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Intestinal pH and Gastrointestinal Transit Profiles in Cystic Fibrosis Patients Measured by Wireless Motility Capsule

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Abstract

Background and Aims

The effect of the cystic fibrosis transmembrane conductance regulator protein (CFTR) defect in pancreatic insufficient (PI) patients with cystic fibrosis (CF) on the gastrointestinal pH profile is poorly defined. Adequate and efficient neutralization of the gastric acidity in the duodenum is important for nutrient absorption and timely release of pancreatic enzyme replacement therapy (PERT). We utilized a wireless motility capsule (WMC) to study intestinal pH profile and gastrointestinal transit profile in CF subjects.

Methods

WMC studies were done on ten adult CF patients with PI while off acid suppression medication and ten age, gender and BMI matched healthy controls. Mean pH over 1 min increments and area under the pH curve over 5 min increments was calculated for the first hour post gastric emptying. Paired t-test was used to compare means of the pH recordings, transit profiles and analysis of time interval required to reach and maintain pH >5.5 and 6.0.

Results

A statistically significant difference was observed between mean pH values during the first 23 min of small bowel transit (p < 0.05). In CF subjects, there was a significant delay in time interval required to reach and sustain pH 5.5 and pH 6.0 (p < 0.001), which is required for PERT dissolution. Only small bowel transit in CF subjects was noted to be significantly delayed (p = 0.004) without a compensatory increase in whole gut transit time.

Conclusions

We have demonstrated a significant delay in the small intestinal transit and a deficient buffering capacity required to neutralize gastric acid in the proximal small bowel of patients with CF.

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Abbreviations

CFTR:

Cystic fibrosis transmembrane conductance regulator protein

CF:

Cystic fibrosis

PERT:

Pancreatic enzyme replacement therapy

WMC:

Wireless motility capsule

PI:

Pancreatic insufficiency

AUC:

Area under the curve

GET:

Gastric emptying time

SBTT:

Small bowel transit time

CTT:

Colon transit time

WGT:

Whole gut transit time

BMI:

Body mass index

References

  1. Ferrone M, Raimondo M, Scolapio JS. Pancreatic enzyme pharmacotherapy. Pharmacotherapy. 2007;27:910–920.

    Article  PubMed  CAS  Google Scholar 

  2. Kraisinger M, Hochhaus G, Stecenko A, Bowser E, Hendeles L. Clinical pharmacology of pancreatic enzymes in patients with cystic fibrosis and in vitro performance of microencapsulated formulations. J Clin Pharmacol. 1994;34:158–166.

    Article  PubMed  CAS  Google Scholar 

  3. Garcia MA, Yang N, Quinton PM. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest. 2009;119:2613–2622.

    Article  PubMed  CAS  Google Scholar 

  4. Chen EY, Yang N, Quinton PM, Chin WC. A new role for bicarbonate in mucus formation. Am J Physiol Lung Cell Mol Physiol. 2010;299:L542–L549.

    Article  PubMed  CAS  Google Scholar 

  5. Couper RT, Corey M, Moore DJ, Fisher LJ, Forstner GG, Durie PR. Decline of exocrine pancreatic function in cystic fibrosis patients with pancreatic sufficiency. Pediatr Res. 1992;32:179–182.

    Article  PubMed  CAS  Google Scholar 

  6. Clarke LL, Harline MC. Dual role of CFTR in cAMP-stimulated HCO3- secretion across murine duodenum. Am J Physiol. 1998;274:G718–G726.

    PubMed  CAS  Google Scholar 

  7. Pratha VS, Hogan DL, Martensson BA, Bernard J, Zhou R, Isenberg JI. Identification of transport abnormalities in duodenal mucosa and duodenal enterocytes from patients with cystic fibrosis. Gastroenterology. 2000;118:1051–1060.

    Article  PubMed  CAS  Google Scholar 

  8. Dutta SK, Hubbard VS, Appler M. Critical examination of therapeutic efficacy of a pH-sensitive enteric-coated pancreatic enzyme preparation in treatment of exocrine pancreatic insufficiency secondary to cystic fibrosis. Dig Dis Sci. 1988;33:1237–1244.

    Article  PubMed  CAS  Google Scholar 

  9. Youngberg CA, Berardi RR. Comparison of gastrointestinal pH in cystic fibrosis and healthy subjects. Dig Dis Sci. 1987;32:472–480.

    Article  PubMed  CAS  Google Scholar 

  10. Borowitz D, Durie PR. Gastrointestinal outcomes and confounders in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2005;41:273–285.

