Abstract
An association between asthma and gastroesophageal reflux disease (GERD) has long been recognized both mechanistically and epidemiologically. The clinical relevance of this interplay continues to be explored, with special interest given to the role of GERD in the worsening of asthma. The effect of GERD is most frequently contemplated in patients with asthma that is difficult to control.
Medical and surgical anti-reflux trials attempting to alter asthma symptoms have reported mixed but generally underwhelming results, although asthma symptom scores are generally improved following effective treatment of GERD. Many of the pharmaceutical studies can be criticised for having too short a duration or for likely incomplete acid suppression.
Few trials have specifically studied pediatric populations. Because GERD is a common condition, particularly in young children, the role reflux plays in the worsening of asthma symptoms and the potential benefit on asthma of anti-reflux therapy warrants further exploration. Whether or not treating symptomatic GERD reduces the symptoms and severity of asthma in children, GERD coexisting with asthma should be aggressively treated. GERD symptoms in most patients with or without asthma can be controlled medically with continuous use of proton pump inhibitors such as omeprazole and lansoprazole and to a lesser extent by histamine H2 receptor antagonists such as famotidine and cimetidine.
Similar content being viewed by others
References
Salter HH. Asthma: its pathology and treatment. New York (NY): William Wood Company, 1882
Osier W. The principles and practices of medicine. Birmingham (AL): LB Adams, 1892
Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Chichester: John Wiley & Sons Ltd, 2003
Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastroesophageal reflux during infancy: a pediatric practice-based survey Arch Pediatr Adolesc Med 1997; 151: 569–72
Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastroesophageal reflux disease during childhood: a pediatric practice-based survey. Arch Pediatr Adolesc Med 2000; 154: 150–4
Vandenplas Y, Goyvaerts H, Helven R, et al. Gastroesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. Pediatrics 1991; 88(4): 834–40
Brodzicki J, Trawinska M, Korzon M. Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis. Med Sci Monit 2002; 8(7): CR529–37
Bibi H, Khvolis E, Shoseyov D, et al. The prevalence of gastroesophageal reflux in children with tracheomalacia and laryngomalacia. Chest 2001; 119: 409–13
Waring JP, Feiler MJ, Hunter JG, et al. Childhood gastroesophageal reflux symptoms in adult patients. J Pediatr Gastroenterol Nutr 2002; 25: 334–8
Faubion WA, Zein NN. Gastroesophageal reflux in infants and children. Mayo Clinic Proceedings 1998; 73(2): 166–73
Dimenas E. Quality of life in patients with upper gastrointestinal symptoms: an improved evaluation of treatment regimens? Scand J Gastroenterol 1993; 28: 681–7
National Institutes of Health/National Heart, Lung, and Blood Institute. National asthma education and prevention program expert panel report 2: guidelines for the diagnosis and management of asthma. Bethesda (MD): National Institutes of Health/National Heart, Lung, and Blood Institute; 1997, Publication no. 97-4051
Coultas DB, Samet JM. Epidemiology and natural history of childhood asthma. In: Tinkelman DG, Naspitz CK, editors. Childhood asthma: pathophysiology and treatment. 2nd ed. New York (NY): Marcel Dekker, 1993: 71–114
Cropp GJA. Special features of asthma in children [abstract]. Chest 1985; 87 Suppl.: 55
Tucci F, Resti M, Fontana R, et al. Gastroesophageal reflux and bronchial asthma: prevalence and effect of cisapride therapy. J Pediatr Gastroenterol Nutr 1993; 17: 265–70
Cinquetti M, Micelli S, Voltolina C, et al. The pattern of gastroesophageal reflux in asthmatic children. J Asthma 2002; 39(2): 135–42
Sheikh S, Stephen T, Howell L, et al. Gastroesophageal reflux in infants with wheezing. Pediatr Pulmonol 1999; 28: 181–6
Marten ME, Grunstein MM, Larsen GL. The relationship of gastroesophageal reflux to nocturnal wheezing in children with asthma. Ann Allergy 1982; 49(6): 318–22
Davis RS, Larsen GL, Grunstein MM. Respiratory response to intraesophageal acid infusion in asthmatic children during sleep. J Allergy Clin Immunol 1983; 72(4): 393–8
Ekstrom T, Tibbling L. Gastro-oesophageal reflux and triggering of bronchial asthma: negative report. Eur J Respir Dis 1987; 71(3): 177–80
Ekstrom T, Tibbling L. Esophageal acid perfusion, airway function, and symptoms in asthmatic patients with marked bronchial hyperreactivity. Chest 1989; 96(5): 995–8
Harding SM, Guzzo MR, Richter JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med 2000; 162: 34–9
