Abstract
Intestinal malabsorption is severe and of early onset in virtually all people who have cystic fibrosis. The main cause is deficiency of pancreatic enzymes, but bicarbonate deficiency, abnormalities of bile salts, mucosal transport and motility, and anatomical structural changes are other contributory factors.
Appropriate pancreatic replacement therapy will achieve normal or near normal absorption in many patients. It is important to identify both malabsorption and evidence of a pancreatic lesion in all patients who are to receive pancreatic enzymes. All who have evidence of fat malabsorption are deemed pancreatic insufficient and candidates for enzyme replacement therapy. Effective treatment should allow a normal diet to be taken, control symptoms, correct malabsorption and achieve a normal nutritional state and growth.
The occurrence of fibrosing colonopathy in some patients receiving very high doses of those enzymes that have the copolymer Eudragit™ L30 D55 in their covering has resulted in guidelines in the UK to avoid dosages greater than the equivalent of 10 000 IU lipase/kg/day for all patients and also to avoid preparations containing this copolymer in children and adolescents.
For patients not responding to 10 000 IU lipase/kg/day, review of adherence to treatment, change of enzyme preparation, variation of the time of administration and reduction in gastric acid may improve absorption. The importance of excluding other gastrointestinal disorders as a cause of the patient’s symptoms and the need for early investigations, rather than merely increasing the dosage of enzymes, is stressed. With modern enzymes, adequate control of gastrointestinal symptoms and absorption can be achieved at dosages of 10 000 IU lipase/kg/day or only slightly more, and a normal nutritional state and growth rate maintained in most patients with cystic fibrosis.
Similar content being viewed by others
References
Littlewood JM, Wolfe SP. Nutrition in cystic fibrosis. In: Heatley RV, Green JH, Losowsky MS, editors. Consensus in clinical nutrition. Cambridge: Cambridge University Press, 1994: 388–419
Bronstein MN, Sokol RJ, Abman SH, et al. Pancreatic insufficiency, growth, and nutrition in infants identified by newborn screening as having cystic fibrosis. J Pediatr 1992; 120: 533–40
Couper R, Corey M, Durie PR, et al. Longitudinal evaluation of serum trypsinogen measurement in pancreatic-insufficient and pancreatic sufficient patients with cystic fibrosis. J Pediatr 1995; 127(3): 408–13
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
Forstner G, Gall G, Corey M, et al. Digestion and absorption of nutrients in cystic fibrosis. In: Sturgess JM, editor. Perspectives in cystic fibrosis. Toronto: Canadian Cystic Fibrosis Foundation, 1980: 137–48
Balasubramanian K, Zentler-Monro P, Batten JC, et al. Increased intragastric acid-resistant activity and lipolysis in pancreatic steatorrhoea due to cystic fibrosis. Pancreas 1992; 7: 305–10
Zentler-Monro PL, Assoufi BA, Balasubramanian K, et al. Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis. Pancreas 1992; 7: 311–9
Hoffman RD, Isenberg JN, Powell GK. Carbohydrate malabsorption in normal in school age cystic fibrosis children. Dig Dis Sci 1987; 32: 1071–4
Murphy JL, Wooton SA, Bond SA, et al. Energy content of stools in normal healthy controls and patients with cystic fibrosis. Arch Dis Child 1991; 66: 495–500
Littlewood JM. Value of comprehensive assessment and investigation in the management of cystic fibrosis. In: Escobar H, Basquero L, Suarez L, editors. Clinical ecology of cystic fibrosis. Amsterdam: Elsevier, 1993: 181–7
Littlewood JM. Abdominal pain in cystic fibrosis. J R Soc Med 1995; 88: 7–15
Zentler-Munro PL. Pancreatic exocrine insufficiency and cystic fibrosis. Curr Opin Gastroenterol 1989; 5: 706–10
Durie PR, Forstner GG. Pathophysiology of the exocrine pancreas in cystic fibrosis. JR Soc Med 1989; 82Suppl. 16: S2–10
