Abstract：OBJECTIVE: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheezing. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms. METHODS: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB. RESULTS: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported. CONCLUSIONS: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.
Darryl J. Adamko,Carina M. Majaesic,Christopher Skappak等. 婴幼儿胃食管反流相关性咳嗽治疗的初步研究[J]. 中国当代儿科杂志, 2012, 14(5): 321-327.
Darryl J. Adamko,Carina M. Majaesic,Christopher Skappak et al. A pilot trial on the treatment of gastroesophageal reflux-related cough in infants[J]. CJCP, 2012, 14(5): 321-327.
［1］Loughlin GM. Respiratory consequences of dysfunctional swallowing and aspiration［J］. DyspHagia, 1989, 3(3):126-130.
［2］Irwin RS, Madison JM, Fraire AE. The cough reflex and its relation to gastroesophageal reflux［J］. Am J Med, 2000, 108 (Suppl 4a): 73S-78S.
［3］Orenstein SR, Shalaby TM, Kelsey SF, Frankel E. Natural history of infant reflux esophagitis: symptoms and morphometric histology during one year without pharmacotherapy［J］. Am J Gastroenterol, 2006, 101(3):628-640.
［4］RudolpH CD, Mazur LJ, Liptak GS, Baker RD, Boyle JT, Colletti RB, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition［J］ J Pediatr Gastroenterol Nutr, 2001, 32 (Suppl 2):S1-31.
［5］Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus［J］. Am J Gastroenterol, 2006, 101(8):1900-1920.
［6］Gouda BB, Lydon AM, Badhe A, Shorten GD. A comparison of the effects of ranitidine and omeprazole on volume and pH of gastric contents in elective surgical patients［J］. Eur J Anaesthesiol, 2004, 21(4):260-264.
［7］Kemmotsu O, Mizushima M, Morimoto Y, Numazawa R, Kaseno S, Yamamura T, et al. Effect of preanesthetic intramuscular ranitidine on gastric acidity and volume in children［J］. J Clin Anesth, 1991, 3(6):451-455.
［8］Hyman PE, Abrams C, Dubois A. Effect of metoclopramide and bethanechol on gastric emptying in infants［J］. Pediatr Res, 1985, 19(10):1029-1032.
［9］Sheikh S, Stephen T, Howell L, Eid N. Gastroesophageal reflux in infants with wheezing［J］. Pediatr Pulmonol, 1999, 28(3):181-186.
［10］Augood C, MacLennan S, Gilbert R, Logan S. Cisapride treatment for gastro-oesophageal reflux in children［J］. Cochrane Database Syst Rev, 2003(4):CD002300.
［11］Richter JE. A critical review of current medical therapy for gastroesophageal reflux disease［J］. J Clin Gastroenterol, 1986, 8 (Suppl 1):72-80.
［12］Kato S, Ebina K, Fujii K, Chiba H, Nakagawa H. Effect of omeprazole in the treatment of refractory acid-related diseases in childhood: endoscopic healing and twenty-four-hour intragastric acidity［J］. J Pediatr, 1996, 128(3):415-421.
［13］Estevao-Costa J, Fragoso AC, Prata MJ, Campos M, Trindade E, Dias JA, et al. Gastric emptying and antireflux surgery［J］. Pediatr Surg Int, 2011, 27(4):367-371.
［14］Sachdeva P, Malhotra N, Pathikonda M, Khayyam U, Fisher RS, Maurer AH, et al. Gastric emptying of solids and liquids for evaluation for gastroparesis［J］. Dig Dis Sci, 2011, 56(4):1138-1146.
［15］Nahata MCaH, T.F. Pediatric Drug Formulary［M］. 4th ed. Philadelphia: Lippincott Williams ＆Wilkins 2000.
［16］Chan-Yeung M, Manfreda J, DimichWard H, Ferguson A, Watson W, Becker A. A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants［J］. Arch Pediatr Adolesc Med, 2000, 154(7):657-663.
［17］Demeester TR, Johnson LF, JosepH GJ, Toscano MS, Hall AW, Skinner DB. Patterns of gastroesophageal reflux in health and disease［J］. Ann Surg, 1976, 184(4):459-470.
［18］Richter JE, Bradley LA, Demeester TR, Wu WC. Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender［J］. Dig Dis Sci, 1992, 37(6):849-856.
［19］Nordenstedt H, Nilsson M, Johansson S, Wallander MA, Johnsen R, Hveem K, et al. The relation between gastroesophageal reflux and respiratory symptoms in a populationbased study: the nord-trondelag health survey［J］. Chest, 2006, 129(4):1051-1056.
［20］Debley JS, Carter ER, Redding GJ. Prevalence and impact of gastroesophageal reflux in adolescents with asthma: a population-based study［J］. Pediatr Pulmonol, 2006,41(5):475-481.
