CYSTIC FIBROSIS

Disease

Brief Summary

Cystic fibrosis or CF is an inherited disease caused by mutations in the cystic fibrosis transmembrane conductance regulator or CFTR gene, which is located on chromosome 7. This gene is very large and complex with more than 1,800 different mutations found to cause the condition as well as provides instructions for the CFTR protein.

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Child affected by Cystic Fibrosis

Frequency

It occurs in 1 in 2,500 to 3,500 white newborns. Cystic fibrosis is less common in other ethnic groups, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.

Inheritance

Cystic fibrosis (CF) is a genetic disorder that is inherited in an autosomal recessive manner. An individual must inherit two copies of the defective CF gene, one from each parent, in order to develop the condition.

Brief Summary

History of Disease

It was in 1938 that American pathologist Dr. Dorothy Andersen provided the first description for Cystic Fibrosis in medical literature, initially calling it “cystic fibrosis of the pancreas.” This was based on her autopsy findings of children who died of malnutrition. During this era, other physicians referred to the disease as “mucoviscidosis,” which strongly suggested the presence of thickened mucus. In a New York City emergency room, during a heatwave in the summer of 1948, Dr. Paul di Sant’Agnese observed dehydrated infants. He discovered that the sweat of children with CF had abnormally high concentrations of salt. The protein defect was finally described in the 1980s and the responsible gene was also identified.

Pathogenesis

Achondroplasia is caused by a mutation in the FGF3 gene in chromosome 4 at 4p 16.3. This mutation causes a decreased production of fibroblast growth factor receptor 3 which is crucial in the conversion of cartilage into bone which is vital in the proper development of a person. This mutation is inherited in an autosomal dominant manner. More than 80 percent of people with achondroplasia have parents with normal characteristics and are born with achondroplasia due to a recent (de novo) gene modification (mutation).

Pathogenesis

Cystic fibrosis or CF is an inherited disease caused by mutations in what is known as the cystic fibrosis transmembrane conductance regulator or CFTR gene which is located on chromosome 7. This gene is very large and complex with more than 1,800 different mutations found to cause the condition as well as provides instructions for the CFTR protein.

Cystic fibrosis is inherited in an autosomal recessive pattern, which means that unlike sex-linked disorders, it is not inherited solely from the mother or father. Rather, the condition is inherited when an individual receives a mutated copy of the CFTR gene from both parents. When an individual has only one copy of the mutated gene, the functional gene is able to compensate for the defect and the individual is healthy. In the case that both parents are carriers for the mutated gene, there is a 25% chance of them passing the disease on to their child, a 50% chance that the child will be a carrier for the condition and a 25% chance that their child will neither have CF nor carry the gene for it. The most common reasons why the mutated gene may remain undetected in many individuals could either be because they never have children with another CF carrier or they never have any offspring with CF.

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Mutated gene that causes Cystic Fibrosis

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Inheritance pattern of Cystic Fibrosis

Symptoms

salty-tasting skin

frequent coughing, sometimes with

phlegm

shortness of breath or wheezing

poor weight gain despite excessive appetite

frequent lung infections including pneumonia or bronchitis

greasy, bulky stools

nasal polyps

infertility

Social Concerns

Because of the discovery of the CF gene, opportunities for clinical advancements in the detection and management of the disease have been provided. With these opportunities though, a variety of complex social and ethical dilemmas also present themselves. The most controversial issue would be that of the screening for cystic fibrosis and gene therapy.

Newborn screening for cystic fibrosis remains controversial largely because the implementation of such is more of a scientific decision than it is a resolution of conflicting normative values that underlie a number of policy issues related to the condition. It touches on the subject of morality which may concern a more conservative population. Additionally, gene therapy or the insertion of a normally functioning gene into deficient host cells using a suitable vector is a potential treatment or cure for cystic fibrosis. This does, however, have many potential and actual risks. Because of this, many propose that evidence of efficacy in adults should be demonstrated before any trials are conducted in children to strengthen the visibility of its benefits. Many serious diseases in adults, such as cystic fibrosis, have their onset in childhood. If early treatment provides greater hopes of benefit, children may be more appropriate targets for gene therapy in CF than adults. It may be unethical to deny them access to properly constructed, ethically approved clinical trials from which they might benefit. Ultimately, it always boils down to the child’s capability to comprehend the situation and their consent as well.

Clinical Trials

Treatment

At present, there is unfortunately still no definite cure for cystic fibrosis. However, many treatments exist for the symptoms and complications of this disease. The main goals of treatment for someone with cystic fibrosis are to prevent and treat infections, keep the airways and lungs as clear as possible, and maintain adequate calories and nutrition. Available clinical treatment would include the following:

Medications that target gene mutations

This includes a relatively new medication that combines three drugs to treat the most common genetic mutation causing CF.

Antibiotics and anti-inflammatory medications

These are also used to treat and prevent lung infections as well as lessen the swelling in the airways in the lungs.

Mucus-thinning drugs

This would include hypertonic saline and can help a patient improve their lung function.

Bronchodilators

These are otherwise known as inhaled medication and can also aid in keeping the airways open by relaxing the muscles around the bronchial tubes.

Oral pancreatic enzymes

These can help your digestive tract absorb nutrients and acid-reducing medications will assist these pancreatic enzymes in working better.

Stool softeners

These may be used to prevent constipation or bowel obstruction.

Specific drugs for diabetes or liver disease

When needed, these may also be recommended.

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Treatment for Cystic Fibrosis

Clinical Trials

Title:

Phase II Study of Digitoxin to Treat Cystic Fibrosis

Intervention Phase:

The phase II of the clinical trials admits digitoxin to stable Cystic Fibrosis (CF) patients to test the drug’s effectiveness on interleukin 8 (IL-8) and neutrophil count in induced sputum.

Procedure:

Stable adult cystic fibrosis patients are randomly assigned to three treatments: 0.05 mg tabs of digitoxin, 0.1 mg tabs of digitoxin, and placebo, wherein each patient receives one dose daily for 28 days.

Goal:

The primary goal of the study is to assess the effectiveness of digitoxin on Il-8 in induced sputum in stable cystic patients.

Further details at:

https://clinicaltrials.gov/ct2/show/NCT00782288

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