Top

Published in:

01-07-2016 | Review

Beyond pancreatic insufficiency and liver disease in cystic fibrosis

Authors: Stephanie Demeyer, Kris De Boeck, Peter Witters, Katrien Cosaert

Published in: European Journal of Pediatrics | Issue 7/2016

Abstract

Cystic fibrosis is a life shortening hereditary disease, primarily leading to progressive pulmonary infection and exocrine pancreatic dysfunction. Several gastrointestinal complications other than malabsorption can arise during the disease course and with the progressively increasing life span of patients with CF; new and more rare complications are being recognized. We review the literature on gastrointestinal manifestations in CF, excluding the liver and pancreas.

Conclusion: We describe the clinical presentation and treatment of more common conditions like gastroesophageal reflux, small intestinal bacterial overgrowth, intussusception, meconium ileus, distal intestinal obstruction syndrome, and constipation, and we also discuss what is known on celiac disease, appendicitis, fibrosing colonopathy, inflammation and inflammatory bowel disease and gastrointestinal cancer.

What is Known:

• Gastrointestinal complications arise early in the course of the disease and have a severe impact on the quality of life of the patients.

What is New:

• This review is a concise summary of the current literature on gastrointestinal complications of cystic fibrosis.

• We focused on clinical presentation and diagnostic investigations and provide a comprehensive resume of the current treatment options.

Agrons GA, Corse WR, Markowitz RI, Suarez ES, Perry DR (1996) Gastrointestinal manifestations of cystic fibrosis: radiologic-pathologic correlation. Radiographics 16:871–893PubMedCrossRef

Alexander CL, Urbanski SJ, Hilsden R, Rabin H, MacNaughton WK, Beck PL (2008) The risk of gastrointestinal malignancies in cystic fibrosis: casereport of a patient with a near obstructing villous adenoma found on colon cancer screening and Barrett’s esophagus. J Cyst Fibros 7:1–6. doi:10.1016/j.jcf.2007.07.005 PubMedCrossRef

Almberger M, Lannicelli E, Antonelli M, Matrunola M, Cimino G, Passariello R (2001) The role of MRI in the intestinal complications in cystic fibrosis. Clin Imaging 25:344–348. doi:10.1016/S0899-7071(01)00326-6 PubMedCrossRef

Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–123. doi:10.1126/science.1224820 PubMedPubMedCentralCrossRef

Baker SS, Borowitz D, Duffy L, Fitzpatrick L, Gyamfi J, Baker RD (2005) Pancreatic enzyme therapy and clinical outcomes in patients with cystic fibrosis. J Pediatr 146:189–193PubMedCrossRef

Bijvelds MJ, Bot AG, Escher JC, De Jonge HR (2009) Activation of intestinal Cl-secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology 137:976–985. doi:10.1053/j.gastro.2009.05.037 PubMedCrossRef

Bodet-Milin C, Querellou S, Oudoux A, Haloun A, Horeau-Llanglard D, Carlier T, Bizais Y, Couturier O (2006) Delayed gastric emptying scintigraphy in cystic fibrosis patients before and after lung transplantation. J Heart Lung Transplant 25:1077–1083. doi:10.1016/j.healun.2006.04.013 PubMedCrossRef

Borowitz D, Durie PR, Clarke LL, Werlin SL, Taylor CJ, Semler J, De Lisle RC, Lewindon P, Lichtman SM, Sinaasappel M, Baker RD, Baker SS, Verkade HJ, Lowe ME, Stallings VA, Janghorbani M, Butler R, Heubi J (2005) Gastrointestinal outcomes and confounders in cystic fibrosis. J Pediatr Gastroenterol Nutr 41:273–285PubMedCrossRef

10.

Bostick RM, Potter JD, McKenzie DR, Sellers TA, Kushi LH, Steinmetz KA, Folsom AR (1993) Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women’s Health Study. Cancer Res 53:4230–4237PubMed

11.

Bresso F, Askling J, Astegiano M, Demarchi B, Sapone N, Rizzetto M, Gionchetti P, Lammers KM, de Leone A, Riegler G, Nimmo ER, Drummond H, Noble C, Torkvist L, Ekbom A, Zucchelli M, Lofberg R, SatsangiJ PS, D’Amato M (2007) Potential role for the common cystic fibrosis DeltaF508 mutation in Crohn’s disease. Inflamm Bowel Dis 13:531–536. doi:10.1002/ibd.20067 PubMedCrossRef

12.

