The prognosis of cystic fibrosis is determined by lesions in. Intestinal cystic fibrosis

Cystic fibrosis I Cystic fibrosis (mucoviscidosis; lat. mucus + iscidus sticky + -ōsis; synonym: cystofibrosis, )

Clinical picture is diverse and depends on the predominant damage to certain exocrine glands, the degree of sclerosis in various organs, the presence of complications and the age of the patients. There are pulmonary, intestinal, mixed (enteropulmonary), atypical forms of M. and meconium obstruction. for clinical forms conditionally, because with a purely pulmonary form, there is a decrease in the enzymatic activity of the glands gastrointestinal tract, and with purely intestinal pneumosclerosis, pneumosclerosis gradually forms and, with age, pronounced pulmonary fibrosis joins. Meconium obstruction is the first sign of a severe intestinal form of M. in a newborn in the first days of life; subsequently a mixed form develops. Atypical include forms that occur with isolated damage to individual exocrine glands (for example, the liver), and mild erased forms. The leading syndrome that determines the severity and disease is pulmonary.

The first symptoms of the disease occur more often in the first year of life, less often at an older age. The earlier the disease appears, the more severe it is and the more serious the prognosis.

Pulmonary syndrome with M. usually begins with pneumonia (Pneumonia) . The most common pathogens that cause it in children with M. are staphylococcus and Pseudomonas aeruginosa. Sometimes, before symptoms of pneumonia appear, a child experiences dry paroxysmal symptoms for a long time. As pneumonia develops, the cough becomes painful, paroxysmal, and whooping cough. caused by irritation of the bronchial mucosa with viscous, difficult to separate sputum. , the mucus in the nose of patients is also viscous and sticky.

Pneumonic foci, atelectasis, areas of emphysema, and pneumosclerosis create a motley clinical and radiological picture typical of M. The process in the lungs is always bilateral. Characterized by a protracted recurrent course of pneumonia, often with abscess formation and the early appearance of bronchiectasis. Some patients develop destructive pneumonia involving the pleura.

In severe cases of pulmonary syndrome, the process progresses steadily, and exacerbations often occur. quickly becomes purulent. Deformations of the chest are observed: barrel-shaped, keeled, rarely funnel-shaped. hard, sometimes amphoric (above cavities). Dry and moist rales are heard, with obstructive syndrome - dry wheezing. With the accumulation of sputum, often in the lower parts of the lungs, it is weakened and there is little wheezing.

Symptoms of respiratory failure (Respiratory failure) gradually increase: at rest, cyanosis, tachycardia. Symptoms of cor pulmonale develop (cor pulmonale) , pulmonary and heart failure. Deformations of fingers and toes appear in the form of drumsticks, nails in the form of watch glasses. Children lag behind in physical development, dystrophic skin changes appear ( rice. 3 ), it becomes dry, peels off, becomes thinner, becomes brittle, loses its shine, becomes thinner, acquires a grayish tint, thickens, easily breaks, flakes, and linear thickenings appear on them in the form of stripes and whitish spots.

X-ray examination reveals pulmonary emphysema, diffuse pneumosclerosis with fibrous compactions in the root zones ( rice. 4 ). On bronchograms, deformation of the bronchi is determined, their “choppedness”, convergence, cylindrical, saccular and teardrop-shaped ( rice. 5 ). Bronchoscopy reveals diffuse catarrhal-purulent. Damage to the bronchi is always bilateral, diffuse. In some patients, bronchi (Bronchi) are found V in the form of an additional bronchus, bronchomegaly, the departure of the bronchus of the middle lobe of the right lung from the upper lobe bronchus. The high frequency of malformations in M. indicates their connection with the underlying disease.

In children with pulmonary syndrome, external respiration is significantly impaired according to the obstructive-restrictive type; respiratory, metabolic or mixed acidosis develops early . With a milder course of pulmonary syndrome, the process proceeds according to the type of slowly progressing Bronchitis and with rare exacerbations, children are satisfactory.

Intestinal syndrome is caused by a sharp decrease in the activity of pancreatic and intestinal enzymes. It is characterized by a violation of the breakdown and absorption of fats, proteins, and carbohydrates from food. In patients, stools become more frequent up to 2-5 times a day, become copious and fatty, and have a gray, sharp, foul-smelling stool. Sometimes it is dense, scanty (“sheep” feces), there is a tendency to constipation (possibly), which is caused by the increased viscosity of pancreatic and intestinal secretions and good absorption of water in the intestines. However, the color of the feces remains light gray, and a drop of fat is released at the end of the bowel movement. Children lose weight, despite being preserved. During a scatological examination, large quantities of neutral, some fatty acids and soap, undivided muscle fibers, etc. are found.

