Cystic+Fibrosis

=**__Cystic Fibrosis__**=

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people worldwide //(Cystic Fibrosis Foundation),// with the greatest population being Caucasians, occurring in 1 in 2,500 to 3,500 =====

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and instead of acting as alubricant, it plugs up tubes, ducts, and passageways (//NHLBI//). The mucus that obstructs airways can lead to severe breathing problems, bacterial infections, chronic coughing, wheezing, =====

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and inflammation. The buildup of the mucus overtime will cause infections and will ultimately result in permanent lung damage (//NHLBI//). Those with CF may also notice digestive problems as well. The thick, sticky mucus interferes with the proper function of the pancreas by blocking the ducts. These blocked ducts don’t allow insulin and enzymes to be released. When insulin isn’t being released, blood sugar levels aren’t properly controlled in a natural way, and other means of obtaining that insulin may be needed. When the enzymes of the pancreas aren’t released, the enzymes aren’t able to reach the digestive system such as the intestines to help with digestion. CF was once considered to be a fatal disease, with nearly most with CF not living past their teens. Today with improved technology and treatments, many people with CF live well into adulthood. Those who live with CF continually experience medical problems with their respiratory, digestive, and reproductive systems. It is found that most men with CF are infertile because mucus blocks the tubes that carry sperm, causing them to not develop properly. Infertility is less common with women who live with CF, but it does happen //(Genetics Home Reference).// =====

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In order to inherit cystic fibrosis your mother and father must both be carries of the gene. The guilty gene that causes CF is called CFTR. There are three possible genomic outcomes associated with CF. A child who inherits the CFTR gene from the mother and the father will have cystic fibrosis. A child who receives one normal CFTR gene from one parent and a defective CFTR gene will be carrier. The last possibility would be the child that receives the normal gene from both parents, neither being a carrier nor having cystic fibrosis. Mathematically speaking, if both parents are carriers there is a 25% chance of having cystic fibrosis, 50% chance of being a carrier, and a 25% chance of not having CF or being a carrier(NHLBI).=====

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The image listed above shows the overall inheritance pattern of cystic fibrosis. As we can see in the picture both mom and dad are CF carriers, represented by the color purple. The possible offspring are then listed below. The blue child is the unaffected child, receiving normal genes. The two purple children containing both a normal and a CF gene are carriers. The red child affected with cystic fibrosis, received both CFTR genes from both parents.=====

**__Treatment__**
People who are affected with cystic fibrous need to maintain a regular treatment routine in order to maintain optimal lung function and to live a healthy life. Treatments for CF most commonly involve techniques that trigger strong coughs to help aid to loosen the mucus from airways (//Cystic Fibrosis Foundation//). Other therapies for CF also include drug therapies such as inhalation medications and antibiotics.

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Clearing the airways is the main goal for cystic fibrous treatments. One of the airway clearance techniques is called “postural drainage and percussion. In order to perform this routine, the person with cystic fibrous stands, sits, or lies in a position that will help loosen up mucus. Once the person is in position, their chest and back is pounded or clapped on to make the mucus even looser to make it easier to produce strong coughs. There are devices such as a mechanical vest or a device in which patients blow into that shakes the mucus lose.=====

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Most commonly we see the use of inhalation medications which are more time efficient and easily done. Inhalation drugs are mists that are made in a mist form that include liquid medicines. The liquid medication is given through a nebulizer that is attached to a small air compressor that blows air into the nebulizer cup making the mist. A mask or mouthpiece is then used for the inhalation of the drug. Some of the medications can also be given to patients in the form of metered dose inhalers. Inhaled medications that are used to treat CF are known as mucolytics which thin the mucus allowing it to be easier to cough out(//Cystic Fibrosis Foundation//). There are two types of nebulizers, the most common is the breah-enhanced nebulizer as it is more efficient compared to the unvented nebulizers. Some research has been done that has come up with a jet nebulizer that allows for the liquid medicine to be produced only during inspiration (Leung, Louca & Coates, 2004). The difference with the jet nebulizers to the unvented and breath-enhanced nebulizers is the inspiration flow into the devices (Leung, Louca & Coates, 2004).=====



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Cystic fibrosis (CF) is an autosomal genetic disease that is recessive. The disease is caused by a mutation in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) (Bobadilla, Macek, Fine, & Farrell, 2002).The wild type CFTR gene is about 250,000 base pairs long with 27 exons and is 1480 amino acids long. The gene is found in region q31.2 on the long arm of human chromosome 7 (Bownas, 2003). The structure of the CFTR gene can be seen in Figure 1.=====

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The CFTR regulates ionic balance by letting chloride ions be transported across epithelial cell membranes (Brooker, 2009). The most common mutation on this gene is a three nucleotide deletion at the 508th codon called F508del. This mutation causes a deletion of the phenylalanine residue and terminally causes intracellular processing errors to occur in the CFTR gene. The F508del mutation is responsible for about two-thirds of all CFTR mutations (Bobadilla et al., 2002). The normal CFTR gene synthesizes the CFTR protein and it is transported to the endoplasmic reticulum and Golgi apparatus before being integrated into the cell membrane. When the CFTR protein with the F508del mutation gets to the endoplasmic reticulum, it recognizes the mutation and the protein is not allowed to reach the cell membrane (Bownas, 2003).=====

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Although the F508del mutation is the one most commonly associated with cystic fibrosis, the disease is susceptible to other genetic influences. One of these that can influence the outcome of CF is mannan-binding lectin (MBL). MBL is a recognition molecule of the complement system (functions in host defense) and is encoded by a gene on chromosome 10. MBL modifies the outcome of cystic fibrosis through its binding to important bacteria that cause the symptoms of CF to be increased in severity. Examples are //Pseudomonas aeruginosa// and //Staphylococcus aureus,// which are both opportunistic pathogens that cause airway inflammation and other symptoms that can lead to death. By having high numbers of MBL that can bind to these harmful bacteria, the severity of the symptoms can be reduced (Chalmers, Fleming, Hill, & Kilpatrick, 2011).=====

**Resources:**
Bobadilla, J.L., Macek Jr., M., Fine, J.P., & Farrell, P.M. (2002). Cystic fibrosis: A worldwide analysis of CFTR mutations - correlation with incidence data and application to screening. //Human Mutation, 19,// 575-606.

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Chalmers, J.D., Fleming, G.B., Hill, A.T., & Kilpatrick, D.C. (2011). Impact of mannose-binding lectin insufficiency on the course of cystic fibrosis: A review and meta-analysis. //Glycobiology, 21//(3), 271-282=====

Cystic Fibrosis (2010). Diseases and Conditions. Retrieved from []

Cystic Fibrosis Foundation. (n.d.). //Cystic Fibrosis Foundation//. Retrieved March 29, 2012, from []

Genetics Home Reference. (n.d.). //Cystic Fibrosis//. Retrieved April 1, 2012, from []

Leung, K., Louca, E., & Coates, A. L. (2004). Comparison of Breath-Enhanced to Breath-Actuated Nebulizers for Rate, Consistency, and Efficiency. //Chest//, //126//(5), 1619-1627.

NHLBI: Organization. (n.d.). //What Is Cystic Fibrosis?// Retrieved March 30, 2012, from []