Skip to main content
PMC home page
Postgraduate Medical Journal logoLink to Postgraduate Medical Journal
. 2004 Dec;80(950):701–705. doi: 10.1136/pgmj.2004.019265

Gastro-oesophageal reflux and bronchial asthma: current status and future directions

J Mathew 1, M Singh 1, S Mittal 1
PMCID: PMC1743171  PMID: 15579608

Abstract

In recent years there have been several reports suggesting an association between bronchial asthma and gastro-oesophageal reflux; however a cause and effect relationship has not been proven yet. Confirmation of such a relationship is likely to have far reaching implications on the management of asthma. Reliable assessment of this issue is hampered by the presence of various lacunae in most of the published studies. Hence it is essential to carefully examine the strength of data suggesting a link between asthma and reflux. This article critically analyses currently available literature on the subject (including published reviews, meta-analyses, and randomised clinical trials in the English language) and summarises valid conclusions that can be drawn; it also proposes a framework for future studies to resolve the issue.

Full Text

The Full Text of this article is available as a PDF (72.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allgood P. C., Bachmann M. Medical or surgical treatment for chronic gastrooesophageal reflux? A systematic review of published evidence of effectiveness. Eur J Surg. 2000 Sep;166(9):713–721. doi: 10.1080/110241500750008475. [DOI] [PubMed] [Google Scholar]
  2. Andze G. O., Brandt M. L., St Vil D., Bensoussan A. L., Blanchard H. Diagnosis and treatment of gastroesophageal reflux in 500 children with respiratory symptoms: the value of pH monitoring. J Pediatr Surg. 1991 Mar;26(3):295–300. doi: 10.1016/0022-3468(91)90505-n. [DOI] [PubMed] [Google Scholar]
  3. Balson B. M., Kravitz E. K., McGeady S. J. Diagnosis and treatment of gastroesophageal reflux in children and adolescents with severe asthma. Ann Allergy Asthma Immunol. 1998 Aug;81(2):159–164. doi: 10.1016/S1081-1206(10)62803-7. [DOI] [PubMed] [Google Scholar]
  4. Bendig D. W., Seilheimer D. K., Wagner M. L., Ferry G. D., Barrison G. M. Complications of gastroesophageal reflux in patients with cystic fibrosis. J Pediatr. 1982 Apr;100(4):536–540. doi: 10.1016/s0022-3476(82)80748-8. [DOI] [PubMed] [Google Scholar]
  5. Berquist W. E., Rachelefsky G. S., Kadden M., Siegel S. C., Katz R. M., Fonkalsrud E. W., Ament M. E. Gastroesophageal reflux-associated recurrent pneumonia and chronic asthma in children. Pediatrics. 1981 Jul;68(1):29–35. [PubMed] [Google Scholar]
  6. Boeree M. J., Peters F. T., Postma D. S., Kleibeuker J. H. No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux. Eur Respir J. 1998 May;11(5):1070–1074. doi: 10.1183/09031936.98.11051070. [DOI] [PubMed] [Google Scholar]
  7. Bosheva M., Ivancheva D., Genkova N., Lutzkanova Z., Klinkanova M. Gastroesophageal reflux in children with cystic fibrosis. Folia Med (Plovdiv) 1998;40(3B):124–126. [PubMed] [Google Scholar]
  8. Chopra K., Matta S. K., Madan N., Iyer S. Association of gastroesophageal reflux (GER) with bronchial asthma. Indian Pediatr. 1995 Oct;32(10):1083–1086. [PubMed] [Google Scholar]
  9. Cinquetti M., Micelli S., Voltolina C., Zoppi G. The pattern of gastroesophageal reflux in asthmatic children. J Asthma. 2002 Apr;39(2):135–142. doi: 10.1081/jas-120002194. [DOI] [PubMed] [Google Scholar]
  10. Coughlan J. L., Gibson P. G., Henry R. L. Medical treatment for reflux oesophagitis does not consistently improve asthma control: a systematic review. Thorax. 2001 Mar;56(3):198–204. doi: 10.1136/thorax.56.3.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crowell M. D., Zayat E. N., Lacy B. E., Schettler-Duncan A., Liu M. C. The effects of an inhaled beta(2)-adrenergic agonist on lower esophageal function: a dose-response study. Chest. 2001 Oct;120(4):1184–1189. doi: 10.1378/chest.120.4.1184. [DOI] [PubMed] [Google Scholar]
