SpringerLink
Log in

Cystic Fibrosis

  • Chapter
  • First Online:
Textbook of Pediatric Gastroenterology, Hepatology and Nutrition

  • 2847 Accesses

Abstract

The cystic fibrosis transmembrane regulator protein (CFTR) is a chloride and bicarbonate channel situated at the apical surface of secretory membranes. Cystic fibrosis (CF) results from a dysfunction of this ion channel. CFTR dysfunction affects the pancreas, hepatobiliary system, and the intestinal tract. This chapter describes the gastrointestinal and nutritional manifestations of CF with current medical management including gastrointestinal aspects of novel therapies targeting the basic defect of CF.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352:1992–2001.

    CAS  Google Scholar 

  2. Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration. 2000;67(2):117–33.

    CAS  Google Scholar 

  3. De Boeck K, Wilschanski M, Castellani C, et al. Cystic fibrosis: terminology and diagnostic algorithms. Thorax. 2006;61:627–35.

    Google Scholar 

  4. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017;181S:S4–S15.

    Google Scholar 

  5. Wilschanski M, Famini H, Strauss-Liviatan N, et al. Nasal potential difference measurements in patients with atypical cystic fibrosis. Eur Respir J. 2001;17:1208–15.

    CAS  Google Scholar 

  6. De Jonge HR, Ballmann M, Veeze H, et al. Ex vivo CF diagnosis by intestinal current measurements (ICM) in small aperture, circulating using chambers. J Cyst Fibros. 2004;3:159–63.

    Google Scholar 

  7. Wilschanski M, Yaakov Y, Omari I, et al. Comparison of nasal potential difference and intestinal current measurements as surrogate markers for CFTR function. J Pediatr Gastroenterol Nutr. 2016;63(5):e92–7.

    Google Scholar 

  8. Argent BE, Gray MA, Steward MC, Case RM. Cell physiology of pancreatic ducts. In: Johnson LR, editor. Physiology of the gastrointestinal tract. 4th ed. Netherlands: Elsevier; 2006. p. 1371–96.

    Google Scholar 

  9. Quinton PM. Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet. 2008;372(9636):415–7.

    CAS  Google Scholar 

  10. Kopelman H, Corey M, Gaskin K, et al. Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas. Gastroenterology. 1988;95:349–55.

    CAS  Google Scholar 

  11. Freedman SD, Kern HF, Scheele GA. Acinar lumen pH regulates endocytosis, but not exocytosis, at the apical plasma membrane of pancreatic acinar cells. Eur J Cell Biol. 1998;75:153–62.

    CAS  Google Scholar 

  12. Wilschanski M, Durie PR. Patterns of GI disease in adulthood associated with mutations in the CFTR gene. Gut. 2007;56(8):1153–63.

    CAS  Google Scholar 

  13. Gaskin KJ, Durie PR, Hill RE, et al. Colipase and maximally activated pancreatic lipase in normal subjects and patients with steatorrhea. J Clin Invest. 1982;69:427–34.

    CAS  Google Scholar 

  14. Choi JY, Muallem D, Kiselyov K, Lee MG, Thomas PJ, Muallem S. Aberrant CFTR-dependent HCO3-transport in mutations associated with cystic fibrosis. Nature. 2001;410:94–7.

    CAS  Google Scholar 

  15. Kristidis P, Bozon D, Corey M, et al. Genetic determination of exocrine pancreatic function in cystic fibrosis. Am J Hum Genet. 1992;50:1178–84.

    CAS  Google Scholar 

  16. Durno C, Corey M, Zielenski J, et al. Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis. Gastroenterology. 2002;123:1857–64.

    Google Scholar 

  17. Ooi CY, Dorfman R, Cipolli M, et al. Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis. Gastroenterology. 2011;140:153–61.

    CAS  Google Scholar 

  18. Rosendahl J, Landt O, Bernadova J, et al. CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated? Gut. 2013;62(4):582–92.

    CAS  Google Scholar 

  19. Borowitz D. Update on the evaluation of pancreatic exocrine status in cystic fibrosis. Curr Opin Pulm Med. 2005;11:524–7.

