- Cystic fibrosis: causes
- Cystic fibrosis:genetic basis
- Cystic fibrosis: symptoms and course
- Cystic fibrosis: diagnosis and monitoring
- Cystic fibrosis: monitoring
- Cystic fibrosis: treatment
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Cystic fibrosis is a genetic disease that is most often associated with the respiratory system - abnormalities in lung function are observed in as many as 90 percent of patients. But cystic fibrosis also affects the digestive and reproductive systems, making the symptoms of cystic fibrosis very diverse and inconclusive. What is cystic fibrosis, how is it diagnosed and what are the treatment options?
Cystic fibrosis(cystic fibrosis, Latinmucoviscidosis , cystic fibrosis, CF, mucoviscoidosis, mucoviscidosis) is an incurable disease caused by genetic. It is caused by a mutation of the chloride channel gene, which is found in the membranes of cells that make up many organs. This defect changes the composition of the secretions produced by the cells.
The symptoms of cystic fibrosis concern mainly those systems in which there is a continuous production of mucus secretions, that is:
- respiratory system
- digestive system
- reproductive system
The course of the disease is progressive, and the most serious complications usually involve the lungs.
Unfortunately, there is no fully effective causal treatment for cystic fibrosis yet, but research into new therapies is being conducted all over the world.
Cystic fibrosis: causes
Cystic fibrosis is caused by a genetic defect in the CFTR protein that forms a chloride channel in the plasma membrane. The role of this channel is to allow chloride ions to pass through the membrane. In mucus-producing cells, the ejection of these ions to the outside of the cell causes the water molecules to be dragged along. As a result, the mucus becomes thinner and less sticky.
In cystic fibrosis, the composition of the mucus is disturbed and its consistency is thick and sticky, which leads to clogging of the outgoing ducts. This pathology affects both glandular cells located in the walls of the bronchi and in other organs (pancreas, liver, digestive tract, genital tract).
In the cells of the sweat glands, the altered channel prevents the back uptake of chloride ions into the cells. This results in a significant increase in the amount of chloride in the sweat. The determination of their concentration is the basis of the so-called the sweat test, which is one of the tests performed when cystic fibrosis is suspected.
Cystic fibrosis:genetic basis
Cystic fibrosis in the European population occurs with the frequency of about 1/2500 births.
The inheritance of this disease is autosomal recessive. This means that both boys and girls can get sick.
The disease manifests itself when a mutation occurs in both alleles (variants) of the gene encoding the chloride channel.
If only one variant is mutated, the person is a he althy carrier of the mutation.
The risk of developing the disease in a child of two he althy carrier parents is 1: 4.
There are many different mutations in the chloride channel gene responsible for cystic fibrosis. Depending on the type of the gene defect, the disease takes forms of different severity.
Cystic fibrosis: symptoms and course
- Cystic fibrosis and the respiratory system
Abnormalities in the functioning of the respiratory system affect over 90% of patients with cystic fibrosis, and at the same time lead to the most serious complications of this disease.
Patients suffer from chronic cough, progressive dyspnoea, and reduced exercise tolerance.
Thick and sticky mucus remains in the airways and blocks their lumen, limiting the penetration of immune cells and drugs.
Such conditions favor the multiplication of bacteria and the development of infections.
Recurrent pneumonia and bronchitis are often caused by bacteria of the genusPseudomonas aeruginosa , which are highly resistant to antibiotics.
Cystic fibrosis is often associated with polyps and chronic inflammation in the nasal cavity and paranasal sinuses. Typically there is a purulent runny nose, fever and characteristic headaches.
Chronic inflammation of the airways leads to a gradual weakening and destruction of their walls, which results in a progressive widening of their lumen (bronchiectasis) and pulmonary fibrosis.
Increasing pulmonary resistance causes hypertrophy and overload of the right ventricle, known as the cor pulmonale.
The components of chronic hypoxia are the so-called stick fingers. The final stage of lung damage is advanced respiratory failure.
- Cystic fibrosis and the digestive system
The symptoms of cystic fibrosis on the part of the digestive system concern both the parenchymal organs (pancreas, liver) and the lumen of the digestive tract (intestine).