  12. Davis R. S., Larsen G. L., Grunstein M. M. Respiratory response to intraesophageal acid infusion in asthmatic children during sleep. J Allergy Clin Immunol. 1983 Oct;72(4):393–398. doi: 10.1016/0091-6749(83)90505-5. [DOI] [PubMed] [Google Scholar]
  13. De Vita C., Berni Canani F., Cirillo B., Della Rotonda G. M., Berni Canani R. Reflusso gastroesofageo "silente" e patologia delle alte vie respiratorie in età pediatrica. Acta Otorhinolaryngol Ital. 1996 Oct;16(5):407–411. [PubMed] [Google Scholar]
  14. DeMeester T. R., Bonavina L., Iascone C., Courtney J. V., Skinner D. B. Chronic respiratory symptoms and occult gastroesophageal reflux. A prospective clinical study and results of surgical therapy. Ann Surg. 1990 Mar;211(3):337–345. doi: 10.1097/00000658-199003000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Donato L., Livolsi A., Gaugler C., Escande B., Weiss L., Ducoloné A. Rôle du reflux gastro-oesophagien dans l'asthme du nourrisson et du jeune enfant. Arch Pediatr. 2002 Aug;9 (Suppl 3):396s–401s. doi: 10.1016/s0929-693x(02)00150-1. [DOI] [PubMed] [Google Scholar]
  16. Donnelly R. J., Berrisford R. G., Jack C. I., Tran J. A., Evans C. C. Simultaneous tracheal and esophageal pH monitoring: investigating reflux-associated asthma. Ann Thorac Surg. 1993 Nov;56(5):1029–1034. doi: 10.1016/0003-4975(95)90008-x. [DOI] [PubMed] [Google Scholar]
  17. Ekström T., Lindgren B. R., Tibbling L. Effects of ranitidine treatment on patients with asthma and a history of gastro-oesophageal reflux: a double blind crossover study. Thorax. 1989 Jan;44(1):19–23. doi: 10.1136/thx.44.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Field S. K., Sutherland L. R. Does medical antireflux therapy improve asthma in asthmatics with gastroesophageal reflux?: a critical review of the literature. Chest. 1998 Jul;114(1):275–283. doi: 10.1378/chest.114.1.275. [DOI] [PubMed] [Google Scholar]
  19. Field S. K., Underwood M., Brant R., Cowie R. L. Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996 Feb;109(2):316–322. doi: 10.1378/chest.109.2.316. [DOI] [PubMed] [Google Scholar]
  20. Fitzgerald J. M., Allen C. J., Craven M. A., Newhouse M. T. Chronic cough and gastroesophageal reflux. CMAJ. 1989 Mar 1;140(5):520–524. [PMC free article] [PubMed] [Google Scholar]
  21. Ford G. A., Oliver P. S., Prior J. S., Butland R. J., Wilkinson S. P. Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: a placebo-controlled cross-over study. Postgrad Med J. 1994 May;70(823):350–354. doi: 10.1136/pgmj.70.823.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Foroutan Hamid Reza, Ghafari Masomeh. Gastroesophageal reflux as cause of chronic respiratory symptoms. Indian J Pediatr. 2002 Feb;69(2):137–139. doi: 10.1007/BF02859373. [DOI] [PubMed] [Google Scholar]
  23. Gastal O. L., Castell J. A., Castell D. O. Frequency and site of gastroesophageal reflux in patients with chest symptoms. Studies using proximal and distal pH monitoring. Chest. 1994 Dec;106(6):1793–1796. doi: 10.1378/chest.106.6.1793. [DOI] [PubMed] [Google Scholar]
  24. Gastal O. L., Castell J. A., Castell D. O. Frequency and site of gastroesophageal reflux in patients with chest symptoms. Studies using proximal and distal pH monitoring. Chest. 1994 Dec;106(6):1793–1796. doi: 10.1378/chest.106.6.1793. [DOI] [PubMed] [Google Scholar]
  25. González Morales J. E., Leal de Hernández L., González Spencer D. Asma asociada a reflujo gastroesofágico. Rev Alerg Mex. 1998 Jan-Feb;45(1):16–21. [PubMed] [Google Scholar]
  26. Gustafsson P. M., Kjellman N. I., Tibbling L. A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux. Eur Respir J. 1992 Feb;5(2):201–206. [PubMed] [Google Scholar]
  27. Harding S. M. Nocturnal asthma: role of nocturnal gastroesophageal reflux. Chronobiol Int. 1999 Sep;16(5):641–662. doi: 10.3109/07420529908998733. [DOI] [PubMed] [Google Scholar]
