Cystic fibrosis (cystic fibrosis). Description of the symptoms of cystic fibrosis in adults Signs of the intestinal form of cystic fibrosis in adult children

Cystic fibrosis is one of the most common genetic diseases in humans. With this disease, the glands of the respiratory system, the gastrointestinal tract and others, form too thick mucus.

Pulmonary disease over time can cause the lower right side of the heart (right ventricle) to collapse.

Complications in digestion

Cystic fibrosis makes patients more prone to diarrhea. Viscous secretions clog the pancreatic ducts, preventing the release of enzymes necessary for the digestion of fats and proteins. Secretions prevent the body from absorbing fat-soluble vitamins (A, D, E, K).

Cystic fibrosis affects the pancreas, and because this organ controls blood sugar levels, people with cystic fibrosis can develop diabetes. In addition, the bile duct can become clogged and inflamed, leading to liver problems such as cirrhosis.

Treatment and therapy of cystic fibrosis

In order to minimize the symptoms and complications of cystic fibrosis, several treatments are used, their main goals are:

infection prevention
reduction in the amount and liquefaction of the consistency of secretions from the lungs
improved breathing
calorie control and proper nutrition

To achieve these goals, cystic fibrosis therapy may include:

Antibiotics. The latest generation of drugs are great at fighting bacteria that cause lung infections in patients with cystic fibrosis. One of the biggest problems with the use of antibiotics is the emergence of drug-resistant bacteria. In addition, prolonged use of antibiotics can cause fungal infections in the mouth, throat, and respiratory system.
Mucolytic drugs. The mucolytic drug makes the mucus thinner and therefore improves sputum separation.
Bronchodilators. The use of medications such as salbutamol can help keep the bronchi open, which encourages expectoration of mucus and secretions.
Bronchial drainage. In patients with cystic fibrosis, mucus must be manually removed from the lungs. Drainage is often done by beating the chest and back with the hands. Sometimes an electrical device is used for this. You can also wear an inflatable vest that emits high frequency vibrations. Most adults and children suffering from cystic fibrosis need to have a bronchial drain at least twice a day for 20 minutes to half an hour.
Enzyme oral therapy and proper nutrition. Cystic fibrosis can lead to malnutrition because the pancreatic enzymes needed for digestion do not reach the small intestine. So people with cystic fibrosis may need more calories than healthy people. A high-calorie diet, special water-soluble vitamins and pills containing pancreatic enzymes will help you not lose weight or even gain weight.
Lung transplant. A doctor may recommend a lung transplant if there are serious breathing problems, life-threatening pulmonary complications, or if the bacteria have developed resistance to the antibiotics used.
Analgesics. Ibuprofen may slow the destruction of the lungs in some children with cystic fibrosis.

Lifestyle for people with cystic fibrosis

If your child suffers from cystic fibrosis, one of the best things you can do is learn as much as you can about the disease. Diet, therapy and early detection of infections are very important.

As with adult patients, it is important to perform daily "percussive" procedures to remove mucus from the child's lungs. A doctor or pulmonologist can suggest the best way to perform this very important procedure.

Be aware of vaccinations. In addition to regular vaccines, also get pneumococcal and flu shots. Cystic fibrosis does not attack the immune system, but it does make children more susceptible and prone to complications.
Encourage your child to lead a normal life. Physical exercise is of paramount importance for people of any age suffering from cystic fibrosis. Regular exercise helps expel mucus from the airways and strengthens the heart and lungs.
Make sure your child is following healthy diet. Talk to your family doctor or dietitian about your child's dietary needs.
Use nutritional supplements. Give your child fat-soluble vitamin and pancreatic enzyme supplements.
See to it that the child drank a lot of liquid, - it will help thin the mucus. This is especially important during the summer season when children are more active and tend to lose a lot of fluids.
Do not smoke in the house and even in the car, and do not allow others to smoke in the presence of your child. Passive smoking is harmful to everyone, but people with cystic fibrosis are particularly affected.
Remember to always wash your hands. Teach all your family members to wash their hands before eating, after using the toilet, when they get home from work or school. Hand washing is the best way to prevent infection.

In cystic fibrosis, adding protein and calories to the diet is important. After medical advice, you can also take additional multivitamins containing vitamins A, D, E and K.

Enzymes and mineral salts

All patients with cystic fibrosis should take pancreatic enzymes. These enzymes help the body metabolize fats and proteins.

People who live in hot climates may need a little extra table salt.

Eating habits

Eat when you have an appetite. This means that it is better to have several small meals throughout the day.
Always have a variety of nutritious snacks on hand. Try to eat something every hour.
Try to eat regularly even if it's just a few sips.
Add grated cheese in soups, sauces, pies, vegetables, boiled potatoes, rice, pasta or dumplings.
Use skim milk, partially skimmed, fortified cream or milk, for cooking or just drinking.
Add sugar to juices or hot chocolate. When you eat cereal, try adding raisins, dates, or nuts.

Cystic fibrosis (CF) is a common hereditary disease, potentially lethal. It became possible to diagnose it only in the second half of the 20th century. Prior to this, most patients with cystic fibrosis died in infancy from concomitant diseases.

Cystic fibrosis (cystic fibrosis) is a systemic hereditary disease caused by a mutation of a gene that affects cellular salt metabolism. As a result, an increased amount of thick, viscous mucus is produced that clogs the ducts. With cystic fibrosis, all mucus-forming organs are affected - the lungs, bronchi, liver, intestinal glands, pancreas, sweat, sex and salivary glands.

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Who has cystic fibrosis

Cystic fibrosis occurs throughout the world, mainly in representatives of the Caucasian race, but individual cases of the disease have been recorded among representatives of all races.

The frequency of diseases is the same for both sexes. The gene that causes the disease has a recessive inheritance pattern, so a sick child is born only when both mother and father are carriers of the mutated gene. The birth rate of a child with cystic fibrosis in this case is 25 % . Carriers of a genetic mutation (and their number exceeds 5% of the total population of the Earth) do not show any signs of the disease.

