Pediatric Gastroenterology, Hepatology & Nutrition

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

DOI QR Code

Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux

  • Woodley, Frederick W. (Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital) ;
  • Moore-Clingenpeel, Melissa (Biostatistics Core, Nationwide Children's Hospital) ;
  • Machado, Rodrigo Strehl (Department of Pediatrics, Federal University of Sao Paulo) ;
  • Nemastil, Christopher J. (Division of Pulmonary Medicine, Nationwide Children's Hospital) ;
  • Jadcherla, Sudarshan R. (Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital) ;
  • Hayes, Don Jr (Department of Pediatrics, The Ohio State University College of Medicine) ;
  • Kopp, Benjamin T. (Department of Pediatrics, The Ohio State University College of Medicine) ;
  • Kaul, Ajay (Division of Gastroenterology, Cincinnati Children's Hospital Medical Center) ;
  • Di Lorenzo, Carlo (Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital) ;
  • Mousa, Hayat (Department of Pediatrics, The Ohio State University College of Medicine)
  • Received : 2017.04.12
  • Accepted : 2017.07.15
  • Published : 2017.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Methods: Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to < 18 years) and 16 age-matched children without cystic fibrosis. Results: Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Conclusion: Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

Keywords

References

  1. Simren M, Silny J, Holloway R, Tack J, Janssens J, Sifrim D. Relevance of ineffective oesophageal motility during oesophageal acid clearance. Gut 2003;52:784-90. https://doi.org/10.1136/gut.52.6.784
  2. Helm JF, Dodds WJ, Pelc LR, Palmer DW, Hogan WJ, Teeter BC. Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med 1984;310:284-8. https://doi.org/10.1056/NEJM198402023100503
  3. Boyd DD, Carney CN, Powell DW. Neurohumoral control of esophageal epithelial electrolyte transport. Am J Physiol 1980;239:G5-11.
  4. Hamilton BH, Orlando RC. In vivo alkaline secretion by mammalian esophagus. Gastroenterology 1989;97:640-8. https://doi.org/10.1016/0016-5085(89)90635-5
  5. Meyers RL, Orlando RC. In vivo bicarbonate secretion by human esophagus. Gastroenterology 1992;103:1174-8. https://doi.org/10.1016/0016-5085(92)91501-T
  6. Orlando RC. Esophageal mucosal defense mechanisms. Part 1 Oral cavity, pharynx, and esophagus. GI Motil Online 2006. doi: 10.1038/gimo15.
  7. Abdulnour-Nakhoul S, Nakhoul NL, Orlando RC. Lumen-to-surface pH gradients in opossum and rabbit esophagi: role of submucosal glands. Am J Physiol Gastrointest Liver Physiol 2000;278:G113-20. https://doi.org/10.1152/ajpgi.2000.278.1.G113
  8. Abdulnour-Nakhoul S, Nakhoul HN, Kalliny MI, Gyftopoulos A, Rabon E, Doetjes R, et al. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands. Am J Physiol Regul Integr Comp Physiol 2011;301:R83-96. https://doi.org/10.1152/ajpregu.00648.2010
  9. Sivalingam M, Sitaram S, Hasenstab KA, Wei L, Woodley FW, Jadcherla SR. Effects of esophageal acidification on troublesome symptoms: an approach to characterize true acid GERD in dysphagic neonates. Dysphagia 2017;32:509-19. https://doi.org/10.1007/s00455-017-9792-4
  10. Frazzoni M, Manta R, Mirante VG, Conigliaro R, Frazzoni L, Melotti G. Esophageal chemical clearance is impaired in gastro-esophageal reflux disease--a 24-h impedance-pH monitoring assessment. Neurogastroenterol Motil 2013;25:399-406, e295. https://doi.org/10.1111/nmo.12080