    Google Scholar 

  20. Kalnins D, Durie PR, Pencharz P. Nutritional management of cystic fibrosis patients. Curr Opin Clin Nutr Metab Care. 2007;10(3):348–54.

    Google Scholar 

  21. Cade A, Walters MP, McGinley N, et al. Evaluation of fecal pancreatic elastase-1 as a measure of pancreatic exocrine function in children with cystic fibrosis. Pediatr Pulmonol. 2000;29(3):172–6.

    CAS  Google Scholar 

  22. Weintraub A, Blau H, Mussaffi H, et al. Exocrine pancreatic function testing in patients with cystic fibrosis and pancreatic sufficiency: a correlation study. J Pediatr Gastroenterol Nutr. 2009;48:306–10.

    Google Scholar 

  23. Walkowiak J, Nousia-Arvanitakis S, Agguridaki C, et al. Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test. J Pediatr Gastroenterol Nutr. 2003;36(4):474–8.

    CAS  Google Scholar 

  24. Wier HA, Kuhn RJ. Pancreatic enzyme supplementation. Curr Opin Pediatr. 2011;23(5):541–4.

    CAS  Google Scholar 

  25. Giuliano CA, Dehoorne-Smith ML, Kale-Pradhan PB. Pancreatic enzyme products: digesting the changes. Ann Pharmacother. 2011;45(5):658–66.

    CAS  Google Scholar 

  26. Graff GR, Maguiness K, McNamara J, et al. Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo- controlled, two-period crossover, superiority study. Clin Ther. 2010;32(1):89–103.

    CAS  Google Scholar 

  27. Graff GR, McNamara J, Royall J, et al. Safety and tolerability of a new formulation of pancrelipase delayed-release capsules (CREON) in children under seven years of age with exocrine pancreatic insufficiency due to cystic fibrosis: an open-label, multicentre, single-treatment-arm study. Clin Drug Investig. 2010;30(6):351–64.

    CAS  Google Scholar 

  28. Trapnell BC, Maguiness K, Graff GR, et al. Efficacy and safety of Creon 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis. J Cyst Fibros. 2009;8(6):370–7.

    CAS  Google Scholar 

  29. Borowitz D, Konstan M, O’Rourke A, et al. Coefficients of fat and nitrogen absorption in healthy subjects and individuals with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007;12:47–52.

    Google Scholar 

  30. Wooldridge JL, Heubi JE, Amaro-Galvez R, et al. EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. J Cyst Fibros. 2009;8(6):405–17.

    CAS  Google Scholar 

  31. Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Consensus committee. J Pediatr. 1995;127(5):681–4.

    CAS  Google Scholar 

  32. Ellis L, Kalnins D, Corey M, et al. Do infants with cystic fibrosis need a protein hydrolysate formula? A prospective, randomized, comparative study. J Pediatr. 1998;132(2):270–6.

    CAS  Google Scholar 

  33. Colombo C, Fredella C, Russo MC, et al. Efficacy and tolerability of Creon for Children in infants and toddlers with pancreatic exocrine insufficiency caused by cystic fibrosis: an open-label, single-arm, multicenter study. Pancreas. 2009;38(6):693–9.

    CAS  Google Scholar 

  34. Kalnins D, Ellis L, Corey M, et al. Enteric-coated pancreatic enzyme with bicarbonate is equal to standard enteric-coated enzyme in treating malabsorption in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2006;42(3):256–61.

    CAS  Google Scholar 

  35. Brady MS, Garson JL, Krug SK, et al. An enteric-coated high-buffered pancrelipase reduces steatorrhea in patients with cystic fibrosis: a prospective, randomized study. J Am Diet Assoc. 2006;106(8):1181–6.

    CAS  Google Scholar 

  36. Freedman S, Orenstein D, Black P, et al. Increased fat absorption from enteral formula through an in-line digestive cartridge in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2017;65:97–101.