Now in Russia more than 1500 patients with cystic fibrosis have been recorded. The number of unrecorded cases exceeds 15 thousand people.

How the disease develops

In cystic fibrosis, the viscous mucus produced by the bronchi accumulates and clogs the small bronchi, leading to impaired ventilation and blood supply to the lungs. The resulting respiratory failure is the most common cause of death in cystic fibrosis.

Mucus accumulations are easily infected by pathogenic microbes, leading to severe, irreversible changes in the lungs and their destruction.

The affected pancreas (in 80% of cases) leads to disruption of the digestive tract due to a lack of digestive enzymes. As a result of blockage of the ducts, cysts form. Stagnation of bile leads to cirrhosis of the liver, gallstones. Diabetes mellitus often develops. Affected sweat glands remove an increased amount of salt from the body along with sweat.

Currently, 96% of cases of cystic fibrosis are diagnosed in children under two years of age. Others are diagnosed at an older age.

Cause of cystic fibrosis in children

The only cause of cystic fibrosis is a child receiving a mutated CFTR gene from both parents at the time of conception.

This gene is responsible for the production of a protein that regulates the transport of sodium and chloride ions across the cell membrane.

Main symptoms

Depending on the nature of the disease, signs of cystic fibrosis may appear both immediately after birth and at a later age. The most common symptoms:

The skin is slightly salty;
body weight - reduced, thinness below the norm, even with excellent appetite;
disrupted bowel function - chronic diarrhea (often fetid), high fat content in feces;
breathing - wheezing, whistling;
cough - paroxysmal, painful, with the separation of a large amount of sputum;
frequent pneumonia;
"drumsticks" - thickening of the fingertips, often with deformed nails;
polyps in the nose - as a result of the growth of the mucous membrane of the cavity and sinuses of the nose;
rectal prolapse - periodic prolapse of the rectum.

Types and forms of the disease

Depending on which organs are mainly affected, the forms of the disease are distinguished:

Pulmonary - about 20% of patients. Accompanied by severe bilateral pneumonia with abscesses, then pulmonary and heart failure develops;
intestinal - occurs in 5% of patients. Leads to the formation of intestinal ulcers, intestinal obstruction, diabetes mellitus, urolithiasis, enlargement and cirrhosis of the liver;
mixed - the most common pulmonary-intestinal form (about 80% of cases). Combines signs of pulmonary and intestinal forms.

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Diagnostic methods

To establish the diagnosis, a medical history, clinical examination and special laboratory tests are necessary:

Sweat test and DNA study can reliably differentiate cystic fibrosis from the following diseases:

whooping cough;
bronchiectasis;
diabetes insipidus;
glycogen disease;
hereditary ectodermal dysplasia.

Methods of treatment of cystic fibrosis

To date, cystic fibrosis is incurable. Treatment is now only symptomatic, aimed at improving the patient's well-being and mitigating clinical manifestations.

Treatment is carried out continuously, throughout life. Early diagnosis of the disease, immediately started treatment will greatly facilitate and prolong the life of the patient.

Diet

Patients with cystic fibrosis urgently need a properly selected diet:

Increased caloric content of food - should be 20 - 30% higher than the age norm (increase the amount of protein);
fat restriction;
salt is a must, especially in hot weather;
liquid - constantly, in sufficient quantity;
vitamin-containing foods are a must every day (fruits, vegetables, natural juices, butter).

Treatment with drugs

Mucolytics - thinning mucus and helping to remove it (Ambroxol, Pulmozim, Acetylcysteine). Used mainly in the form of inhalation;
antibiotics - for infections of the respiratory system (Gentamicin, Tsiprobay, Tienam, Tobramycin, Tazicef). They are used in the form of injections, tablets, inhalations;
enzymes - to compensate for pancreatic insufficiency (Polyzyme, Pancitrate, Pancreatin, Creon, Meksaz);
vitamins - are prescribed constantly due to poor absorption and increased need, especially fat-soluble vitamins (solutions of vitamins A, D, E in a double dose);
hepatoprotectors - with liver damage (ursofalk, ursosan);
kinesitherapy - daily special exercises and breathing exercises;
oxygen concentrator - in case of serious exacerbations of the disease;
organ transplantation - to prolong life with severe damage to the lungs, liver, heart. Complicated and expensive operations that prolong life, but do not cure the disease.

Physiotherapy

Physiotherapy is aimed at improving the functioning of the bronchi, is carried out daily:

Postural drainage - active rhythmic tapping with a palm folded in a boat on the ribs in certain areas. Used at any age;
autogenic drainage - based on independent special breathing. Slow breath through the nose - holding the breath - the maximum possible active exhalation;
PEP mask - allows you to create different exhalation pressure when using special nozzles;
flutter is a simulator that allows you to create, along with exhalation resistance, also oscillations that pass to the bronchi and contribute to the separation of sputum.

Preventive actions

The genetic nature of the disease makes it difficult to prevent.

Primary

Mass dissemination of information about the disease;
DNA examination of couples about to have a baby for the presence of a mutated gene;
perinatal diagnosis - makes it possible to prevent the birth of a sick child.

Secondary

Monitoring the patient's condition is constant;
monthly medical examination;
ongoing treatment appropriate to the course of the disease

Forecast

At present, the prognosis is still unfavorable. Death is observed in more than half of the cases. Life expectancy with cystic fibrosis in Europe is about 40 years, in the USA and Canada - about 50, in Russia - less than 30.

Currently, there are no reliable methods of curing this disease; the life expectancy of patients on average is no more than 40 years.

People diagnosed with cystic fibrosis suffer only physically. Mentally, they are absolutely complete, among them there are many talented, intellectually developed, gifted people. Having lived to adulthood, they can create families, and even be parents of clinically healthy children - in the absence of a damaged gene in a spouse.

If you have cystic fibrosis, do not despair. Seek help from a pulmonologist and gastroenterologist. If necessary, a nutritionist, physiotherapist, endocrinologist, cardiologist, psychologist and other specialists are involved in the treatment.

