Cystic+Fibrosis

Cystic Fibrosis (CF)
Cystic fibrosis, also known as CF. It is an autosomal recessive disorder that causes a build up of mucus in the lungs and pancreas. The build up of mucus causes chronic bacterial and fungal infections, which eventually leads to a shortened life (apx. 40 years). CF It is caused by a mutation on the 7th chromosome, usually a deletion in the f508 gene. This causes a misfolded Cystic Fibrosis transmembrane conductance regulator protein.

Figure 1.http://cyfbin.weebly.com/cyfb.html. A normal vs. mutant CFTR channel


 * Root Causes **

Two mutation in 7th chromosome à misfolded CFTR protein à cannot utilize ATP properly in Cl-/SCN- ion channel à Dysregulation of ions à lack of movement of water à build up of mucus outside cell in lungs, pancreas, gastrointestinal track à good place for bacteria to hide à chronic infections especially in the lungs

**Affected Tissues-** Epithelial Cells

 * =====Lungs=====
 * =====Pancreas=====
 * =====Liver=====
 * =====Intestine=====
 * Reproductive

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The first mutation to cause CF is said to have occurred around 3,000 BCE due to migration, gene mutations, and new conditions in nourishment5. By 1905, Karl Landsteiner had described CF, which was connected to celiac disease and bronchiectasis in 1936 by Guido Fanconi. Dorothy H. Andersen wrote “Cystic Fibrosis of the Pancreas and Its relation to Celiac Disease”6 in 1938 which confirmed the diagnosis of Fanconi. In 1985 it was found that only one locus existed for CF; using this knowledge, Francis Collins found the first mutation in 1988 on the seventh chromosome, leading to over 1000 different mutations being discovered. Lap-Chee Tsui lead a team that discovered the gene responsible for CF in 1989, resulting in CF becoming the first genetic disorder to be figured out by the process of reverse genetics7. People famous for their struggle include Kenneth Keith Kallenbach (Howard Stern Show), Eva Markvoort (subject of //65 Redroses//), Laura Rothenberg (//My So Called Lungs//), and possibly Frédéric Chopin8.=====

**Common Symptoms1**

 * =====Very salty-tasting skin=====
 * =====Persistent coughing (with phlegm)=====
 * =====Wheezing=====
 * =====Shortness of Breath=====
 * =====Excessive appetite but poor weight gain=====
 * =====Greasy, bulky stool=====
 * Club Fingers

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There are many treatments for CF, depending on age and mutation. Kalydeco™, a pill for the G551D mutation, helps the defective CFTR protein work to allow salt and fluid to move into the airways. Airway clearance techniques help reduce the severity of lung infections and improve lung function. While there are many different techniques, one is where patients with CF sit, stand, or lie while the chest and back is pounded or clapped to help shake the mucus loose. Inhaled medications are often used, mainly in an aerosol compound given via nebulizer, due to the rapid transport to the affected airways. To prevent inflammation in the lungs, ibuprofen is often used to slow the rate of lung function deterioration. A common antibiotic, azithromycin, can also be employed to preserve and improve lung function while minimizing the number of hospital stays. Implanted devices, ports, allow repeated access to the bloodstream for regular admission of drugs, while patients with CF need special diets to ward off infection and sometimes undergo “tube-feeding”. Antioxidant treatments have recently been applied as well due to the lack of natural antioxidants provided in CF lungs.=====

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Since CF research receives funding, new advances are always being found. Recently, 37 teenagers were studied against those without cystic fibrosis to determine the effect on the heart. It was determined that there is right ventricular enlargement in CF patients, which may progress to heart failure. Regardless that this shows direct involvement of the disease on the heart, there is not significant evidence to prove it9. To track the decline of lung function due to CF, a study was completed which showed that adolescents are at a higher risk of sharply decreasing lung function than younger patients or adults. It was also seen that on average adults who were “middle aged” lost 2% of their forced expiratory volume per year10. As mentioned above, antioxidant treatments are used as a standard treatment to increase healthiness. A study completed in 2011 gave patients an antioxidant-rich multivitamin supplement twice daily and found that vitamin A levels were normal and subjects experienced modest improvements in weight, pulmonary function, and β-carotene levels11. These increases are positive and show the benefits of antioxidants in the diet of a CF patient. While there is much research being done on the disease, much more is yet to occur. =====

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Also, currently there is research being done on the microbiomes in the lungs and gut. Scientists are studying more closely the complex polymicrobial communities that develop in the airways of a person with CF, thus increasing their knowledge of respiratory tract infections. This type of research is important because although it may not help cure CF it will allow for better diagnoses, screening and treatment against dangerous and life threatening bacterial infections. (Zhao). =====

**References**

 * 1) =====WHO (2004). Molecular genetic epidemiology of cystic fibrosis. //World Health Organization//.=====
 * 2) =====Bownas, J. (2003). CFTR: The gene associated with cystic fibrosis. Oak Ridge National Laboratory. []=====
 * 3) =====Cystic Fibrosis Foundation (2012). Therapies for Cystic Fibrosis. []=====
 * 4) =====Wetmore, D. R., Joseloff, E., Pilewski, J., Lee, D. P., Lawton, K. A., Mitchell, M.W., Milburn, M.V., Ryals, J. A., Guo, L. (2010) Metabolomic profiling reveals biochemical pathways and biomarkers associated with pathogenesis in cystic fibrosis cells. Journal of Biological Chemistry, 285: 30516-30522.=====
 * 5) =====Busch, R. (1990) On the history of cystic fibrosis. //Acta Univ Carol Med (Praha)//, 36 (1-4): 13-15=====
 * 6) ===== Andersen, D. H. (1938) Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study//.// //Am J Dis Child//, 56 :344–399 =====
 * 7) ===== Pearson, H. (2009) Human genetics: One gene, twenty years. //Nature//, 460: 164-169 =====
 * 8) ===== Cystic Fibrosis Trust Forum. (2010) Famous people living with cf. [] =====
 * 9) =====Baño-Rodrigo, A., Salcedo-Posadas, A., Villa-Asensi, J. R., Tamariz-Martel, A., Lopez- Neyra, A., Blanco-Iglesias, E. (2012) Right ventricular dysfunction in adolescentswith mild cystic fibrosis. //J. Cystic Fibrosis//, 11 (4): 274-280.=====
 * 10) =====Liou, T.G., Elkin, E. P., Pasta, D. J., Jacobs, J. R., Konstan, M. W., Morgan, W. J., Wagener, J. S. (2010) Year-to-year changes in lung function in individuals with cystic fibrosis. //J. Cystic Fibrosis//, 9 (4): 250-256.=====
 * 11) =====Sagel, S. D., Sontag, M. K., Anthony, M. M., Emmett, P., Papas, K. A. (2011) Effect on an antioxidant-rich multivitamin in cystic fibrosis. //J. Cystic Fibrosis//, 10 (1): 31- 36.=====
 * 12) Zhao, Elborn, LiPuma, Airway infection and the microbiome. Cystic Fibrosis. June2014. 64. 32-46