Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
권호 표지
DOI QR코드

DOI QR Code

Lactobacillus rhamnosus GG Usage in the Prevention of Gastrointestinal and Respiratory Tract Infections in Children with Gastroesophageal Reflux Disease Treated with Proton Pump Inhibitors: A Randomized Double-Blinded Placebo-Controlled Trial

  • Received : 2019.10.03
  • Accepted : 2020.02.11
  • Published : 2020.05.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Proton-pump inhibitors (PPIs) are frequently used to treat gastroesophageal reflux disease (GERD) in children, but recent evidence suggests a potential association between PPI treatment and some types of infections. The aim of this study was to assess the effectiveness of Lactobacillus rhamnosus GG (LGG) for the prevention of gastrointestinal and respiratory tract infections in children with GERD treated with PPI (omeprazol). Methods: Children younger than 5 years with GERD were assigned by a computer-generated list to receive LGG (109 colony-forming units) or placebo, twice daily, concomitantly with PPI treatment for 4-6 weeks; they were followed up for 12 weeks after therapy. The primary outcome measures were the percentage of children with a minimum of one episode of respiratory tract infection and the percentage of children with a minimum of one episode of gastrointestinal infection during the study. Results: Of 61 randomized children, 59 patients (LGG n=30; placebo n=29, mean age 11.3 months) were analyzed. There was no significant difference found between the LGG and placebo groups, either for the proportion of children with at least one respiratory tract infection (22/30 vs. 25/29, respectively; relative risk [RR] 0.85, 95% confidence interval [CI] 0.66-1.10) or for the proportion of children with at least one gastrointestinal infection (9/30 vs. 9/29, respectively; RR 0.97, 95% CI 0.45-2.09). Conclusion: LGG was not effective in the prevention of infectious complications in children with GERD receiving PPI. Caution is needed in interpreting these results, as the study was terminated early due to slow subject recruitment.

