Cystic fibrosis

Cystic Fibrosis (CF), also called Mucoviscidosis, is an autosomal, recessive, hereditary diseaseof the exocrine glands. It affects the lungs, sweat glandsand the digestive system. It causes chronic respiratory and digestive problems.

Symptoms

The first manifestation of CF is sometimes meconium ileus, occurring in 16% of infants who develop CF. [1]

Other symptoms of CF manifest during early childhood. Both lungsand pancreasproduce abnormally viscous mucus. This mucus begins to build up and starts to clog the opening to the pancreas and the lungs. The mucus in the lungs can become a growth medium for bacteria, resulting in chronic respiratory infections and eventual permanent damage to the lung tissue. A chronic and loose sounding cough is common in people with CF. These thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food. Frequent and foul smelling stools are often an early sign of CF along with fatty oil that is visible in the stool. This can compromise growth and overall nutrition if proper treatment to aid digestion is not utilized early in life. As lung function deteriorates, CF patients can develop pulmonary hypertensionand eventually cor pulmonale. Death usually occurs from severe infection, pneumonia, or heart failure.

The disease can be diagnosed by symptoms such as a high salt concentration in a baby's sweat (via sweat test) or by genetic testing. Prior to genetic testing, a sweat test was the gold standard for diagnosis of CF. The disease can also be diagnosed prenatally through chorionic villus samplingor amniocentesis.

History and statistics

Cystic fibrosis was first described as a disease in the late 1930s by Dorothy Hansine Andersen. It is the most common genetic disease among people with European ancestry. Approximately one in every 25 people of European descent is a carrier of one of the cystic fibrosis mutations, having one normal gene and one CF gene. Since cystic fibrosis is recessive, both copies of the gene have to be CF genes to cause the symptoms that occur in about 1 in every 2500 children. The high incidence of this lethal gene can be explained by the fact that CF carriers, who don't show any symptoms, enjoy some protection against cholera, since the extreme water loss in the intestines is prevented. More recently, evidence suggests CF genes could give protection against typhoid fever. People from areas where cholera and typhoid fever are not problems show a much lower incidence of CF. Genetic counselingand genetic testingis recommended for families who may be carriers of cystic fibrosis.

In 1988, the first mutation for CF, ΔF508, was discovered by Francis Collins, Lap-Chee Tsuiand John R. Riordanon the seventh chromosome of the human genome. Research has subsequently found over 1000 different mutations that may cause CF, however ΔF508 accounts for approximately 70% of CF patients in Europe(this percentage varies regionally).

Biological causes

Cystic fibrosis is exclusively heritable as both parents must carry the recessive genes for a child to acquire the disease. At the genetic level, cystic fibrosis is most often the result of an in-frame deletion of three base pairs in the DNA. Cystic fibrosis results from the production of an abnormal form of a protein called cystic fibrosis transmembrane conductance regulator(CFTR). CFTR functions in transporting chloride ionsacross epithelial cellsfound in the lungand intestinaltract. In CF patients, CFTR does not function properly, causing accumulation of ions inside epithelial cells. Since water follows ions by osmosis, this results in water depletion and viscous mucuson the surface of alveoli. The most common CFTR proteinabnormality is a mutation termed ΔF508, which is characterized by the deletion of the DNAbasepair sequence at chromosomelocation 7q31.1-31.2 that codes for a single amino acid, phenylalanine.

Recent medical research is beginning to show that an imbalance of essential fatty acidsmay play a role in cystic fibrosis. Tissue samples from both mice, and more recently humans, with CF show an excess of arachidonic acid(AA) and a deficiency of docosahexaenoic acid(DHA). Research has also indicated that healthy individuals with one copy of the CF geneand one copy of the normal gene have fatty acidlevels in between those of CF patients and people with no CFTR gene mutations. Further research is needed to show how this is linked to the CFTR gene defect and what implications this may have on treatment of cystic fibrosis.

