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Erschienen in: Digestive Diseases and Sciences 3/2014

01.03.2014 | Original Article

Children with Cystic Fibrosis Have Prolonged Chemical Clearance of Acid Reflux Compared to Symptomatic Children Without Cystic Fibrosis

verfasst von: Frederick W. Woodley, Rodrigo S. Machado, Don Hayes Jr., Carlo Di Lorenzo, Ajay Kaul, Beth Skaggs, Karen McCoy, Alpa Patel, Hayat Mousa

Erschienen in: Digestive Diseases and Sciences | Ausgabe 3/2014

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Abstract

Objectives

Few studies compare gastroesophageal reflux (GER) parameters of cystic fibrosis (CF) children and symptomatic non-CF children. We aimed to compare the impedance-pH (IMP-pH) parameters for these two groups and to test the hypothesis that prolonged acid exposure in CF patients is due to delayed chemical clearance (CC).

Methods

IMP-pH tracings from 16 CF children (median 8.2 years) and 16 symptomatic non-CF children (median 8.3 years) were analyzed. Software was used to generate IMP-pH reports and parameter data were extracted. IMP-pH was used to calculate the mean CC for each patient.

Results

pH studies showed no difference in acid GER (AGER) frequency (p = 0.587); however, mean AGER duration, duration of longest AGER, AGER index, and DeMeester scores were all significantly higher for CF patients. IMP showed no difference in GER frequency [neither acidic (p = 0.918) nor non-acidic (p = 0.277)], but total bolus clearance was more efficient in CF patients (p = 0.049). A larger percentage of total GER reached the proximal esophagus in non-CF children (p = 0.039). Analyses of two-phase AGER episodes showed that these events were more acidic (p = 0.003) and the CC phase was significantly prolonged in the CF cohort (p = 0.001).

