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Published in: BMC Pulmonary Medicine 1/2013

Open Access 01-12-2013 | Research article

Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study

Authors: D Lakmali Amarasiri, Arunasalam Pathmeswaran, H Janaka de Silva, Channa D Ranasinha

Published in: BMC Pulmonary Medicine | Issue 1/2013

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Abstract

Background

Gastro-esophageal reflux disease (GERD) predisposes to airway disease through a vagally-mediated esophago-bronchial reflex. This study investigates this vagal response to esophageal acid perfusion.

Methods

40 asthmatics with mild stable asthma participated. Each subject underwent spirometry and autonomic function testing (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) four times: a) before intubation, b) after intubation, and then immediately after perfusion with, in random order, c) concentrated lime juice solution (pH 2–3) and d) 0.9% saline. Subjects were blinded to the solution perfused.

Results

Asthmatics were of mean (SD) age 34.3 years (1.3), and 67.5% of them were females. pH monitoring demonstrated that 20 subjects had abnormal reflux and 20 did not. In each group 10 subjects had a positive GERD symptom score. Following perfusion with acid compared to saline, all subjects showed significant decreases in FEV1 and PEFR and significant increases in the mean valsalva ratio and heart rate difference on deep breathing from baseline values, but no changes in FVC or heart rate ratio on standing. There were no significant differences in any of the parameters between subjects with and without reflux.