Some of the earliest symptoms of cystic fibrosis may be prolonged jaundice and delayed meconium release by the newborn. Cloggingintestines through thick meconium can cause neonatal meconium obstruction.
Intestinal obstruction caused by hard stools in elderly patients is called Distal Intestine Obstructive Syndrome (DIOS).
Symptoms include stool retention, vomiting and abdominal pain, and a characteristic pattern of fluid levels on an abdominal X-ray.
Blocking the pancreatic ducts by thick mucus traps digestive enzymes, which gradually destroy the pancreatic tissue and lead to recurrent inflammation. Pancreatic enzymes do not reach their target site (small intestine) and cannot perform their functions properly. This causes disorders of digestion and absorption of fats and carbohydrates.
Nutritional deficiencies slow down the growth and development of the child.
Reducing protein absorption can lead to generalized edema.
Lack of fat absorption prevents absorption of soluble fats - vitamin A, vitamin D, vitamin E and vitamin K.
Undigested fats are the cause of the so-called fatty stools - they have a greasy texture and a foul odor.
The progressive destruction of the pancreas may result in endocrine failure and decreased insulin production.
The consequence of these disorders is secondary diabetes. It is estimated that about 30% of CF patients develop diabetes before the age of 30.
Disturbances in bile secretion and composition lead to the development of gallstone disease. Chronic cholestasis causes secondary damage to the liver and may cause the so-called biliary cirrhosis.
Blocking the flow of bile exacerbates the symptoms of the malabsorption syndrome.
Thick mucus remaining in the intestines causes troublesome stomach pains. As in the respiratory tract, this mucus becomes a breeding ground for bacteria.
Excessive colonization of the small intestine is called bacterial overgrowth syndrome (SIBO syndrome).
- Cystic fibrosis and other organs
Increased mucus density in a woman's genital tract can lead to fertility problems. However, complete infertility affects men more often than women.
A typical disease of the reproductive system accompanying cystic fibrosis in men is congenital aplasia (lack of education) of the vas deferens. Even when the vas deferens are well developed, they can, like other organs, become blocked by thick mucus. Often, a reduction in sperm count and / or motility is also observedsemen.
Excessive s alt loss with sweat leads to electrolyte disturbances, causing changes in the functioning of various organs - muscle weakness, heart rhythm disturbances, lower blood pressure.
Children with cystic fibrosis are especially prone to dehydration
Blood coagulation disorders associated with decreased intestinal absorption of vitamin K are observed in some patients. The worsening of these symptoms may also be caused by impaired liver function, in which the synthesis of plasma coagulation factors takes place.
Osteoporosis may develop through a similar mechanism caused by vitamin D malabsorption.
Cystic fibrosis: diagnosis and monitoring
- Newborn screening for cystic fibrosis
Since June 2009, all newborns in Poland are included in the cystic fibrosis screening program financed by the Ministry of He alth.
They make it possible to recognize the disease before the first symptoms appear. The test consists in taking a drop of blood from the heel of a newborn on a special tissue paper, and then subjecting it to laboratory analysis.
The result of the analysis may be within the normal range - then the test is completed - or be significantly different from it.
In such a case, the parents are informed about the necessity to undertake further diagnostics and treatment in a specialist clinic.
If the blood test result is on the borderline between normal and pathology, a second blood sample is taken. Re-analysis allows you to confirm or exclude a high probability of the disease.
- Genetic testing for cystic fibrosis
A child with abnormal screening results, clinical signs of cystic fibrosis, or a family history of the disease should undergo genetic testing.
It consists in searching for mutations within the gene encoding the CFTR protein. Currently available tests allow the detection of about 500 of the most common mutations (out of over 1,900 known).
In cases of patients with rare mutations, it may happen that the genetic test will be negative despite the presence of the disease.
- Sweat test
The sweat test is a relatively simple test that measures the concentration of chloride ions in sweat. The patient is given a drug (pilocarpine) to increase the secretion of sweat by the sweat glands.
A positive test result is a chloride ion concentration above 60 mmol / L in two independent measurements.
Resulta non-diagnostic test is a concentration within 30-60 mmol / l - in this case the patient should be referred for a verification genetic test.
Chloride concentration below 30 mmol / l is a negative result - further tests are performed only if there are typical symptoms of cystic fibrosis.
The sweat test result may be false positive in patients with hormonal disorders (hypothyroidism, adrenal insufficiency), eating disorders or other metabolic diseases.
In such cases, it is important to carefully analyze all clinical symptoms and perform additional tests.
- Prenatal diagnosis in cystic fibrosis
People planning to have children can undergo genetic tests of the CFTR gene sequence, estimating the risk of their children getting sick. They should be considered especially in the presence of cystic fibrosis in their family members.
Diagnostic options during pregnancy include chorionic villus sampling (collection of placental fragments) or amniocentesis (collection of amniotic fluid sample). These are invasive methods, so the decision to conduct them requires awareness of the risk of possible complications.
In the case of pregnancy conducted using assisted reproductive techniques (in vitro), there is a possibility of preimplantation diagnostics. It consists in testing the mutation of the CFTR gene in reproductive cells before fertilization, or testing the embryo before implanting it into the uterus.
Cystic fibrosis: monitoring
Patients suffering from cystic fibrosis should undergo regular checkups to assess the degree of disease progression and occurrence of possible complications.
Chest imaging (chest X-ray or computed tomography) as well as pulmonary function tests (spirometry) are usually performed.
Pulse oximetry is an additional test to assess the patient's respiratory efficiency.
Sputum should also be collected for microbiological testing at each follow-up visit. The type of microorganisms colonizing the respiratory tract is the key factor determining the selection of an antibiotic therapy regimen.
The abdominal organs (liver, pancreas, spleen) are assessed by ultrasound. Additionally, the concentrations of laboratory markers of dysfunction of these organs - liver enzymes and pancreatic enzymes - are monitored.
A sign of a disturbance in digestion of fats is the increase in their concentration in the stool.
Tests allowing early detection of diabetes (concentrationFasting Blood Glucose and Oral Glucose Tolerance Test (OGTT). It is very important to constantly monitor the nutritional status.
Cystic fibrosis: treatment
To date, no causal treatment for cystic fibrosis has been invented. The therapeutic methods used so far were to alleviate the effects of the disease, extend the survival of patients and improve their quality of life.
There are high hopes now for a group of modern drugs that directly affect the CFTR protein defect underlying cystic fibrosis.
It is still very important to carry out both pharmacological therapy and the use of various forms of physiotherapy, diet and psychotherapy at the same time.
- Drug treatment of cystic fibrosis
The following groups of drugs are used in the treatment of cystic fibrosis:
- mucus-thinning drugs (so-called mucolytics) in the form of aerosols, such as dornase alfa and hyperosmotic substances that attract water molecules (hypertonic NaCl, mannitol)
- antibiotics, used both prophylactically and in chronic infections and exacerbations of the disease. The treatment of recurring respiratory infections is one of the greatest therapeutic challenges.
Antibiotics are administered both by inhalation (tobramycin, colistin) and orally (azithromycin, ciprofloxacin).
A particularly important problem is the treatment of long-term infections with bacteriaPseudomonas aeruginosa . The chronic nature of the disease favors the development of multidrug-resistant bacteria strains - bronchodilators (especially before inhaling inhaled antibiotics)
- non-steroidal anti-inflammatory drugs and / or glucocorticosteroids to reduce inflammation in the lungs
- substitutes for pancreatic enzymes (lipase) and fat-soluble vitamins (A, D, E and K)
- bisphosphonates in the treatment of osteoporosis
If you develop diabetes, you need to administer insulin.
- New Cystic Fibrosis Drugs
The group of new drugs used in the treatment of cystic fibrosis includes the so-called CFTR protein modulators: Lumacaftor, increasing the amount of CFTR proteins in the cell membrane, and Ivacaftor, enhancing their action.
Both drugs can only be used in patients with certain mutations in the CFTR gene, as only some of them respond to this type of therapy. These drugs can be used in combination therapy.
A significant disadvantage of these preparations is a very high price.