    CAS  Google Scholar 

  37. Stevens J, Wyatt C, Brown P, et al. Absorption and safety with sustained use of RELiZORB evaluation (ASSURE) study in patients with cystic fibrosis receiving enteral feeding. J Pediatr Gastroenterol Nutr. 2018;67:527–32.

    Google Scholar 

  38. Butt AM, Ip W, Ellis L, et al. The fate of exogenous enzymes in patients with cystic fibrosis and pancreatic insufficiency (abstr). J Pediatr Gastroenterol Nutr. 2001;33:391.

    Google Scholar 

  39. Bartlett JR, Friedman KJ, Ling S, et al. Genetic modifiers of modifiers of liver disease in cystic fibrosis. JAMA. 2009;302:1076–83.

    CAS  Google Scholar 

  40. Wilschanski M, Rivlin J, Cohen S, et al. Clinical and genetic risk factors for cystic fibrosis related liver disease. Pediatrics. 1999;103(1):52–7.

    CAS  Google Scholar 

  41. Debray D, Rainteau D, Barbu V, et al. Defects in gallbladder emptying and bile acid homeostasis in mice with cystic fibrosis transmembrane conductance regulator deficiencies. Gastroenterology. 2012;142:1581–91.

    CAS  Google Scholar 

  42. Colombo C, Battezzati PM, Srazzabosco M, et al. Liver and biliary problems in cystic fibrosis. Semin Liver Dis. 1998;18:227–35.

    CAS  Google Scholar 

  43. Witters P, Libbrecht L, Roskams T, et al. Liver disease in cystic fibrosis presents as non – cirrhotic portal hypertension. J Cyst Fibros. 2017;16(5):e11–3.

    Google Scholar 

  44. Debray D, Kelly D, Houwen R, Strandvik B, Colomco C. Best practice guidance for the diagnosis and management of cystic fibrosis associated liver disease. J Cyst Fibros. 2011;10:S29–36.

    Google Scholar 

  45. Shapira R, Hadzic R, Francavilla R, et al. Retrospective review of cystic fibrosis presenting as infantile liver disease. Arch Dis Child. 1999;81:125–8.

    CAS  Google Scholar 

  46. Mueller-Abt PR, Frawly KJ, Greer RM, Lewindon PJ. Comparison of ultrasound and biopsy findings in children with cystic fibrosis liver disease. J Cyst Fibros. 2008;7:215–21.

    Google Scholar 

  47. Lewindon PJ, Lewindon PJ, Puertolas-Lopez MV, Ramm LE, et al. Accuracy of transient elastography data combined with APRI in detection and staging of liver disease in pediatric patients with cystic fibrosis. Clin Gastroenterol Hepatol. 2019;17(12):2561–9.

    Google Scholar 

  48. Lindblad A, Glaumann H, Strandvik B. A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease. Hepatology. 1998;27(1):166–74.

    CAS  Google Scholar 

  49. Ooi CY, Nightingale S, Durie PR, Freedman SD. Ursodeoxycholic acid in cystic fibrosis-associated liver disease. J Cys Fibros. 2012;11:72–3.

    CAS  Google Scholar 

  50. Trauner M, Halilbasic E, Claudel T, et al. Potential of nor-ursodeoxycholic acid in cholestatic and metabolic disorders. Dig Dis. 2015;33:433–9.

    Google Scholar 

  51. Fiorotto R, Scirpo R, Trauner M, et al. Loss of CFTR affects biliary epithelium innate immunity and causes TLR4-NF-kappaB-mediated inflammatory response in mice. Gastroenterology. 2011;141:1498–508. 1508 e1491-1495.

    CAS  Google Scholar 

  52. Milkiewicz P, Skiba G, Kelly D. Transplantation for cystic fibrosis: outcome following early liver transplantation. J Gastroenterol Hepatol. 2002;17(2):208–13.

    Google Scholar 

  53. Sathe M, Houwen R. Meconium ileus in cystic fibrosis. J Cyst Fibros. 2017;16(Suppl 2):S32–9.

    Google Scholar 

  54. Sun L, Rommens JM, Corvol H, et al. Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat Genet. 2012;44(5):562–9.

    CAS  Google Scholar 

  55. Dorfman R, Li W, Lin F, et al. Modifier gene study of meconium ileus in cystic fibrosis; statistical considerations and gene map** results. Hum Genet. 2009;126:763–78.