Meconium obstruction develops in the first day of a child’s life and is caused by the formation of dense viscous meconium plugs in the small intestine, sometimes extending up to 3-8 cm. If the plug is not washed away, then a section of the small intestine appears, from which the child, as a rule, dies.

Light erased forms of M. proceed according to the type chronic bronchitis, chronic pancreatitis a With enzymatic deficiency, chronic enterocolitis (see Enteritis) . In some cases, diabetes mellitus develops against the background of pancreatic sclerosis .

In many patients with M., an increase in the size of the liver, fatty, protein, or protein-fatty degeneration of hepatocytes is detected (according to autopsy, biopsy, and echography of the liver). These changes exist for a long time without clinical manifestations, while the levels of liver enzymes also remain normal. In some cases, liver damage can lead to cirrhosis, which is characterized by the slow progressive development of portal hypertension syndrome (see Portal hypertension) with long-term normal hepatocyte function. Liver cirrhosis develops much less frequently.

Metabolic nephropathies are often observed with M., which is manifested by hyperphosphaturia, oxaluria, proteinuria, cystinuria: against the background of these changes, it can develop. In patients with M., the adrenal cortex is noted, and delayed sexual development is characteristic.

Cystic fibrosis can be complicated by pleurisy, pneumothorax, lung destruction, hemoptysis, intestinal obstruction, rectal prolapse, diabetes mellitus, chronic cor pulmonale, secondary disaccharidase deficiency, and celiac disease syndrome.

Diagnosis diagnosed based on medical history (complicated, early onset of the disease), clinical symptoms and results laboratory research. Reliable M. is considered when a high content of sodium and chlorine is detected in sweat, a high concentration of sodium in the nail plates of the fingers. Pathognomonic for M. is the sodium and chlorine content in sweat in children under 1 year of age over 40 mmol/l, in children over one year and in adults - over 60 mmol/l; sodium in the nail plates of the hands over 80 mmol/kg(for any age).

When studying the sodium and chlorine content in sweat, to increase sweating, a skin area is treated with pilocarpine, which is why the test is often called pilocarpine. skin inner surface the forearms are cleaned with alcohol and distilled water, then two electrodes are placed on this area: a gauze pad moistened with a solution containing sodium chloride is placed under the negative electrode, and a gauze pad moistened with a 0.5% pilocarpine solution is placed under the positive electrode (anode). continues 10 min at current strength 4 mA(current strength is gradually increased from 0 to 4 mA), after which the current is gradually reduced and the electrodes are removed. The area of ​​skin on which the electrode with the pilocarpine pad was placed is treated with distilled water, dried, after which a piece of pre-weighed ash-free filter paper (3x4) is placed on it. cm). To prevent the evaporation of sweat, the filter paper is covered with plastic film, which is glued to the edges with an adhesive plaster. collected within 30 min, then the filter paper is removed with tweezers and immediately weighed to determine the amount of sweat absorbed into it. To obtain a reliable result, the amount of sweat must be at least 100 mg.

After weighing, filter paper is poured into a weighing bottle with 10 ml distilled water and leave to elute electrolytes for at least 4 h. Can be eluted up to 20 h, in order to carry out further research the next day, but you need to make sure that the lid in the bottle is thoroughly ground in and does not evaporate. The sodium concentration in the eluate is determined using a flame photometer, and the chlorine concentration is determined by titration using Mohr's method.

To determine sodium in nail plates, the method of Kopito and Shvakhman, modified by Veltishchev and Glotova, is used. For research, cut pieces of nails from the fingers should be used (in children under 1 year of age, from the hands and feet). They are cleaned, washed with distilled water, then dried in a thermostat 1 h at 37°. For hanging nails (10 mg) add 0.2 ml concentrated nitrogen acid, then put in a water bath until the nails are completely dissolved (2-3 min). Add 4.8 ml distilled water, mix thoroughly, then determine the sodium concentration using a flame photometer and convert it into mmol/kg nails Such a study is convenient in that it can be carried out in another medical institution where there is a fiery one, and is indispensable in cases where it is difficult to obtain for research (children with eczema and other skin diseases).