Hereditary diseases are very difficult to diagnose. All about the symptoms and stages of development of a genetic disease - cystic fibrosis.

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The cough is so severe that it causes the person to vomit. In adult patients, the cough is persistent, as it takes on a chronic form.

Other main symptoms include:

earthy or pale skin color;
lethargy;
with a good appetite, weight loss;
changes in the structure of the chest. It resembles the shape of a barrel. There is a curvature;
possible paralysis of the heart muscle;
there is shortness of breath even at rest;
possible collapse of the lungs;
pneumothorax develops;
the finger phalanges are deformed.

With a long course of the disease, the nasopharynx is affected, as a result of this, the patient also has such pathologies as:

the appearance of adenoids;
polyps form in the nasopharynx;
diagnosed with tonsillitis and sinusitis.

Intestinal symptoms

With this type of cystic fibrosis, patients develop:

pyelonephritis and ulcer develop;
The patient suffers from intestinal obstruction.

Mucus provokes the formation putrefactive processes. The patient has:

emptying becomes very frequent;
increased dryness appears in the mouth;
pains appear on the right side of the abdomen;
the tone of the abdominal muscles decreases;
jaundice;
due to severe depletion, polyhypovitaminosis appears.

With complications, biliary cirrhosis is diagnosed.

Mixed symptoms

This form is characterized by a severe course of the disease. There are both pulmonary and intestinal symptoms. In mixed cystic fibrosis, there is 4 degrees of the disease.

If the disease in a patient is 10 years old, there is a dry cough, in which there is no sputum production. Shortness of breath can only be after exertion.
In the course of the disease up to 15 years, the presence of chronic bronchitis with a strong cough and sputum production is characteristic. In humans, the finger phalanges are deformed.
If the duration of the disease is 3-5 years, the patient is diagnosed with heart and lung failure. They are characterized by a severe form of the current for several months. Treatment of these processes is impossible, so the disease ends in death.

Important! All symptoms are characterized by pathological changes in the internal organs.

Diagnostic methods

Diagnostic measures for detecting cystic fibrosis in humans are quite extensive, since the disease causes pathological changes not only in the respiratory system, but in other internal organs. The most important are the following diagnostic measures:

Coprological analysis, which allows the doctor to determine how much fat, elastase and muscle fibers the patient has.
A genetic study is carried out to identify DNA in the body that is susceptible to mutation. They are what cause cystic fibrosis in humans.
Be sure the patient gives a general analysis of urine and blood.
An analysis is carried out that reveals the patient's glucose tolerance.
Be sure to visit an ENT doctor.
Using ultrasound, the patient is scanned in the abdomen.
To evaluate the effectiveness of drug treatment, the doctor examines the functioning of the lungs, their capacity and bronchial conduction. Therefore, spirometry is one of the important diagnostic procedures.
If the patient has a pulmonary or mixed form of the disease, a bronchoscopy is performed, which allows the specialist to examine the consistency of sputum.
With the help of microbiological studies, the composition of sputum is studied.
An important place in the diagnosis is occupied by bronchography, with the help of which the doctor can detect bronchiectasis in a patient.
A chest x-ray is prescribed to reveal pathological changes that have occurred in the lungs and bronchi.
A biochemical blood test is prescribed to detect enzymes in the liver and pancreas.
The patient is tested for blood sugar.
Conduct a coprogram that will reveal the amount of fat in the feces.
Electrocardiography is prescribed to detect changes in the heart.
The doctor measures the weight and height of the patient.
External respiration is studied.
The patient is also shown fibrogastroduodenoscopy.

Treatment

Since the disease is incurable and leads to the death of the patient, the doctor's task is to select effective drugs. medicines that increase life expectancy and improve as far as possible its quality in patients. Therefore, the specialist selects for each patient certain drugs that are aimed at:

reduction of sputum and its viscosity;
to cleanse the bronchi and lungs;
on preventing the appearance of infections in the respiratory system;
on the positive adaptation of the patient due to psycho-emotional factors;
to proper nutrition.

Important! Treatment is carried out strictly under the supervision of a physician.

The patient is taught breathing exercises, which will contribute to the discharge of viscous mucus.
Be sure to prescribe mucolytic drugs. The most effective is ACC.
If infectious diseases are detected, antibiotic therapy is prescribed.
If cirrhosis of the liver, acute infections and allergic reactions are observed, corticosteroids are prescribed, as well as Hepral and similar drugs.
The patient must undergo a course of oxygen therapy.

In case of violations of the pancreas, it is necessary to drink one of the drugs:

Pantsitrate;
Creon;
Pancreas.

Important! The patient must take these drugs for life.

Necessarily carry out the removal of polyps in the nose and adenoids.
If diabetes is detected, the doctor prescribes insulin. It is also very important for such patients to follow a diet.
It is necessary to regularly take courses of vitamins A, K, E and multivitamins.
The patient is prescribed antihistamines, as well as antifungal drugs: Chevorin, Nystatin.
To reduce pulmonary hypertension, eufillin is indicated.
To improve the work of the myocardium, cocarboxylase, potassium orotate are prescribed.
When diagnosing cor pulmonale, the patient should drink Digoxin and glucocorticoids.

Properly selected treatment gives the patient a chance to live more by 10-15 years. If earlier mortality in cystic fibrosis was 15-16 years old, now life expectancy is 31-34 years.

Cystic fibrosis is a severe genetic disease, the main cause of which is heredity. The disease affects all the secretion glands, respiratory organs and the entire digestive system. In a sick person, irreversible processes occur in the body, so it is very important to diagnose and treat this disease early. With the right therapy, the symptoms of cystic fibrosis in adults are gradually smoothed out. A few decades ago, this disease was considered fatal, modern medicine has the ability to significantly alleviate the patient's condition.

The mechanism of the onset of the disease

Cystic fibrosis in adults is a pathological condition that occurs due to a gene mutation. In this case, the gene that is located on the seventh chromosome is changed. The disease is transmitted only if both parents are carriers of such a gene, while the risk of getting sick is 25%.