Conclusions

Compared to symptomatic non-CF children, CF children do not have more frequent reflux. Actually, they have better bolus clearance efficiency following reflux and may even have better control over the number of GER episodes that reach the proximal esophagus. CC of AGER, however, is significantly prolonged in the CF cohort, likely due to hyperacidity of refluxed gastric contents.
Literatur
1.
Zurück zum Zitat Scott RB, O’Loughlin EV, Gall DG. Gastroesophageal reflux in patients with cystic fibrosis. J Pediatr. 1985;106:223–227.PubMedCrossRef Scott RB, O’Loughlin EV, Gall DG. Gastroesophageal reflux in patients with cystic fibrosis. J Pediatr. 1985;106:223–227.PubMedCrossRef
2.
Zurück zum Zitat Vinocur CD, Marmon L, Schidlow DV, et al. Gastroesophageal reflux in the infant with cystic fibrosis. Am J Surg. 1985;149:182–186.PubMedCrossRef Vinocur CD, Marmon L, Schidlow DV, et al. Gastroesophageal reflux in the infant with cystic fibrosis. Am J Surg. 1985;149:182–186.PubMedCrossRef
3.
Zurück zum Zitat Ledson MJ, Tran J, Wallshaw MJ. Prevalence and mechanisms of gastroesophageal reflux in adult cystic fibrosis patients. J R Soc Med. 1998;91:7–9.PubMedCentralPubMed Ledson MJ, Tran J, Wallshaw MJ. Prevalence and mechanisms of gastroesophageal reflux in adult cystic fibrosis patients. J R Soc Med. 1998;91:7–9.PubMedCentralPubMed
4.
Zurück zum Zitat Brodzicki J, Trawinska-Bartnicka M, Korzon M. Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis. Med Sci Monit. 2002;8:CR529–CR537.PubMed Brodzicki J, Trawinska-Bartnicka M, Korzon M. Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis. Med Sci Monit. 2002;8:CR529–CR537.PubMed
5.
Zurück zum Zitat Cucchiara S, Santamaria F, Andreotti MR, et al. Mechanisms of gastro-oesophageal reflux in cystic fibrosis. Arch Dis Child. 1991;66:617–622.PubMedCrossRef Cucchiara S, Santamaria F, Andreotti MR, et al. Mechanisms of gastro-oesophageal reflux in cystic fibrosis. Arch Dis Child. 1991;66:617–622.PubMedCrossRef
6.
Zurück zum Zitat Blondeau K, Pauwels A, DuPont LJ, et al. Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010;50:161–166.PubMedCrossRef Blondeau K, Pauwels A, DuPont LJ, et al. Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010;50:161–166.PubMedCrossRef
7.
Zurück zum Zitat Helm JF, Dodds WJ, Riedel DR, et al. Determinants of esophageal acid clearance in normal subjects. Gastroenterology. 1983;85:607–612.PubMed Helm JF, Dodds WJ, Riedel DR, et al. Determinants of esophageal acid clearance in normal subjects. Gastroenterology. 1983;85:607–612.PubMed
8.
Zurück zum Zitat Boyd DD, Carney CN, Powell DW. Neuro-hormonal control of esophageal epithelial electrolyte transport. Am J Physiol. 1980;239:G5–G11.PubMed Boyd DD, Carney CN, Powell DW. Neuro-hormonal control of esophageal epithelial electrolyte transport. Am J Physiol. 1980;239:G5–G11.PubMed
9.
Zurück zum Zitat Hamilton BH, Orlando RC. In vivo alkaline secretion by mammalian esophagus. Gastroenterology. 1989;97:640–648.PubMed Hamilton BH, Orlando RC. In vivo alkaline secretion by mammalian esophagus. Gastroenterology. 1989;97:640–648.PubMed
10.
Zurück zum Zitat Myers RL, Orlando RC. In vivo bicarbonate secretion by human esophagus. Gastroenterology. 1992;103:1174–1178. Myers RL, Orlando RC. In vivo bicarbonate secretion by human esophagus. Gastroenterology. 1992;103:1174–1178.
11.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
12.
Zurück zum Zitat Woodley FW, Hayes J, Mousa H. Acid gastroesophageal reflux in symptomatic infants is primarily a function of classic 2-phase and pH-only acid reflux event types. J Pediatr Gastroenterol Nutr. 2009;48:550–558.PubMedCrossRef Woodley FW, Hayes J, Mousa H. Acid gastroesophageal reflux in symptomatic infants is primarily a function of classic 2-phase and pH-only acid reflux event types. J Pediatr Gastroenterol Nutr. 2009;48:550–558.PubMedCrossRef
13.
