Cystic fibrosis (also known as CF, mucoviscoidosis, or mucoviscidosis) is a hereditary disease that affects mainly the exocrine (mucus) glands of the lungs, liver, pancreas, and intestines, causing progressive disability due to multisystem failure.
Thick mucus production, as well as a less competent immune system, results in frequent lung infections. Diminished secretion of pancreatic enzymes is the main cause of poor growth, fatty diarrhea and deficiency in fat-soluble vitamins. Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF.
Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing. Newborn screening tests are increasingly common and effective. The diagnosis of CF may be confirmed if high levels of salt are found during a sweat test, although some false positives may occur.
There is no cure for CF, and most individuals with cystic fibrosis die young: many in their 20s and 30s from lung failure. However, with the continuous introduction of many new treatments, the life expectancy of a person with CF is increasing. Lung transplantation is often necessary as CF worsens.
Cystic fibrosis is one of the most common life-shortening, childhood-onset inherited diseases. In the United States, 1 in 3900 children are born with CF. It is most common among Europeans and Ashkenazi Jews; one in twenty-two people of European descent are carriers of one gene for CF, making it the most common genetic disease in these populations. Ireland has the highest rate of CF carriers in the world (1 in 19).
CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and mucus. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene can produce a functional CFTR protein. Therefore, CF is considered an autosomal recessive disease.
Causes:
In cystic fibrosis, a defective gene alters a protein that regulates the normal movement of salt (sodium chloride) in and out of cells. This results in thick, sticky secretions in the respiratory and digestive tracts, as well as in the reproductive system. It also causes increased salt in sweat.
The affected gene, which is inherited from a child's parents, is a recessive gene. With recessive genes, children need to inherit two copies of the gene, one from each parent, in order to have the disease. If children inherit only one copy, they won't develop cystic fibrosis, but will be carriers and possibly pass the gene to their own children.
If two people who carry the defective gene conceive a child, there's a 25 percent chance the child will have cystic fibrosis, a 50 percent chance the child will be a carrier of the cystic fibrosis gene, and a 25 percent chance the child will neither have the disease nor be a carrier.
People who carry the cystic fibrosis gene are healthy and have no symptoms — they may be carriers and not know it. Although parents often blame themselves when a child is born with cystic fibrosis, it's important to remember that the causes of cystic fibrosis are not the result of anything a parent consciously does.
The role of fatty acids
Some experts believe that an imbalance of essential fatty acids may play a role in cystic fibrosis. People with cystic fibrosis appear to have excessively high levels of arachidonic acid and a deficiency of another fatty acid, docosahexaenoic acid.
Healthy people who carry one cystic fibrosis gene have fatty acid levels midway between those of people with cystic fibrosis and people with no genetic mutations for the disease. But the exact nature of the relationship between fatty acid levels and the gene defect that causes cystic fibrosis isn't clear.
Symptoms:
The specific signs and symptoms of cystic fibrosis can vary with the severity of the disease. For example, one child with cystic fibrosis may have respiratory problems but not digestive problems, while another child may have both. In addition, the signs and symptoms of cystic fibrosis may vary with age.
Signs and symptoms in newborns
In some newborns, the first sign may be a blockage of their intestines (meconium ileus). This occurs when meconium — tarry, greenish-black stools normally passed by an infant during the first day or two after birth — becomes so thick it can't move through the intestines. Other signs in newborns may include:
* Failure to grow.
* Bulky and greasy stools (steatorrhea).
* Frequent respiratory infections.
Signs and symptoms in children and young adults
Cystic fibrosis symptoms in children and young adults may include:
* Salty taste to the skin. People with cystic fibrosis tend to have higher than normal amounts of salt (sodium chloride) in their sweat. This may be one of the first signs parents notice because they can taste the salt when they kiss their child.
* Blockage in the bowels.
* Foul-smelling, greasy stools.
* Delayed growth.
* Thick sputum. It's easy for parents to overlook this sign because young children tend to swallow their sputum rather than cough it up.
* Coughing or wheezing.
* Frequent chest and sinus infections with recurring pneumonia or bronchitis.
* Protrusion of part of the rectum through the anus (rectal prolapse). This is often caused by stools that are difficult to pass or by frequent coughing.
* Enlargement or rounding (clubbing) of the fingertips and toes. Although clubbing eventually occurs in most people with cystic fibrosis, it also occurs in some people born with heart disease and other types of lung problems.
Cystic fibrosis may also be accompanied by:
* Growths (polyps) in the nasal passages.
* Cirrhosis of the liver due to inflammation or obstruction of the bile ducts.
* Displacement of one part of the intestine into another part of the intestine (intussusception) in children older than age 4.