The ΔF508 mutation is estimated to be up to 52,000 years old. Numerous hypotheses have been put forward as to why this recessive lethal mutation has persisted and spread in the human population. With the discovery that choleratoxin requires CFTR to function properly, it was hypothesized that carriers for cystic fibrosis benefited from resistance to cholera and other diarrhoeas (Gabriel 1994). Results of in vivostudies in mice and humans have not confirmed this hypothesis (Cuthbert 1995, Hogenauer 2000). Intact CFTR has also been found to be essential for the entry of Salmonella typhiinto cells (Pier 1998), suggesting that carriers for cystic fibrosis might be resistant to typhoid fever. No in vivo study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are endemic, is not immediately explicable.

Complications

Cross-infection

In the past, CF patients often participated in summer "CF Camps" and other recreational gatherings. However, concern for cross-infection with Pseudomonas aeruginosa, MRSA, Burkholderia cepacia, and other bacteria have largely ended these social events. These infections thrive in the thick mucus of CF patients' lungs and cause complications and possibly death. Therefore CF patients who do not have a certain bacteria type cannot meet with those who do. Because of this risk CF patients must remain in isolation during hospital stays, and special precautions must be taken. This risk previously caused many CF clinics to recommend that CF patients live in isolation and never meet. However recently these views have been changed because of the possible psychological problems this may cause; instead CF patients are encouraged to exercise caution, avoid direct physical contact, and possibly wear surgical masks.

Digestion

In addition to pulmonary infections, most people with CF also have problems with digestion, particularly the digestion of fats. This leads to malabsorption and difficulty gaining and maintaining weight, which in turn affects overall health. This is due to the abnormally sticky mucus that blocks the release of digestive enzymesfrom the pancreas. Pancreatic insufficiency is treated with supplemental enzymes. Usually water-miscible forms of the fat-soluble vitaminsA, D, E, and K are required as the decreased fat absorption can lead to deficiencies of these vitamins.

Diabetes

CF patients also have an increased incidence of diabetes mellitusbecause of the pancreatic blockage. The chronic blocking causes the Islets of Langerhansto degrade over time and decrease insulinproduction, causing hyperglycemia. There is also evidence that patients with CF become more resistant to the insulin that is produced. This can be triggered by infections or treatment with corticosteroids.

Fertility

At least 97% of men with CF are sterile due to the absence of vas deferens. There are new technologies that are offering hope to men with CF who desire to father a child since spermis present. This would involve aspiration and In vitro fertilization. Having a discussion with a fertilityspecialist would be helpful in those cases. Additionally, men who do not have cystic fibrosis but are born with congenital absence of the vas deferens have an increased risk being carriers of the CF gene.

Women with CF may also have impaired fertility, as thicker cervical mucus may reduce the likelihood of conception. In the presence of thicker mucus it makes it harder for natural conception to occur.

Other complications

Many CF patients, to some degree, experience the widening of the tips of their fingers, known as "clubbing". The condition affects fingers and toes, and results in the tip of the digit being round and enlarged. This can also be seen in people with COPDor severe heart disease.

Since people with CF are prone to poor absorption of nutrients, osteoporosiscan occur in early adulthood due to low bone density. It is important for people with CF to have regular DEXAscans to measure bone density and begin treatment if needed. When diagnosed early, treatment can help prevent more serious complications.

Some CF patients have hearing lossas a side effect of long-term use of the -mycin / -micingroup of drugs such as Vancomycinor Tobramycin, which are used to combat lung infections. Although this side-effect is well-known and understood, often doctors must prescribe the antibiotics anyways to keep the patient alive and healthy, and the hearing loss must be considered a trade-off.

Treatment

Image:CF Treatment.jpg

Daily chest physiotherapy and aerosol breathing treatments are very commonly prescribed for CF treatment. Typical physical therapy involves manual chest percussion (pounding), positive pressure techniques and/devices or possibly using a device such as the ThAIRapy Vestor the Intrapulmonary Percussive Ventilator(IPV) to achieve the same effect: loosening of the thick mucus. Aerosolized medicines commonly given include albuterol, ipratropium bromideand Pulmozymeto loosen secretions and decrease inflammation. It was found that CFers who surf were healthier; consequently, some hospitals use a nebulised 6%-8% Saline solution on those CFers who do not have asthma to loosen the secretions. Inhaled aminoglycosideantibioticsare sometimes given to fight infections.