Conclusions

Acid stimulation of the distal esophagus results in increased parasympathetic activity and concomitant broncho-constriction in asthmatics irrespective of their reflux state. This strengthens the hypothesis that GER triggers asthma-like symptoms through a vagally mediated esophago-bronchial reflex and encourages a possible role for anti-cholinergic drugs in the treatment of reflux-associated asthma.
Literature
1.
go back to reference Harding SM: Gastresophageal reflux and asthma: insight into the association. J Allergy Clin Immunol. 1999, 104 (2 Pt 1): 251-259.CrossRefPubMed Harding SM: Gastresophageal reflux and asthma: insight into the association. J Allergy Clin Immunol. 1999, 104 (2 Pt 1): 251-259.CrossRefPubMed
2.
go back to reference Canning BJ, Fischer A: Neural regulation of airway smooth muscle tone. Respir Physiol. 2001, 125 (1–2): 113-127.CrossRefPubMed Canning BJ, Fischer A: Neural regulation of airway smooth muscle tone. Respir Physiol. 2001, 125 (1–2): 113-127.CrossRefPubMed
3.
go back to reference Canning BJ, Mazzone SB: Reflex mechanisms in gastresophageal reflux disease and asthma. Am J Med. 2003, 115 (Suppl 3A): 45S-48S.CrossRefPubMed Canning BJ, Mazzone SB: Reflex mechanisms in gastresophageal reflux disease and asthma. Am J Med. 2003, 115 (Suppl 3A): 45S-48S.CrossRefPubMed
4.
go back to reference Harding SM, Richter JE: The role of gastresophageal reflux in chronic cough and asthma. Chest. 1997, 111 (5): 1389-1402. 10.1378/chest.111.5.1389.CrossRefPubMed Harding SM, Richter JE: The role of gastresophageal reflux in chronic cough and asthma. Chest. 1997, 111 (5): 1389-1402. 10.1378/chest.111.5.1389.CrossRefPubMed
5.
go back to reference Field SK: A critical review of the studies of the effects of simulated or real gastresophageal reflux on pulmonary function in asthmatic adults. Chest. 1999, 115 (3): 848-856. 10.1378/chest.115.3.848.CrossRefPubMed Field SK: A critical review of the studies of the effects of simulated or real gastresophageal reflux on pulmonary function in asthmatic adults. Chest. 1999, 115 (3): 848-856. 10.1378/chest.115.3.848.CrossRefPubMed
6.
go back to reference Mansfield LE, Stein MR: Gastresophageal reflux and asthma: a possible reflex mechanism. Ann Allergy. 1978, 41 (4): 224-226.PubMed Mansfield LE, Stein MR: Gastresophageal reflux and asthma: a possible reflex mechanism. Ann Allergy. 1978, 41 (4): 224-226.PubMed
7.
go back to reference Spaulding HS, Mansfield LE, Stein MR, Sellner JC, Gremillion DE: Further investigation of the association between gastresophageal reflux and bronchoconstriction. J Allergy Clin Immunol. 1982, 69 (6): 516-521. 10.1016/0091-6749(82)90176-2.CrossRefPubMed Spaulding HS, Mansfield LE, Stein MR, Sellner JC, Gremillion DE: Further investigation of the association between gastresophageal reflux and bronchoconstriction. J Allergy Clin Immunol. 1982, 69 (6): 516-521. 10.1016/0091-6749(82)90176-2.CrossRefPubMed
8.
go back to reference Perpina M, Pellicer C, Marco V, Maldonado J, Ponce J: The significance of the reflex bronchoconstriction provoked by gastresophageal reflux in bronchial asthma. Eur J Respir Dis. 1985, 66 (2): 91-97.PubMed Perpina M, Pellicer C, Marco V, Maldonado J, Ponce J: The significance of the reflex bronchoconstriction provoked by gastresophageal reflux in bronchial asthma. Eur J Respir Dis. 1985, 66 (2): 91-97.PubMed
9.
go back to reference Schan CA, Harding SM, Haile JM, Bradley LA, Richter JE: Gastresophageal reflux-induced bronchoconstriction. An intraesophageal acid infusion study using state-of-the-art technology. Chest. 1994, 106 (3): 731-737.PubMed Schan CA, Harding SM, Haile JM, Bradley LA, Richter JE: Gastresophageal reflux-induced bronchoconstriction. An intraesophageal acid infusion study using state-of-the-art technology. Chest. 1994, 106 (3): 731-737.PubMed
10.
go back to reference Harding SM, Schan CA, Guzzo MR, Alexander RW, Bradley LA, Richter JE: Gastresophageal reflux-induced bronchoconstriction. Is microaspiration a factor?. Chest. 1995, 108 (5): 1220-1227. 10.1378/chest.108.5.1220.CrossRefPubMed Harding SM, Schan CA, Guzzo MR, Alexander RW, Bradley LA, Richter JE: Gastresophageal reflux-induced bronchoconstriction. Is microaspiration a factor?. Chest. 1995, 108 (5): 1220-1227. 10.1378/chest.108.5.1220.CrossRefPubMed