Diagnosis:
Sweat test
The standard diagnostic test for cystic fibrosis is a sweat test, which measures the amount of sodium or chloride in a person's sweat. During the procedure, a small amount of an odorless sweat-producing chemical is applied to a small area on the arm or leg. An electrode attached to the area stimulates a very weak and painless electric current, causing a tingling or warm feeling. After several minutes, sweat is collected from the stimulated area and sent to a laboratory for analysis.
The sweat test is performed on two separate samples, which are usually taken on one occasion, to ensure that a false-positive or false-negative result hasn't occurred. A consistently high level of salt indicates cystic fibrosis. This test doesn't show whether someone has a mild or severe case of the disease, however, and it can't predict how well someone with cystic fibrosis will do.
In addition, the sweat test may not always be useful in newborns. That's because babies may not produce enough sweat for a reliable diagnosis in the first month of life. For this reason, doctors usually don't perform a sweat test until an infant is at least several months old.
Other tests
If your newborn has signs and symptoms of cystic fibrosis, your doctor may perform a genetic analysis of a blood sample to confirm the diagnosis. Tests may also help determine the extent and severity of cystic fibrosis. Among these are tests to measure how well the lungs, pancreas and liver are working.
Because cystic fibrosis is an inherited disease, your doctor may suggest testing the brothers and sisters of a child with cystic fibrosis, even if they show no signs or symptoms. Other family members, especially first cousins, also may want to be tested. In most cases family members can be screened with a sweat test, although in some cases genetic blood testing may be appropriate.
Treatment:
Many treatments exist for the symptoms and complications of cystic fibrosis. The main goal is to prevent infections, reduce the amount and thickness of secretions in the lungs, improve airflow, and maintain adequate calories and nutrition.
To accomplish these objectives, cystic fibrosis treatment may include:
Antibiotics- Newer antibiotics may more effectively fight the bacteria that cause lung infections in people with cystic fibrosis. Among these are aerosolized antibiotics that send medication directly into airways. One of the major drawbacks of long-term use of antibiotics is the development of bacteria that are resistant to drug therapy. In addition, using antibiotics over a long period of time can lead to fungal infections of the mouth, throat and respiratory tract.
Mucus-thinning drugs- When your white blood cells attack bacteria in your airways, DNA in your cells is released, making the mucus in your airways even thicker. The aerosolized drug dornase alfa (Pulmozyme) is an enzyme that fragments DNA, making mucus thinner and easier to cough up. Side effects of the drug may include airway irritation and sore throat.
Bronchodilators- Use of medications such as albuterol, which can be delivered by an inhaler or a nebulizer, may help keep open the bronchial tubes by clearing thick secretions.
Bronchial airway drainage- People with cystic fibrosis need a way to physically remove thick mucus from their lungs. This is often done by manually clapping with cupped hands on the front and back of the chest — a procedure that's best performed with the person's head over the edge of the bed so that gravity helps clear the secretions.
In some cases an electric chest clapper, known as a mechanical percussor, is used. An inflatable vest that vibrates at high frequency also can help people with cystic fibrosis cough up secretions. Many adults and children with pulmonary cystic fibrosis need to have bronchial airway drainage at least twice a day for 20 to 30 minutes. Older children and adults can learn to do this themselves, especially if they use mechanical aids, such as vests and percussors. Young children need the aid of parents, grandparents or older siblings.
Oral enzymes and better nutrition- Cystic fibrosis can cause you to become malnourished because the pancreatic enzymes needed for digestion don't reach your small intestine, preventing food from being absorbed. As a result, you may need many more calories than you otherwise would. Supplemental high-calorie nutrition, special fat-soluble vitamins and enteric-coated oral pancreatic enzymes can help you maintain or even gain weight.
Lung transplantation- Your doctor may suggest lung transplantation if you have severe breathing problems, life-threatening pulmonary complications or increasing resistance to antibiotics used to treat lung infections. Whether you're a good candidate for the procedure depends on a number of factors, including your overall health, certain lifestyle factors and the availability of donor organs. Because both lungs are affected by cystic fibrosis, both need to be replaced. If your chest isn't large enough to hold two adult donor lungs, your surgeon is likely to use two lower lobes contributed by two living donors. However it's performed, lung transplantation is a major operation and may lead to serious complications, especially post-surgical infections.
Pain relievers- Ibuprofen (Advil, Motrin, others) may slow lung deterioration in some children with cystic fibrosis.
Future treatments:
Major progress in cystic fibrosis research came in 1989, when researchers identified the genetic mutation that causes the disease. Since then scientists have been studying ways to insert copies of the normal gene into cells of the respiratory tract.
The challenge has been to find a reliable way to deliver the normal genetic material to affected cells that line the airways. Several methods have been developed as delivery systems, including using modified viruses, fat capsules (liposomes) and synthetic vectors. Clinical trials are under way to test the effectiveness of these delivery systems.