Despite certain conditions, such a disease occurs in medical practice quite often. This is due to the fact that every 20th inhabitant is the carrier of such a gene.

Cystic fibrosis manifests itself already in early childhood, but with a mild course of the disease, the correct diagnosis is not immediately made.

Forms of the disease

The form of the disease directly depends on the most affected area. For example, if the lung tissue is more affected, then they speak of cystic fibrosis of the lungs, but this does not mean at all that other organs are not at all susceptible to this pathology. It is worth remembering that in any form of the disease, pathological changes affect absolutely all important organs.

In medical practice, the following forms of cystic fibrosis are distinguished:

pulmonary;
intestinal;
mixed.

Each of the forms of cystic fibrosis has certain symptoms and features of therapy. But in any case, early diagnosis and treatment is very important in order to alleviate the patient's condition.

With constant treatment and the absence of complications, patients with cystic fibrosis live only up to 40 years.

Pulmonary form

This form of the disease is characterized by the appearance of a strong cough, which often ends in vomiting.. If the disease begins at an early age, and in many people the first symptoms are observed from birth, then in an adult the cough becomes chronic.

The main signs of the pulmonary form of the disease are such health disorders:

pallor of the skin and a grayish tint of some areas of the skin;
weakness and lethargy;
pronounced weight loss with good nutrition;
hacking cough, which is somewhat reminiscent of whooping cough.

When coughing, viscous sputum comes out, often with mucus and particles of pus. Purulent contents always indicate the addition of a bacterial infection. Viscous sputum can lead to mucostasis, as well as complete blockage of the bronchi. Due to this, severe pneumonia develops, which is difficult to treat. In this case, other symptoms of the disease may be added:

cyanosis of the skin;
the sternum begins to bulge forward and resembles a barrel;
even in a state of complete rest, shortness of breath is observed;
lack of appetite and weight loss;
the phalanges on the fingers are noticeably curved.

With prolonged cystic fibrosis, changes occur in the nasopharynx. Due to this, concomitant diseases can develop - adenoids, polyps, chronic tonsillitis and sinusitis.

Women with cystic fibrosis can have children, but lung failure often develops during childbirth. Men suffering from this disease are infertile, but their life expectancy is higher.

intestinal form

This form of the disease is characterized by secretory insufficiency of the gastrointestinal tract. In the intestines, stagnation is observed, which is accompanied by excessive release of gases and, as a result, bloating. In the intestinal form, the following symptoms are observed:

frequent urge to go to the toilet;
dryness of the oral mucosa;
reduced muscle tone;
hypotrophy, which always leads to weight loss;
polyhypovitaminosis;
frequent pain in the abdomen, under the right rib and in the muscles.

With this form of the disease, various complications are often manifested by such pathologies:

peptic ulcer;
chronic pyelonephritis;
disaccharidase deficiency;
urolithiasis disease;
complete or partial intestinal obstruction.

Sometimes, biliary cirrhosis can develop against the background of cystic fibrosis., in which there is a strong burning sensation of the skin and its pronounced yellowness.

The intestinal form of cystic fibrosis is considered very severe and difficult to treat.

mixed form

The worst prognosis is if cystic fibrosis occurs in a mixed form. Then all the symptoms of the pulmonary and intestinal forms are noticeable.. There are 4 stages of the disease of this form, and the severity of symptoms in each case is different:

Unproductive and dry cough that does not produce sputum. Shortness of breath occurs only after strong physical exertion. This stage of the disease can last up to 10 years.
Chronic bronchitis develops, coughing away a large amount of viscous sputum. When stressed, there is severe shortness of breath. The phalanges of the fingers are noticeably curved. This stage of the disease can last from 2 to 15 years.
At this stage, the bronchopulmonary process begins to progress and give complications. At the same time, respiratory and heart failure become clearly visible. This stage lasts from 3 to 5 years;
The last stage is characterized by the fact that heart and respiratory failure become severe. This condition lasts for several months and ends in death.

The sooner treatment is started, the better the prognosis. Cystic fibrosis that develops in adults often responds well to therapy. The main thing is not to miss the onset of the disease.

Sometimes the disease proceeds in a latent form, in which case changes can be detected through x-rays.

Diagnosis of the disease

It is very important to diagnose this dangerous disease as early as possible, in which case the prognosis is much more favorable than with an untimely diagnosis and treatment.. For timely diagnosis, the following methods are used:

Bronchoscopy - necessary to study the consistency of sputum formed.
Complete blood and urine tests.
Sweat test. To date, this is the most informative method for determining cystic fibrosis;
Bronchography - necessary to determine emerging bronchiectasis.
DNA analysis to determine the mutating gene.
Microbiological examination of outgoing sputum.
Spirometry, to determine the condition of the lung tissue.
X-ray, to detect changes in the bronchi and lungs.
A coprogram is necessary to study the amount of fat contained in the feces.

According to the doctor's testimony, other studies may be prescribed that will clarify the diagnosis, but usually the above measures are enough to diagnose the pathology.

In pulmonary and mixed forms of cystic fibrosis, bronchoscopy is considered the main diagnostic method.

Treatment

Cystic fibrosis is not amenable to full treatment, therefore, therapy is only symptomatic and is aimed at restoring breathing and normalizing the functions of important organs. So, with different forms of the disease, such therapy can be shown:

Lung form. With this course of the disease, it is very important to restore normal breathing, as well as to prevent concomitant infections. In this case, mucolytics and enzyme preparations are prescribed. In addition, physiotherapy exercises and gentle chest massage are recommended.
intestinal form. In this case, you just need to stick to a diet that will have a large amount of proteins. Patients should eat a lot of meat products, fish, cottage cheese and eggs. At the same time, the consumption of fats and carbohydrates is reduced, enzymes and vitamin preparations can be prescribed to improve digestion.
If the pathology is complicated by acute bronchitis or pneumonia, then antibiotics are included in the therapy. In severe pneumonia, hormonal drugs may be prescribed.
To support the work of the heart muscle, metabolites are often prescribed;
If there is no effect after the prescribed treatment, then bronchial lavage with special solutions is indicated.

