Summary
Cystic fibrosis (CF) is the commonest lethal hereditary disease in Caucasians. The disease involves a gene mutation located at the long arm of chromosome 7, and more than 300 mutations have been identified. CF is a systemic illness affecting the upper respiratory tract and airways, sweat and salivary glands, pancreas, gastrointestinal tract, liver and male reproductive system. The course is highly variable depending on the specific molecular abnormalities in the mutant gene.
The current approach to therapy now involves the use of: (i) chest physiotherapy; (ii) bronchodilators when there is evidence of airways hyperreactivity; (iii) oral and intravenous antibiotics for acute pulmonary exacerbations and aerosolised antibiotics for prevention; (iv) recombinant human deoxyribonuclease I (dornase alfa) to promote airways clearance; (v) amiloride to improve sputum viscosity; (vi) pancreatic enzyme replacement therapy along with nutritional support and supplements; (vi) vitamins; and (vii) ursodeoxycholic acid in selected patients.
The use of antiprotease and anti-inflammatory agents has been shown to be useful in preventing the damage secondary to chronic lung infection. In patients with severely impaired lung function, lung transplantations have been performed with good results. Finally, it seems probable that lung disease in CF patients will be ameliorated or prevented in the future with early gene therapy, using vectors such as recombinant adenoviruses, adeno-associated virus, lipofection or retrovirus. However, this will require extensive basic and clinical research.
Similar content being viewed by others
References
Tsui LC, Buchwald M, Barker D, et al. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science 1985; 230: 1054–7
Kerem BS, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 245: 1066–80
Kerem E, Corey M, Kerem BS, et al. The relation between genotype and phenotype in cystic fibrosis — analysis of the most common mutation (delta F508). N Engl J Med 1990; 323: 1517–22
Knowles MR, Stutts MJ, Spock A. Abnormal ion permeation through cystic fibrosis respiratory epithelium. Science 1983; 221: 1067–70
Anderson MP, Gregory RF, Thompson S, et al. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 1991; 253: 202–5
Maclusky I, Levison H. Cystic fibrosis. In: Chernick V, editor. Kendig’s disorders of the respiratory tract in children. 5th ed. Philadelphia: Saunders, 1990
Williams MT. Chest physiotherapy and cystic fibrosis. Chest 1994; 106: 1872–82
Bauer ML, McDougal J, Schoumacher RA. Comparison of manual and mechanical chest percussion in hospitalized patients with cystic fibrosis. J Pediatr 1994; 124: 250–4
Konstan MW, Stern RC, Doershuk CF. Efficacy of the flutter device for airway mucus clearance in patients with cystic fibrosis. J Pediatr 1994; 124: 689–93
Zach MS, Oberwaldner B, Forche G, et al. Bronchodilators increase airway instability in cystic fibrosis. Am Rev Respir Dis 1985; 131: 537–43
Pattishall EN. Longitudinal response of pulmonary function to bronchodilators in cystic fibrosis. Pediatr Pulmonol 1990; 9: 80–5
Sanchez I, Holbrow J, Chernick V. Acute bronchodilator response to a combination of beta-adrenergic and anticholinergic agents in patients with cystic fibrosis. J Pediatr 1992; 120: 486–8
Sanchez I, De Koster J, Holbrow J, et al. The effect of high doses of inhaled salbutamol and ipratropium bromide in stable cystic fibrosis patients. Chest 1993; 104: 842–6
Shennib H, Adoumie R, Noirclerc M. Current status of lung transplantation for cystic fibrosis. Arch Intern Med 1992; 152: 1585–8
Ramsey BW, Astley SJ, Aitken ML, et al. Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am Rev Respir Dis 1993; 148: 145–51
Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med 1994; 331: 637–42
Knowles MR, Church ML, Waltner WE, et al. A pilot study of aerosolyzed amiloride for the treatment of lung disease in cystic fibrosis. N Eng J Med 1990; 322: 1189–94
Knowles MR, Clarke LL, Boucher RC. Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Eng J Med 1991; 325: 533–8
Schidlow DV, Taussig LM, Knowles MR. Cystic Fibrosis Foundation consensus conference report on pulmonary complication of cystic fibrosis. Pediatr Pulmonol 1993; 15: 187–98
Meyer K, Lewandoski JR, Zimmerman JJ, et al. Human neutrophil elastase and elastase/α1-antiprotease complex in cystic fibrosis. Am Rev Resp Dis 1991; 144: 580–5
McElvaney NG, Hubbard RC, Berrier P, et al. Aerosol α1-antitrypsin treatment for cystic fibrosis. Lancet 1991; 337: 392–4
Vogelmeier Buhl R, Hogt RF, et al. Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. J Appl Physiol 1990; 69: 1843–8
Rosenstein BJ, Eigen H. Risks of alternate day prednisone in patients with cystic fibrosis. Pediatrics 1991; 87: 245–6
Konstan MW, Byard PJ, Hoppel CL, et al. Effect of high-dose Ibuprofen in patients with cystic fibrosis. N Engl J Med 1995; 332: 848–54
Miller AD. Human gene therapy comes of age. Nature 1992; 357: 455–60
Auriel DT, Agarwal S, Romer MU, et al. Gene transfer to respiratory epithelial cells via the receptor-mediated endocytosis pathway. Am J Respir Cell Mol Biol 1992; 6: 247–55
Rosenfeld MA, Yoshimura Trapnell et al. In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell 1992; 68: 143–55
Forstner G, Durie PR. Cystic fibrosis. In: Walker WA, Durie PR, Hamilton JR, et al., editors. Pediatric gastrointestinal disease. Philadelphia: Decker Inc., 1991: 1179–95
Therapeutic approaches in cystic fibrosis: memorandum from ajoint WHO/ICF(M) A meeting. Bull WHO 1994; 72: 341-52
Ramsey BW, Farrell PM, Pencharz P, et al. Nutritional assessment and management in cystic fibrosis: a consensus report. Am J Clin Nutr 1992; 55: 108–16
Pencharz PB, Durie PR. Nutritional management of cystic fibrosis. Annu Rev Nutr 1993; 13: 111–36
Forstner G. Pancreatic disease in cystic fibrosis. In: Durie P, editor. Cystic fibrosis symposium. Marietta, GA: Solvay Pharmaceuticals, 1992
Heijerman HG. New modalities in the treatment of exocrine pancreatic insufficiency in cystic fibrosis. Neth J Med 1992; 41: 105–9
Darling PB, LePage G, LeRoy et al. Effect of taurine supplements on fat absorption in cystic fibrosis. Pediatr Res 1985; 19: 578–82
Smyth 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
Goldberg DM, Durie PR. Biochemical tests in the diagnosis of chronic pancreatitis and in the evaluation of pancreatic insufficiency. Clin Biochem 1993; 26: 253–75
Park RW, Grand RJ. Gastrointestinal manifestations of cystic fibrosis: a review. Gastroenterology 1981; 81: 1143–61
Colombo C, Apostolo MG, Assaisso M, et al. Liver disease in cystic fibrosis. Neth J Med 1992; 41: 119–22
Galabert Montet JC, Lengrand D, et al. Effects of ursodeoxycholic on liver function in patients with cystic fibrosis and chronic cholestasis. J Pediatr 1992; 121: 138–41
Colombo C, Crosignani A, Assaisso M, et al. Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a doseresponse study. Hepatology 1992; 16: 924–30
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sanchez, I., Guiraldes, E. Drug Management of Noninfective Complications of Cystic Fibrosis. Drugs 50, 626–635 (1995). https://doi.org/10.2165/00003495-199550040-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199550040-00005