In doubtful cases, in the presence of clinical signs of M. and concentrations of sodium and chlorine in sweat that are close to normal, a stress test with deoxycorticosterone acetate (DOXA) can be used. To do this, after determining the concentration of sodium and chlorine in sweat (pilocarpine test), a hypochloride diet is prescribed for 4 days (no diet is required in children under 2 years of age); on the 4th day at 20 h and on the 5th day at 8 h 0.5% oil solution of DOXA is administered intramuscularly (children under 6 months 0.2 ml, from 6 months. up to 3 years 0.4 ml, from 3 to 7 years 0.6 ml, from 7 to 10-12 years 0.8 ml, over 12 years old and adults 1.0 ml). In 4 - 6 h After the second injection of DOX, sweat is collected for re-examination. In children who do not suffer from M., the concentration of sodium and chlorine in sweat after a load with DOXA decreases by more than 25% compared to the initial level; in children suffering from M., it remains unchanged, decreases slightly, or even increases.

Differential diagnosis pulmonary form of M. is carried out with chronic pneumonia and hereditary lung lesions (idiopathic pulmonary hemosiderosis, Kartagener syndrome, chronic pneumonia in immunodeficiency states, Marfan's disease). The intestinal form of cystic fibrosis is differentiated from other syndromes of impaired intestinal absorption - Celiac disease (), Disaccharidase deficiency , Exudative enteropathy , intestinal dysbiosis. The main thing in the differential diagnosis is the study of electrolytes.

Treatment. The diet of patient M. should be age-appropriate, contain an increased amount of protein by 10-15% and a normal amount of fats and carbohydrates. At the same time, only easily digestible foods (butter and vegetable oil) are included in the diet. should not contain coarse fiber. In children with secondary lactase deficiency, milk is excluded. For severe intestinal syndrome and symptoms caused by insufficiency of various vitamins, it is prescribed parenterally.

In case of intestinal syndrome, enzyme preparations are used for replacement purposes: pancreatin, panzinorm, cotazim-forte, festal, etc. The enzyme depends on the severity of the disease and is selected individually. The criteria for dose sufficiency are the disappearance of abdominal pain, normalization of stool, and the absence of neutral fat during scatological examination. Enzyme preparations are taken with meals.

Treatment of pulmonary syndrome includes measures to reduce the viscosity of sputum and improve bronchial drainage, antibacterial therapy, combating intoxication and hypoxia, hypovitaminosis, and heart failure. To reduce the viscosity of sputum, inhalation of enzyme preparations (chymopsin, chymotrypsin, crystalline fibrinolysin) or mucolytic drugs, acetylcysteine, mucosolvin is used. To thin the sputum, acetylcysteine ​​and mucosolvin can be administered intramuscularly, and mucosolvin can also be administered orally. Bromhexine and mucaltin have a weaker diluting effect. To improve bronchial drainage, vibration of the chest, therapeutic exercises, postural exercises are performed; in young children, sputum is removed with an electric suction.

In case of exacerbation of the pulmonary process, antibacterial therapy is prescribed for at least 3-4 weeks. are selected taking into account the antibiogram, but if this study cannot be carried out, then they are based on the fact that the most common causative agents of the inflammatory process in the lungs in patients with M. are staphylococcus and Pseudomonas aeruginosa. Along with antibiotics, antifungal drugs (nystatin, chevorin) and antihistamines are used. During the period of exacerbation, UHF and microwave therapy is also carried out. and then electrophoresis of sodium and magnesium preparations (calcium preparations are contraindicated, because they increase pneumosclerosis); Prescribe multivitamins, to reduce pulmonary hypertension - aminophylline 7-10 mg/kg body weight per day orally (dose divided into 3 doses) for 4-5 weeks. from the onset of exacerbation. Drugs that improve myocardium are indicated: potassium orotate, cocarboxylase. For decompensation of the pulmonary heart, digoxin is used (1-1.5 mg/kg per day in terms of prednisolone, taking into account the daily rhythm of the adrenal glands for 3-4 weeks). the same dose is prescribed for rapid progression of pneumosclerosis, and for chronic adrenal insufficiency that has developed as a result of purulent intoxication and hypoxia - at a dose of 0.4 mg/kg per day with prednisolone, taking into account the circadian rhythm.