    CAS  Google Scholar 

  56. Dray X, Bienvenu T, Desmazes-Dufue V, et al. Distal intestinal obstruction syndrome in adults with cystic fibrosis. Clin Gastroenterol Hepatol. 2004;2:498–503.

    Google Scholar 

  57. Norkina O, Kaur S, Ziemer D, DeLisle RC. Inflammation of the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2004;286(6):G1032–41.

    CAS  Google Scholar 

  58. Werlin SL, Benuri-Silbiger I, Kerem E, et al. Evidence of intestinal inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010;51:304–8.

    CAS  Google Scholar 

  59. Flass T, Tong S, Frank DN, et al. Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis. PLoS One. 2015;10(2):e0116967.

    Google Scholar 

  60. Houwen RH, van der Doef HP, Sermet I, et al. Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr. 2010;50(1):38–42.

    Google Scholar 

  61. Shidrawi RG, Murugan N, Westaby D, Gyi K, Hodson ME. Emergency colonoscopy for DIOS in CF patients. Gut. 2002;51:285–6.

    CAS  Google Scholar 

  62. Colombo C, Ellemunter H, Houwen R, Munck A, Taylor C, Wilschanski M. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros. 2011;10(Suppl 2):S24–8.

    Google Scholar 

  63. Munck A, Alberti C, Colombo C, et al. International prospective study of distal intestinal obstruction syndrome in cystic fibrosis: associated factors and outcome. J Cyst Fibros. 2016;15(4):531–9.

    Google Scholar 

  64. Robertson MD, Choe KA, Joseph PM. Review of the abdominal manifestations of cystic fibrosis in the adult patient. Radiographics. 2006;26(3):679–90.

    Google Scholar 

  65. Wilschanski M, Fisher D, Hadas-Halperin I, et al. Findings on routine abdominal ultrasonography in cystic fibrosis patients. J Pediatr Gastroenterol Nutr. 1999;28(2):182–5.

    CAS  Google Scholar 

  66. Button BM, Roberts S, Kotsimbos TC, et al. Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation. J Heart Lung Transplant. 2005;24(10):1522–9.

    Google Scholar 

  67. Malfroot A, Dab I. New insights on gastro-oesophageal reflux in cystic fibrosis by longitudinal follow up. Arch Dis Child. 1991;66:1339–45.

    CAS  Google Scholar 

  68. Smythe RL van Velzen D, Smyth AR, et al. Strictures of ascending colon in cystic fibrosis and high strength pancreatic enzymes. Lancet. 1994;343:85–6.

    Google Scholar 

  69. FitzSimmons SC, Burkhart GA, Borowitz D, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med. 1997;336(18):1283–9.

    CAS  Google Scholar 

  70. Rivlin J, Lerner A, Augarten A, et al. Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis. J Pediatr. 1998;132(1):177–9.

    CAS  Google Scholar 

  71. Kyne L, Kelly CP. Recurrent Clostridium difficile diarrhoea. Gut. 2001;49(1):152–3.

    CAS  Google Scholar 

  72. Quraishi MN, Widlak M, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017;46(5):479–93.

    CAS  Google Scholar 

  73. Peach SL, Borriello SP, Gaya H, et al. Asymptomatic carriage of Clostridium difficile in patients with cystic fibrosis. J Clin Pathol. 1986;39(9):1013–8.

    CAS  Google Scholar 

  74. Wu TC, McCarthy VP, Gill VJ. Isolation rate and toxigenic potential of Clostridium difficile isolates from patients with cystic fibrosis. J Infect Dis. 1983;148(1):176.

    CAS  Google Scholar 

  75. Dunwoody R, Steel A, Land J, Simmonds N. Clostridium difficile and cystic fibrosis: management strategies and the role of faecal transplantation. Paediatr Respir Rev. 2018;26:16–8.