Gilbert J, Kelleher J, Littlewood JM, et al. Ileal pH in cystic fibrosis. Scand J Gastroenterol 1988; 23Suppl. 143: 132–4
Robinson PJ, Smith AL, Sly PD. Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Dig Dis Sci 1990; 35: 1299–304
Geus WP, Gan KH, Lamers CBHW, et al. Simultaneously measured duodenal and gastric pH in patients with cystic fibrosis: effect of omeprazole [abstract 153]. Neth J Med 1999; 54 Suppl.: S63
Zentler-Munro PL, Fitzpatrick JWF, Batten JC, et al. Effect of intraduodenal acidity on aqueous phase bile acid and lipid concentrations in pancreatic steatorrhoea due to cystic fibrosis. Gut 1984; 25: 500–7
Walters MP, Littlewood JM. Faecal bile acid and dietary residue excretion in cystic fibrosis: age group variations. J Pediatr Gastroenterol Nutr 1998; 27: 296–300
Roy CC, Weber AM, Morin CL, et al. Abnormal biliary composition in cystic fibrosis: effect of pancreatic enzymes. N Engl J Med 1977; 292: 1301–5
Sinaasappel M. Relationship between intestinal function and chloride secretion in patients with cystic fibrosis. Neth J Med 1992; 41: 110–4
Kalivianakis M, Minich DM, Bijleveld CMA, et al. Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long chain fatty acids. Am J Clin Nutr 1999; 69: 127–34
Dalzell AM, Freestone NS, Billington D, et al. Small intestinal permeability and oro-caecal transit time in cystic fibrosis. Arch Dis Child 1990; 65; 585–8
Seal S, McClean P, Walters M, et al. Stable isotope studies of pancreatic enzyme release in vivo. Postgrad Med J 1996; 72Suppl. 2: 37–8
Oppenheimer EH, Esterly JR. Pathology of cystic fibrosis: review of the literature and comparison with 146 autopsied cases. Perspect Pediatr Pathol 1975; 2: 241–78
Wong LTK, Turtle S, Davidson AGF. Secretin pancreozymin stimulation test and confirmation of the diagnosis of cystic fibrosis. Gut 1982; 23: 744–50
Brown GA, Sule D, Williams J, et al. Faecal chymotrypsin: a reliable index of exocrine pancreatic function. Arch Dis Child 1988; 63: 785–9
Brown RC, Chalmers DM, Rowe VL, et al. Comparison of the diagnostic value of serum pancreatic isoamylase and immunoreactive trypsin measurement in patients with cystic fibrosis. J Clin Pathol 1982; 35: 547–9
Soldan W, Henker J, Sprossig C. Sensitivity and specificity of quantitative determination of pancreatic elastase 1 in feces of children. J Pediatr Gastroenterol Nutr 1997; 24: 53–5
Gullo L, Graziano L, Babbini S, et al. Faecal elastase 1 in children with cystic fibrosis. Eur J Paediatr 1997; 156: 770–2
Cade A, Walters MP, McGinley M, et al. Evaluation of fecal elastase-1 as a measure of pancreatic exocrine function in children with cystic fibrosis. Pediatr Pulmonol 2000; 29: 172–6
Weizman Z, Forstner GG, Gaskin KJ, et al. The Bentiromide test for assessing pancreatic dysfunction using analysis of PABA in plasma and urine: studies in cystic fibrosis and Shwachman’s syndrome. Gastroenterology 1985; 89: 596–604
Green MR, Austin S, Weaver LT. Dual marker one day pancreolauryl test. Arch Dis Child 1993; 68: 649–52
Littlewood JM. Gastrointestinal complications in cystic fibrosis. JR Soc Med 1992; 85Suppl. 118: 13–9
Schmerling DH, Forrer JCW, Prader A. Faecal fat and nitrogen in healthy children and in children with malabsorption and maldigestion. Pediatrics 1970; 46: 690–5
Gilbert J, Kelleher J, Walters MP, et al. Markers for faecal fat estimation in monitoring steatorrhoea in cystic fibrosis. Gut 1988; 29: 1286–8
Bekers O, Postma C, Lombarts AJ. Determination of faecal fat by near-infrared spectroscopy. Eur J Clin Chem Clin Biochem 1995; 33: 83–6
Van de Kamer JH, Huinink H, Ten B, et al. Rapid method for the determination of fat in faeces. J Biol Chem 1949; 177: 347–55
Walters MP, Kelleher J, Gilbert J, et al. Clinical monitoring of steatorrhoea in cystic fibrosis. Arch Dis Child 1990; 63: 99–102
Tran M, Forget P, Van der Neucker A, et al. The acid steatocrit: a much improved method. J Pediatr Gastroenterol Nutr 1994; 19: 299–303
Van der Neucker A, Pestel A, Tran TM, et al. Clinical use of acid steatocrit. Acta Paediatr 1997; 86(5): 466–9