Bruzzese E, Callegari ML, Raia V, Viscovo S, Scotto R, Ferrari S, Morelli L, Buccigrossi V, Lo Vecchio A, Ruberto E, Guarino A (2014) Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomized clinical trial. PLoS One 9:e87796. doi:10.1371/journal.pone.0087796 PubMedPubMedCentralCrossRef

13.

Bruzzese E, Raia V, Gaudiello G, Polito G, Buccigrossi V, Formicola V, Guarino A (2004) Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther 20:813–819. doi:10.1111/j.1365-2036.2004.02174.x PubMedCrossRef

14.

Buiter HD, Holswilder-OldeScholtenhuis MA, Bouman K, van Baren R, Bilardo CM, Bos AF (2013) Outcome of infants presenting with echogenic bowel in the second trimester of pregnancy. Arch Dis Child Fetal Neonatal Ed 98:F256–F259. doi:10.1136/archdischild-2012-302017 PubMedCrossRef

15.

Button BM, Heine RG, Catto-Smith AG, Phelan PD (1998) Postural drainage in cystic fibrosis: is there a link with gastro-oesophageal reflux? J Paediatr Child Health 34:330–334PubMedCrossRef

16.

Carlyle BE, Borowitz DS, Glick PL (2012) A review of pathophysiology and management of fetuses and neonates with meconiumileus for the pediatric surgeon. J Pediatr Surg 47:772–781. doi:10.1016/j.jpedsurg.2012.02.019 PubMedCrossRef

17.

Cavell B (1981) Gastric emptying in infants with cystic fibrosis. Acta Paediatr Scand 70:635–638PubMedCrossRef

18.

Chung JL, Kong MS, Lin JN, Wang KL, Lou CC, Wong HF (1994) Intussusception in infants and children: risk factors leading to surgical reduction. J Formos Med Assoc 93:481–485PubMed

19.

Collins CE, Francis JL, Thomas P, Henry RL, O’Loughlin EV (1997) Gastric emptying time is faster in cystic fibrosis. J Pediatr Gastroenterol Nutr 25:492–498PubMedCrossRef

20.

Colombo C, Ellemunter H, Houwen R, Munck A, Taylor C, Wilschanski M (2011) Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros 10:S24–S28. doi:10.1016/S1569-1993(11)60005-2 PubMedCrossRef

21.

Condino AA, Hoffenberg EJ, Accurso F (2005) Frequency of ASCA seropositivity in children with cystic fibrosis. J Pediatr Gastroenterol Nutr 41:23–26PubMedCrossRef

22.

Coughlin JP, Gauderer MW, Stern RC, Doershuk CF, Izant RJ Jr, Zollinger RM Jr (1990) The spectrum of appendiceal disease in cystic fibrosis. J Pediatr Surg 25:835–839. doi:10.1016/0022-3468(90)90186-D PubMedCrossRef

23.

Cucchiara S, Raia V, Minella R, Frezza T, De Vizia B, De Ritis G (1996) Ultrasound measurement of gastric emptying time in patients with cystic fibrosis and effect of ranitidine on delayed gastric emptying. J Pediatr 128:485–488PubMedCrossRef

24.

DallaVecchia LK, GrosfeldJL WKW, Rescorla FJ, Scherer LR, Engum SA (1998) Intestinal atresia and stenosis: a 25-year experience with 277 cases. Arch Surg 133(5):490–497

25.

De Lisle RC, Roach E, Jansson K (2007) Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol 293:G577–G584. doi:10.1152/ajpgi.00195.2007 PubMedCrossRef

26.

Del Campo R, Garriga M, Pérez-Aragón A, Guallarte P, Lamas A, Máiz L, Bayón C, Roy G, Cantón R, Zamora J, Baquero F, Suárez L (2014) Improvement of digestive health and reduction in proteobacterial populations in the gut microbiota of cystic fibrosis patients using a Lactobacillus reuteri probiotic preparation: a double blind prospective study. J Cyst Fibros 13:716–722. doi:10.1016/j.jcf.2014.02.007 PubMedCrossRef

27.