Children with M. are under the dispensary supervision of a local doctor and pulmonologist, because, despite the generalization of the process and changes in many organs and systems, damage to the respiratory system is observed in the majority of patients and it is this that determines the severity and prognosis of the disease. Parents must be trained in patient care and treatment methods such as massage, therapeutic, and aerosol therapy. The objectives of dispensary observation are monitoring the functional state of the bronchopulmonary, cardiovascular systems, gastrointestinal tract, kidneys, liver and the correct dose of enzyme preparations, timely implementation of restorative therapy during exacerbations of the disease, and in the period of remission - sanitation of foci of chronic infection. Treatment is carried out on an outpatient basis and at home, where the child can be provided with individual and excluded treatment. Only in severe conditions or the presence of complications is it indicated. Intensive therapy is carried out for patients with respiratory failure of II-III degree, with decompensation of the pulmonary heart, with pleural complications, destruction of the lungs, hemoptysis is indicated for meconium obstruction, in the absence of effect from conservative therapy for intestinal obstruction in older children, sometimes with destruction in the lungs . For bronchiectasis, surgical treatment is not recommended, because the process is always common.

Children with cystic fibrosis receive all medications for outpatient treatment free of charge.

Sanatorium treatment is indicated for children with mild and moderate intestinal forms of M. For children with the pulmonary form of M., sanatorium treatment is useful if it is possible to create special groups. Patients with M. are recommended to be sent to local sanatoriums. The selection criteria are intestinal disorders when prescribing enzyme preparations, the absence of decompensation of the pulmonary heart and the inflammatory process in the lungs.

Staying patients with M. in preschool institutions is inappropriate. Attending school in good and satisfactory condition is possible, but an additional day off per week and free attendance at school on days of treatment and examination at the clinic (at the pulmonology center), and exemption from exams are required. The question of the possibility of vaccinations for children with M. is decided individually.

Children with M. are not removed from the dispensary register, but upon reaching the age of 15 are transferred under the supervision of a therapist to a clinic for adults.

Forecast with M. it is serious and depends on the severity of the disease, the age at which the first symptoms appeared (if the disease appeared in the first year of life, the prognosis is worse), early diagnosis and targeted treatment. is largely determined by the severity of the pulmonary syndrome (with chronic colonization of the lungs by Pseudomonas aeruginosa, the prognosis is worse).

In recent years, due to improved diagnosis and earlier prescription of adequate therapy, the life expectancy of patients has increased. However, due to the chronic course of the disease, patients require constant monitoring and treatment. If in the 50s 80% of patients died before the age of 10 years, then in the 80s it was about 36% (the majority of deaths were under the age of one year). The earlier the diagnosis is made, targeted treatment is started and relapses of the disease are carried out, the more favorable the prognosis.

Bibliography: Congenital and hereditary lung diseases in children, ed. Yu.E. Veltishcheva et al., p. 170, M., 1986; Reiderman M.I. Cystic fibrosis, M., 1974, bibliogr.; Fadeeva M.A. Differential and principles of treatment of cystic fibrosis in children. Question ocher mat. and children, vol. 29, no. 11, p. 3, 1984.

Rice. 1. Microscopic specimen of the pancreas in a mixed form of cystic fibrosis: 1 - interlobular and intralobular ducts dilated and filled with acidophilic layered secretion; 2 - growths connective tissue. Hematoxylin and eosin staining; ×80.

X-ray of the chest (direct projection) of a 3-month-old child with a mixed form of cystic fibrosis: emphysema, pneumosclerosis, infiltrative process in the upper lobe of the right lung">

Rice. 2. Plain X-ray of the chest (direct projection) of a 3-month-old child with a mixed form of cystic fibrosis: emphysema, pneumosclerosis, infiltrative process in the upper lobe of the right lung.

Cystic fibrosis (cystic fibrosis) is a hereditary disease that is caused by a mutation in the cystic fibrosis transmembrane regulator gene. It manifests itself in systemic damage to the exocrine glands and is accompanied by severe dysfunction of the gastrointestinal tract, respiratory system and a number of other organs and systems.

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General information

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

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

The name “cystic fibrosis” (from the Latin mucus - mucus, viscus - viscous) was proposed in 1946 by Sidney Farber, an American.

The incidence varies widely among different ethnic groups. Cystic fibrosis is most common in Europe (average 1:2000 - 1:2500), but the disease has been reported in representatives of all races. The incidence 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 gender of the child does not affect the incidence of the disease.