Cystic fibrosis is not completely curable, so many doctors agree that the only way out may be a lung transplant. However, in this case, the prognosis is also not very favorable, because the patient will have to constantly take medication, and no one will give guarantees that the transplanted organ will not be rejected.

Cystic fibrosis (CF) is an inherited disorder caused by a mutation in the cystic fibrosis transmembrane regulator gene. It manifests itself in a systemic lesion of the external secretion glands and is accompanied by severe dysfunctions of the gastrointestinal tract, respiratory organs and a number of other organs and systems.

ICD-10	E84
ICD-9	277.0
DiseasesDB	3347
Medline Plus	000107
eMedicine	ped/535
OMIM	219700
MeSH	D003550

General information

The first mention of the disease dates back to 1905 - at that time, the Austrian physician Karl Landsteiner, when describing cystic changes in the pancreas with meconial obstruction in two children, expressed the idea of the relationship of these phenomena.

The disease was described in detail, singled out as an independent nosological unit and proved its hereditary nature by the American pathologist Dorothy Anderson in 1938.

The name "cystic fibrosis" (from Latin Mucus - mucus, viscus - viscous) in 1946 suggested using Sidney Farber, American.

The prevalence varies widely among different ethnic groups. The most common cystic fibrosis occurs in Europe (average 1:2000 - 1:2500), but the disease has been reported in representatives of all races. The frequency of cystic fibrosis in the indigenous population of Africa and Japan is 1:100,000. In Russia, the average prevalence of the disease is 1:10,000.

The sex of the child does not affect the incidence of the disease.

Inheritance occurs in an autosomal recessive manner. Carriers of one defective gene (allele) do not develop cystic fibrosis. If both parents are carriers of the mutated gene, the risk of having a child with cystic fibrosis is 25%.

In Europe, every 30th inhabitant is a carrier of a defective gene.

Forms

Depending on the location of the lesion, cystic fibrosis is divided into:

Pulmonary (respiratory) form of the disease (15-20% of all cases). It is manifested by signs of damage to the respiratory apparatus due to the accumulation of a large amount of viscous sputum that is difficult to separate in small and medium bronchi.
Intestinal form (5% of all cases). Manifested in violation of digestion and assimilation of food, increased thirst.
Mixed form (pulmonary-intestinal, which accounts for 75-80% of cases). Since this form combines the clinical signs of the respiratory and intestinal forms of cystic fibrosis, it is characterized by a more severe course of the disease and the variability of its manifestations.

Separately, meconium ileus is distinguished, in which, as a result of reduced activity of pancreatic enzymes and insufficient production of the liquid part of the secretion by intestinal epithelial cells, meconium (original feces) adhering to the intestinal wall clogs the lumen and causes intestinal obstruction.

There are also mutations of the CFTR gene due to varieties:

atypical forms that manifest themselves in isolated lesions of the endocrine glands (cirrhotic, edematous - anemic);
erased forms, which are usually detected by chance, since they proceed similarly to other diseases and are diagnosed as cirrhosis of the liver, sinusitis, chronic obstructive pulmonary disease, recurrent bronchitis and male infertility.

Reasons for development

Cystic fibrosis is caused by mutations in the CFTR gene located on the long arm of chromosome 7. This gene is found in many animals (cows, mice, etc.). It contains about 250,000 base pairs and consists of 27 exons.

The protein encoded by this gene and responsible for the transport of chloride and sodium ions across the cell membrane is located mainly in the epithelial cells of the respiratory tract, intestines, pancreas, salivary and sweat glands.

The CFTR gene itself was identified in 1989, and by now about 2000 variants of its mutations and 200 polymorphisms (variable regions in the DNA sequence) have been discovered.
In representatives of the European race, the F508del mutation is most common. The maximum number of cases of this mutation was registered in the UK and Denmark (85%), and the minimum - among the population of the Middle East (up to 30%).

Some mutations are often found in members of certain ethnic groups:

in Germany - mutation 2143delT;
in Iceland, the Y122X mutation;
Ashkenazi Jews have W1282X.

In Russia, 52% of the mutations causing cystic fibrosis are due to the F508del mutation, 6.3% to the CFTRdele2.3(21kb) mutation, and 2.7% to the W1282X mutation. There are also such types of mutations as N1303K, 2143delT, G542X, 2184insA, 3849+10kbC-T, R334W and S1196X, but their frequency does not exceed 2.4%.

The severity of the disease depends on the type of mutation, its localization in a certain region, and the specifics of its impact on the function and structure of the encoded protein. F508del, CFTRdele2.3(21kb), W1282X, N1303K, and G542X mutations are characterized by a severe course of the disease and the presence of concomitant complications and exocrine pancreatic insufficiency.

Severe cases of cystic fibrosis also include a disease caused by mutations DF508, G551D, R553X, 1677delTA, 621+1G-A and 1717-1G-A.

In a milder form, cystic fibrosis occurs, caused by mutations R117H, 3849+10kbC-T, R 374P, T338I, G551S.

With mutations G85E, R334W and 5T, the severity of the disease varies.

Mutations that block protein synthesis include mutations G542X, W1282X, R553X, 621+1G-T, 2143delT, 1677delTA.

Mutations causing disruption of post-translational modification of proteins and their transformation into mature RNA (processing) include DelF508, dI507, S549I, S549R, N1303K mutations.

Mutations have also been identified:

protein dysregulators (G551D, G1244E, S1255P);
reducing the conductivity of chlorine ions (R334W, R347P, R117H);
reducing the level of protein or normal RNA (3849+10kbC-T, A455E, 5T, 1811+1.6kbA-G).

As a result of the mutation, the structure and functions of the CFTR protein are disturbed, so the secret of the endocrine glands (sweat, mucus, saliva) becomes thick and viscous. The content of protein and electrolytes in the secret increases, the concentration of sodium, calcium and chlorine increases, and the evacuation of the secret from the excretory ducts becomes much more difficult.

As a result of the delay of a thick secretion, the ducts expand and small cysts form.