Zurück zum Zitat Rudolph CD, Mazur LJ, Liptak GS, 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 Pediatric Gastroenterol Nutr. 2001;32:S1–S31.CrossRef Rudolph CD, Mazur LJ, Liptak GS, 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 Pediatric Gastroenterol Nutr. 2001;32:S1–S31.CrossRef
14.
Zurück zum Zitat Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004;53:1024–1031.PubMedCrossRef Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004;53:1024–1031.PubMedCrossRef
15.
Zurück zum Zitat Helm JF, Dodds WJ, Pelc LR, et al. Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med. 1984;310:284–288.PubMedCrossRef Helm JF, Dodds WJ, Pelc LR, et al. Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med. 1984;310:284–288.PubMedCrossRef
16.
Zurück zum Zitat Woodley FW, Machado RS, Benner J, et al. Normal values for chemical clearance of acid gastroesophageal reflux in infants and children. Gastroenterol. 2013;144:399–400. Woodley FW, Machado RS, Benner J, et al. Normal values for chemical clearance of acid gastroesophageal reflux in infants and children. Gastroenterol. 2013;144:399–400.
17.
Zurück zum Zitat Kim BJ, Choi SC, Kim JJ, et al. Pathological bolus exposure plays a significant role in eliciting non-cardiac chest pain. J Gastroenterol Hepatol. 2010;25:1855–1860.PubMedCrossRef Kim BJ, Choi SC, Kim JJ, et al. Pathological bolus exposure plays a significant role in eliciting non-cardiac chest pain. J Gastroenterol Hepatol. 2010;25:1855–1860.PubMedCrossRef
18.
Zurück zum Zitat Meyers RL, Orlando RC. In vivo bicarbonate secretion by human esophagus. Gastroenterology. 1992;103:1174–1178.PubMed Meyers RL, Orlando RC. In vivo bicarbonate secretion by human esophagus. Gastroenterology. 1992;103:1174–1178.PubMed
19.
Zurück zum Zitat Boyd DD, Carney CN, Powell DW. Neurohumoral control of esophageal epithelial electrolyte transport. Am J Physiol. 1980;239:G5–G11.PubMed Boyd DD, Carney CN, Powell DW. Neurohumoral control of esophageal epithelial electrolyte transport. Am J Physiol. 1980;239:G5–G11.PubMed
20.
Zurück zum Zitat Hamilton BH, Orlando RC. In vivo alkaline secretion by mammalian esophagus. Gastroenterology. 1989;97:640–648.PubMed Hamilton BH, Orlando RC. In vivo alkaline secretion by mammalian esophagus. Gastroenterology. 1989;97:640–648.PubMed
21.
Zurück zum Zitat 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–G120.PubMed 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–G120.PubMed
22.
Zurück zum Zitat Abdulnour-Nakhoul S, Nakhoul HN, Medhat K, et al. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands. Am J Physiol Regul Integr Comp Physiol. 2011;301:R83–R96.PubMedCrossRef Abdulnour-Nakhoul S, Nakhoul HN, Medhat K, et al. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands. Am J Physiol Regul Integr Comp Physiol. 2011;301:R83–R96.PubMedCrossRef
23.
Zurück zum Zitat Trezise AEO, Buchwald M. In vivo cell-specific expression of cystic fibrosis transmembrane conductance regulator. Nature. 1991;353:434–437.PubMedCrossRef Trezise AEO, Buchwald M. In vivo cell-specific expression of cystic fibrosis transmembrane conductance regulator. Nature. 1991;353:434–437.PubMedCrossRef
24.
Zurück zum Zitat Van Slyke DD. Studies of acidosis –XVII. Determination of the bicarbonate concentration of the blood and plasma. J Biol Chem. 1922;52:495–499. Van Slyke DD. Studies of acidosis –XVII. Determination of the bicarbonate concentration of the blood and plasma. J Biol Chem. 1922;52:495–499.
25.
Zurück zum Zitat Chauncey HH, Levine DM, Kass G, et al. Composition of human saliva; parotid gland secretory gland rate and electrolyte concentration in children with cystic fibrosis. Arch Oral Biol. 1962;7:707–713.PubMedCrossRef Chauncey HH, Levine DM, Kass G, et al. Composition of human saliva; parotid gland secretory gland rate and electrolyte concentration in children with cystic fibrosis. Arch Oral Biol. 1962;7:707–713.PubMedCrossRef
26.
Zurück zum Zitat Kaufman E, Lamster IB. The diagnostic applications of saliva—a review. Crit Rev Oral Biol Med. 2002;13:197–212.PubMedCrossRef Kaufman E, Lamster IB. The diagnostic applications of saliva—a review. Crit Rev Oral Biol Med. 2002;13:197–212.PubMedCrossRef
27.
Zurück zum Zitat Bradley PJ, Guntinas-Lichius O. Salivary gland disorders and diseases: diagnosis and management. New York: NY. Georg Thieme Verlag; 2001. Bradley PJ, Guntinas-Lichius O. Salivary gland disorders and diseases: diagnosis and management. New York: NY. Georg Thieme Verlag; 2001.
28.
Zurück zum Zitat Davies H, Bagg J, Goodchild M, et al. Defective regulation of electrolyte and protein secretion in submandibular saliva of cystic fibrosis. Acta Paediatr Scand. 1991;80:1094–1095.PubMedCrossRef Davies H, Bagg J, Goodchild M, et al. Defective regulation of electrolyte and protein secretion in submandibular saliva of cystic fibrosis. Acta Paediatr Scand. 1991;80:1094–1095.PubMedCrossRef
29.
Zurück zum Zitat Aps JK, Delanghe J, Martens LC. Salivary electrolyte concentrations are associated with cystic fibrosis transmembrane regulator genotypes. Clin Chem Lab Med. 2002;40:345–350.PubMedCrossRef Aps JK, Delanghe J, Martens LC. Salivary electrolyte concentrations are associated with cystic fibrosis transmembrane regulator genotypes. Clin Chem Lab Med. 2002;40:345–350.PubMedCrossRef
30.
Zurück zum Zitat Goncalves AC, de Lima Marson FA, de Holanda Mendona RM et al. Saliva as a potential tool for cystic fibrosis diagnosis. Diagn Pathol. 2013;8:46. Goncalves AC, de Lima Marson FA, de Holanda Mendona RM et al. Saliva as a potential tool for cystic fibrosis diagnosis. Diagn Pathol. 2013;8:46.
31.
Zurück zum Zitat Hardt M, Witkowska HE, Webb S, et al. Assessing the effects of diurnal variation on the composition of human parotid saliva: quantitative analysis of native peptides using iTRAQ reagents. Anal Chem. 2005;77:4947–4954.PubMedCrossRef Hardt M, Witkowska HE, Webb S, et al. Assessing the effects of diurnal variation on the composition of human parotid saliva: quantitative analysis of native peptides using iTRAQ reagents. Anal Chem. 2005;77:4947–4954.PubMedCrossRef
32.
Zurück zum Zitat Blomfield J, Allars HM, Rush AR, et al. Parotid serous hypersecretion in cystic fibrosis. Aust Paediatr J. 1974;10:75–81. Blomfield J, Allars HM, Rush AR, et al. Parotid serous hypersecretion in cystic fibrosis. Aust Paediatr J. 1974;10:75–81.
33.
Zurück zum Zitat Blomfield J, Van Lennep EW, Shorey CD, et al. Ultrastructure of the in vitro formation of hydroxyapatite in submandibular saliva of children with cystic fibrosis. Arch Oral Biol. 1974;19:1153–1160.PubMedCrossRef Blomfield J, Van Lennep EW, Shorey CD, et al. Ultrastructure of the in vitro formation of hydroxyapatite in submandibular saliva of children with cystic fibrosis. Arch Oral Biol. 1974;19:1153–1160.PubMedCrossRef
34.
Zurück zum Zitat Lidums I, Holloway RH. Motility abnormalities in the columnar-lined esophagus. Gastroenterol Clin. 1997;26:519–531.CrossRef Lidums I, Holloway RH. Motility abnormalities in the columnar-lined esophagus. Gastroenterol Clin. 1997;26:519–531.CrossRef
35.
Zurück zum Zitat Ko SB, Zeng W, Dorwart MR, et al. Gating for CFTR by STATS domain of SLC26 transporters. Nat Cell Biol. 2004;6:343–350.PubMedCrossRef Ko SB, Zeng W, Dorwart MR, et al. Gating for CFTR by STATS domain of SLC26 transporters. Nat Cell Biol. 2004;6:343–350.PubMedCrossRef
36.
Zurück zum Zitat Stewart AK, Yamamoto A, Nakakuki M, et al. Functional coupling of apical Cl−/HCO3 − exchange with CFTR in stimulated secretion by guinea pig interlobular pancreatic duct. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1307.PubMedCrossRef Stewart AK, Yamamoto A, Nakakuki M, et al. Functional coupling of apical Cl/HCO3 exchange with CFTR in stimulated secretion by guinea pig interlobular pancreatic duct. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1307.PubMedCrossRef
37.