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

In Europe, every 30th person 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 manifests itself as signs of damage to the respiratory apparatus due to the accumulation of a large amount of viscous, difficult to separate sputum in the small and medium bronchi.
• Intestinal form (5% of all cases). It manifests itself in impaired digestion and absorption of food, increased thirst.
• Mixed form (pulmonary-intestinal, which accounts for 75-80% of cases). Since this form combines the clinical signs of respiratory and intestinal forms of cystic fibrosis, it is characterized by a more severe course of the disease and variability in 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) adhered to the intestinal wall clogs the lumen and causes intestinal obstruction.

There are also types of mutations in the CFTR gene:

• atypical forms that manifest themselves in isolated lesions of the endocrine glands (cirrhotic, edematous-anemic);
• erased forms, 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 chlorine 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 to date, 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 most common mutation is F508del. 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 common in certain ethnic groups:

• in Germany - mutation 2143delT;
• in Iceland - mutation Y122X;
• for Ashkenazi Jews - W1282X.

In Russia, 52% of mutations causing cystic fibrosis are the F508del mutation, 6.3% are the CFTRdele2.3(21kb) mutation, 2.7% are the W1282X mutation. There are also types of mutations such 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 particular region and the specificity of its effect on the function and structure of the encoded protein. The severe course of the disease and the presence of concomitant complications and exocrine pancreatic insufficiency are distinguished by mutations F508del, CFTRdele2,3(21kb), W1282X, N1303K and G542X.

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

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

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

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

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

Mutations have also been identified:

• protein dysregulation (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 disrupted, so the secretions of the endocrine glands (sweat, mucus, saliva) become thick and viscous. The content of protein and electrolytes in the secretion increases, the concentration of sodium, calcium and chlorine increases, and the evacuation of secretions from the excretory ducts becomes much more difficult.

As a result of retention of thick secretions, the ducts expand and small cysts form.

Constant stagnation of mucus (mucostasis) causes atrophy of glandular tissue and its gradual replacement with connective tissue (fibrosis), and early sclerotic changes in organs develop. 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 protein dysfunction, an increased amount of chloride ions gradually accumulates in cells 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 increased absorption of water from the pericellular space, and a lack of water in the pericellular space causes thickening of the secretion of the exocrine glands.

When it is difficult to evacuate thick secretions, the bronchopulmonary and digestive systems are primarily affected.

Impaired 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 (dilatation of the bronchi) and emphysematous (inflated) areas of the lung.

Bronchiectasis is observed 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, and foci of goblet cell hyperplasia and squamous metaplasia are observed.

When the bronchi are completely blocked by mucus, zones of collapse of the lung lobe (atelectasis) are formed, as well as sclerotic changes in the lung tissue (diffuse pneumosclerosis develops). In all layers of the bronchial wall there is infiltration of lymphocytes, neutrophils and plasma cells.

The mouths of the mucous bronchial glands dilate, purulent plugs are revealed in them, and in the lumens of bronchiectasis there is a large amount of fibrin, disintegrating leukocytes, necrotic bronchial epithelium and colonies of cocci. The muscle layer is atrophied, and the walls of bronchiectasis are thinned.

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

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

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

Other changes in the heart area are also observed. Patients are diagnosed with:

• myocardial dystrophy (metabolic disorder of the heart muscle) with interstitial sclerosis;
• foci of myocardial myxomatosis;
• thinning of muscle fibers;
• lack of transverse striations in places;
• sclerotic foci (interstitial sclerosis) in the vascular area;
• moderate swelling of the vascular endothelium;
• cardiac dystrophy, expressed to varying degrees.

Valvular and parietal endocarditis is possible.

When the secretion of the pancreas thickens, blockage of its ducts often occurs during the period of intrauterine development. In such cases, pancreatic enzymes produced by this gland in normal quantities 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 interlobular and intralobular ducts and flattening and atrophy of the epithelium. Inside the lobules and between them, there is a proliferation of connective tissue and its infiltration by neutrophils and lymphohistiocytic elements. Hyperplasia of the islet apparatus, atrophy of the gland parenchyma and fatty degeneration of the tissue also develop.

The intestinal epithelium becomes flattened and includes an increased number of goblet cells, and mucus accumulation is present in the crypts. The mucous membrane is infiltrated with lymphoid cells including 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 relative preservation of pancreatic function for a long time.

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

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

Almost all patients experience thickening of the connective tissue and scar 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 approximately 5 times. This pathology is observed throughout the patient’s life, so a hot climate is contraindicated for people suffering from cystic fibrosis (the risk of heat stroke increases, and convulsions are possible due to the development of metabolic alkalosis).