    Article  PubMed  Google Scholar 

  11. Waldum HL, Qvigstad G, Fossmark R, Kleveland PM, Sandvik AK. Rebound acid hypersecretion from a physiological, pathophysiological and clinical viewpoint. Scand J Gastroenterol. 2010;45:389–394.

    Article  PubMed  Google Scholar 

  12. Hasler WL, Coleski R. Differences in intragastric pH in diabetic vs. idiopathic gastroparesis: relation to degree of gastric retention. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1384–G1391.

    Article  PubMed  CAS  Google Scholar 

  13. Rao SSC, Kuo B, McCallum RW, et al. Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clinical gastroenterology and hepatology: the official clinical practice. Am J Gastroenterol. 2009;7(5):537–44.

    Google Scholar 

  14. Kuo B, McCallum RW. Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther. 2008;27:186–196.

    Article  PubMed  CAS  Google Scholar 

  15. Kaunitz JD, Akiba Y. Review article: duodenal bicarbonate—mucosal protection, luminal chemosensing and acid-base balance. Aliment Pharmacol Ther. 2006;24:169–176.

    Article  PubMed  Google Scholar 

  16. Allen A, Flemstrom G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol. 2005;288:C1–C19.

    PubMed  CAS  Google Scholar 

  17. Steward MC, Ishiguro H. Molecular and cellular regulation of pancreatic duct cell function. Curr Opin Gastroenterol. 2009;25:447–453.

    Article  PubMed  CAS  Google Scholar 

  18. Montrose MHA, Yasutada TK, Kaunitz JD. Gastroduodenal mucosal defense. In: Johnson LR, eds. Physiology of the Gastrointestinal Tract. Amsterdam: Elsevier; 2006:1260–1291.

  19. Clarke LL, Stien X, Walker NM. Intestinal bicarbonate secretion in cystic fibrosis mice. JOP. 2001;2:263–267.

    PubMed  CAS  Google Scholar 

  20. Tovar JA, Izquierdo MA, Eizaguirre I. The area under pH curve: a single-figure parameter representative of esophageal acid exposure. J Pediatr Surg. 1991;26:163–167.

    Article  PubMed  CAS  Google Scholar 

  21. Proesmans M, De Boeck K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur J Pediatr. 2003;162:760–763.

    Article  PubMed  CAS  Google Scholar 

  22. Canani RB, Cirillo P. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117:e817–e820.

    Article  PubMed  Google Scholar 

  23. Ramsey BW, Davies J. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663–1672.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Gregory E. Wilding for an early discussion on analytical methods of SmartPill data. This study was funded by a grant from Cystic Fibrosis Foundation Therapeutics, Inc. Funding #: BOROWI08A0.

Conflict of interest

Jack Semler is an employee of SmartPill Corporation and owns stock in the corporation. Daniel Gelfond, Changxing Ma and Drucy Borowitz have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children’s Hospital of Buffalo, State University of New York at Buffalo School of Medicine and Biomedical Sciences, 219 Bryant Street, Buffalo, NY, 14222, USA

    Daniel Gelfond

  2. Department of Biostatistics, State University of New York at Buffalo School of Public Health and Health Professions, 706 Kimball, 3435 Main Street, Buffalo, NY, USA

    Changxing Ma

  3. SmartPill Corporation, 847 Main Street, Buffalo, NY, USA

    Jack Semler

  4. Department of Pediatrics, Division of Pediatric Pulmonology, Women and Children’s Hospital of Buffalo, State University of New York at Buffalo School of Medicine and Biomedical Sciences, 219 Bryant street, Buffalo, NY, 14222, USA

    Drucy Borowitz

Authors
  1. Daniel Gelfond
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  2. Changxing Ma
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  3. Jack Semler
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  4. Drucy Borowitz
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Corresponding author

Correspondence to Daniel Gelfond.

Additional information

This study was approved by the University of Buffalo Children and Youth Institutional Review Board Children and Youth IRB Women and Children’s Hospital of Buffalo, Buffalo, NY. Approval date: 6 October 2008.

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Gelfond, D., Ma, C., Semler, J. et al. Intestinal pH and Gastrointestinal Transit Profiles in Cystic Fibrosis Patients Measured by Wireless Motility Capsule. Dig Dis Sci 58, 2275–2281 (2013). https://doi.org/10.1007/s10620-012-2209-1

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  • DOI: https://doi.org/10.1007/s10620-012-2209-1

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