  28. Harding S. M., Richter J. E., Guzzo M. R., Schan C. A., Alexander R. W., Bradley L. A. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996 Apr;100(4):395–405. doi: 10.1016/S0002-9343(97)89514-9. [DOI] [PubMed] [Google Scholar]
  29. Harding S. M., Schan C. A., Guzzo M. R., Alexander R. W., Bradley L. A., Richter J. E. Gastroesophageal reflux-induced bronchoconstriction. Is microaspiration a factor? Chest. 1995 Nov;108(5):1220–1227. doi: 10.1378/chest.108.5.1220. [DOI] [PubMed] [Google Scholar]
  30. Harmanci E., Entok E., Metintas M., Vardareli E., Elbek O. Gastroesophageal reflux in the patients with asthma. Allergol Immunopathol (Madr) 2001 Jul-Aug;29(4):123–128. doi: 10.1016/s0301-0546(01)79044-1. [DOI] [PubMed] [Google Scholar]
  31. Harper P. C., Bergner A., Kaye M. D. Antireflux treatment for asthma. Improvement in patients with associated gastroesophageal reflux. Arch Intern Med. 1987 Jan;147(1):56–60. doi: 10.1001/archinte.147.1.56. [DOI] [PubMed] [Google Scholar]
  32. Jack C. I., Calverley P. M., Donnelly R. J., Tran J., Russell G., Hind C. R., Evans C. C. Simultaneous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal reflux. Thorax. 1995 Feb;50(2):201–204. doi: 10.1136/thx.50.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kastelik Jack A., Jackson Warren, Davies Trevor W., Wright Graham A., Redington Anthony E., Wedgwood Kevin R., Morice Alyn H. Measurement of gastric emptying in gastroesophageal reflux-related chronic cough. Chest. 2002 Dec;122(6):2038–2041. doi: 10.1378/chest.122.6.2038. [DOI] [PubMed] [Google Scholar]
  34. Keller R., Breitenbücher A. Gastroösophagealer Reflux und Lungenkrankheiten. Pneumologie. 1990 Feb;44 (Suppl 1):153–157. [PubMed] [Google Scholar]
  35. Kiljander T. O., Salomaa E. R., Hietanen E. K., Terho E. O. Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole. Chest. 1999 Nov;116(5):1257–1264. doi: 10.1378/chest.116.5.1257. [DOI] [PubMed] [Google Scholar]
  36. Kjellén G., Tibbling L., Wranne B. Effect of conservative treatment of oesophageal dysfunction on bronchial asthma. Eur J Respir Dis. 1981 Jun;62(3):190–197. [PubMed] [Google Scholar]
  37. Laukka M. A., Cameron A. J., Schei A. J. Gastroesophageal reflux and chronic cough: which comes first? J Clin Gastroenterol. 1994 Sep;19(2):100–104. doi: 10.1097/00004836-199409000-00004. [DOI] [PubMed] [Google Scholar]
  38. Levin T. R., Sperling R. M., McQuaid K. R. Omeprazole improves peak expiratory flow rate and quality of life in asthmatics with gastroesophageal reflux. Am J Gastroenterol. 1998 Jul;93(7):1060–1063. doi: 10.1111/j.1572-0241.1998.329_q.x. [DOI] [PubMed] [Google Scholar]
  39. Mansfield L. E., Hameister H. H., Spaulding H. S., Smith N. J., Glab N. The role of the vague nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention. Ann Allergy. 1981 Dec;47(6):431–434. [PubMed] [Google Scholar]
  40. Meier J. H., McNally P. R., Punja M., Freeman S. R., Sudduth R. H., Stocker N., Perry M., Spaulding H. S. Does omeprazole (Prilosec) improve respiratory function in asthmatics with gastroesophageal reflux? A double-blind, placebo-controlled crossover study. Dig Dis Sci. 1994 Oct;39(10):2127–2133. doi: 10.1007/BF02090360. [DOI] [PubMed] [Google Scholar]
  41. Mokhlesi B., Morris A. L., Huang C. F., Curcio A. J., Barrett T. A., Kamp D. W. Increased prevalence of gastroesophageal reflux symptoms in patients with COPD. Chest. 2001 Apr;119(4):1043–1048. doi: 10.1378/chest.119.4.1043. [DOI] [PubMed] [Google Scholar]
  42. Nagel R. A., Brown P., Perks W. H., Wilson R. S., Kerr G. D. Ambulatory pH monitoring of gastro-oesophageal reflux in "morning dipper" asthmatics. BMJ. 1988 Nov 26;297(6660):1371–1373. doi: 10.1136/bmj.297.6660.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Parameswaran K., Allen C. J., Kamada D., Efthimiadis A., Anvari M., Hargreave F. E. Sputum cell counts and exhaled nitric oxide in patients with gastroesophageal reflux, and cough or asthma. Can Respir J. 2001 Jul-Aug;8(4):239–244. doi: 10.1155/2001/418490. [DOI] [PubMed] [Google Scholar]