Amarri S, Harding M, Coward WA, et al. 13 carbon mixed triglyceride breath test and pancreatic supplementation in cystic fibrosis. Arch Dis Child 1997; 76: 349–51
Swart GR, Sinaasappel M, Hoekstra JH, et al. The faecal fat balance and the 13C mixed triglyceride breath test; diagnostic precision as determined in repeated studies in patients with cystic fibrosis [abstract 552]. Pediatr Pulmonol 1998; Suppl. 17: 363
Elliott RB, Escobar LC, Lees HR, et al. Acomparison between two pancreatin microsphere preparations in cystic fibrosis. N Z Med J 1992; 105: 107–8
Smyth RL, Ashby D, O’Hea U, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-controlled study. Lancet 1995; 346: 1247–51
Jones R, Franklin K, Spicer R, et al. Colonic strictures in children with cystic fibrosis on low strength pancreatic enzymes [letter]. Lancet 1995; 346: 1230
Ramsden WH, Moya EF, Littlewood JM. Colonic wall thickness, pancreatic enzyme dose and type of preparation in cystic fibrosis. Arch Dis Child 1998; 79: 339–43
Committee on Safety of Medicines. Report of the Pancreatic Enzymes Working Party; London: Committee on Safety of Medicines, 1995
Smyth RL, vanVeltzen D, Smyth AR, et al. Strictures of the ascending colon in cystic fibrosis and high strength pancreatic enzymes. Lancet 1994; 343: 85–6
Littlewood JM. Update on intestinal strictures. J R Soc Med 1999; 92Suppl. 37: 41–9
Littlewood JM. Management of malabsorption in cystic fibrosis: influence of recent developments on clinical practice. Postgrad Med J 1996; 72Suppl. 2: S56–62
Littlewood JM. Implications of the Committee on Safety of Medicines 10,000IU lipase/kg/day recommendation for use of pancreatic enzymes in cystic fibrosis. Arch Dis Child 1996; 74: 466–8
van Velzen D, Ball LM, Dezfulian AR, et al. Comparative and experimental pathology of fibrosing colonopathy. Postgrad Med J 1996; 72Suppl. 2: S39–48
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: 1283–9
Prescott P. Pancreatic enzymes and fibrosing colonopathy [letter]. Lancet 1999; 354: 250
Bakowski MT, Prescott P. Patterns of use of pancreatic enzyme supplements in fibrosing colonopathy: implications for pathogenesis. Pharmacoepidemiol Drug Saf 1997; 6: 347–58
Prescott P, Bakowski MT. Pathogenesis of fibrosing colonopathy: the role of methacrylic acid copolymer. Pharmacoepidemiol Drug Saf 1999; 8: 377–84
Borowitz DS, Grand RJ, Durie PR. Fibrosing colonopathy in patients with cystic fibrosis. J Pediatr 1995; 127: 681–4
FitzSimmons SC, Lowenfels AB. Reply. Pancreatic enzymes and colonic strictures with cystic fibrosis: a case controlled study. Gastroenterol 1998; 114: 611–2
Powell CJ. Colonic toxicity from pancreatins: a contemporary safety issue. Lancet 1999; 353: 911–5
Lloyd-Still JD, Beno DWA, Uhing MR, et al. Pancreatic enzymes and fibrosing colonopathy [letter]. Lancet 1999; 354: 251
Dodge JA. Colonic wall thickness and pancreatic enzymes in cystic fibrosis [letter]. Arch Dis Child 1999; 81: 97
Connett GJ, Lucas JS, Atchley JTM, et al. Colonic wall thickening is related to age and not dose of high strength pancreatic microspheres in children with cystic fibrosis. Eur J Gastroenterol Hepatol 1999; 11: 181–3
Atkinson SN. A comparative study of enzyme activity acid resistance and dissolution characteristics of four enteric coated microsphere preparations of pancreatic. Eur J Clin Res 1991; 1: 37–45
Walters MP, Littlewood JM. Pancreatin preparations used in the treatment of cystic fibrosis: lipase content and in vitro release. Aliment Pharmacol Ther 1996; 10: 433–40
Meyer JH, Elahoff J, Porter-Fink V, et al. Human postprandial gastric emptying of 1–3 millimeter spheres. Gastroenterology 1988; 94: 1315–25
Taylor CJ, Hillel PG, Ghosal S, et al. Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis. Arch Dis Child 1999; 80: 149–52
Mischler EH, Parrell S, Farrell PM, et al. Comparison of effectiveness of pancreatic enzyme preparations in cystic fibrosis. Am J Dis Child 1982; 136: 1060–3