Cunningham K, Riddell P, Maddern G, et al. Relationships between autonomic nerve dysfunction, gastric emptying and esophageal transit in gastroesophageal reflux [abstract]. Gastroenterology 1990; 98: A34
Arasu TS, Wyllie R, Fitzgerald JF, et al. Gastroesophageal reflux in infants and children comparative accuracy of diagnostic methods. J Pediatr 1980; 96(5): 798–803
Le Luyer B, Texte D, Segond G, et al. Value and role of esophageal scintigraphy in the diagnosis of gastroesophageal reflux in infants and children. Pediatrie 1983; 38(5): 291–302
Thomas EJ, Kumar R, Bharathi Dasan J, et al. Gastroesophageal reflux in asthmatic children not responding to asthma medication: a scintigraphic study in 126 patients with correlation between scintigraphic and clinical findings of reflux. J Clin Imaging 2003; 27: 333–6
Boonyaprapa S, Alderson PO, Garfinkel DJ, et al. Detection of pulmonary aspiration in infants and children with respiratory disease: concise communication. J Nucl Med 1980; 21(4): 314–8
Mahajan L, Wyllie R, Oliva L, et al. Reproducibility of 24-hour intraesophageal pH monitoring in pediatric patients. Pediatrics 1998; 101: 260–3
Baer M, Maki M, Nurminen J, et al. Esophagitis and findings of long-term esophageal pH recording in children with repeated lower respiratory tract symptoms. J Pediatr Gastroenterol Nutr 1986; 5(2): 187–90
Vandenplas Y, Belli D, Benhamou P, et al. A critical appraisal of current management practices for infant regurgitation: recommendations of a working party. Eur J Pediatr 1997; 156: 342–57
Buts JP, Barudi C, Otte JB. Double-blind controlled study on the efficacy of sodium-alginate in reducing gastroesophageal reflux assessed by 24h continuous pH monitoring in infants and children. Eur J Pediatr 1987; 146: 156–8
Orenstein SR, Shalaby TM, Devandry SN, et al. Famotidine for infant gastro-oesophageal reflux: a multi-center, randomized, placebo-controlled, withdrawal trial. Aliment Pharmacol Ther 2003; 17: 1097–107
Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. J Pediatr 2000; 137: 800–7
Isreal DM, Hassall E. Omeprazole and other proton pump inhibitors: pharmacology, efficacy, and safety, with special reference to use in children. J Pediatr Gastroenterol Nutr 1998; 27: 568–79
Franco MT, Salvia G, Terrin G, et al. Lansoprazole in the treatment of gastro-oesophageal reflux disease in childhood. Dig Liver Dis 2000; 32: 660–6
Sicherer, SH. Clinical aspects of gastrointestinal food allergy in childhood. Pediatrics 2003; 111(6): 1609–16
Markowitz JE, Spergel JM, Ruchelli E, et al. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol 2003; 98(4): 777–82
Mansfield LE, Stein MR. Gastroesophageal reflux and asthma: a possible reflex mechanism. Ann Allergy 1978; 41: 224–6
Canning BJ, Widdicombe JG, editors. Innervation of the airways. Respir Physiol 2001; 125 (special issue): 1–154
Canning BJ. Inflammation in asthma: the role of nerves and the potential influence of gastroesophageal reflux disease. In: Stein MR, ed. Gastroesophageal reflux disease and airway disease. New York (NY): Marcel Dekker, 1999: 19–54
Canning BJ. Role of nerves in asthmatic inflammation and potential influence of gastroesophageal reflux disease. Am J Med 2001; 111(8A): 13S–7S
Kohrogi H, Hamamoto J, Kawano O, et al. The role of substance P release in the lung with esophageal acid. Am J Med 2001 Dec 3; 111Suppl. 8A: 25S–30S
Tuchman DN, Boyle JT, Pack AI, et al. Comparison of airway responses following tracheal or esophageal acidification in the cat. Gastroenterology 1984; 87: 872–81
Jack CI, Calverley PM, Donnelly RJ, et al. Simultanous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal reflux. Thorax 1995; 50: 201–4
Harding SM, Schan CA, Guzzo MR, et al. Gastroesophageal reflux-induced bronchoconstriction. Chest 1995; 108: 1220–7
Herve P, Denjean A, Jain R, et al. Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. Am Rev Respir Dis 1986; 134: 986–99
Mazzone SB, Canning BJ. Central nervous system control of the airways: pharmacological implications. Curr Opin Pharmacol 2002 Jun; 2(3): 220–8
Roussos C, Macklem PT. The respiratory muscles. N Engl J Med 1982; 307: 786–97
Kaliner MK, Shelhamer JH, Davis PB, et al. Autonomic nervous system abnormalities and allergies. Ann Int Med 1982; 96: 349–57
Dodds WJ, Dent J, Hogan WJ, et al. Effect of atropine on esophageal motor function in humans. Am J Physiol 1981; 240: G290–6
Lodi U, Harding SM, Coghlan HC, et al. Autonomic regulation in asthmatics with gastroesophageal reflux. Chest 1997; 111: 65–70
Ekstrom T, Tibbling L. Influence of theophylline on gastro-oesophageal reflux and asthma. Eur J Clin Pharmacol 1988; 35: 353–6
DiMarino AJ, Cohen S. Effect of an oral beta-2 adrenergic agonist on lower esophageal sphincter pressure in normals and in patients with achalasia. Dig Dis Sci 1982; 27: 1063–6
Crowell MD, Zayat EN, Lacy BE, et al. The effects of an inhaled β2-adrenergic agonist on lower esophageal function, a dose response study. Chest 2001; 120: 1184–9