Symptoms

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

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

Over the course of 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 a deficiency of pancreatic enzymes. Symptoms of this form of the disease are:

• bloating;
• frequent bowel movements
• significantly increased fecal output;
• fetidity and light color of stool, the presence of a significant amount of fat in it.

Possible rectal prolapse when sitting on a potty (observed in 10-20% of patients).

There is often a feeling of dryness in the mouth, which occurs due to the viscosity of saliva, so eating dry food is difficult, and while eating, patients are forced to drink large quantities of liquid.

At the initial stages, appetite may be increased or normal, but due to digestive disorders, hypovitaminosis and malnutrition subsequently develop. As the disease develops, signs of cirrhosis and cholestatic hepatitis (increased fatigue, weight loss, jaundice, darkening of urine, disturbances in behavior and consciousness, abdominal pain, etc.) appear.

Cystic fibrosis of the lungs, due to overproduction of viscous secretions in the bronchopulmonary system, causes obstructive syndrome, which manifests itself:

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

An unproductive cough is possible.

The infectious-inflammatory process is chronic and recurrent. Complications are observed 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;
• presence of shortness of breath at rest;
• barrel-shaped deformation of the chest;
• deformation of the fingers (the terminal phalanges resemble drumsticks) and nails (resemble watch glasses);
• decreased physical activity;
• decreased appetite;
• low body weight.

Bronchial contents usually include Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae. Flora may be resistant to antibiotics.

The pulmonary form is fatal due to severe respiratory and heart failure.

Signs of cystic fibrosis in the mixed form include symptoms of intestinal and pulmonary forms.
The 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, cirrhosis of the liver or male infertility.

Cystic fibrosis in adults often causes infertility. 97% of men with cystic fibrosis have congenital absence, atrophy, or obstruction of the spermatic cord, and most women with cystic fibrosis experience decreased fertility due to increased viscosity of cervical mucus. At the same time, some women retain their reproductive function. Mutations of the CFTR gene are also sometimes found in men who do not have signs of cystic fibrosis (the mutation in 80% of such cases results in aplasia of the vas deferens).

Cystic fibrosis does not affect mental development. The severity of the disease and its prognosis depend on the timing of the disease manifestation - the later the first symptoms appear, the milder the disease 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 condition of the bronchopulmonary system. There are 4 stages:

• 1st, which is characterized by unstable functional changes, dry cough without sputum production, slight or moderate shortness of breath during exercise. 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 shortness of breath at rest and worsening with exertion, deformation of the terminal phalanges of the fingers. When listening, the presence of hard breathing with moist, “crackling” wheezing is revealed. This stage lasts from 2 to 15 years.
• Stage 3, at which complications arise and the pathological process in the bronchopulmonary system progresses. The formation of bronchiectasis, zones of diffuse pneumofibrosis and limited pneumosclerosis, and cysts occurs. Heart failure (right ventricular type) and severe respiratory failure are observed. The duration of the stage is from 3 to 5 years.
• Stage 4, which is characterized by severe cardiorespiratory failure, ending in death within several months.

Diagnostics

The diagnosis of cystic fibrosis is based on:

• musculoskeletal diagnostic signs, including family history, period of manifestation of the disease, its progressive course, the presence of characteristic damage to the digestive and bronchopulmonary systems, problems with childbirth (the presence of infertility or reduced fertility);
• data from basic laboratory diagnostic methods;
• DNA diagnostics.

Laboratory methods to detect cystic fibrosis in children include:

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

DNA diagnostics helps to most accurately diagnose cystic fibrosis. Typically used for research:

• Liquid blood, which in an amount of about 1 ml is placed in a test tube with an anticoagulant (heparin should not be used).
• A blood stain about 2 cm in diameter, dried at room temperature, placed on gauze or filter paper. Samples can be studied over several years.
• Histological samples that are used for analysis of the deceased.

Possible use:

• Direct diagnostics, allowing to identify a specific mutation in a specific gene.
• Indirect diagnosis, which analyzes the inheritance of genetic markers linked to the disease gene. This 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 (polymerase chain reaction) method 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 examination methods also help to diagnose cystic fibrosis:

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

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

Exocrine pancreatic function is assessed using a fecal pancreatic elastase 1 (E1) test. 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 through prenatal diagnosis. DNA samples are isolated at 9-14 weeks of pregnancy from chorionic villus sampling. At later stages of family contact, amniotic fluid (16-21 weeks) or fetal blood obtained by cordocentesis (after 21 weeks) is used for diagnosis.