  11. Vaezi MF, Singh S, Richter JE. Role of acid and duodenogastric reflux in esophageal injury: a review of animal and human studies. Gastroenterology 1995;108:1897-907. https://doi.org/10.1016/0016-5085(95)90156-6
  12. Tuttle SG, Rufin F, Bettarello A. The physiology of heartburn. Ann Intern Med 1961;55:292-300. https://doi.org/10.7326/0003-4819-55-2-292
  13. Pauwels A, Blondeau K, Mertens V, Farre R, Verbeke K, Dupont LJ, et al. Gastric emptying and different types of reflux in adult patients with cystic fibrosis. Aliment Pharmacol Ther 2011;34:799-807. https://doi.org/10.1111/j.1365-2036.2011.04786.x
  14. Pauwels A, Decraene A, Blondeau K, Mertens V, Farre R, Proesmans M, et al. Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis. Chest 2012;141:1568-74. https://doi.org/10.1378/chest.11-1573
  15. Woodley FW, Machado RS, Hayes D Jr, Di Lorenzo C, Kaul A, Skaggs B, et al. Children with cystic fibrosis have prolonged chemical clearance of acid reflux compared to symptomatic children without cystic fibrosis. Dig Dis Sci 2014;59:623-30. https://doi.org/10.1007/s10620-013-2950-0
  16. Woodley FW, Machado R, Di Lorenzo C, Mousa H. Chemical clearance in infants and children with acid reflux in the physiologic range. J Pediatr Gastroenterol Nutr 2015;60:783-6. https://doi.org/10.1097/MPG.0000000000000777
  17. Pauwels A, Blondeau K, Dupont LJ, Sifrim D. Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis. Am J Gastroenterol 2012;107:1346-53. https://doi.org/10.1038/ajg.2012.213
  18. Navarro J, Rainisio M, Harms HK, Hodson ME, Koch C, Mastella G, et al. Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF. Eur Respir J 2001;18:298-305. https://doi.org/10.1183/09031936.01.00068901
  19. Dodds WJ, Dent J, Hogan WJ, Helm JF, Hauser R, Patel GK, et al. Mechanisms of gastroesophageal reflux in patients with reflux esophagitis. N Engl J Med 1982; 307:1547-52. https://doi.org/10.1056/NEJM198212163072503
  20. Richter J. Do we know the cause of reflux disease? Eur J Gastroenterol Hepatol 1999;11 Suppl 1:S3-9.
  21. Orlando RC. Overview of the mechanisms of gastroesophageal reflux. Am J Med 2001;111 Suppl 8A: 174S-7S. https://doi.org/10.1016/S0002-9343(01)00828-2
  22. Maclean JE, Solomon M, Corey M, Selvadurai H. Cystic fibrosis newborn screening does not delay the identification of cystic fibrosis in children with negative results. J Cyst Fibros 2011;10:333-7. https://doi.org/10.1016/j.jcf.2011.04.002
  23. Martinucci I, de Bortoli N, Savarino E, Piaggi P, Bellini M, Antonelli A, et al. Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn. Neurogastroenterol Motil 2014;26:546-55. https://doi.org/10.1111/nmo.12299
  24. Woodley FW, Fernandez S, Mousa H. Diurnal variation in the chemical clearance of acid gastroesophageal reflux in infants. Clin Gastroenterol Hepatol 2007;5:37-43. https://doi.org/10.1016/j.cgh.2006.10.003
  25. Frazzoni M, Savarino E, de Bortoli N, Martinucci I, Furnari M, Frazzoni L, et al. Analyses of the post-reflux swallow-induced peristaltic wave index and nocturnal baseline impedance parameters increase the diagnostic yield of impedance-pH monitoring of patients with reflux disease. Clin Gastroenterol Hepatol 2016; 14:40-6. https://doi.org/10.1016/j.cgh.2015.06.026
  26. Mekus F, Ballmann M, Bronsveld I, Bijman J, Veeze H, Tummler B. Categories of deltaF508 homozygous cystic fibrosis twin and sibling pairs with distinct phenotypic characteristics. Twin Res 2000;3:277-93. https://doi.org/10.1375/136905200320565256
  27. Vanscoy LL, Blackman SM, Collaco JM, Bowers A, Lai T, Naughton K, et al. Heritability of lung disease severity in cystic fibrosis. Am J Respir Crit Med 2007; 175:1036-43. https://doi.org/10.1164/rccm.200608-1164OC