  44. Ruth M., Carlsson S., Månsson I., Bengtsson U., Sandberg N. Scintigraphic detection of gastro-pulmonary aspiration in patients with respiratory disorders. Clin Physiol. 1993 Jan;13(1):19–33. doi: 10.1111/j.1475-097x.1993.tb00314.x. [DOI] [PubMed] [Google Scholar]
  45. Saye Z., Forget P. P. Effect of cisapride on esophageal pH monitoring in children with reflux-associated bronchopulmonary disease. J Pediatr Gastroenterol Nutr. 1989 Apr;8(3):327–332. doi: 10.1097/00005176-198904000-00011. [DOI] [PubMed] [Google Scholar]
  46. Schindlbeck N. E., Heinrich C., Huber R. M., Müller-Lissner S. A. Effects of albuterol (salbutamol) on esophageal motility and gastroesophageal reflux in healthy volunteers. JAMA. 1988 Dec 2;260(21):3156–3158. [PubMed] [Google Scholar]
  47. Sheikh S., Stephen T., Howell L., Eid N. Gastroesophageal reflux in infants with wheezing. Pediatr Pulmonol. 1999 Sep;28(3):181–186. doi: 10.1002/(sici)1099-0496(199909)28:3<181::aid-ppul4>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  48. Sontag S. J., O'Connell S., Khandelwal S., Miller T., Nemchausky B., Schnell T. G., Serlovsky R. Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy. Gastroenterology. 1990 Sep;99(3):613–620. doi: 10.1016/0016-5085(90)90945-w. [DOI] [PubMed] [Google Scholar]
  49. Sontag Stephen J., O'Connell Susan, Khandelwal Sharad, Greenlee Herbert, Schnell Thomas, Nemchausky Bernard, Chejfec Gregorio, Miller Todd, Seidel Jean, Sonnenberg Amnon. Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol. 2003 May;98(5):987–999. doi: 10.1111/j.1572-0241.2003.07503.x. [DOI] [PubMed] [Google Scholar]
  50. Storr M., Meining A., Allescher H. D. Pathophysiology and pharmacological treatment of gastroesophageal reflux disease. Dig Dis. 2000;18(2):93–102. doi: 10.1159/000016970. [DOI] [PubMed] [Google Scholar]
  51. Teichtahl H., Kronborg I. J., Yeomans N. D., Robinson P. Adult asthma and gastro-oesophageal reflux: the effects of omeprazole therapy on asthma. Aust N Z J Med. 1996 Oct;26(5):671–676. doi: 10.1111/j.1445-5994.1996.tb02938.x. [DOI] [PubMed] [Google Scholar]
  52. Tucci F., Resti M., Fontana R., Noccioli B., Mattei R., Monterisi N., Pellegrini T., Jenuso R., Adami Lami C. Reflusso gastroesofageo e patologia respiratoria. Pediatr Med Chir. 1993 Jan-Feb;15(1):11–15. [PubMed] [Google Scholar]
  53. Tucci F., Resti M., Fontana R., Novembre E., Lami C. A., Vierucci A. Gastroesophageal reflux and bronchial asthma: prevalence and effect of cisapride therapy. J Pediatr Gastroenterol Nutr. 1993 Oct;17(3):265–270. doi: 10.1097/00005176-199310000-00006. [DOI] [PubMed] [Google Scholar]
  54. Vincent D., Cohen-Jonathan A. M., Leport J., Merrouche M., Geronimi A., Pradalier A., Soulé J. C. Gastro-oesophageal reflux prevalence and relationship with bronchial reactivity in asthma. Eur Respir J. 1997 Oct;10(10):2255–2259. doi: 10.1183/09031936.97.10102255. [DOI] [PubMed] [Google Scholar]
  55. Wright R. A., Miller S. A., Corsello B. F. Acid-induced esophagobronchial-cardiac reflexes in humans. Gastroenterology. 1990 Jul;99(1):71–73. doi: 10.1016/0016-5085(90)91231-t. [DOI] [PubMed] [Google Scholar]
  56. Yellon R. F., Coticchia J., Dixit S. Esophageal biopsy for the diagnosis of gastroesophageal reflux-associated otolaryngologic problems in children. Am J Med. 2000 Mar 6;108 (Suppl 4A):131S–138S. doi: 10.1016/s0002-9343(99)00352-6. [DOI] [PubMed] [Google Scholar]
  57. Young Lisa R., Hadjiliadis Denis, Davis R. Duane, Palmer Scott M. Lung transplantation exacerbates gastroesophageal reflux disease. Chest. 2003 Nov;124(5):1689–1693. doi: 10.1378/chest.124.5.1689. [DOI] [PubMed] [Google Scholar]

Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES