TREATMENT CYTIC FIBROSIS

The cystic fibrosis treatment is to prevent and control infections in lungs, loosen and remove the thick, sticky mucus from lungs,prevent blockages in intestines and provide adequate nutrition.

Treatment includes digestive enzyme supplements, dietary changes, immunizations, physical therapy, and medications. More recently, some cytic fibrosis patients with terminal lung disease have received lung transplants. Treatment for Cystic Fibrosis Lung Problems Common treatments for lung problems seen in cystic fibrosis may include:

 v  Antibiotics for infections of the airways
v  Chest physical therapy
v  Exercise

Other treatments for lung problems may include:

v    Oxygen

v    Lung transplantation.

In addition for children can be given salt tablets or salt-water solutions. Children with CF usually take extra vitamins.Keeping a child's immunizations (vaccine shots) extremely important to protect them from infections. especially for whooping cough (pertussis), influenza, chickenpox, and measles. child should get a flu shot and a pneumococcal vaccine every year or as recommended by doctor. Keep a record of all child's immunizations.

MEDICATION

Most people with cystic fibrosis have ongoing, low-grade lung infections, which may require hospitalization. Antibiotics are the primary treatment for cystic fibrosis.

The different types of antibiotics used as cystic fibrosis treatments include:

Ø  Oral antibiotics for relatively mild airway infections
Ø  Inhaled antibiotics, such as tobramycin, which may be used alone or with oral antibiotics
Ø  Intravenous antibiotics for severe infections or when none of the oral antibiotics work
Ø  Antibiotics, such as azithromycin (Zithromax), that also reduce inflammation.

If have cystic fibrosis,  may be given several different types of antibiotics. The type of antibiotic doctor recommends will depend on:

A number of medications can help people with CF.
Ø  enzyme pills to be taken before eating to help digest food
Ø  anti-inflammatories to slow the deterioration of the lungs
Ø  antibiotics to treat or prevent lung infections
Ø  inhaled medications to make breathing easier
Ø  multivitamins (especially vitamins A, D, E, and K) to ensure proper nutrition for normal growth and development
Ø  The strains of bacteria involved
Ø  How serious  condition is
Ø  previous history of antibiotic use.

DIAGNOSTIC TEST

1)    SWEAT TEST

The sweat test is considered the “gold standard” for the diagnosis of CF. Though many centers may perform sweat test “screenings”, the only acceptable procedure for diagnosis is called quantitative pilocarpine iontophoresis.. There are two sweat test methods approved by the Cystic Fibrosis Foundation ; the Gibson-Cooke procedure and the Wescor Macroduct  Sweat Collection System. Both methods stimulate localized sweating on the forearm or on the thigh using a chemical called pilocarpine. Sweat is then collected on filter paper or gauze (Gibson-Cooke) or in microbore tubing (Macroduct®). The sweat collected is weighed and analyzed for chloride concentration. Results are interpreted as follows:

RESULT :

Chloride Concentration for Infants (birth to 6 months)	Result
0 - 29 mmol/L	Cystic fibrosis is unlikely
30 - 59 mmol/L	Intermediate
≥ 60 mmol/L	Indicative of cystic fibrosis

Chloride Concentration for Infants (older than 6 months) children and adults	Result
0 - 39 mmol/L	Cystic fibrosis is unlikely
40 - 59 mmol/L	Intermediate
≥ 60 mmol/L	Indicative of cystic fibrosis

2)    NEWBORN SCREENING

   Newborn screening is completed on all infants by collecting blood samples, usually from a heelstick, shortly after birth. These blood samples are collected as blood spots that are allowed to dry on a special filter paper. The dried blood spots are then tested for a variety of diseases. Every state performs newborn screening testing for infants, but not all states include a test for CF

Obtaining blood from newborn screening

3)    CFTR MUTATION ANALYSIS

All individuals carry two copies of the CFTR gene, one inherited from the father and one inherited from the mother. To have CF, an individual must have two abnormal copies, or mutations of the CFTR gene. If the individual has only one mutation, he or she will not be affected with CF, but will be a “carrier”. Because carriers have one abnormal CFTR gene, they can pass this gene to their offspring, placing their children at risk for CF.

More than 1,000 CFTR mutations have been identified. In white populations, the most common mutation is called F508del (previously called ∆F508), and occurs in approximately 70 percent of those CF.

Commercially available mutation screening panels detect most cases of CF. The accuracy of the test will depend on how many mutations are tested and the ethnic origin of the patient (see table below). However, because there are so many described mutations and many more that have not been identified, some patients with clinical features of CF may have only one or no CFTR gene mutations identified by mutation analysis.

Type of clases (CFTR) mutation

Detection of Cystic Fibrosis by Mutation Analysis

25 Mutation Test
Ethnic Group	Detection Rate
Caucasian	90%
African American	69%
Hispanic	57%
Ashkenazi Jewish	97%
Other	unknown

4)    PRENATAL SCREENING

5)OTHER TEST

1)    SPUTUM CULTURE

To detect the presence of bacteria Pseudomonas

2)    X-ray test

3)    LUNG FUNCTION TEST

To measure inspiratory,expiratory capacity, respiratory rate, and blood oxygen level

SIGNS AND SYMPTOMS

Cystic fibrosis signs and symptoms vary, depending on the severity of the disease. Even in the same person, symptoms may worsen or improve as time passes. Some people may not experience symptoms until adolescence or adulthood.