11.
go back to reference Wesseling G, Brummer RJ, Wouters EF, Ten Velde GP: Gastric asthma? No change in respiratory impedance during intraesophageal acidification in adult asthmatics. Chest. 1993, 104 (6): 1733-1736. 10.1378/chest.104.6.1733.CrossRefPubMed Wesseling G, Brummer RJ, Wouters EF, Ten Velde GP: Gastric asthma? No change in respiratory impedance during intraesophageal acidification in adult asthmatics. Chest. 1993, 104 (6): 1733-1736. 10.1378/chest.104.6.1733.CrossRefPubMed
12.
go back to reference Tan WC, Martin RJ, Pandey R, Ballard RD: Effects of spontaneous and simulated gastresophageal reflux on sleeping asthmatics. Am Rev Respir Dis. 1990, 141 (6): 1394-1399. 10.1164/ajrccm/141.6.1394.CrossRefPubMed Tan WC, Martin RJ, Pandey R, Ballard RD: Effects of spontaneous and simulated gastresophageal reflux on sleeping asthmatics. Am Rev Respir Dis. 1990, 141 (6): 1394-1399. 10.1164/ajrccm/141.6.1394.CrossRefPubMed
13.
go back to reference Kjellen G, Tibbling L, Wranne B: Bronchial obstruction after esophageal acid perfusion in asthmatics. Clin Physiol. 1981, 1 (3): 285-292. 10.1111/j.1475-097X.1981.tb00897.x.CrossRefPubMed Kjellen G, Tibbling L, Wranne B: Bronchial obstruction after esophageal acid perfusion in asthmatics. Clin Physiol. 1981, 1 (3): 285-292. 10.1111/j.1475-097X.1981.tb00897.x.CrossRefPubMed
14.
go back to reference Singh V, Aggarwal V, Bansal S, Nijhawan S, Chaudhary N: Effect of intraesophageal acid instillation on airway reactivity in patients with asthma. J Assoc Physicians India. 2000, 48 (6): 601-602.PubMed Singh V, Aggarwal V, Bansal S, Nijhawan S, Chaudhary N: Effect of intraesophageal acid instillation on airway reactivity in patients with asthma. J Assoc Physicians India. 2000, 48 (6): 601-602.PubMed
15.
go back to reference Chakrabarti S, Singh K, Singh V, Nain CK, Jindal SK: Airway response to acid instillation in esophagus in bronchial asthma. Indian J Gastroenterol. 1995, 14 (2): 44-47.PubMed Chakrabarti S, Singh K, Singh V, Nain CK, Jindal SK: Airway response to acid instillation in esophagus in bronchial asthma. Indian J Gastroenterol. 1995, 14 (2): 44-47.PubMed
16.
go back to reference Herve P, Denjean A, Jian R, Simonneau G, Duroux P: Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. Am Rev Respir Dis. 1986, 134 (5): 986-989.CrossRefPubMed Herve P, Denjean A, Jian R, Simonneau G, Duroux P: Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. Am Rev Respir Dis. 1986, 134 (5): 986-989.CrossRefPubMed
17.
go back to reference Vincent D, Cohen-Jonathan AM, Leport J, Merrouche M, Geronimi A, Pradalier A, Soule JC: Gastro-esophageal reflux prevalence and relationship with bronchial reactivity in asthma. Eur Respir J. 1997, 10 (10): 2255-2259. 10.1183/09031936.97.10102255.CrossRefPubMed Vincent D, Cohen-Jonathan AM, Leport J, Merrouche M, Geronimi A, Pradalier A, Soule JC: Gastro-esophageal reflux prevalence and relationship with bronchial reactivity in asthma. Eur Respir J. 1997, 10 (10): 2255-2259. 10.1183/09031936.97.10102255.CrossRefPubMed
18.
go back to reference Cuttitta G, Cibella F, Visconti A, Scichilone N, Bellia V, Bonsignore G: Spontaneous gastresophageal reflux and airway patency during the night in adult asthmatics. Am J Respir Crit Care Med. 2000, 161 (1): 177-181. 10.1164/ajrccm.161.1.9808014.CrossRefPubMed Cuttitta G, Cibella F, Visconti A, Scichilone N, Bellia V, Bonsignore G: Spontaneous gastresophageal reflux and airway patency during the night in adult asthmatics. Am J Respir Crit Care Med. 2000, 161 (1): 177-181. 10.1164/ajrccm.161.1.9808014.CrossRefPubMed
19.
go back to reference Wu DN, Tanifuji Y, Kobayashi H, Yamauchi K, Kato C, Suzuki K, Inoue H: Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma. Chest. 2000, 118 (6): 1553-1556. 10.1378/chest.118.6.1553.CrossRefPubMed Wu DN, Tanifuji Y, Kobayashi H, Yamauchi K, Kato C, Suzuki K, Inoue H: Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma. Chest. 2000, 118 (6): 1553-1556. 10.1378/chest.118.6.1553.CrossRefPubMed
20.
go back to reference Wright RA, Miller SA, Corsello BF: Acid-induced esophagobronchial-cardiac reflexes in humans. Gastroenterology. 1990, 99 (1): 71-73.PubMed Wright RA, Miller SA, Corsello BF: Acid-induced esophagobronchial-cardiac reflexes in humans. Gastroenterology. 1990, 99 (1): 71-73.PubMed