Other research is focusing on modifying the protein that the cystic fibrosis gene produces. This may help normalize the movement of salt and water in and out of the cells.
Thick mucus production, as well as a less competent immune system, results in frequent lung infections. Diminished secretion of pancreatic enzymes is the main cause of poor growth, fatty diarrhea and deficiency in fat-soluble vitamins. Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF.
Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing. Newborn screening tests are increasingly common and effective. The diagnosis of CF may be confirmed if high levels of salt are found during a sweat test, although some false positives may occur.
There is no cure for CF, and most individuals with cystic fibrosis die young: many in their 20s and 30s from lung failure. However, with the continuous introduction of many new treatments, the life expectancy of a person with CF is increasing. Lung transplantation is often necessary as CF worsens.
Cystic fibrosis is one of the most common life-shortening, childhood-onset inherited diseases. In the United States, 1 in 3900 children are born with CF. It is most common among Europeans and Ashkenazi Jews; one in twenty-two people of European descent are carriers of one gene for CF, making it the most common genetic disease in these populations. Ireland has the highest rate of CF carriers in the world (1 in 19).
CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and mucus. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene can produce a functional CFTR protein. Therefore, CF is considered an autosomal recessive disease.
Causes:
In cystic fibrosis, a defective gene alters a protein that regulates the normal movement of salt (sodium chloride) in and out of cells. This results in thick, sticky secretions in the respiratory and digestive tracts, as well as in the reproductive system. It also causes increased salt in sweat.
The affected gene, which is inherited from a child's parents, is a recessive gene. With recessive genes, children need to inherit two copies of the gene, one from each parent, in order to have the disease. If children inherit only one copy, they won't develop cystic fibrosis, but will be carriers and possibly pass the gene to their own children.
If two people who carry the defective gene conceive a child, there's a 25 percent chance the child will have cystic fibrosis, a 50 percent chance the child will be a carrier of the cystic fibrosis gene, and a 25 percent chance the child will neither have the disease nor be a carrier.
People who carry the cystic fibrosis gene are healthy and have no symptoms — they may be carriers and not know it. Although parents often blame themselves when a child is born with cystic fibrosis, it's important to remember that the causes of cystic fibrosis are not the result of anything a parent consciously does.
The role of fatty acids
Some experts believe that an imbalance of essential fatty acids may play a role in cystic fibrosis. People with cystic fibrosis appear to have excessively high levels of arachidonic acid and a deficiency of another fatty acid, docosahexaenoic acid.
Healthy people who carry one cystic fibrosis gene have fatty acid levels midway between those of people with cystic fibrosis and people with no genetic mutations for the disease. But the exact nature of the relationship between fatty acid levels and the gene defect that causes cystic fibrosis isn't clear.
Symptoms:
The specific signs and symptoms of cystic fibrosis can vary with the severity of the disease. For example, one child with cystic fibrosis may have respiratory problems but not digestive problems, while another child may have both. In addition, the signs and symptoms of cystic fibrosis may vary with age.
Signs and symptoms in newborns
In some newborns, the first sign may be a blockage of their intestines (meconium ileus). This occurs when meconium — tarry, greenish-black stools normally passed by an infant during the first day or two after birth — becomes so thick it can't move through the intestines. Other signs in newborns may include:
* Failure to grow.
* Bulky and greasy stools (steatorrhea).
* Frequent respiratory infections.
Signs and symptoms in children and young adults
Cystic fibrosis symptoms in children and young adults may include:
* Salty taste to the skin. People with cystic fibrosis tend to have higher than normal amounts of salt (sodium chloride) in their sweat. This may be one of the first signs parents notice because they can taste the salt when they kiss their child.
* Blockage in the bowels.
* Foul-smelling, greasy stools.
* Delayed growth.
* Thick sputum. It's easy for parents to overlook this sign because young children tend to swallow their sputum rather than cough it up.
* Coughing or wheezing.
* Frequent chest and sinus infections with recurring pneumonia or bronchitis.
* Protrusion of part of the rectum through the anus (rectal prolapse). This is often caused by stools that are difficult to pass or by frequent coughing.
* Enlargement or rounding (clubbing) of the fingertips and toes. Although clubbing eventually occurs in most people with cystic fibrosis, it also occurs in some people born with heart disease and other types of lung problems.
Cystic fibrosis may also be accompanied by:
* Growths (polyps) in the nasal passages.
* Cirrhosis of the liver due to inflammation or obstruction of the bile ducts.
* Displacement of one part of the intestine into another part of the intestine (intussusception) in children older than age 4.
Diagnosis:
Sweat test
The standard diagnostic test for cystic fibrosis is a sweat test, which measures the amount of sodium or chloride in a person's sweat. During the procedure, a small amount of an odorless sweat-producing chemical is applied to a small area on the arm or leg. An electrode attached to the area stimulates a very weak and painless electric current, causing a tingling or warm feeling. After several minutes, sweat is collected from the stimulated area and sent to a laboratory for analysis.