Dhaliwal J, Leach S, Katz T, Nahidi L, Pang T, Lee JM, Strachan R, Day AS, Jaffe A, Ooi CY (2015) Intestinal inflammation and impact on growth in children with cystic fibrosis. JPGN 60:521–526. doi:10.1097/MPG.0000000000000683 PubMed

28.

DiMango E, Walker P, Keating C, Berdella M, Robinson N, Langfelder-Schwind E, Levy D, Liu X (2014) Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis. BMC Pulm Med 14:21. doi:10.1186/1471-2466-14-21 PubMedPubMedCentralCrossRef

29.

Dupuis A, Keenan K, Ooi CY, Dorfman R, Sontag MK, Naehrlich L, Castellani C, Strug LJ, Rommens JM, Gonska T (2015) Prevalence of meconium ileus marks the severity of mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Genet Med. 18. doi: 10.1038/gim.2015.79

30.

Duytschaever G, Huys G, Bekaert M, Boulanger L, De Boeck K, Vandamme P (2011) Cross-sectional and longitudinal comparisons of the predominant fecal microbiota composition of a group of pediatric patients with cystic fibrosis and their healthy subjects. Appl Environ Microb 77:8015–8024. doi:10.1128/AEM.05933-11 CrossRef

31.

Duytschaever G, Huys G, Bekaert M, Boulanger L, De Boeck K, Vandamme P (2013) Dysbiosis of bifidobacteria and Clostridium cluster XIVa in the cystic fibrosis fecalmicrobiotia. J Cyst Fibros 12:206–215. doi:10.1016/j.jcf.2012.10.003 PubMedCrossRef

32.

Escobar MA, Grosfeld JL, Burdick JJ, Powell RL, Jay CL, Wait AD, West KW, Billmire DF, Scherer LR 3rd, Engum SA, Rouse TM, Ladd AP, Rescorla FJ (2005) Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes. Surgery 138:560–571. doi:10.1016/j.surg.2005.06.049 PubMedCrossRef

33.

Farrelly PJ, Charlesworth C, Lee S, Southern KW, Baillie CT (2014) Gastrointestinal surgery in cystic fibrosis: a 20-year review. J Pediatr Surg 49:280–283. doi:10.1016/j.jpedsurg.2013.11.038 PubMedCrossRef

34.

Feigelson J, Letter SJ (1975) Gastro-esophageal reflux in mucoviscidosis. Nouv Presse Med 4:2729–2730PubMed

35.

FitzSimmons SC, Burkhart GA, Borowitz D, Grand RJ, Hammerstrom T, Durie PR, Lloyd-Still JD, Lowenfels AB (1997) High-dose pancreatic-enzyme supplements and fibrosingcolonopathy in children with cystic fibrosis. N Engl J Med 336:1283–1289. doi:10.1056/NEJM199705013361803 PubMedCrossRef

36.

Fluge G, Olesen HV, Gilljam M, Meyer P, Pressler T, Storrösten OT, Karpati F, Hjelte L (2009) Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients. J Cyst Fibros 8:198–202. doi:10.1016/j.JCF.2009.02.002 PubMedCrossRef

37.

Freedman SD, Katz MH, Parker EM, Laposata M, Urman MY, Alvarez JG (1999) A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice. Proc Natl Acad Sci U S A 96:13995–14000PubMedPubMedCentralCrossRef

38.

Freiman JP, FitzSimmons SC (1996) Colonic strictures in patients with cystic fibrosis: Results of a survey of 114 cystic fibrosis care centers in the United States. J Pediatr Gastroenterol Nutr 22:153–156PubMedCrossRef

39.

Fridge JL, Conrad C, Gerson L, Castillo RO, Cox K (2007) Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr 44:212–218. doi:10.1097/MPG.0b013e31802c0ceb PubMedCrossRef

40.

Gallati S (2014) Disease-modifying genes and monogenic disorders: experience in cystic fibrosis. Appl Clin Genet 7:133–146. doi:10.2147/TACG.S18675 PubMedPubMedCentralCrossRef

41.

Gilles DR, Wagener JS, Accurso FJ, Rutler-Simon N (1995) Short-term effects of postural drainage with clapping vs autogenic drainage on oxygen saturation and sputum recovery in patients with cystic fibrosis. Chest 108:952–954. doi:10.1378/chest.108.4.952 CrossRef

42.