People with cystic fibrosis have a higher than normal level of salt in their sweat. Parents often can taste the salt when they kiss their children. Most of the other signs and symptoms of cystic fibrosis affect the respiratory system and digestive system. However, adults diagnosed with cystic fibrosis are more likely to have atypical symptoms, such as recurring bouts of inflamed pancreas (pancreatitis), infertility and recurring pneumonia.

Respiratory signs and symptoms

The thick and sticky mucus associated with cystic fibrosis clogs the tubes that carry air in and out of your lungs. This can cause signs and symptoms such as:

·         A persistent cough that produces thick mucus (sputum)

·         Wheezing

·         Breathlessness

·         Exercise intolerance

·         Repeated lung infections

·         Inflamed nasal passages or a stuffy nose

Digestive signs and symptoms

The thick mucus can also block tubes that carry digestive enzymes from your pancreas to your small intestine. Without these digestive enzymes, your intestines aren't able to completely absorb the nutrients in the food you eat. The result is often:

·         Foul-smelling, greasy stools

·         Poor weight gain and growth

·         Intestinal blockage, particularly in newborns (meconium ileus)

·         Severe constipation

Frequent straining while passing stool can cause part of the rectum  the end of the large intestine  to protrude outside the anus (rectal prolapse). When this occurs in children, it may be a sign of cystic fibrosis. Parents should consult a physician knowledgeable about cystic fibrosis. Rectal prolapse in children may sometimes require surgery. Rectal prolapse in children with cystic fibrosis is less common than it was in the past, which may be due to earlier testing, diagnosis and treatment of cystic fibrosis.

Other problems

People with cystic fibrosis can also experience a number of other problems, including:

• sinusitis
• nasal polyps
• thin, weakened bones (osteoporosis) – this can occur as a result of repeated infections, poor growth, lack of physical activity and malnutrition
• swelling and pain in the joints (arthritis or arthralgia) from late childhood
• difficulty conceiving children – most men with cystic fibrosis are unable to have children naturally (although some fertility treatments may still work) because the tubes that carry sperm don't develop correctly; women can become pregnant, however
• liver problems caused by the tiny bile ducts in the liver becoming blocked by mucus
• leaking of small amounts of urine, particularly during coughing fits (stress incontinence)

  

 How Are Genetics Related to Cystic Fibrosis?

The development of cystic fibrosis is caused by genetics. The disease occurs when there is a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is the gene responsible for the movements of negatively charged particles known as chloride ions into and out of cells. 

 The component chloride comes from sodium chloride, which is a common salt present in sweat. The component holds important roles in the cells, including controlling the flow of chloride ions that control the water movement in tissues, a function that results in the production of thin, freely flowing mucus.There are more than 180 known mutations in the CFTR gene that causes cystic fibrosis and disrupt the normal work of the chloride channels. 

Due to the defect, the chloride is unable to properly regulate the flow of chloride ions and water through the cells. Therefore, the cells near the lungs, pancreas, and other organs end up producing thick and sticky mucus instead of the normal watery and slippery substance. Genetics and environmental factors also impact the severity of the disease.

The very existence of 180 known mutations and numerous other unknowns make it difficult to find a cure or define an effective treatment for the disease.Mutations in the CFTR gene cause cystic fibrosis. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. Chloride is a component of sodium chloride, a common salt found in sweat. 

Mode of inheritance and risk of passing on the CF gene

CF has a simple Mendelian autosomal recessive inheritance (figure 2). This means that people with CF have two copies of the mutant CFTR gene, one inherited from each parent. Carriers have one normal and one mutant CFTR gene and their health is not affected because the normal CFTR gene ensures production of enough protein to allow normal cellular function. 

Carriers have a 50% chance of passing their mutant CFTR gene onto their children. When both parents are carriers there is a 25% chance in every pregnancy that the child will have CF, a 25% chance that the child will have two normal CFTR genes and a 50% chance that the child will be a carrier (figure 2).

Figure 2: Simple Mendelian autosomal recessive inheritance. Affected individuals will have two copies of the mutant CFTR gene, one inherited from each parent. 

 The Gene Is Found  

As these studies of chloride transport were progressing, many scientists were engaged in an intense race to find the gene responsible for cystic fibrosis. That effort culminated in 1989, when a large group of collaborators, led by Lap-Chee Tsui and John R. Riordan of the Hospital for Sick Children in Toronto and by Francis S. Collins, then at the University of Michigan and now the Director of the Human Genome Project at NIH, announced it had isolated the gene.

 Aware that the protein product of the gene probably influenced the movement of chloride directly or indirectly, they named the protein the cystic fibrosis transmembrane conductance regulator (CFTR). While searching for the gene, the team also identified an abnormality in the DNA that appeared to account for about 70 percent of cystic fibrosis cases. That aberration, often denoted as the AF508 mutation consists of the deletion of three nucleotides ( DNA building blocks) from the gene. That loss causes the protein product of the gene to lack a single amino acid: phenylalanine at position 508.