Cystic fibrosis

Cystic fibrosis (CF), also called mucoviscidosis, is an autosomal recessive hereditary disease that affects the lungs, sweat glands and the digestive system.

Symptoms

The symptoms of CF usually develop during early childhood. Both lungs and pancreas produce 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. As lung function deteriorates, CF patients develop pulmonary hypertension and eventually cor pulmonale. Death usually occurs from severe infection or heart failure. These thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food.

The disease can be diagnosed by symptoms such as a high salt concentration in a baby's sweat or by genetic testing.

Males are also frequently sterile because of the obstruction or absence of the vas deferens.

History and statistics

Cystic fibrosis (CF) was first described as a disease in the late 1930s. It is the most common genetic disease among people with European ancestry. Approximately one in every 25 people of European descent is a carrier for the cystic fibrosis gene, 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. People from areas where cholera is not a problem show a much lower incidence of CF. Genetic counseling and genetic testing is recommended for families who may be carriers of cystic fibrosis.

In 1988, the gene for CF was discovered by Francis Collins and Lap-Chee Tsui on the seventh chromosome of the human genome.

Biological causes

Cystic fibrosis is heritable as both parents must carry the recessive genes for a child to acquire the disease. At the genetic level, cystic fibrosis is 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 ions across epithelial cells found in the lung and intestinal tract. 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 mucus on the surface of alveolus. The most common CFTR protein abnormality is a mutation termed ΔF508, which is characterized by the deletion of the DNA basepair sequence at chromosome location 7q that codes for a single amino acid, phenylalanine.

Recent medical research is beginning to show that an imbalance of essential fatty acids may 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 gene and one copy of the normal gene have fatty acid levels 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.

Scientists have recently made the hypothesis that cystic fibrosis dates back to a genetic mutation 52,000 years ago, well before any formation of civilization. After this, they questioned why it has been able to survive being eliminated by evolution. They found an answer in the fact that people with one gene for cystic fibrosis are more apt to survive cholera. The people with that trait have half the number of channels as usual and can produce enough water to flush out the toxins made by the cholera bacteria without causing the dehydration and salt loss that is the usual cause of death. Cystic fibrosis also seems to be more common in cooler areas, because people in hot climates would tend to sweat more and lose more salt (needed in the body) in their sweat.

Complications

Cross-infection

CF patients often cannot interact with each other socially due to worries of cross-infection of Pseudomonas, MRSA, Burkholderia cepacia, and other bacteria. 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 enzymes from the pancreas. Pancreatic insufficiency is treated with supplemental enzymes. Usually water-miscible forms of the fat-soluble vitamins A, 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 mellitus because of the pancreatic blockage. The chronic blocking causes the Islets of Langerhans to degrade over time and decrease insulin production, causing hyperglycemia.

Other complications

Cystic fibrosis also causes a defect in the vas deferens causing sterility in approximately 98% of males with the disease. Also, men who were born with congenital absence of the vas deferens have an increased risk to be carriers of CF.

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.

Treatment

Daily chest physiotherapy and aerosol breathing treatments are very commonly prescribed for CF treatment. Typical physical therapy involves manual chest percussion (pounding), or possibly using a device such as the ThAIRapy Vest or the Intrapulmonary Percussive Ventilator (IPV) to achieve the same effect: loosening of the thick mucus. Aerosolized medicines commonly given include albuterol, ipratropium bromide, and Pulmozyme to loosen secretions and decrease inflammation. Inhaled aminoglycoside antibiotics are 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 intravenous antibiotics through a PICC 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. These procedures include the intake of digestion enzymes, nutritional supplements, percussion and postural drainage of the lungs, improved antibiotics and inhalation of aerosols containing medication. A few attempts at gene therapy were initially successful, but failed to produce acceptable long-term results.

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

Notable people with cystic fibrosis

• Bob Flanagan

References

• Gabriel SE, Brigman KN, Koller BH, Boucher RC, Stutts MJ. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science 1994;266:107-9. PMID 7524148.
• Wiuf C. Do delta F508 heterozygotes have a selective advantage? Genet Res 2001;78:41-7. PMID 11556136.

External links

• CF World Wide (http://www.cfww.org/)
• Cystic Fibrosis Foundation (http://www.cff.org)
• Recent medical research at the Cystic Fibrosis Foundation (http://www.cff.org/research/)
• UK Cystic Fibrosis Trust (http://www.cftrust.org.uk)
• GeneTests GeneReview on Cystic Fibrosis (http://www.genetests.org/query?dz=cf)
• Cystic Fibrosis Australia Inc (http://www.cysticfibrosisaustralia.org.au/)
• Cystic Fibrosis HopeSource foundation, Ireland (http://www.cfhopesource.org/)
• A story on CF research (http://www.science.ca/scientists/scientistprofile.php?pID=19)
• Cystic-L - Cystic Fibrosis Information and Support (http://www.cystic-l.org/)
• Ask James about Cystic Fibrosis (http://www.ajcf.com/)
• Pulmozyme - A Treatment for Cystic Fibrosis (http://www.pulmozyme.com/)
• Cystic Fibrosis Information and Resources (http://www.cystic-fibrosis-symptom.com/)
• Cystic Fibrosis WebRing (http://webring.ajcf.com/)
• Norma Kennedy Plourde's CF Resource (http://www3.nbnet.nb.ca/normap/CF.htm)
• Description of Cystic Fibrosis (http://www.wellcome.ac.uk/en/genome/genesandbody/hg06f006.html) from the Wellcome Trustda:cystisk fibrose

de:Mukoviszidose es:Fibrosis quística he:סיסטיק פיברוזיס nl:mucoviscidose sv:Cystisk fibros fr:Mucoviscidose