Hafen GM, Taylor AC, Oliver MR, Stokes KB, Rao P, Robertson CF, Ranganathan SC (2005) Intussusceptions arising from two different sites in a child with cystic fibrosis. Pediatr Pulmonol 40:358–361. doi:10.1002/ppul.20246 PubMedCrossRef

43.

Hamilton JD, Dyer NH, Dawson AM, O’Grady FW, Vince A, Fenton JC, Mollin DL (1970) Assessment and significance of bacterial overgrowth in the small bowel. Q J Med 39:265–285PubMed

44.

Hendriks HJ, van Kreel B, Forget PP (2001) Effects of therapy with lansoprazole on intestinal permeability and inflammation in young cystic fibrosis patients. J Pediatr Gastroenterol Nutr 33:260–265PubMedCrossRef

45.

Herbella FA, Neto SP, Santoro IL, Figueiredo LC (2015) Gastroesophageal reflux disease and non-esophageal cancer. World J Gastroenterol 21:815–819. doi:10.3748/wjg.v21.i3.815 PubMedPubMedCentral

46.

Hernandez-Jimenez I, Fischman D, Cheriyath P (2008) Colon cancer in cystic fibrosis patients: is this a growing problem? J Cyst Fibros 7:343–346. doi:10.1016/j.jcf.2008.02.006 PubMedCrossRef

47.

Hoffman LR, Pope CE, Hayden HS, Heltshe S, Levy R, McNamara S, Jacobs MA, Rohmer L, Radey M, Ramsey BW, Brittnacher MJ, Borenstein E, Miller SI (2014) Escherichia coli dysbiosis correlates with gastrointestinal dysfunction in children with cystic fibrosis. Clin Infect Dis 58:396–399. doi:10.1093/cid/cit715 PubMedCrossRef

48.

Holsclaw DS, Rocmans C, Shwachman H (1971) Intussusception in patients with cystic fibrosis. Pediatrics 48:51–58PubMed

49.

Houwen RH, van der Doef HP, Sermet I, Munck A, Hauser B, Walkowiak J, Robberecht E, Colombo C, Sinaasappel M, Wilschanski M (2010) Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr 50:38–42. doi:10.1097/MPG.0b013e3181a6e01d PubMedCrossRef

50.

Ibele AR, Koplin SA, Slaughenhoupt BL, Kryger JV, Friedl A, Lund DP (2007) Colonic adenocarcinoma in a 13-year-old with cystic fibrosis. J Pediatr Surg 42:E1–E3. doi:10.1016/j.jpedsurg.2007.07.024 PubMedCrossRef

51.

Johnson JA, Bush A, Buchdahl R (2010) Does presenting with meconium ileus affect the prognosis of children with cystic fibrosis? Pediatr Pulmonol 45:951–958. doi:10.1002/ppul.21271 PubMedCrossRef

52.

Kamath BM, Bhargava S, Markowitz JE, Ruchelli E, Scanlin TF, Mascarenhas M (2003) A girl with cystic fibrosis and failure to thrive. J Pediatr 143:115–119. doi:10.1016/S0022-3476(03)00138-0 PubMedCrossRef

53.

Kaukinen K, Partanen J, Maki M, Collin P (2002) HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol 97:695–699PubMedCrossRef

54.

Kolida S, Gibson GR (2011) Synbiotics in health and disease. Annu Rev Food Sci Technol 2:373–393. doi:10.1146/annurev-food-022510-133739 PubMedCrossRef

55.

Larson JM, Tavakkoli A, Drane WE, Toskes PP, Moshiree B (2010) Advantages of azithromycin over erythromycin in improving the gastric emptying half-time in adult patients with gastroparesis. J Neurogastroenterol Motil 16:407–413. doi:10.5056/jnm.2010.16.4.407 PubMedPubMedCentralCrossRef

56.

Lerner A, Gal N, Mares AJ, Maor E, Iancu TC (1991) Pitfall in diagnosis of Crohn’s disease in a cystic fibrosis patient. J Pediatr Gastroenterol Nutr 12:369–371PubMedCrossRef

57.