Permanent stagnation of mucus (mucostasis) causes atrophy of the glandular tissue and its gradual replacement with connective tissue (fibrosis), early sclerotic changes develop in the organs. With secondary infection, the disease is complicated by purulent inflammation.

Pathogenesis

Cystic fibrosis is caused by the inability of a defective protein to fully perform its functions.
As a result of violations of protein functions in cells, an increased amount of chloride ions gradually accumulates and the electrical potential of the cell changes.

A change in electrical potential causes sodium ions to enter the cell. An excess of sodium ions provokes an increased absorption of water from the pericellular space, and a lack of water in the pericellular space causes a thickening of the secretion of exocrine glands.

With difficult evacuation of a thick secret, the bronchopulmonary and digestive systems are primarily affected.

Violation of the patency of small bronchi and bronchioles leads to the development of chronic inflammation and destruction of the connective tissue framework. Further development of the disease is accompanied by the formation of saccular, cylindrical and teardrop-shaped bronchiectasis (bronchial dilation) and emphysematous (swollen) areas of the lung.

Bronchiectasis occurs with equal frequency in the upper and lower lobes of the lungs. In most cases, they are not detected in children in the first month of life, but by the 6th month they are observed in 58% of cases, and after six months - in 100% of cases. At this age, various changes are found in the bronchi (catarrhal or diffuse bronchitis, endobronchitis).

The bronchial epithelium is exfoliated in some places, foci of goblet cell hyperplasia and squamous metaplasia are observed.

With complete blockage of the sputum of the bronchi, zones of decline in the lobe of the lung (atelectasis) are formed, as well as sclerotic changes in the lung tissue (diffuse pneumosclerosis develops). In all layers of the bronchial walls there is an infiltration of lymphocytes, neutrophils and plasma cells.

The mouths of the mucous bronchial glands expand, purulent plugs are detected in them, and in the lumen of bronchiectasis there is a large amount of fibrin, decaying leukocytes, necrotic bronchial epithelium and colonies of cocci. The muscular layer is atrophied, and the walls of bronchiectasis are thinned.

In the case of a bacterial infection, against the background of impaired immunity, abscess formation begins and destructive changes develop (Pseudomonas aeruginosa is sown in 30% of cases). With the accumulation of foam cells and eosinophilic masses with the inclusion of lipids due to a violation of homeostasis, the development of secondary lipoproteonosis occurs.

By the age of 24, pneumonia is detected in 82% of cases.

Life expectancy in cystic fibrosis depends on the state of the bronchopulmonary system, since in a patient, due to a progressive change in the vessels of the pulmonary circulation, the amount of oxygen in the blood gradually decreases and the right sections of the heart increase and expand (a “cor pulmonale” develops).

There are other changes in the region of the heart. Patients are diagnosed with:

myocardial dystrophy (impaired metabolism of the heart muscle) with interstitial sclerosis;
foci of myocardial myxomatosis;
thinning of muscle fibers;
lack of transverse striation in places;
sclerotic lesions (interstitial sclerosis) in the vascular area;
moderate swelling of the vascular endothelium;
cardiodystrophy, expressed in varying degrees.

Valvular and parietal endocarditis is possible.

With a thickening of the secret of the pancreas, blockage of its ducts often occurs even during the period of intrauterine development. In such cases, the pancreatic enzymes produced by this gland in normal amounts are not able to reach the duodenum, so they accumulate and cause tissue breakdown in the gland itself. By the end of the first month of life, the pancreas of such patients is an accumulation of fibrous tissue and cysts.

The cyst occurs as a result of expansion of the interlobular and intralobular ducts and flattening and atrophy of the epithelium. Inside the lobules and between them, there is an overgrowth of connective tissue and its infiltration with neutrophils and lymphohistiocytic elements. Hyperplasia of the islet apparatus, atrophy of the parenchyma of the gland and fatty degeneration of the tissue also develop.

The intestinal epithelium becomes flattened and includes an increased number of goblet cells, and accumulation of mucus is present in the crypts. The mucous membrane is infiltrated with lymphoid cells with the inclusion of neutrophils.

Mutations that are accompanied by a decrease in the conductivity of chloride ions or the level of protein or normal RNA cause the slow development of chronic pancreatitis with the relative preservation of pancreatic function for a long time.

Cystic fibrosis in newborns in 20% of cases leads to blockage of thick meconium in the distal small intestine.

In some cases, the disease is accompanied by prolonged neonatal jaundice, which is caused by the viscosity of bile and increased production of bilirubin.

In almost all patients, there is a compaction of the connective tissue and cicatricial changes in the liver (fibrosis). In 5-10% of cases, the pathology progresses and causes biliary cirrhosis and portal hypertension.

Also in the liver, the presence of:

focal or diffuse fatty and protein degeneration of cells;
stagnation of bile in the interlobular bile ducts;
lymphohistiocytic infiltrates in the interlobular layers.

Cystic fibrosis is accompanied by an abnormal function of the sweat glands - the concentration of sodium and chlorine in the secretion is increased, and the amount of salt exceeds the norm by about 5 times. This pathology is observed throughout the life of the patient, therefore, a hot climate is contraindicated for people suffering from cystic fibrosis (the risk of heat stroke increases, convulsions are possible due to the development of metabolic alkalosis).

Symptoms

Cystic fibrosis in most cases manifests itself before the age of one.

In 10% of cases, the symptoms of the disease (meconium ileus or meconium ileus) are detected by ultrasound during fetal development in the 2nd-3rd trimester.

In some children, intestinal obstruction is detected in the first days of life. Signs of meconium ileus are:

lack of physiological excretion of meconium;
bloating;
anxiety;
regurgitation;
vomiting, in which the presence of bile is detected in the vomit.

For two days, the child's condition worsens - pallor and dryness of the skin appear, tissue turgor decreases, lethargy and adynamia appear. Dehydration develops and intoxication increases. In some cases, complications may develop (intestinal perforation and peritonitis).