    Google Scholar 

  76. Roberts DM, Craft JC, Mather FJ, et al. Prevalence of giardiasis in patients with cystic fibrosis. J Pediatr. 1988;112:555–9.

    CAS  Google Scholar 

  77. Lewindon PJ, Robb TA, Moore DJ, et al. Bowel dysfunction in cystic fibrosis: importance of breath testing. J Paediatr Child Health. 1998;34:79–82.

    CAS  Google Scholar 

  78. Fridge JL, Conrad C, Gerson L, et al. Risk factors for small bowel overgrowth in Cystic Fibrosis. J Pediatr Gastroenterol Nutr. 2007;44:212–8.

    Google Scholar 

  79. Duytschaever G, Huys G, Bekaert M, Boulanger L, et al. Dysbiosis of bifidobacteria and Clostridium cluster XIVa in the cystic fibrosis fecal microbiota. J Cyst Fibros. 2013;12(3):206–15.

    Google Scholar 

  80. DeLisle RC, Roach EA, Norkina O. Eradication of small intestinal bacterial overgrowth in the cystic fibrosis mouse reduces mucus accumulation. J Pediatr Gastroenterol Nutr. 2006;42:46–52.

    Google Scholar 

  81. Hoen AG, Li J, Moulton LA, et al. Association between gut microbial colonization in early like and respiratory outcomes in Cystic Fibrosis. J Peds. 2015;167:138–47.

    Google Scholar 

  82. Hayden HS, Eng A, Pope CE, et al. Fecal dysbiosis in infants with cystic fibrosis is associated with early linear growth failure. Nat Med. 2020;26:215–21.

    CAS  Google Scholar 

  83. Dhaliwal J, Leach S, Katz T, et al. Intestinal inflammation and impact on growth in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2015;60(4):521–6.

    Google Scholar 

  84. Meeker SM, Mears KS, Sangwan N, et al. CFTR dysregulation drives active selection of the gut microbiome. PLoS Pathog. 2020;16:e1008251.

    CAS  Google Scholar 

  85. Valletta EA, Mastella G. Incidence of celiac disease in a cystic fibrosis population. Acta Paed Scand. 1989;78:784–5.

    Google Scholar 

  86. Cohen-Cymberknoh M, Wilschanski M. Concomitant cystic fibrosis and coeliac disease: reminder of an important clinical lesson. BMJ Case Rep. 2009;2009:bcr07.2008.0578. Epub 2009 Mar 5

    Google Scholar 

  87. Lloyd-Still J. Crohn’s disease and cystic fibrosis. Dig Dis Sci. 1994;39:880–5.

    CAS  Google Scholar 

  88. Neglia JP, FitzSimmons SC, Maissoneuve P, et al. The risk of cancer among patients with cystic fibrosis cystic fibrosis and cancer study group. N Engl J Med. 1995;332:494–9.

    CAS  Google Scholar 

  89. Than BLN, Linnekamp JF, Starr TK, et al. CFTR is a tumor suppressor gene in murine and human intestinal cancer. Oncogene. 2016;35:4179–87.

    CAS  Google Scholar 

  90. Maisonneuve P, Marshall BC, Knapp EA, Lowenfels AB. Cancer risk in cystic fibrosis: a 20-year nationwide study from the United States. J Natl Cancer Inst. 2013;105(2):122–9.

    CAS  Google Scholar 

  91. Billings JL, Dunitz JM, et al. Early Colon Screening of adult patients with Cystic Fibrosis reveals high incidence of adenomatous colon polyps. J Clin Gastroenterol. 2014;48:e85–8.

    Google Scholar 

  92. Fink AK, Yanik EL, Marshall BC, et al. Cancer risk among lung transplant recipients with Cystic Fibrosis. J Cyst Fibros. 2016;16:91–7.

    Google Scholar 

  93. Yamada A, Komaki Y, Komaki F, et al. Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis. Lancet Oncol. 2018;19(6):758–67.