Lazenby JP, Guzzo MR, Harding SM, et al. Oral corticosteroids increase esophageal acid contact times in patients with stable asthma. Chest 2002; 121: 625–34
Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2000
Meier JH, McNally PR, Punja M, et al. Does omeprazole (Prilosec) improve respiratory function in asthmatics with gastroesophageal reflux? Dig Dis Sci 1994; 39: 2127–33
Khoshoo V, Le T, Haydel RM, et al. Role of gastroesophageal reflux in older children with persistent asthma. Chest 2003; 123: 1008–13
Irwin RS, Boulet LP, Cloutier MM, et al. Managing cough as a defense mechanism and as a symptom: a consensus panel report of the American College of Chest Physicians. Chest 1998; 114(2 Suppl.): 133S–81S
Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppression therapy improves asthma outcome. Am J Med 1996; 100: 395–405
Field SK, Sutherland LR. Does medical antireflux therapy improve asthma in asthmatics with gastroesophageal reflux? A critical review of the literature. Chest 1998; 114: 275–83
Harper PC, Bergner A, Kaye MD. Antireflux treatment for asthma: improvement in patients with associated gastroesophageal reflux. Arch Int Med 1987; 147(1): 56–60
Gustafsson PM, Kjellman NI, Tibbling L. A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux. Eur Respir J 1992; 5: 201–6
Lecci A, Maggi CA. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin Ther Targets 2003 Jun; 7(3): 343–62
Zhang Q, Lehmann A, Rigda R, et al. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut 2002 Jan; 50(1): 19–24
Gunthorpe MJ, Benham CD, Randall A, et al. The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol Sci 2002 Apr; 23(4): 183–91
Torphy TJ. Phosphodiesterase isozymes: molecular targets for novel antiasthma agents. Am J Respir Crit Care Med 1998 Feb; 157(2): 351–70
Chang TW. The pharmacological basis of anti-IgE therapy. Nat Biotechnol 2000 Feb; 18(2): 157–62
Lukacs NW. Role of chemokines in the pathogenesis of asthma. Nat Rev Immunol 2001 Nov; 1(2): 108–16
Barnes PJ. Cytokine modulators as novel therapies for asthma. Annu Rev Pharmacol Toxicol 2002; 42: 81–98
Schleimer RP, Bochner BS. The role of adhesion molecules in allergic inflammation and their suitability as targets of antiallergic therapy. Clin Exp Allergy 1998 Aug; 28Suppl. 3: 15–23
Norrashidah AW, Henry RL. Fundoplication in children with gastro-oesophageal reflux disease. J Paediatr Child Health 2002; 38: 156–9
Field SK, Gelfand G, McFadden SD. The effects of antireflux surgery on asthmatics with gastroesophageal reflux. Chest 1999; 116: 766–74
Bowrey DJ, Peters JH, DeMeester TR. Gastroesophageal reflux disease in asthma: effects of medical and surgical antireflux therapy on asthma control. Ann Surg 2000; 231(2): 161–72
Sontag SJ, O’Connell S, Khandelwal S, et al. Antireflux surgery in asthmatics with reflux (GER) improves pulmonary symptoms and function [abstract]. Gastroenterology 1990; 98: A128
Larrain A, Carrasco E, Galleguillos F, et al. Medical and surgical treatment of asthma associated with gastroesophageal reflux. Chest 1991; 99: 1330–5
Andze GO, Brandt ML, St. Vil D, et al. Diagnosis and treatment of gastroesophageal reflux in 500 children with respiratory symptoms: the value of pH monitoring. J Pediatr Surg 1991; 26: 295–300
Ahrens P, Heller K, Beyer P, et al. Antireflux surgery in children suffering from reflux-associated respiratory diseases. Pediatr Pulmonol 1999; 28: 89–93
Wise RA. Clinical trial of acid reflux therapy in asthma: grant number 1U01HL072968-01, 2003 [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2005 May 20]
Wenzl TG. Evaluation of gastroesophageal reflux events in children using multichannel intraluminal electrical impedance. Am J Med 2003; Suppl. 3A: 161S–5S
Acknowledgments
Dr Canning’s research is supported financially through grants provided by the National Institutes of Health/National Heart, Lung and Blood Institute. Dr Canning is a consultant for GlaxoSmithKline and UCB Research, has collaborated with investigators from AstraZeneca, Sepracor, and Amgen, and has previously served as a consultant for Merck, Altana, and Sanofi-Aventis. Dr Scarupa is a consultant for Genentech and Sanofi-Aventis Pharmaceuticals. He is also an investigator or sub-investigator in collaborative studies with GlaxoSmithKline, Altana, AstraZeneca, Dyax, Dynavax, Pfizer, and Novartis Pharmaceuticals. The authors do not have investments in nor patents held with any person or group within the pharmaceutical industry.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Scarupa, M.D., Mori, N. & Canning, B.J. Gastroesophageal Reflux Disease in Children with Asthma. Pediatr-Drugs 7, 177–186 (2005). https://doi.org/10.2165/00148581-200507030-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00148581-200507030-00004