［21］Wong BC, Kinoshita Y. Systematic review on epidemiology of gastroesophageal reflux disease in Asia［J］. Clin Gastroenterol Hepatol, 2006, 4(4):398-407.
［22］Saglani S, Nicholson AG, Scallan M, BalfourLynn I, Rosenthal M, Payne DN, et al. Investigation of young children with severe recurrent wheeze: any clinical benefit? ［J］. Eur Respir J, 2006, 27(1):29-35.
［23］Christie DL, O'Grady LR, Mack DV. Incompetent lower esophageal sphincter and gastroesophageal reflux in recurrent acute pulmonary disease of infancy and childhood［J］. J Pediatr, 1978, 93(1):23-27.
［24］Goldstein JL, Johanson JF, Suchower LJ, Brown KA. Healing of gastric ulcers with esomeprazole versus ranitidine in patients who continued to receive NSAID therapy: a randomized trial［J］. Am J Gastroenterol, 2005, 100(12):2650-2657.
［25］Khoshoo V, Dhume P. Clinical response to 2 dosing regimens of lansoprazole in infants with gastroesophageal reflux［J］. J Pediatr Gastroenterol Nutr, 2008, 46(3):352-354.
［26］Chicella MF, Batres LA, Heesters MS, Dice JE. Prokinetic drug therapy in children: a review of current options［J］. Ann Pharmacother, 2005, 39(4):706-711.
［27］Machida HM, Forbes DA, Gall DG, Scott RB. Metoclopramide in gastroesophageal reflux of infancy［J］. J Pediatr, 1988, 112(3):483-487.
［28］Carroccio A, Iacono G, Montalto G, Cavataio F, Soresi M, Notarbartolo A. Domperidone plus magnesium hydroxide and aluminum hydroxide: a valid therapy in children with gastroesophageal reflux. A double-blind randomized study versus placebo［J］. Scand J Gastroenterol, 1994, 29(4):300-304.
［29］Farrell RL, Roling GT, Castell DO. Stimulation of the incompetent lower esophageal sphincter. A possible advance in therapy of heartburn［J］. Am J Dig Dis, 1973, 18(8):646-650.
［30］Teper AM, Kofman CD, Szulman GA, Vidaurreta SM, Maffey AF. Fluticasone improves pulmonary function in children under 2 years old with risk factors for asthma［J］. Am J Respir Crit Care Med, 2005, 171(6):587-590.
［31］Merkus PJ, de Jongste JC. Inhaled corticosteroids in wheezy infants［J］. Am J Respir Crit Care Med, 2005,172(8):1058-1059.
［32］El Serag HB, Gilger M, Kuebeler M, Rabeneck L. Extraesophageal associations of gastroesophageal reflux disease in children without neurologic defects［J］. Gastroenterology, 2001, 121(6):1294-1299.
［33］Loughlin GM, Lefton-Greif MA. Dysfunctional swallowing and respiratory disease in children［J］. Adv Pediatr, 1994, 41:135-162.
［34］Sifrim D, Castell D, Dent J, Kahrilas PJ. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux［J］. Gut 2004, 53(7):1024-1031.
［35］Conley SF, Werlin SL, Beste DJ. Proximal pH-metry for diagnosis of upper airway complications of gastroesopHageal reflux［J］. J Otolaryngol, 1995, 24(5):295-298.
［37］Rosen R, Nurko S. The importance of multichannel intraluminal impedance in the evaluation of children with persistent respiratory symptoms［J］. Am J Gastroenterol, 2004, 99(12):2452-2458.
［38］Lopez-Alonso M, Moya MJ, Cabo JA, Ribas J, del Carmen MM, Silny J, et al. Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux［J］. Pediatrics, 2006, 118(2):e299-e308.
［39］Wilson SL, Thach BT, Brouillette RT, Abu-Osba YK. Coordination of breathing and swallowing in human infants［J］. J Appl Physol, 1981,50(4):851-858.
［40］Morgan WJ, Stern DA, Sherrill DL, Guerra S, Holberg CJ, Guilbert TW, et al. Outcome of asthma and wheezing in the first 6 years of life: followup through adolescence［J］. Am J Respir Crit Care Med, 2005,172(10): 1253-1258.
［41］Eid NS, Morton RL. Rational approach to the wheezy infant［J］. Paediatr Respir Rev, 2004, 5 (Suppl A): S77-S79.
［42］Gold BD. Is gastroesophageal reflux disease really a life-long disease: do babies who regurgitate grow up to be adults with GERD complications?［J］. Am J Gastroenterol, 2006, 101(3): 641-644.
［43］Khoshoo V, Edell D, Thompson A, Rubin M. Are we overprescribing antireflux medications for infants with regurgitation? ［J］. Pediatrics, 2007, 120(5): 946-949.