Lewindon PJ, Robb TA, Moore DJ, Davidson GP, Martin AJ (1998) Bowel dysfunction in cystic fibrosis: importance of breath testing. J Pediatr Child Health 34:79–82. doi:10.1046/j.1440-1754.1998.00159.x CrossRef

58.

Li L, Somerset S (2014) The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies. Clin Nutr 33:571–580. doi:10.1016/j.clnu.2014.04.004 PubMedCrossRef

59.

Lisowska A, Madry E, Pogorzelski A, Szydłowski J, Radzikowski A, Walkowiak J (2010) Small intestine bacterial overgrowth does not respond to intestinal inflammation in cystic fibrosis. Scand J Clin Lab Invest 70(5):332–336. doi:10.3109/00365513.2010.486869 CrossRef

60.

Lisowska A, Pogorzelski A, Oracz G, Siuda K, Skorupa W, Rachel M, Cofta S, Piorunek T, Walkowiak J (2011) Oral antibiotic therapy improves fat absorption in cystic fibrosis patients with small intestine bacterial overgrowth. J Cyst Fibros 10:418–421. doi:10.1016/j.jcf.2011.06.008 PubMedCrossRef

61.

Lisowska A, Wojtowicz J, Walkowiak J (2009) Small intestine bacterial overgrowth is frequent in cystic fibrosis: combined hydrogen and methane measurements are required for its detection. Acta Biochim Pol 56:631–634PubMed

62.

Lloyd-Still JD (1994) Crohn’s disease and cystic fibrosis. Dig Dis Sci 39:880–885PubMedCrossRef

63.

Maisonneuve P, FitzSimmons SC, Naglia JP, Campbell PW, Lowenfels AB (2003) Cancer risk in non-transplanted and transplanted cystic fibrosis patients: a 10-year study. J Natl Cancer I 95:381–387. doi:10.1093/jnci/95.5.381 CrossRef

64.

Manco M, Putignani L, Bottazzo GF (2010) Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev 31:817–844. doi:10.1210/er.2009-0030 PubMedCrossRef

65.

Maslowski KM, Mackay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12:5–9. doi:10.1038/ni0111-5 PubMedCrossRef

66.

McCarthy VP, Mischler EH, Hubbard VS, Chernick MS, di Sant’Agnese PA (1984) Appendiceal abscess in cystic fibrosis. A diagnostic challenge. Gastroenterology 86:564–568PubMed

67.

Mertens V, Blondeau K, Pauwels A, Farre R, Vanaudenaerde V, Vos R, Verleden G, Van Raemdonck DE, Dupont LJ, Sifrim D (2009) Azithromycin reduces gastroesophageal reflux and aspiration in lung transplant recipients. Dig Dis Sci 54:972–979. doi:10.1007/s10620-009-0725-4 PubMedCrossRef

68.

Miazga A, Osinski M, Cichy W, Zaba R (2015) Current reviews on the etiopathogenesis, clinical manifestation, diagnostics, treatment and correlation with other nosological entities of SIBO. Adv Med Sci 60:118–124. doi:10.1016/j.advms.2014.09.001 PubMedCrossRef

69.

Morten JR, Ansari N, Glanville AR, Meagher AP, Lord RV (2009) Distal intestinal obstruction syndrome (DIOS) in patients with cystic fibrosis after lung transplantation. J Gastrointest Surg 13:1448–1453. doi:10.1007/s11605-009-0924-5 CrossRef

70.

Moshiree B, McDonald R, Hou W, Toskes PP (2010) Comparison of the effect of azithromycin versus erythromycin on antroduodenal pressure profiles of patients with chronic functional gastrointestinal pain and gastroparesis. Dig Dis Sci 55:675–683. doi:10.1007/s10620-009-1038-3 PubMedCrossRef

71.

Mousa HM, Woodley FW (2012) Gastroesophageal reflux in cystic fibrosis: current understandings of mechanisms and management. Curr Gastroenterol Rep 14:226–235. doi:10.1007/s11894-012-0261-9 PubMedCrossRef

72.

Munck A (2014) Cystic fibrosis: evidence for gut inflammation. Int J Biochem Cell Biol 52:180–183. doi:10.1016/j.biocel.2014.02.005 PubMedCrossRef

73.