Zurück zum Zitat Rozmanic V, Tjesic-Drinkovic D, Banac Srdan, et al. Gastroesophageal reflux and gastric hyperacidity in cystic fibrosis patients. Pedijatrija Danas 2010;6(1):45–52. Rozmanic V, Tjesic-Drinkovic D, Banac Srdan, et al. Gastroesophageal reflux and gastric hyperacidity in cystic fibrosis patients. Pedijatrija Danas 2010;6(1):45–52.
38.
Zurück zum Zitat Cox KL, Isenberg JN, Ament MEI. Gastric acid hypersecretion in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1981;1:559–565.CrossRef Cox KL, Isenberg JN, Ament MEI. Gastric acid hypersecretion in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1981;1:559–565.CrossRef
39.
Zurück zum Zitat Sawaf NW, Orzel JA, Weiland FL. Gastroesophageal reflux demonstrated by hepatobiliary imaging in scleroderma. J Nucl Med. 1987;28:387–389.PubMed Sawaf NW, Orzel JA, Weiland FL. Gastroesophageal reflux demonstrated by hepatobiliary imaging in scleroderma. J Nucl Med. 1987;28:387–389.PubMed
40.
Zurück zum Zitat Simren M, Silny J, Holloway R, et al. Relevance of ineffective esophageal motility during oesophageal acid clearance. Gut. 2003;52:784–790.PubMedCrossRef Simren M, Silny J, Holloway R, et al. Relevance of ineffective esophageal motility during oesophageal acid clearance. Gut. 2003;52:784–790.PubMedCrossRef
41.
Zurück zum Zitat Pauley KM, Lee BH, Gauna AE, et al. Mechanisms of salivary gland secretory dysfunction in Sjorgren’s syndrome. In: Harrison A ed. Insights and perspectives in rheumatology. 2012. ISBN:978-953-3007-846-5. Pauley KM, Lee BH, Gauna AE, et al. Mechanisms of salivary gland secretory dysfunction in Sjorgren’s syndrome. In: Harrison A ed. Insights and perspectives in rheumatology. 2012. ISBN:978-953-3007-846-5.
42.
Zurück zum Zitat de Veer AJ, Bos JT, Niezen-de Boer RC, et al. Symptoms of gastroesophageal reflux disease in severely mentally retarded people: a systematic review. BMC Gastroenterol. 2008;8:23–35.PubMedCentralPubMedCrossRef de Veer AJ, Bos JT, Niezen-de Boer RC, et al. Symptoms of gastroesophageal reflux disease in severely mentally retarded people: a systematic review. BMC Gastroenterol. 2008;8:23–35.PubMedCentralPubMedCrossRef
43.
Zurück zum Zitat Ruigómez A, Wallander MA, Lundborg P, et al. Gastroesophageal reflux disease in children and adolescents in primary care. Scand J Gastroenterol. 2010;45:139–146.PubMedCrossRef Ruigómez A, Wallander MA, Lundborg P, et al. Gastroesophageal reflux disease in children and adolescents in primary care. Scand J Gastroenterol. 2010;45:139–146.PubMedCrossRef
44.
Zurück zum Zitat Kellogg DL, Hodges GJ, Orozco CR, et al. Cholinergic mechanisms of cutaneous active vasodilation during heat stress in cystic fibrosis. J Appl Physiol. 2007;103:963–968.PubMedCrossRef Kellogg DL, Hodges GJ, Orozco CR, et al. Cholinergic mechanisms of cutaneous active vasodilation during heat stress in cystic fibrosis. J Appl Physiol. 2007;103:963–968.PubMedCrossRef
45.
Zurück zum Zitat Zheng W, Kuhlicke J, Jackel K, et al. Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium. FASEB J. 2009;23:204–213.PubMedCrossRef Zheng W, Kuhlicke J, Jackel K, et al. Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium. FASEB J. 2009;23:204–213.PubMedCrossRef
46.
Zurück zum Zitat Ribeiro CMP, Paradiso AM, Carew MA, et al. Cystic fibrosis airway epithelial Ca2+ I signaling. J Biol Chem. 2005;280:10202–10209.PubMedCrossRef Ribeiro CMP, Paradiso AM, Carew MA, et al. Cystic fibrosis airway epithelial Ca2+ I signaling. J Biol Chem. 2005;280:10202–10209.PubMedCrossRef
Metadaten
Titel
Children with Cystic Fibrosis Have Prolonged Chemical Clearance of Acid Reflux Compared to Symptomatic Children Without Cystic Fibrosis
verfasst von
Frederick W. Woodley
Rodrigo S. Machado
Don Hayes Jr.
Carlo Di Lorenzo
Ajay Kaul
Beth Skaggs
Karen McCoy
Alpa Patel
Hayat Mousa
Publikationsdatum
01.03.2014
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 3/2014
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-2950-0

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