CF patients are typically hospitalized somewhat regularly, often every 6 months depending on the severity of the case. Patients often have intravenousantibiotics through a PICCline , Central Line or chest port.

Earlier approaches to diabetes treatment among CF patients generally did not address long-term effects because of the short CF life expectancy. However due to improving treatment of CF patients and their resulting longer lifespan, it is increasingly common to address diabetes symptoms that are not immediately harmful. As maintaining body weight is important for CF patients, a typical diabetic diet is not feasible and therefore insulin doses are instead adjusted to fit the typical high-calorie/high-fat CF diet.

Due to advances in medical treatment, the median life expectancy of a newborn with cystic fibrosis increased from 4 years (in the 1960s) to 32 years today. It is not unheard of to have patients, or PWCF (Person with Cystic Fibrosis) reaching ages of 40 or 50+. Modern treatment now includes the intake of digestionenzymes, nutritional supplements, percussion and postural drainage of the lungs, improved antibiotics and inhalation of aerosols containing medication. A few attempts at gene therapywere initially successful, but failed to produce acceptable long-term results.

Aerobic exerciseis of great benefit to people with CF. Due to the severity of coughing and the subsequent spitting up of phlegmmost CF patients are unwilling to, or are unable to exercise in public areas. Walking, riding in a forest, or swimming in a river provides a better alternative to exercising in public. These activities give the CFer the privacy to cough and clear their lungs of phlegm, and they don't have to worry about disturbing any other person who has not had experience with a Cystic Fibrosis patient. Exercising privately also has the added benefit of limiting exposure to other people and/or exercise equipment that can hold MRSA, B. cepacia, Pseudomonas, etc.

Some cystic fibrosis patients go on to have a single or double lung transplant.

Notable people with cystic fibrosis

• Lisa Bentley, Canadian super smiler and Ironman triathlete [2]
• Christopher Davies, Southern Redbackscricketer.[3]
• Gunnar Esiason, son of Americanfootballlegend Boomer Esiason.
• Bob Flanagan, Americanwriter, poet, performance artist, and comic.
• Frankie Abernathy, from the San Diego Season(2004) of The Real World.
• Andrew Simmons, Britishprofessional wrestler.
• Bill Williams, software developer
• Alice Martineau, British singer-songwriter and model [4]
• Grégory Lemarchal, French singer and winner of the show Star Academy.
• Alexandra Deford, Daughter of sports writer Frank Deford, subject of Deford's book Alex: Life Of A Child

References

• Gabriel SE, Brigman KN, Koller BH, Boucher RC, Stutts MJ. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science1994;266:107-9. PMID 7524148.
• Wiuf C. Do delta F508 heterozygotes have a selective advantage? Genet Res 2001;78:41-7. PMID 11556136.
• Steve Conway. Jan, 2001. Seacroft and St James's University Hospitals, Leeds, UK. Pregnancy and fertility
• Laura Bachrach, M.D 1994 Osteopenia and Osteoporosis in CF Patients
• McCallum, Theresa J., Jeff M. Milunsky, et. al. Fertility in Men With Cystic Fibrosis

External links

• CF World Wide
• Cystic Fibrosis Foundation
• Canadian Cystic Fibrosis Foundation
• Recent medical research at the Cystic Fibrosis Foundation
• UK Cystic Fibrosis Trust
• GeneTests GeneReview on Cystic Fibrosis
• Cystic Fibrosis Australia Inc
• Cystic Fibrosis HopeSource foundation, Ireland
• A story on CF research
• Cystic-L - Cystic Fibrosis Information and Support
• Ask James about Cystic Fibrosis
• CF 4 Christians Information and Support
• Pulmozyme - A Treatment for Cystic Fibrosis
• Cystic Fibrosis Information and Resources
• Cystic Fibrosis WebRing
• Norma Kennedy Plourde's CF Resource
• Description of Cystic Fibrosisfrom the Wellcome Trust
• Cystic Fibrosis Male Infertility
• Breath4CF a site funding and encouraging NZ pwcf into physical exercisecs:Cystická fibróza

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It uses material from the http://en.wikipedia.org/wiki/Cystic+fibrosis Wikipedia article Cystic fibrosis.