Prenatal diagnosis is carried out if both parents have mutations or if a sick child in the family is homozygous. Prenatal diagnosis is recommended even if mutations are present in only one parent. A similar mutation identified 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 is carried out for the activity of aminopeptidase, gamma-glutamyl transpeptidase and the intestinal form of alkaline phosphatase (cystic fibrosis is characterized by a decrease in the amount of these intestinal enzymes).

If mutations of the CFTR gene cannot be identified, and a 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 assistance of doctors, kinesiotherapists 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 the lifestyle of healthy children. Patients with cystic fibrosis need:

• providing adequate, protein-rich and without restrictions on 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 diluting them;
• antimicrobial and anti-inflammatory therapy;
• vitamin therapy;
• timely treatment of complications.

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

Since pancreatic insufficiency in cystic fibrosis is not completely corrected, the sufficiency of the dose is indicated by the normalization of stool character and frequency, as well as laboratory data (steatorrhea and creatorrhoea are not detected in the coprogram, the concentration of triglycerides is normalized in the lipid profile).

Respiratory cystic fibrosis requires the use of:

• Mucolytic therapy, which includes the use of thiols that can effectively dilute bronchial secretions. N-acetylcysteine, which has not only a mucolytic but also an antioxidant effect, is used orally, intravenously or inhaled. Inhalations through a mask using recombinant human DNAse (Pulmozyme, Dornase alfa) are effective. Inhalation with hypertonic sodium chloride solution (7%) dilutes and evacuates sputum well.
• Kinesitherapy. To cleanse the pathological secretions of the bronchial tree and prevent infectious lesions of the lungs, postural drainage, autogenous drainage, percussion and klopf massage (consisting of vibration of the chest) 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 bronchial secretions and the results of laboratory tests for sensitivity to antibiotics. Since the use of various antibiotic regimens prevents or delays the development of chronic infection of the bronchopulmonary system, antibiotics are used long time and can be prescribed for preventive purposes.

To treat Pseudomonas aeruginosa infection, antibiotics are usually given intravenously.
The criterion for discontinuation of antibiotic therapy is the return of the main symptoms of exacerbation to the initial state for the patient.

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

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

Since damage to lung tissue is affected by the body's excessive immune response, macrolides, nonsteroidal 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 examination of external respiratory function, 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.

Liqmed reminds you: the sooner you seek help from a specialist, the greater your chances of maintaining health and reducing the risk of complications.

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Cystic fibrosis is a severe hereditary disease associated with a specific systemic disorder of the exocrine glands. When they are affected, patients experience pathological symptoms from various body systems. The disease is a chronic incurable illness with a progressive course.

If you translate the name of the disease from Latin into Russian, you get “sticky mucus” - a phrase that fully reflects the nature of the disease in question. Today, several hundred mutations have been discovered in the cystic fibrosis gene. In European countries, the incidence rate is 1:2500. Since cystic fibrosis is a congenital, genetically determined pathology, it cannot be contracted after birth.

However, the disease occurs not only in children, but also in adults. This is due to the fact that for quite a long time it may not show any symptoms. In most cases, cystic fibrosis is diagnosed in early childhood. The birth of a child with cystic fibrosis occurs when he receives one mutated gene from each of his parents. If only one gene is inherited, the child will not get sick, but will become a carrier of the disease.

With the disease described, all the glands of the human body produce a viscous and thick secretion, which accumulates in the ducts and internal organs, causing their dysfunction. At the same time it suffers:

• respiratory system– due to blockage of the bronchial lumen with mucous secretion in cystic fibrosis, the process of gas exchange is inevitably disrupted, infectious complications, pulmonary hypertension and respiratory failure develop;
• pancreas– mucus blocks the ducts of the gland, which leads to the activation of digestive enzymes directly in the pancreas, and not in the intestines, as this should normally happen. This contributes to the destruction of the organ, the formation of cysts in it, the development of inflammation, and disruption of hormonal function;
• liver– due to stagnation of bile, the liver suffers from constant inflammation, its connective tissue grows, the functioning of the organ is disrupted, and ultimately cirrhosis develops;
• digestive system– the excretory ducts become clogged, the process of food absorption is disrupted, and intestinal obstruction is also possible;
• heart– with the disease described, secondary damage to the heart often occurs, since the heart muscle with pulmonary hypertension is forced to work with triple strength. Many patients develop heart failure over time;
• genitourinary system– men with cystic fibrosis are in most cases. Women also experience problems conceiving due to too much high level the viscosity of the mucus produced by the cervix.