Beverley DW, Kelleher J, MacDonald A, et al. Comparison of four pancreatic extracts in cystic fibrosis. Arch Dis Child 1987; 62: 564–8
Stead RJ, Skypala I, Hodson ME, et al. Enteric coated micro-spheres of pancreatin in the treatment of cystic fibrosis: comparison with a standard enteric coated preparation. Thorax 1987; 42: 533–7
George DE, Pinero R, Miller AB, et al. Comparison of two pancreatic enzyme supplements in patients with cystic fibrosis. Adv Ther 1990; 7: 109–18
Brady MS, Rickard KA, Yu PL, et al. Effectiveness and safety of small vs. large doses of enteric coated pancreatic enzymes in reducing steatorrhoea in children with cystic fibrosis: a randomized prospective study. Pediatr Pulmonol 1991; 10: 79–85
Brady MS, Rickard K, Yu PL, et al. Effectiveness of enteric coated pancreatic enzymes given before meals in reducing steatorrhoea in children with cystic fibrosis. J Am Diet Assoc 1992; 92: 813–7
Beker LT, Fink RJ, Shamas FH, et al. Comparison of weight based dosages of enteric-coated microtablet enzyme preparations in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 1994; 19: 191–7
Sinaasappel M, Swart GR, Hoekstra JH, et al. Double blind, cross over study to prove the equivalence of Creon 10,000 minimicrospheres versus Creon 8000 microspheres in patients with cystic fibrosis [poster 536]. Pediatr Pulmonol 1998; Suppl. 17: 358
Patchell CJ, Smyth RL, Bush A, et al. Creon 10,000 minimicrospheres versus Creon 8,000 microspheres preference study [poster 157]. Neth J Med 1999; 54Suppl. 64: S64
Morrison G, Morrison JM, Redmond AOR, et al. Comparison between a standard pancreatic supplement and a high enzyme preparation. Aliment Pharmacol Ther 1992; 6; 549–55
Chazalette JP. A double blind placebo controlled trial of a pancreatic enzyme formulation (Panzytrat 25,000) in the treatment of impaired lipid digestion in patients with cystic fibrosis. Drug Invest 1993; 5: 274–80
Bowler IM, Wolfe SP, Owens HM, et al. A double blind lipase for lipase comparison of a high and standard pancreatic enzyme preparation in cystic fibrosis. Arch Dis Child 1993; 68: 227–30
Friesen C, Prestidge C. Comparison of a high strength pancreatic enzyme preparation and a standard strength preparation in cystic fibrosis. Adv Ther 1995; 12: 236–44
Taylor CJ, McGaw J, Ghosal S, et al. Evaluation of Creon 25,000 compared to standard lipase pancreatic enzyme supplementation in cystic fibrosis patients. Isr J Med Sci 1996; 32: S220
Robinson PJ, Natoli G. Comparison of high-dose and standard dose pancreatic enzyme capsules in children with cystic fibrosis. Aust J Hosp Pharm 1998; 28: 160–4
Durie PR, Kalnins D, Ellis L. Uses and abuses of enzyme therapy in cystic fibrosis. J R Soc Med 1998; 91Suppl. 34: 2–13
Gavin J, Ellis J, Dewar AL, et al. Dietary fibre and the occurrence of gut symptoms in cystic fibrosis. Arch Dis Child 1997; 76: 35–7
Collins CE, O’Loughlin EV, Henry RL. Fat gram target to achieve high energy intake in cystic fibrosis. J Pediatr Child Health 1997; 31: 142–7
Anthony H, Collins CE, Davidson G, et al. Pancreatic replacement therapy in cystic fibrosis: Australian guidelines. J Paediatr Child Health 199; 35: 125–9
Rubinstein S, Moss R, Lewiston N. Constipation and meconium ileus equivalent in patients with cystic fibrosis. Pediatrics 1986; 78: 473–9
Malfroot A, Dab I. New insights into gastrointestinal reflux in cystic fibrosis by longitudinal follow-up. Arch Dis Child 1991; 66: 1339–45
Heine RG, Button BM, Olinsky A, et al. Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis. Arch Dis Child 1998; 78: 44–8
Ledson MJ, Tran J, Walshaw MJ. Prevalence and mechanisms of gastro-oesophageal reflux in adult cystic fibrosis patients. JR Soc Med 1998; 91: 7–9
Lloyd-Still JD. Cystic fibrosis, Crohn’s disease, biliary abnormalities and cancer. J Pediatr Gastroenterol Nutr 1990; 11: 434–7
Gross V, Schoelmerich J, Denzel K, et al. Relapsing pancreatitis as initial manifestation of cystic fibrosis in a young man without pulmonary disease. Int J Pancreatol 1989; 4: 221–8