    Google Scholar 

  94. Hadjiliadis D, Khoruts A, Zauber AG, et al. Cystic fibrosis colorectal cancer screening consensus recommendations. Gastroenterology. 2018;154:736–45.

    Google Scholar 

  95. Slae M, Wilschanski M. Cystic fibrosis: a gastrointestinal cancer syndrome. Lancet Oncol. 2018;19(6):719–20.

    Google Scholar 

  96. Stallings VA, Stark LJ, Robinson KA, et al. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008;108(5):832–9.

    Google Scholar 

  97. Corey M, McLaughlin FJ, Williams M, et al. A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol. 1988;41(6):583–91.

    CAS  Google Scholar 

  98. Farrell PM, Lai HJ, Li Z, et al. Evidence on improved outcomes with early diagnosis of cystic fibrosis through neonatal screening: enough is enough! J Pedatr. 2005;147:S30–6.

    Google Scholar 

  99. Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002;35(3):246–59.

    Google Scholar 

  100. Turck D, Braegger CP, Colombo C, et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants. Clin Nutr. 2016;35(3):557–77.

    Google Scholar 

  101. Borowitz D, Robinson KA, Rosenfeld M, et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr. 2009;155(6 Suppl):S73–93.

    Google Scholar 

  102. Maqbool A, Schall JI, Gallagher PR, Zemel BS, Strandvik B, Stallings VA. The relationship between type of dietary fat intake and serum fatty acid status in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2012;55(5):605–11.

    CAS  Google Scholar 

  103. Abernathy RS. Bulging fontanelle as presenting sign in cystic fibrosis. Arch Dis Child. 1976;130:1360–2.

    CAS  Google Scholar 

  104. Rayner RJ, Tyrell JC, Hiller EJ, et al. Night blindness and conjunctival xerosis due to vitamin A deficiency in cystic fibrosis. Arch Dis Child. 1989;64:1151–6.

    CAS  Google Scholar 

  105. Hubbard VS, Farrell PM, di Sant’Agnese PA. 25-Hydroxycholecalciferol levels in patients with cystic fibrosis. J Pediatr. 1979;94:84–6.

    CAS  Google Scholar 

  106. Bines AE, Israel EJ. Hypoproteinemia, anemia and failure to thrive in an infant. Gastroenterology. 1991;101:848–56.

    CAS  Google Scholar 

  107. Sokol RJ, Reardon MC, Accurso FJ, et al. Fat-soluble vitamin status during the first year of life in infants with cystic fibrosis. Am J Clin Nut. 1989;50:1064–71.

    CAS  Google Scholar 

  108. Hakim F, Kerem E, Rivlin J, et al. Vitamins A and E and pulmonary exacerbations in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007;45(3):347–53.

    CAS  Google Scholar 

  109. Tangpricha V, Kelly A, Stephenson A, et al. An update on the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis: evidence-based recommendations from the Cystic Fibrosis Foundation. J Clin Endocrinol Metab. 2012;97:1082–93.

    CAS  Google Scholar 

  110. Wilson DC, Rashid M, Durie PR, et al. Treatment of vitamin K deficiency in cystic fibrosis: effectiveness of a daily fat-soluble vitamin combination. J Pediatr. 2001;138(6):851–5.

    CAS  Google Scholar 

  111. Bianchi ML, Romano G, Saraifoger S, et al. BMD and body composition in children and young patients affected by cystic fibrosis. J Bone Miner Res. 2006;21(3):388–96.

    Google Scholar 

  112. Aris RM, Merkel PA, Bachrach LK, et al. Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab. 2005;90(3):1888–96.

    CAS  Google Scholar 

  113. Schwebel C, Pin I, Barnoud D, et al. Prevalence and consequences of nutritional depletion in lung transplant candidates. Eur Respir J. 2000;16(6):1050–5.

    CAS  Google Scholar 

  114. Aris RM, Neuringer IP, Weiner MA, et al. Severe osteoporosis before and after lung transplantation. Chest. 1996;109(5):1176–83.

    CAS  Google Scholar 

  115. Ho T, Gupta S, Brotherwood M, et al. Increased serum vitamin a and e levels after lung transplantation. Transplantation. 2011;92(5):601–6.