21.
go back to reference Lodi U, Harding SM, Coghlan HC, Guzzo MR, Walker LH: Autonomic regulation in asthmatics with gastresophageal reflux. Chest. 1997, 111 (1): 65-70. 10.1378/chest.111.1.65.CrossRefPubMed Lodi U, Harding SM, Coghlan HC, Guzzo MR, Walker LH: Autonomic regulation in asthmatics with gastresophageal reflux. Chest. 1997, 111 (1): 65-70. 10.1378/chest.111.1.65.CrossRefPubMed
22.
go back to reference American Thoracic Society: Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis. 1991, 144 (5): 1202-1218.CrossRef American Thoracic Society: Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis. 1991, 144 (5): 1202-1218.CrossRef
23.
go back to reference Demeester TR, Johnson LF, Joseph GJ, Toscano MS, Hall AW, Skinner DB: Patterns of gastresophageal reflux in health and disease. Ann Surg. 1976, 184 (4): 459-470. 10.1097/00000658-197610000-00009.CrossRefPubMedPubMedCentral Demeester TR, Johnson LF, Joseph GJ, Toscano MS, Hall AW, Skinner DB: Patterns of gastresophageal reflux in health and disease. Ann Surg. 1976, 184 (4): 459-470. 10.1097/00000658-197610000-00009.CrossRefPubMedPubMedCentral
24.
go back to reference Amarasiri DL, Pathmeswaran A, Dassanayake AS, de Silva AP, Ranasinha CD, de Silva HJ: Esophageal motility, vagal function and gastroesophageal reflux in a cohort of adult asthmatics. BMC Gastroenterology. 2012, 12: 140-10.1186/1471-230X-12-140.CrossRefPubMedPubMedCentral Amarasiri DL, Pathmeswaran A, Dassanayake AS, de Silva AP, Ranasinha CD, de Silva HJ: Esophageal motility, vagal function and gastroesophageal reflux in a cohort of adult asthmatics. BMC Gastroenterology. 2012, 12: 140-10.1186/1471-230X-12-140.CrossRefPubMedPubMedCentral
25.
go back to reference Amarasiri LD, Pathmeswaran A, de Silva AP, Dassanayake AS, Ranasinha CD, de Silva HJ: Comparison of a composite symptom score assessing both symptom frequency and severity with a score that assesses frequency alone: a preliminary study to develop a practical symptom score to detect gastro-esophageal reflux disease in a resource-poor setting. Eur J Gastroenterol Hepatol. 2010, 22 (6): 662-668.PubMed Amarasiri LD, Pathmeswaran A, de Silva AP, Dassanayake AS, Ranasinha CD, de Silva HJ: Comparison of a composite symptom score assessing both symptom frequency and severity with a score that assesses frequency alone: a preliminary study to develop a practical symptom score to detect gastro-esophageal reflux disease in a resource-poor setting. Eur J Gastroenterol Hepatol. 2010, 22 (6): 662-668.PubMed
26.
go back to reference Ewing DJ, Clarke BF: Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed). 1982, 285 (6346): 916-918. 10.1136/bmj.285.6346.916.CrossRef Ewing DJ, Clarke BF: Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed). 1982, 285 (6346): 916-918. 10.1136/bmj.285.6346.916.CrossRef
27.
go back to reference Wu DN, Yamauchi K, Kobayashi H, Tanifuji Y, Kato C, Suzuki K, Inoue H: Effects of esophageal acid perfusion on cough responsiveness in patients with br onchial asthma. Chest. 2002, 122 (2): 505-509. 10.1378/chest.122.2.505.CrossRefPubMed Wu DN, Yamauchi K, Kobayashi H, Tanifuji Y, Kato C, Suzuki K, Inoue H: Effects of esophageal acid perfusion on cough responsiveness in patients with br onchial asthma. Chest. 2002, 122 (2): 505-509. 10.1378/chest.122.2.505.CrossRefPubMed
28.
go back to reference Shah PK, Lakhotia M, Mehta S, Jain SK, Gupta GL: Clinical dysautonomia in patients with bronchial asthma. Study with seven autonomic function tests. Chest. 1990, 98 (6): 1408-1413.PubMed Shah PK, Lakhotia M, Mehta S, Jain SK, Gupta GL: Clinical dysautonomia in patients with bronchial asthma. Study with seven autonomic function tests. Chest. 1990, 98 (6): 1408-1413.PubMed
29.
go back to reference Gupta S, Dolwani S: A study of autonomic status and its effect on ventilatory functions in bronchial asthma. Indian J Chest Dis Allied Sci. 1996, 38 (3): 147-156.PubMed Gupta S, Dolwani S: A study of autonomic status and its effect on ventilatory functions in bronchial asthma. Indian J Chest Dis Allied Sci. 1996, 38 (3): 147-156.PubMed
30.