Behrens R, Lang T, Keller KM, et al. Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial. Arch Dis Child 1999; 81: 68–70
Valetta EA, Mastella G. Incidence of coeliac disease in a cystic fibrosis population. Acta Paediatr Scand 1989; 78: 784–5
Colombo C, Battezzati PM, Strazzabosco M, et al. Liver and biliary problems in cystic fibrosis. Semin Liver Dis 1998; 18: 227–35
Hill SM, Phillips AD, Mearns M, et al. Cow’s milk sensitive enteropathy in cystic fibrosis. Arch Dis Child 1989; 64: 1251–5
Chamarthy LM, Reinstein LJ, Schnapf B, et al. Desensitisation to pancreatic enzyme intolerance in a child with cystic fibrosis. Pediatrics 1998; 102: E13
Lowden J, Bhal GK, Ryley HC, et al. Maintenance of growth in cystic fibrosis patients, despite reduction of pancreatic enzyme supplementation. Arch Dis Child 1998; 78: 377–8
Graham DY. Pancreatic enzyme replacement: the effect of antacids and cimetidine. Dig Dis Sci 1982; 27: 485–90
Cox KL, Isenberg JN, Osher AB, et al. The effect of cimetidine on maldigestion in cystic fibrosis. J Pediatr 1979; 94: 488–92
Chalmers DM, Brown RC, Miller MG, et al. Influence of long-term cimetidine as an adjuvant to pancreatic enzyme therapy in cystic fibrosis. Acta Paediatr Scand 1985; 74: 114–7
Kalnins D, Stewart C, Ellis L, et al. Does the addition of bicarbonate to an enzyme microsphere preparation improve efficacy? Pediatr Pulmonol 1998; Suppl. 17: 355
Durie PR, Bell L, Linton W, et al. Effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis. Gut 1980; 21: 778–86
Gow R, Bradbear R, Francis P, et al. Comparative study of varying regimens to improve steatorrhoea and creatorrhoea in cystic fibrosis: effectiveness of an enteral coated preparation with and without antacids and cimetidine. Lancet 1981; II: 1071–4
Heijerman HG, Lamers CB, Dijkman JH, et al. Ranitidine compared with the dimethylprostaglandin E2 analogue enprostil as adjunct to pancreatic enzyme replacement in adult cystic fibrosis. Scand J Gastrenterol 1990; 178 Suppl.: 26–31
Heijerman RG, Lamers CB, Bakker W, et al. Improvement of fecal fat excretion after addition of omeprazole to pancrease in cystic fibrosis is related to residual exocrine function of the pancreas. Dig Dis Sci 1993; 38: 1–6
Hendriks JJE, Wesseling GJ, Forget P, et al. Lansoprazole therapy in young CF patients improved fat absorption, bone mineral content and hyperinflation. Neth J Med 1999; 54 Suppl.: S68
Robinson PJ, Sly PD, Smith AL. Effect of misoprostol on fat malabsorption in cystic fibrosis. Arch Dis Child 1988; 63: 1081–2
Smith LJ, Lacaille F, Lepage G, et al. Taurine decreases fecal fatty acid and sterol excretion in cystic fibrosis: a randomized double blind trial. Am J Dis Child 1991; 145: 1401–4
Sack J, Blau H, Goldfarb D, et al. Hyperuricosuria in cystic fibrosis patients treated with pancreatic enzyme supplements. Isr J Med Sci 1980; 16: 417–9
Wiersbitzky S, Ballke EH, Wolf E, et al. Uric acid serum concentrations in CF children after pancreatic enzyme supplementation. Padiatrie Grenzgebiete 1989; 28: 171–3
Couper R, Lichtman S, Cleghorn G, et al. Serum immunoglobulin G directed against porcine trypsin in pancreatic insufficient cystic fibrosis patients receiving pancreatic enzyme supplements. Pancreas 1991; 6: 558–63
Lee J, Ip W, Durie P. Is fibrosing colonopathy an immune mediated disease? Arch Dis Child 1997; 77: 66–70
Lipkin GW, Vickers DW. Allergy in cystic fibrosis nurses to pancreatic extract. Lancet 1987; I: 392
Twarog FJ, Weinstein SF, Khaw K-T, et al. Hypersensitivity to pancreatic extracts in parents of patients with cystic fibrosis. J Allergy Clin Immunol 1997; 59: 35–40
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Littlewood, J.M., Wolfe, S.P. Control of Malabsorption in Cystic Fibrosis. Paediatr Drugs 2, 205–222 (2000). https://doi.org/10.2165/00128072-200002030-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00128072-200002030-00005