Intestinal cystic fibrosis manifests itself in most cases after the introduction of complementary foods or artificial feeding due to insufficiency of pancreatic enzymes. Symptoms of this form of the disease are:

bloating;
frequent bowel movements
significantly increased excretion of feces;
fetidity and light color of feces, the presence of a significant amount of fat in it.

Possible prolapse of the rectum when planting on a pot (observed in 10-20% of patients).

Often there is a feeling of dryness in the mouth due to the viscosity of saliva, so the intake of dry food is difficult, and in the process of eating, patients are forced to drink large amounts of liquid.

Appetite in the initial stages may be increased or normal, but due to digestive disorders, hypovitaminosis and malnutrition subsequently develop. In the course of the development of the disease, signs of cirrhosis and cholestatic hepatitis join (fatigue, weight loss, jaundice, dark urine, behavioral and consciousness disorders, abdominal pain, etc.).

Cystic fibrosis of the lungs, due to hyperproduction of a viscous secret in the bronchopulmonary system, causes an obstructive syndrome, which manifests itself:

exhalation lengthening;
the appearance of whistling noisy breathing;
attacks of suffocation;
participation in the respiratory act of auxiliary muscles.

Possible unproductive cough.

Infectious-inflammatory process is chronic relapsing. There are complications in the form of purulent-obstructive bronchitis and severe pneumonia with a tendency to abscess formation.

Symptoms of the pulmonary form of the disease are:

pale earthy skin tone;
bluish discoloration of the skin caused by insufficient blood supply;
the presence of shortness of breath at rest;
barrel chest deformity;
deformation of the fingers (terminal phalanges resemble drumsticks) and nails (reminiscent of watch glasses);
reduced motor activity;
loss of appetite;
low body weight.

with cystic fibrosis.

Bronchial contents usually include Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. Flora can show resistance to antibiotics.

The pulmonary form ends in death due to severe respiratory and heart failure.

Signs of cystic fibrosis in the mixed form include symptoms of intestinal and pulmonary forms.
Erased forms of the disease are usually diagnosed in adulthood, since special types of mutations in the CFTR gene cause a milder course of the disease, and its symptoms coincide with those of sinusitis, recurrent bronchitis, chronic obstructive pulmonary disease, liver cirrhosis, or male infertility.

Cystic fibrosis in adults often causes infertility. In 97% of men with cystic fibrosis, a congenital absence, atrophy or obstruction of the spermatic cord is detected, and in most women with cystic fibrosis there is a decrease in fertility due to the increased viscosity of the mucus of the cervical canal. At the same time, in some women, childbearing function is preserved. Mutations of the CFTR gene are also sometimes found in men who do not have signs of cystic fibrosis (the consequence of a mutation in 80% of such cases is aplasia of the vas deferens).

Cystic fibrosis does not affect mental development. The severity of the course of the disease and its prognosis depend on the timing of the manifestation of the disease - the later the first symptoms appear, the easier the disease proceeds and the more favorable the prognosis.

Since cystic fibrosis, due to a large number of mutation variants, is characterized by polymorphism of clinical manifestations, the severity of the disease is assessed by the state of the bronchopulmonary system. There are 4 stages:

1st, which is characterized by intermittent functional changes, dry cough without sputum, slight or moderate shortness of breath during physical exertion. The duration of the first stage can reach 10 years.
Stage 2, which is characterized by the development of chronic bronchitis, the presence of a cough, accompanied by sputum, moderate at rest and aggravated by exertion, shortness of breath, deformity of the terminal phalanges of the fingers. When listening, the presence of hard breathing with wet, "crackling" rales is revealed. This stage lasts from 2 to 15 years.
3rd stage, at which complications arise and the pathological process in the bronchopulmonary system progresses. There is the formation of bronchiectasis, areas of diffuse pneumofibrosis and limited pneumosclerosis, cysts. There is heart failure (right ventricular type) and severe respiratory failure. The duration of the stage is from 3 to 5 years.
Stage 4, which is characterized by severe cardio-respiratory failure, ending in death within a few months.

Diagnostics

The diagnosis of cystic fibrosis is based on:

musculoskeletal signs, including a family history, the duration of the manifestation of the disease, its progressive course, the presence of a characteristic lesion of the digestive and bronchopulmonary systems, problems with childbearing (presence of infertility or reduced fertility);
data of the main laboratory diagnostic methods;
DNA diagnostics.

Laboratory methods for detecting cystic fibrosis in children include:

PRT (pancreatic enzyme immunoreactive trypsin test), which is informative in newborns only during the first month of life. Thanks to this test, the level of this enzyme in the blood is determined. In newborns with cystic fibrosis, the level of immunoreactive trypsin is increased by 5-10 times. The test may give false-positive results if the child has severe prematurity, multiple congenital malformations (MCD), or birth asphyxia.
Sweat test, which is carried out according to the Gibson-Cook method. The method consists in introducing pilocarpine (a drug that stimulates the sweat glands) into the skin using a weak electric current. Sweat in an amount of at least 100 gr. is collected, weighed, after which the concentration of sodium and chlorine ions in it is determined. In the presence of sweat analyzers, the use of the method is simplified. Normally, the concentration in the secretion of the sweat glands of sodium and chlorine does not exceed 40 mmol / l. If a child has adrenogenital syndrome, HIV infection, hypogammaglobulinemia, hypothyroidism, familial, type 2 glycogenosis, glucose-6-phosphatase deficiency, or Klinefelter, mucopolysaccharidosis, nephrogenic diabetes insipidus, pseudohypoaldosteronism, fructosidosis or cealkia, the test may be false positive, and when treated with certain antibiotics - lies non-negative.
NPD test, which consists in measuring the transepithelial nasal electrical potential difference. The potential difference norm is from -5 mV to -40 mV.

DNA diagnosis is the most accurate way to diagnose cystic fibrosis. For research are usually used:

Liquid blood, which in an amount of about 1 ml is placed in a test tube with an anticoagulant (heparin is unacceptable).
Dried at room temperature blood spot about 2 cm in diameter, located on gauze or filter paper. Samples can be examined for several years.
Histological specimens that are used for analysis on the deceased.