Nash EF, Ohri CM, Stephenson AL, Durie PR (2014) Abdominal pain in adults with cystic fibrosis. Eur J Gastroenterol Hepatol 26:129–136. doi:10.1097/MEG.0000000000000011 PubMedCrossRef

74.

Nash EF, Stephenson A, Helm EJ, Ho T, Thippanna CM, Ali A, Whitehouse JL, Honeybourne D, Tullis E, Durie PR (2011) Intussusception in adults with cystic fibrosis: a case series with review of the literature. Dig Dis Sci 56:3695–3700. doi:10.1007/s10620-011-1790-z PubMedCrossRef

75.

Naylor JM, Chow CM, McLean AS, Heard RC, Avolio A (2005) Cardiovascular responses to short-term head-down positioning in healthy young and older adults. Physiother Res Int 10:32–47PubMedCrossRef

76.

Neglia JP, FitzSimmons SC, Maisonneuve P, Schöni MH, Schöni-Affolter F, Corey M, Lowenfels AB (1995) The risk of cancer among patients with cystic fibrosis. Cystic fibrosis and cancer study group. N Engl J Med 332:494–499. doi:10.1056/NEJM199502233320803 PubMedCrossRef

77.

Neuhauser EBD (1946) Roentgen changes associated with pancreatic insufficiency in early life. Radiology 46:319–328PubMedCrossRef

78.

O’Connor J, Lawson J (1972) Fibrocystic disease of pancreas and Crohn’s disease. Br Med J 4:610PubMedPubMedCentralCrossRef

79.

O’Brian CE, Anderson PJ, Stowe CD (2010) Use of chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series. Ann Pharmacother 44:577–581. doi:10.1345/aph.1M642 CrossRef

80.

Pang T, Leach ST, Katz T, Jaffe A, Day AS, Ooi CY (2015) Elevated fecal M2-pyruvate kinase in children with cystic fibrosis: a clue to the increased risk of intestinal malignancy in adulthood? J Gastroenterol Hepatol 30:866–871. doi:10.1111/jgh.12842 PubMedCrossRef

81.

Pauwels A, Blondeau K, Dupont LJ, Sifrim D (2012) Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis. Am J Gastroenterol 107:1346–1353. doi:10.1038/ajg.2012.213 PubMedCrossRef

82.

Pauwels A, Blondeau K, Mertens V, Farre R, Verbeke K, Dupont LJ, Sifrim D (2011) Gastric emptying and different types of reflux in adult patients with cystic fibrosis. Aliment Pharmacol Ther 34:799–807. doi:10.1111/j.1365-2036.2011.04786 PubMedCrossRef

83.

Pauwels A, Decraene A, Blondeau K, Mertens V, Farre R, Proesmans M, Van Bleyenbergh P, Sifrim D, Dupont LJ (2012) Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis. Chest 141:1568–1574. doi:10.1378/chest.11-1573 PubMedCrossRef

84.

Pauwels A, Decraene A, Blondeau K, Mertens V, Sifrim D, Dupont L (2009) Detection of bile acids in sputum as a screening method for assessment of aspiration of duodenogastric contents in patients with cystic fibrosis. J Cyst Fibros 12:761–765

85.

Powell AA, Akare S, Qi W, Herzer P, Jean-Louis S, Feldman RA, Martinez JD (2006) Resistance to ursodeoxycholic acid–induced growth arrest can also result in resistance to deoxycholic acid–induced apoptosis and increased tumorgenicity. BMC Cancer 6:219PubMedPubMedCentralCrossRef

86.

Quinton PM (2008) Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet 372(9636):415–417. doi:10.1016/S0140-6736(08)61162-9 PubMedCrossRef

87.

Quinton PM (2010) Role of epithelial HCO3 transport in mucin secretion: lessons from cystic fibrosis. Am J Physiol Cell Physiol 299(6):C1222–C1233. doi:10.1152/ajpcell.00362.2010 PubMedPubMedCentralCrossRef

88.

Raia V, Maiuri L, de Ritis G, de Vizia B, Vacca L, Conte R, Auricchio S, Londei M (2000) Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients. Pediatr Res 47:344–350. doi:10.1203/00006450-200003000-00010 PubMedCrossRef

89.

