A Millennial view of Cystic Fibrosis
Languages of publication
Although only identified as a distinct disease in the 1930s, it was soon apparent that Cystic Fibrosis (CF) had been present, but unrecognised, in European populations for many years – perhaps even centuries  . Within a decade of the early descriptions, the autosomal recessive nature of this genetic disease had been clarified, and its clinical features had been expanded. Secondary nutritional deficiencies complicated the underlying condition: the first clear description of CF as “a new disease”, which included a speculation about its genetic basis (because there were 2 pairs of sibs in the case series) was published as Vitamin A deficiency in children . The diagnosis was most often made at autopsy. When it was suspected in life, the diagnostic tests used included duodenal intubation to obtain fluid which would show impaired tryptic digestion of the coating of X-Ray film in CF children, and measurement of vitamin A in the blood. Some nutritional improvement could be expected with simple, rather inefficient pancreatic enzyme preparations, but it was not until mid-century that antibiotics began to treat pulmonary infections effectively. As a young doctor in the 1950s I soon became aware that the median age at death for affected children was about one year, and most died before reaching school age.
- 1. Busch R. On the history of Cystic Fibrosis. Acta Univ Carol Med. (Praha) 1990;36:13-15.
- 2. Blackfan KD, Wolbach SD. Vitamin A deficiency in infants. J Pediatr. 1933;3:679-706.
- 3. di Sant’Agnese PA, Darling MD, Perera G, Shea E. Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas. Clinical significance and relationship to the disease. Pediatrics 1953;12:549-563.
- 4. Gibson LE, Cooke RE. Test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 1959;23:545-549.
- 5. Quinton PM, Bijman J. Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis. New Eng J Med 1985;(19)308: 1185-1189.
- 6. Kerem B-S, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 245:1073-1080.
- 7. Riordan JR, Rommens JM, Kerem B-S, et al. Identification of the cystic fibrosis gene: cloning and characterisation of complementary DNA. Science. 1989;245:1066-1073.
- 8. Mateu E, Calafell F, Ramos MD, et al. Can a place of origin of the main cystic fibrosis mutations be identified? American Journal of Human Genetics 2002;70:257-264.
- 9. Cuppens H, Macek M. The Molecular Genetic epidemiology of Cystic Fibrosis. Report of a joint meeting of WHO/ ECFTN/ICF(M)A?ECFS. WHO/HGN/CF/WG/04.02 Geneva, WHO 2004.
- 10. Bombieri C, Claustres M, de Boeck K, Derichs N, et al. Recommendations for the classification of diseases as CFTR-related disorders. Journal of Cystic Fibrosis 2011; 10(Suppl 2):S86-S102.
- 11. Dodge JA, Lewis PA, Stanton M, Wilsher J. Cystic Fibrosis mortality and survival in the United Kingdom 1947-2003. Eur Respir J. 2007;29:522-526.
- 12. Dodge JA, Lewis PA. Cystic fibrosis is no longer an important cause of childhood death in the United Kingdom. Arch Dis Child. 2005;90:547.
- 13. 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):583-591.
- 14. Frederiksen B, Koch C, Høiby N. Antibiotic treatment of initial colonisation with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatric Pulmonology. 1997;23: 330-335.
- 15. Mahadeva R, Webb K, Westerbeek RC, Carroll NR, et al. Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross-sectional study. Brit Med J. 1998; 316:1771-1775.
- 16. Gawande A. The Bell Curve. What happens when patients find out how good their doctors really are? (Based on comparative survival data between US CF centres held by the Cystic Fibrosis Foundation). The New Yorker Nov. 23, 2004.
- 17. Cohen-Cymberknoh M, Shoseyov D, Kerem E. Managing Cystic Fibrosis: Strategies that increase life expectancy and improve quality of life. Am J Respir Crit Care Med. 2011; 183:1463-1471.
- 18. Schechter MS, Shelton BJ, Margolis PA, et al. The association of socioeconomic status with outcomes in cystic fibrosis patients in the United States. Am J Respir Crit Care Med. 2001;163(6):1331-1337.
- 19. Yoshimura K, Iizuka S, Anzai C, et al. Diffuse panbronchiolitis is closely associated with mutations of the CFTR gene. Am J Respir Crit Care Med. 2000;161:A77.
- 20. Hernadez-Jimenez I, Fischman D. Colon cancer in cystic fibrosis patients: Is this a growing problem? Journal of Cystic Fibrosis 2008;7:343-346.
- 21. 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;105:122-129.
- 22. Amaral MD, Kunzelmann K. Molecular targetting of CFTR as a therapeutic approach to cystic fibrosis. Trends in Pharmacological Sciences. 2007;28:334-341.
- 23. Wilschanski M. Novel therapeutic approaches for cystic fibrosis. Discovery Medicine. 2013;15:127-133.
- 24. Lubamba B, Lecourt H, Lebeque P, et al. Preclinical evidence that sildenafil and tadalafil activate chloride transport in cystic fibrosis. Am J Respir Crit Care Med. 2008;177: 506-515.
Publication order reference