Possible use:

Direct diagnostics, which allows you to identify a specific mutation in a specific gene.
Indirect diagnosis, in which the inheritance of genetic markers linked to the gene of the disease is analyzed. It is possible only if there is a child with cystic fibrosis in the family, since it is possible to establish a molecular marker only by analyzing its DNA.

In most cases, the PCR method (polymerase chain reaction) is used for research. The most common types of mutations in the CFTR gene are detected using specially designed diagnostic kits that allow simultaneous detection of several mutations.

Instrumental methods of examination also help to diagnose cystic fibrosis:

radiography, which allows to detect the presence of characteristic changes in the lungs (infiltration, emphysema, expansion of the roots of the lungs, deformation of the lung pattern);
bronchography, which helps to identify a decrease in the number of bronchial branches, breaks in their filling, the presence of cylindrical or mixed bronchiectasis;
bronchoscopy, which can detect the presence of a highly viscous mucopurulent secretion and diffuse purulent endobronchitis;
spirography, which allows to detect the presence of violations of the functions of external respiration according to the obstructive-restrictive type;
a coprogram that allows you to detect the presence of a large amount of indigestible fat.

Cystic fibrosis is also diagnosed by examining the duodenal contents, which helps to detect a decrease in the amount of enzymes or their absence in the duodenal juice.

Exocrine pancreatic function is assessed using a test for the presence of pancreatic elastase 1 (E1) in the feces. Cystic fibrosis is manifested by a significant decrease in the content of elastase 1 (a moderate decrease indicates the presence of chronic pancreatitis, pancreatic tumor, cholelithiasis or diabetes).

Cystic fibrosis can also be detected by prenatal diagnosis. DNA samples are isolated at 9-14 weeks of gestation from a chorionic villus biopsy. At later terms of the family's appeal, amniotic fluid (16-21 weeks) or fetal blood obtained by cordocentesis (after 21 weeks) is used for diagnosis.

Prenatal diagnosis is carried out in the presence of mutations in both parents or in the homozygosity of a sick child in the family. Prenatal diagnosis is also recommended in the presence of mutations in only one parent. A similar mutation detected in the fetus requires differentiation between homozygous gene inactivation and asymptomatic heterozygous carriage. For differential diagnosis at 17-18 weeks, a biochemical study of the amniotic fluid for the activity of aminopeptidase, gamma-glutamyl transpeptidase and the intestinal form of alkaline phosphatase is carried out (cystic fibrosis is characterized by a decrease in the amount of these intestinal enzymes).

If mutations in the CFTR gene cannot be detected, and the child with cystic fibrosis has already died, the fetus is examined using biochemical methods, since prenatal molecular genetic diagnosis is considered uninformative in this case.

Treatment

It is preferable to treat cystic fibrosis in children in specialized centers, since patients need comprehensive medical care, including the help of doctors, kinesitherapists and social workers.

Since cystic fibrosis, as a genetic disease, is incurable, the goal of therapy is to maintain a lifestyle that is as close as possible to that of healthy children. Patients with cystic fibrosis need:

providing adequate, protein-rich and without restriction in the amount of fat, dietary nutrition;
control of respiratory infections;
enzyme therapy using pancreatic preparations;
mucolytic therapy aimed at inhibiting the formation of bronchial secretions and its liquefaction;
antimicrobial and anti-inflammatory therapy;
vitamin therapy;
timely treatment of complications.

For the treatment of malabsorption syndrome (loss of nutrients entering the digestive tract) caused by pancreatic enzyme deficiency, pancreatic enzymes are used in the form of microgranules (Creon 10000, Creon 25000). The drugs are taken with food, and the dose is selected individually.

Since pancreatic insufficiency in cystic fibrosis is not completely corrected, the normalization of the nature of the stool and its frequency, as well as laboratory data, testifies to the sufficiency of the dose (steatorrhea and creatorrhea are not detected in the coprogram, the concentration of triglycerides is normalized in the lipidogram).

Respiratory cystic fibrosis requires the use of:

Mucolytic therapy, which includes the use of thiols that can effectively thin the bronchial secret. Applied orally, intravenously or inhaled, N-acetylcysteine, which has not only a mucolytic, but also an antioxidant effect. Inhalations through a mask using recombinant human DNase (Pulmozyme, Dornase alfa) are effective. Well liquefy and evacuate sputum inhalation with hypertonic sodium chloride solution (7%).
Kinesitherapy. To cleanse the pathological secretion of the bronchial tree and prevent infectious damage to the lungs, postural drainage, autogenous drainage, percussion and bedbug massage (consists of chest vibration) are used. An active breathing cycle, PEP masks and breathing exercises using flutter are also used.
Antibiotic therapy. The drug is selected depending on the type of microorganisms isolated from the bronchial secretion and the results of laboratory tests for sensitivity to antibiotics. Since the use of various antibiotic regimens prevents or delays the development of a chronic infection of the bronchopulmonary system, antibiotics are used for a long time and can be prescribed for prophylactic purposes.

Antibiotics are usually given intravenously to treat Pseudomonas aeruginosa.
The criterion for the abolition of antibiotic therapy is the return of the main symptoms of exacerbation to the initial state for this patient.

Cystic fibrosis is a contraindication to the use of antitussive drugs.

An effective treatment for progressive liver damage in cystic fibrosis has not yet been developed. Usually, patients with initial signs of liver damage are prescribed ursodeoxycholic acid at a dose of at least 15-30 mg / kg / day.

Since the damage to the lung tissue is affected by an excessive immune response of the body, macrolides, non-steroidal anti-inflammatory drugs and systemic and local glucocorticoids are used as anti-inflammatory therapy.

Cystic fibrosis is a disease in which the patient needs regular detailed examinations, including the study of the function of external respiration, coprogram, anthropometry, general urine and blood tests. Once a year, a chest x-ray, echocardiography and ultrasound of the abdominal organs are performed, bone age is determined, and immunological and biochemical blood tests are performed.

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