Reen FJ, Woods DF, Mooij MJ, Adams C, O’Gara F (2012) Respiratory pathogens adopt a chronic lifestyle in response to bile. PLoS One 7:e45978. doi:10.1371/journal.pone.0045978 PubMedPubMedCentralCrossRef

90.

Rezaie A, Pimentel M, Rao SS (2016) How to test and treat small intestinal bacterial overgrowth: an evidence-based approach. Curr Gastroenterol Rep 18:8. doi:10.1007/s11894-015-0482-9 PubMedCrossRef

91.

Rubio-Tapia A, Murray J (2010) Celiac disease. Current Opin Gastroenterol 26:116–122. doi:10.1097/MOG.0b013e3283365263 CrossRef

92.

Rumman N, Sultan M, El-Chammas K, Goh V, Salzman N, Quintero D, Werlin S (2014) Calprotectin in cystic fibrosis. BMC Pediatr 14:133. doi:10.1186/1471-2431-14-133 PubMedPubMedCentralCrossRef

93.

Scotet V, Duguépéroux I, Audrézet MP, Audebert-Bellanger S, Muller M, Blayau M, Férec C (2010) Focus on cystic fibrosis and other disorders evidenced in fetuses with sonographic finding of echogenic bowel: 16-year report from Brittany, France. Am J Obstet Gynecol 203:592. doi:10.1016/j.ajog.2010.08.033, e1-592.e6PubMedCrossRef

94.

Scott RB, O’Loughlin EV, Gall DG (1985) Gastroesophageal reflux in patients with cystic fibrosis. J Pediatr 106:223–227. doi:10.1016/S0022-3476(85)80291-2 PubMedCrossRef

95.

Serban DE, Florescu P, Miu N (2002) Fibrosingcolonopathy revealing cystic fibrosis in a neonate before any pancreatic enzyme supplementation. J Pediatr Gastroenterol Nutr 35:356–359. doi:10.1097/01.MPG.0000024562.65871.FA PubMedCrossRef

96.

Sheikh SI, Ryan-Wenger NA, McCoy KS (2013) Outcomes of surgical management of severe GERD in patients with cystic fibrosis. Pediatr Pulmonol 48:556–562. doi:10.1002/ppul.22630 PubMedCrossRef

97.

Shen O, Rabinowitz R, Yagel S, Gal M (2011) Absent gallbladder on fetal ultrasound: prenatal findings and postnatal outcome. Ultrasound Obstet Gynecol 37(6):673–677. doi:10.1002/uog.8861 PubMedCrossRef

98.

Smyth RL, Croft NM, O’Hea U, Marshall TG, Ferguson A (2000) Intestinal inflammation in cystic fibrosis. Arch Dis Child 82:394–399. doi:10.1136/adc.82.5.394 PubMedPubMedCentralCrossRef

99.

Smyth RL, van Velzen D, Smyth AR, Lloyd DA, Heaf DP (1994) Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. Lancet 343:85–86PubMedCrossRef

100.

Street ME, Spaggiari C, Volta C, Ziveri MA, Viani I, Rossi M, Pisi G, Grzincich G, Bernasconi S (2009) The IGF system and cytokine interactions and relationships with longitudinal growth in prepubertal patients with cystic fibrosis. Clin Endocrinol (Oxf) 70:593–598. doi:10.1111/J.1365-2265.2008.03387.x CrossRef

101.

Sun TT, Wang Y, Cheng H, Xiao HZ, Xiang JJ, Zhang JT, Yu SBS, Martin TA, Ye L, Tsang LL, Jiang WG, Xiaohua J, Chan HC (2014) Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer. Biochim Biophys Acta 1843:618–628. doi:10.1016/j.bbamcr.2013.12.013 PubMedCrossRef

102.

Symonds EL, Omari TI, Webster JM, Davidson GP, Butler RN (2003) Relation between pancreatic lipase activity and gastric emptying rate in children with cystic fibrosis. J Pediatr 143:772–775. doi:10.1067/S0022-3476(03)00581-X PubMedCrossRef

103.

Tabbers MM, Dilorenzo C, Berger MY, Faure C, Langendam MW, Nurko S, Staiano A, Vandenplas Y, Benninga MA (2014) Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr 58:258–274. doi:10.1097/MPG.0000000000000266 PubMedCrossRef

104.

