell biology of laryngeal epithelial defenses in health and disease: further studies. Ann Otol Rhinol Laryngol 112:481–491PubMed
Metadata
Title
Molecular pathways and genetic factors in the pathogenesis of laryngopharyngeal reflux
Authors
Alexios S. Vardouniotis
Alexander D. Karatzanis
Eleni Tzortzaki
Elias Athanasakis
Katerina D. Samara
Georgios Chalkiadakis
Nikolaos Siafakas
George A. Velegrakis
Publication date
01-06-2009
Publisher
Springer-Verlag
Published in
European Archives of Oto-Rhino-Laryngology / Issue 6/2009
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-009-0966-z

Other articles of this Issue 6/2009

European Archives of Oto-Rhino-Laryngology 6/2009 Go to the issue