    CAS  Google Scholar 

  116. Stiebellehner L, Quittan M, End A, et al. Aerobic endurance training program improves exercise performance in lung transplant recipients. Chest. 1998;113(4):906–12.

    CAS  Google Scholar 

  117. Anderson JL, Miles C, Tierney AC. Effect of probiotics on respiratory, gastrointestinal and nutritional outcomes in patients with cystic fibrosis: a systematic review. J Cyst Fibros. 2017;16(2):186–97. https://doi.org/10.1016/j.jcf.2016.004.

    Article  CAS  Google Scholar 

  118. del Campo R, Garriga M, Pérez-Aragón A, et al. 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. 2014;13(6):716–22. https://doi.org/10.1016/j.jcf.2014.02.007.

    Article  Google Scholar 

  119. Bruzzese E, Callegari ML, Raia V, et al. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial. PLoS One. 2014;9(2):e87796. https://doi.org/10.1371/journal.pone.0087796.

    Article  CAS  Google Scholar 

  120. Van Biervliet S, Hauser B, Verhulst S, et al. Probiotics in cystic fibrosis patients: a double blind crossover placebo controlled study: pilot study from the ESPGHAN working group on pancreas/CF. Clin Nutr ESPEN. 2018;27:59–65. https://doi.org/10.1016/j.clnesp.2018.06.008.

    Article  Google Scholar 

  121. Coffey MJ, Garg M, Homaira N, Jaffe A, Ooi CY. Probiotics for people with cystic fibrosis. Cochrane Database Syst Rev. 2020;1:CD012949. https://doi.org/10.1002/14651858.CD012949.pub2.

    Article  Google Scholar 

  122. Ramsey BW, Davies J, NG ME, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663–72.

    CAS  Google Scholar 

  123. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-Ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373(3):220–31.

    CAS  Google Scholar 

  124. Middleton PG, Mall MA, Drevinec P, et al. Elexacaftor-Tezacaftor-Ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381:1809–19.

    CAS  Google Scholar 

  125. Heijerman HG, Mckone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940–194.

    CAS  Google Scholar 

  126. Bodewes F, Wilschanski M. CFTR protein function modulation therapy is finally targeting cystic fibrosis-related gastrointestinal disease. J Pediatr Gastroenterol Nutr. 2018;66(3):372–3.

    Google Scholar 

  127. Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016;4(2):107–15.

    CAS  Google Scholar 

  128. Rosenfeld M, Wainwright CE, Higgins M, et al. Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation. Lancet Respir Med. 2018;6(7):545–53.

    CAS  Google Scholar 

  129. Carrion A, Borowitz DS, Freedman SD, et al. Reduction of recurrence risk of pancreatitis in cystic fibrosis with ivacaftor: case series. J Pediatr Gastroenterol Nutr. 2018;66(3):451–4.

    Google Scholar 

  130. Ooi CY, Syed SA, Rossi L, et al. Impact of CFTR modulation with ivacaftor on gut microbiota and intestinal inflammation. Sci Rep. 2018;8(1):17834. https://doi.org/10.1038/s41598-018-36364-6.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Gastroenterology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    Zev Davidovics & Michael Wilschanski

Authors
  1. Zev Davidovics
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Wilschanski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Wilschanski .

Editor information

Editors and Affiliations

  1. Section of Pediatric Gastroenterology Hepatology and Nutrition, University of Chicago, Chicago, IL, USA

    Stefano Guandalini

  2. Pediatric Liver, GI and Nutrition Center, Child Health, King’s College Hospital, London, UK

    Anil Dhawan

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Davidovics, Z., Wilschanski, M. (2022). Cystic Fibrosis. In: Guandalini, S., Dhawan, A. (eds) Textbook of Pediatric Gastroenterology, Hepatology and Nutrition. Springer, Cham. https://doi.org/10.1007/978-3-030-80068-0_41

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-80068-0_41

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-80067-3

  • Online ISBN: 978-3-030-80068-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation