Cystic fibrosis

From Freepedia

Cystic fibrosis
ICD-10 code: E84
ICD-9 code: 277

Cystic fibrosis (CF), also called mucoviscidosis, is an autosomal recessive hereditary disease of the exocrine glands. It affects the lungs, sweat glands and the digestive system. It causes chronic respiratory and digestive problems.

Contents

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. 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 hypertension and 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 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 sampling or amniocentesis.

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 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. 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 first mutation for CF, ΔF508, was discovered by Francis Collins and Lap-Chee Tsui on 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 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 7q31.1 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.

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 cholera toxin 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 vivo studies 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 typhi into 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, 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 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.

Fertility

98% of men with CF are sterile due to complications from mucus plugs that cause obstructions at birth or the absence of vas deferens. There are new technologies that are offering hope to men with CF who desire to father a child since sperm is present. This would involve aspiration and In vitro fertilisation. Having a discussion with a fertility specialist would be helpful in those cases. Additionally, men who were born with congenital absence of the vas deferens have an increased risk to be carriers of CF.

Women with CF may have some difficulty with conception due to thicker cervical mucus. In the presence of thicker mucus it makes it harder for natural conception to occur.

Other complications

Image:Cf clubbing.jpg

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 COPD or severe heart disease.

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

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 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. It was found that CF sufferers that surf were healthier; consequently, some hospitals use a nebulised 6%-8% Saline solution on those CFs that do not have asthma to loosen the secretions. 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 , 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. 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

References

External links

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