Keywords

References

  1. Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf 2019;10:1-13.
  2. Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, et al.; ESPGHAN, NASPGHAN. Joint ESPGHAN/NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr 2017;64:991-1003. https://doi.org/10.1097/MPG.0000000000001594
  3. Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2018;66:516-54. https://doi.org/10.1097/MPG.0000000000001889
  4. Lucendo AJ, Molina-Infante J, Arias A, von Arnim U, Bredenoord AJ, Bussmann C, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J 2017;5:335-8. https://doi.org/10.1177/2050640616689525
  5. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Functional disorders: children and adolescents. Gastroenterology 2016;150:1456-68.e2. https://doi.org/10.1053/j.gastro.2016.02.015
  6. Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015;47:a1-46. https://doi.org/10.1055/s-0034-1389830
  7. Bell JC, Schneuer FJ, Harrison C, Trevena L, Hiscock H, Elshaug AG, et al. Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal reflux disease in infants: a national survey. Arch Dis Child 2018;103:660-4. https://doi.org/10.1136/archdischild-2017-314161
  8. Ruigomez A, Hungin AP, Lundborg P, Johansson S, Wallander MA, Garcia Rodriguez LA. Treatment patterns in paediatric patients with a new diagnosis of gastroesophageal reflux disease. Eur J Gastroenterol Hepatol 2011;23:232-7. https://doi.org/10.1097/MEG.0b013e328343b06e
  9. Barron JJ, Tan H, Spalding J, Bakst AW, Singer J. Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr 2007;45:421-7. https://doi.org/10.1097/MPG.0b013e31812e0149
  10. De Bruyne P, Ito S. Toxicity of long-term use of proton pump inhibitors in children. Arch Dis Child 2018;103:78-82. https://doi.org/10.1136/archdischild-2017-314026
  11. Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, et al. Proton pump inhibitors affect the gut microbiome. Gut 2016;65:740-8. https://doi.org/10.1136/gutjnl-2015-310376
  12. Rosen R, Amirault J, Liu H, Mitchell P, Hu L, Khatwa U, et al. Changes in gastric and lung microflora with acid suppression: acid suppression and bacterial growth. JAMA Pediatr 2014;168:932-7. https://doi.org/10.1001/jamapediatrics.2014.696
  13. Bruno G, Zaccari P, Rocco G, Scalese G, Panetta C, Porowska B, et al. Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified. World J Gastroenterol 2019;25:2706-19. https://doi.org/10.3748/wjg.v25.i22.2706
  14. Mishiro T, Oka K, Kuroki Y, Takahashi M, Tatsumi K, Saitoh T, et al. Oral microbiome alterations of healthy volunteers with proton pump inhibitor. J Gastroenterol Hepatol 2018;33:1059-66. https://doi.org/10.1111/jgh.14040
  15. Belei O, Olariu L, Dobrescu A, Marcovici T, Marginean O. Is it useful to administer probiotics together with proton pump inhibitors in children with gastroesophageal reflux? J Neurogastroenterol Motil 2018;24:51-7. https://doi.org/10.5056/jnm17059
  16. Surendran Nair M, Amalaradjou MA, Venkitanarayanan K. Antivirulence properties of probiotics in combating microbial pathogenesis. Adv Appl Microbiol 2017;98:1-29. https://doi.org/10.1016/bs.aambs.2016.12.001
  17. Scott AM, Clark J, Julien B, Islam F, Roos K, Grimwood K, et al. Probiotics for preventing acute otitis media in children. Cochrane Database Syst Rev 2019;6:CD012941.
  18. Laursen RP, Hojsak I. Probiotics for respiratory tract infections in children attending day care centers-a systematic review. Eur J Pediatr 2018;177:979-94. https://doi.org/10.1007/s00431-018-3167-1
  19. Urbanska M, Gieruszczak-Bialek D, Szajewska H. Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children. Aliment Pharmacol Ther 2016;43:1025-34. https://doi.org/10.1111/apt.13590
  20. Hojsak I, Szajewska H, Canani RB, Guarino A, Indrio F, Kolacek S, et al.; ESPGHAN Working Group for Probiotics/Prebiotics. Probiotics for the prevention of nosocomial diarrhea in children. J Pediatr Gastroenterol Nutr 2018;66:3-9. https://doi.org/10.1097/MPG.0000000000001637
  21. Szajewska H, Canani RB, Guarino A, Hojsak I, Indrio F, Kolacek S, et al.; ESPGHAN Working Group for ProbioticsPrebiotics. Probiotics for the prevention of antibiotic-associated diarrhea in children. J Pediatr Gastroenterol Nutr 2016;62:495-506. https://doi.org/10.1097/MPG.0000000000001081
  22. Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, et al.; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr 2014;58:531-9. https://doi.org/10.1097/MPG.0000000000000320
  23. Sindhu KN, Sowmyanarayanan TV, Paul A, Babji S, Ajjampur SS, Priyadarshini S, et al. Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2014;58:1107-15. https://doi.org/10.1093/cid/ciu065
  24. Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics 2006;117:e817-20. https://doi.org/10.1542/peds.2005-1655
  25. Orenstein SR, Hassall E, Furmaga-Jablonska W, Atkinson S, Raanan M. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. J Pediatr 2009;154:514-20.e4. https://doi.org/10.1016/j.jpeds.2008.09.054
  26. Winter H, Kum-Nji P, Mahomedy SH, Kierkus J, Hinz M, Li H, et al. Efficacy and safety of pantoprazole delayed-release granules for oral suspension in a placebo-controlled treatment-withdrawal study in infants 1-11 months old with symptomatic GERD. J Pediatr Gastroenterol Nutr 2010;50:609-18. https://doi.org/10.1097/MPG.0b013e3181c2bf41
  27. Writing Committee for the American Lung Association Asthma Clinical Research Centers, Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, et al. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA 2012;307:373-81. https://doi.org/10.1001/jama.2011.2035
  28. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. COMPASS Investigators. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019;157:682-91.e2. https://doi.org/10.1053/j.gastro.2019.05.056