go back to reference Richter JE: Delayed gastric emptying in reflux patients: to be or not to be?. Am J Gastroenterol. 1997, 92 (7): 1077-1078.PubMed Richter JE: Delayed gastric emptying in reflux patients: to be or not to be?. Am J Gastroenterol. 1997, 92 (7): 1077-1078.PubMed
31.
go back to reference Araujo AC, Aprile LR, Dantas RO, Terra-Filho J, Vianna EO: Bronchial responsiveness during esophageal acid infusion. Lung. 2008, 186 (2): 123-128. 10.1007/s00408-008-9072-z.CrossRefPubMed Araujo AC, Aprile LR, Dantas RO, Terra-Filho J, Vianna EO: Bronchial responsiveness during esophageal acid infusion. Lung. 2008, 186 (2): 123-128. 10.1007/s00408-008-9072-z.CrossRefPubMed
32.
go back to reference Rosztóczy A, Makk L, Izbéki F, Róka R, Somfay A, Wittmann T: Asthma and gastroesophageal reflux: clinical evaluation of esophago-bronchial reflex and proximal reflux. Digestion. 2008, 77 (3–4): 218-224. Epub 2008 Jul 19CrossRefPubMed Rosztóczy A, Makk L, Izbéki F, Róka R, Somfay A, Wittmann T: Asthma and gastroesophageal reflux: clinical evaluation of esophago-bronchial reflex and proximal reflux. Digestion. 2008, 77 (3–4): 218-224. Epub 2008 Jul 19CrossRefPubMed
33.
go back to reference Andersen LI, Schmidt A, Bundgaard A: Pulmonary function and acid application in the esophagus. Chest. 1986, 90 (3): 358-363. 10.1378/chest.90.3.358.CrossRefPubMed Andersen LI, Schmidt A, Bundgaard A: Pulmonary function and acid application in the esophagus. Chest. 1986, 90 (3): 358-363. 10.1378/chest.90.3.358.CrossRefPubMed
34.
go back to reference Jiang SP, Huang LW: Role of gastresophageal reflux disease in asthmatic patients. Eur Rev Med Pharmacol Sci. 2005, 9 (3): 151-160.PubMed Jiang SP, Huang LW: Role of gastresophageal reflux disease in asthmatic patients. Eur Rev Med Pharmacol Sci. 2005, 9 (3): 151-160.PubMed
35.
go back to reference Roka R, Rosztoczy A, Izbeki F, Taybani Z, Kiss I, Lonovics J, Wittmann T: Prevalence of respiratory symptoms and diseases associated with gastroesophageal reflux disease. Digestion. 2005, 71: 92-96. 10.1159/000084524.CrossRefPubMed Roka R, Rosztoczy A, Izbeki F, Taybani Z, Kiss I, Lonovics J, Wittmann T: Prevalence of respiratory symptoms and diseases associated with gastroesophageal reflux disease. Digestion. 2005, 71: 92-96. 10.1159/000084524.CrossRefPubMed
36.
go back to reference Davis RS, Larsen GL, Grunstein MM: Respiratory response to intraesophageal acid infusion in asthmatic children during sleep. J Allergy Clin Immunol. 1983, 72 (4): 393-398. 10.1016/0091-6749(83)90505-5.CrossRefPubMed Davis RS, Larsen GL, Grunstein MM: Respiratory response to intraesophageal acid infusion in asthmatic children during sleep. J Allergy Clin Immunol. 1983, 72 (4): 393-398. 10.1016/0091-6749(83)90505-5.CrossRefPubMed
37.
go back to reference Matthews PJ, Knowles CH, Chua YC, Delaney C, Hobson AR, Aziz Q: Effects of the concentration and frequency of acid infusion on the development and maintenance of esophageal hyperalgesia in a human volunteer model. American Journal of Physiology Gastrointestinal and Liver Physiology. 2008, 294 (4): G914-G917. 10.1152/ajpgi.00445.2007.CrossRefPubMed Matthews PJ, Knowles CH, Chua YC, Delaney C, Hobson AR, Aziz Q: Effects of the concentration and frequency of acid infusion on the development and maintenance of esophageal hyperalgesia in a human volunteer model. American Journal of Physiology Gastrointestinal and Liver Physiology. 2008, 294 (4): G914-G917. 10.1152/ajpgi.00445.2007.CrossRefPubMed
38.
go back to reference Cuomo R, De Giorgi F, Adinolfi L, Sarnelli G, Loffredo F, Efficie E, Verde C, Savarese MF, Usai P, Budillon G: Esophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias. Aliment Pharmacol Ther. 2006, 24 (2): 361-370. 10.1111/j.1365-2036.2006.02987.x.CrossRefPubMed Cuomo R, De Giorgi F, Adinolfi L, Sarnelli G, Loffredo F, Efficie E, Verde C, Savarese MF, Usai P, Budillon G: Esophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias. Aliment Pharmacol Ther. 2006, 24 (2): 361-370. 10.1111/j.1365-2036.2006.02987.x.CrossRefPubMed
Metadata
Title
Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study
Authors
D Lakmali Amarasiri
Arunasalam Pathmeswaran
H Janaka de Silva
Channa D Ranasinha
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2013
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/1471-2466-13-33

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