Clinical trials are ongoing, assessing the effectiveness of this group of drugs and their possibilityuse in targeted therapy of cystic fibrosis.
The results available so far indicate an improvement in both the clinical condition and the survival rate of patients.
- Non-pharmacological treatment of cystic fibrosis
Apart from pharmacological therapy, additional methods of treatment also play an extremely important role. These include:
- respiratory rehabilitation, i.e. various physiotherapeutic techniques (massaging, patting, vibrations), supporting the expectoration of mucus remaining in the respiratory tract. Systematic removal of secretions facilitates breathing, reduces inflammation and cleanses the respiratory tract of bacteria deposited in them
- physical activity, recommended for all patients, except in the most severe cases
- breathing exercises, such as blowing into special mouthpiece devices, mobilize secretions and strengthen the airways
- mechanical support for breathing during sleep (non-invasive ventilation), preventing night-time drops in blood oxygen concentration
- oxygen therapy in case of respiratory failure
- preventive vaccinations, including annual vaccination against influenza viruses
- Assisted reproductive techniques in patients with fertility disorders
People with cystic fibrosis should also be provided with psychological support
- Diet in cystic fibrosis
The goal of nutritional treatment of cystic fibrosis patients is to prevent malnutrition by providing adequate caloric intake (120-150% of the normal daily energy requirement).
Diet should be high in protein and high in fat.
You should take care of the right amount of sodium, which is constantly lost in excessive amounts with sweat.
It is important to supplement the deficiencies of vitamins (A, D, E, K) and minerals (zinc, selenium) and the supply of pancreatic enzyme preparations.
Adequate hydration and the consumption of high-fiber foods help prevent constipation.
In cases of extreme malnutrition, consider introducing enteral or parenteral nutrition.
- Cystic fibrosis surgery
Surgical treatment is reserved for the most severe, complicated stages of the disease development.
Advanced respiratory failure, not amenable to treatment by standard methods, is an indication for lung transplantation.
Other pulmonary procedures may also be necessary, such as a lobectomy for severe, complicated infections orembolization of bronchial arteries in the event of massive bleeding.
Advanced cirrhosis may be an indication for a liver transplant.
- The future of CF therapy
Research into new groups of drugs that can be used in the treatment of cystic fibrosis is ongoing. You are looking for a substance:
- activating alternative chloride channels (e.g. UTP analogs)
- blocking sodium channels (e.g. amiloride)
- effectively reducing inflammation in the lungs
- fight against multi-drug resistant strains of bacteria
The hope for patients with cystic fibrosis lies in the research on gene therapy conducted all over the world, which consists in replacing the damaged CFTR gene with its correct version.
Adenoviruses or liposomes (phospholipid vesicles) are used as carriers for the gene, which, after entering the cells, are to introduce the correct DNA into them.
The results of the trials so far have not yet shown its effectiveness, allowing the introduction of this method into standard treatment regimens.
The search for improved treatments for the effects of cystic fibrosis is still ongoing, including new nutritional supplements. The effectiveness of supplementation with probiotics, vitamins and selected amino acids is tested.
The development of molecular biology techniques allows for shifting therapeutic goals from purely symptomatic treatment to searching for methods of precise and individualized therapy.
Important- Cystic Fibrosis Treatment Clinic, Institute of Mother and Child, 01-211 Warsaw, p. Kasprzaka 17A, Leipzig Building, ground floor, gab. 25, phone: 22 32 77 231, 22 32 77 371
- Polish Society for Fighting Cystic Fibrosis
p. Prof. Jana Rudnika 3B, 34-700 Rabka Zdrój, phone no. 18/267 60 60 ext. 331; 342, tel./fax: 18/267 60 60 ext. 349, free helpline: 0 800 111 169 - MATIO Foundation
30-507 Kraków, p. Celna 6, phone no. 12 292 31 80
Krzysztof BialaziteA medical student at Collegium Medicum in Krakow, slowly entering the world of constant challenges of the doctor's work. She is particularly interested in gynecology and obstetrics, paediatrics and lifestyle medicine. A lover of foreign languages, travel and mountain hiking.
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