The sweat test is performed on two separate samples, which are usually taken on one occasion, to ensure that a false-positive or false-negative result hasn't occurred. A consistently high level of salt indicates cystic fibrosis. This test doesn't show whether someone has a mild or severe case of the disease, however, and it can't predict how well someone with cystic fibrosis will do.
In addition, the sweat test may not always be useful in newborns. That's because babies may not produce enough sweat for a reliable diagnosis in the first month of life. For this reason, doctors usually don't perform a sweat test until an infant is at least several months old.
Other tests
If your newborn has signs and symptoms of cystic fibrosis, your doctor may perform a genetic analysis of a blood sample to confirm the diagnosis. Tests may also help determine the extent and severity of cystic fibrosis. Among these are tests to measure how well the lungs, pancreas and liver are working.
Because cystic fibrosis is an inherited disease, your doctor may suggest testing the brothers and sisters of a child with cystic fibrosis, even if they show no signs or symptoms. Other family members, especially first cousins, also may want to be tested. In most cases family members can be screened with a sweat test, although in some cases genetic blood testing may be appropriate.
Treatment:
Many treatments exist for the symptoms and complications of cystic fibrosis. The main goal is to prevent infections, reduce the amount and thickness of secretions in the lungs, improve airflow, and maintain adequate calories and nutrition.
To accomplish these objectives, cystic fibrosis treatment may include:
Antibiotics- Newer antibiotics may more effectively fight the bacteria that cause lung infections in people with cystic fibrosis. Among these are aerosolized antibiotics that send medication directly into airways. One of the major drawbacks of long-term use of antibiotics is the development of bacteria that are resistant to drug therapy. In addition, using antibiotics over a long period of time can lead to fungal infections of the mouth, throat and respiratory tract.
Mucus-thinning drugs- When your white blood cells attack bacteria in your airways, DNA in your cells is released, making the mucus in your airways even thicker. The aerosolized drug dornase alfa (Pulmozyme) is an enzyme that fragments DNA, making mucus thinner and easier to cough up. Side effects of the drug may include airway irritation and sore throat.
Bronchodilators- Use of medications such as albuterol, which can be delivered by an inhaler or a nebulizer, may help keep open the bronchial tubes by clearing thick secretions.
Bronchial airway drainage- People with cystic fibrosis need a way to physically remove thick mucus from their lungs. This is often done by manually clapping with cupped hands on the front and back of the chest — a procedure that's best performed with the person's head over the edge of the bed so that gravity helps clear the secretions.
In some cases an electric chest clapper, known as a mechanical percussor, is used. An inflatable vest that vibrates at high frequency also can help people with cystic fibrosis cough up secretions. Many adults and children with pulmonary cystic fibrosis need to have bronchial airway drainage at least twice a day for 20 to 30 minutes. Older children and adults can learn to do this themselves, especially if they use mechanical aids, such as vests and percussors. Young children need the aid of parents, grandparents or older siblings.
Oral enzymes and better nutrition- Cystic fibrosis can cause you to become malnourished because the pancreatic enzymes needed for digestion don't reach your small intestine, preventing food from being absorbed. As a result, you may need many more calories than you otherwise would. Supplemental high-calorie nutrition, special fat-soluble vitamins and enteric-coated oral pancreatic enzymes can help you maintain or even gain weight.
Lung transplantation- Your doctor may suggest lung transplantation if you have severe breathing problems, life-threatening pulmonary complications or increasing resistance to antibiotics used to treat lung infections. Whether you're a good candidate for the procedure depends on a number of factors, including your overall health, certain lifestyle factors and the availability of donor organs. Because both lungs are affected by cystic fibrosis, both need to be replaced. If your chest isn't large enough to hold two adult donor lungs, your surgeon is likely to use two lower lobes contributed by two living donors. However it's performed, lung transplantation is a major operation and may lead to serious complications, especially post-surgical infections.
Pain relievers- Ibuprofen (Advil, Motrin, others) may slow lung deterioration in some children with cystic fibrosis.
Future treatments:
Major progress in cystic fibrosis research came in 1989, when researchers identified the genetic mutation that causes the disease. Since then scientists have been studying ways to insert copies of the normal gene into cells of the respiratory tract.
The challenge has been to find a reliable way to deliver the normal genetic material to affected cells that line the airways. Several methods have been developed as delivery systems, including using modified viruses, fat capsules (liposomes) and synthetic vectors. Clinical trials are under way to test the effectiveness of these delivery systems.
Other research is focusing on modifying the protein that the cystic fibrosis gene produces. This may help normalize the movement of salt and water in and out of the cells.
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