Terheggen G, Dieninghoff D, Rietschel E, Drebber U, Kruis W, Leifeld L (2011) Successful non-invasive treatment of structuring fibrosing colonopathy in an adult patient. Eur J Med Res 16:411–414. doi:10.1186/2047-783X-16-9-411 PubMedPubMedCentralCrossRef

105.

Van der Doef H, Kokke F, van der Ent CK, Houwen RH (2011) Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal intestinal obstruction syndrome, and constipation. Curr Gastroenterol Rep 13:265–270. doi:10.1007/s11894-011-0185-9 PubMedPubMedCentralCrossRef

106.

Van der Doef HP, Arets HG, Froeling SP, Westers P, Houwen RH (2009) Gastric acid inhibition for fat malabsorption or gastroesophageal reflux disease in cystic fibrosis: longitudinal effect on bacterial colonization and pulmonary function. J Pediatr 155(5):629–633. doi:10.1016/j.jpeds.2009.06.040 PubMedCrossRef

107.

Van der Doef HP, Kokke FT, Beek FJ, Woestenenk JW, Froeling SP, Houwen RH (2010) Constipation in pediatric cystic fibrosis patients: an underestimated medical condition. J Cyst Fibros 9:59–63. doi:10.1016/j.jcf.2009.11.003 PubMedCrossRef

108.

Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, Sondheimer J, Staiano A, Thomson M, Veereman-Wauters G, Wenzl TG (2009) Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 49:498–547. doi:10.1097/MPG.0b013e3181b7f563 PubMedCrossRef

109.

Venuta A, Bertolani P, Casarini R, Ferrari F, Guaraldi N, Gaeretti E (1999) Coexistence of cystic fibrosis and celiac disease. Description of a clinical case and review of the literature. Pediatr Med Chir 21:223–226PubMed

110.

Walkowiak J, Blask-Osipa A, Lisowska A, Oralewska B, Pogorzelski A, Cichy W, Sapiejka E, Kowalska M, Korzon M, Szaflarska-Poplawska A (2010) Cystic fibrosis is a risk factor for celiac disease. Acta Biochim Pol 57:115–118PubMed

111.

Werlin SL, Benuri-Silbiger I, Kerem E, Adler SN, Goldin E, Zimmerman J, Malka N, Cohen L, Armoni S, Yatzkan-Israelit Y, Bergwerk A, Aviram M, Bentur L, Mussaffi H, Bjarnasson I, Wilschanski M (2010) Evidence of intestinal inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 51:304–308. doi:10.1097/MPG.0b013e3181d1b013 PubMed

112.

Wilson N, Schey R (2015) Lubiprostone in constipation: clinical evidence and place in therapy. Ther Adv Chronic Dis 6:40–50. doi:10.1177/2040622314567678 PubMedPubMedCentralCrossRef

113.

Woodley FW, Machado RS, Hayes D Jr, Di Lorenzo C, Kaul A, Skaggs B, McCoy K, Patel A, Mousa H (2014) Children with cystic fibrosis have prolonged chemical clearance of acid reflux compared to symptomatic children without cystic fibrosis. Dig Dis Sci 59:623–630. doi:10.1007/s10620-013-2950-0 PubMedCrossRef

114.

www. kinderformularium.nl, consulted on 15-07-2015

115.

www.uptodate.com, consulted on 15-07-2015

Title: Beyond pancreatic insufficiency and liver disease in cystic fibrosis
Authors: Stephanie Demeyer
Kris De Boeck
Peter Witters
Katrien Cosaert
Publication date: 01-07-2016
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 7/2016
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-016-2719-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Beyond pancreatic insufficiency and liver disease in cystic fibrosis

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2016

The β-glucosidase assay: a new diagnostic tool for necrotizing enterocolitis. Sensitivity, specificity, and predictive values

Occurrence of subdural hematomas in Dutch glutaric aciduria type 1 patients

Screen time is associated with depressive symptomatology among obese adolescents: a HEARTY study

Inflammatory pseudotumor (IPT)—surgical cure of an inflammatory syndrome

Impact of healthcare-associated sepsis on mortality in critically ill infants

Cardiac arrest in infants, children, and adolescents: long-term emotional and behavioral functioning