Modern medicine makes it possible to prolong the life of patients with cystic fibrosis as much as possible. Severe complications leading to progression of the disease and irreversible changes, including death, can occur if medical recommendations are not followed. Children often experience a general delay in physical development, while mental abilities remain normal.

The main cause of the disease is genetic mutations in the seventh chromosome. It is in it that the gene is located, which is responsible for the synthesis of protein (chloride channel) in the exocrine glands. Scientists have not yet been able to figure out why such failures occur.

Important! With the disease in question, damage occurs primarily to the bronchopulmonary and digestive systems. Other organs and systems are also affected, but to a much lesser extent.

Pathological processes in the bronchopulmonary system develop due to congestion in the bronchi. Because of them, the function of cleansing the organ from dust and other substances inhaled by humans is disrupted and active reproduction of pathogenic microflora begins. Gradually, the inflammatory process contributes to the inhibition of the protective function of the bronchial tissue, the frame of the organ itself is destroyed, the lumen of the bronchial tree narrows, which further aggravates the stagnation of viscous secretions.

If we consider the mechanism of damage to the gastrointestinal tract, then even during the period of intrauterine development of the fetus, there is a delay in the formation of endocrine glands. The pancreas becomes deformed and produces excessively thick mucus that clogs the ducts of the organ. As a result, digestive enzymes are activated directly in the organ itself, thereby gradually destroying it.

Forms of cystic fibrosis

The disease can have many manifestations with varying degrees of severity. The classification of cystic fibrosis includes the following forms:

• pulmonary form– is diagnosed in approximately 20% of cases and is characterized by damage to the lungs. Most often, the disease is detected in the first years of a baby’s life, who, due to a lack of oxygen, has symptoms of disorders in almost all internal organs;
• intestinal form– occurs in approximately 10% of patients. The first signs of this type of cystic fibrosis are observed, as a rule, at the age of six months, when the child is transferred to artificial nutrition. He does not digest food properly, develops hypovitaminosis, fecal disturbances and obvious signs of retarded physical development;
• mixed form– diagnosed most often (in approximately 70% of patients) and is characterized by simultaneous damage to the bronchopulmonary system and gastrointestinal tract;
• erased forms– may manifest as bronchitis, sinusitis, infertility in men and women, cirrhosis of the liver;
• meconium ileus– intestinal obstruction in newborns caused by blockage of the terminal ileum by meconium.

The symptoms of the disease can vary depending on many factors, in particular age, the time of appearance of the first clinical signs, duration of the course, etc.

When the pathological process spreads to the bronchopulmonary system in sick children after stopping breastfeeding occurs:

• persistent cough with viscous sputum;
• a slight increase in temperature in the absence of signs of acute intoxication of the body;
• if a secondary infection occurs, severe infection may develop, accompanied by high fever, shortness of breath, severe cough, signs of intoxication (nausea, vomiting, dizziness, etc.);
• with all this, the child does not gain weight well, is lethargic and apathetic;
• the chest becomes barrel-shaped;
• the condition of hair and skin worsens;
• there is shortness of breath, which increases with physical stress;
• bluish tint of the skin.

With secondary damage to the heart due to impaired gas exchange and oxygen supply to tissues, patients develop heart failure, accompanied by symptoms of cystic fibrosis such as:

• shortness of breath, including at complete rest;
• skin cyanosis;
• cardiopalmus;
• swelling of the legs.

If the disease affects the exocrine glands of the pancreas, the patient develops symptoms similar to those that appear in the chronic form of pancreatitis. Observed:

• bloating;
• feeling of heaviness in the stomach;
• girdle pain, which becomes more intense after eating fried and fatty foods;
• frequent episodes.

Children with this genetic pathology experience general weakening and increased susceptibility to infections. Usually the lesion affects the least gallbladder and liver, so the characteristic yellowness of the skin appears already in the later stages. Also with cystic fibrosis, genitourinary disorders are noticeable.

Note! The totality of all the increasing clinical manifestations and symptoms of cystic fibrosis almost inevitably leads to disability. Due to frequent exacerbations, patients become weakened and exhausted by the disease. However, with adequate care and proper treatment, people with this disease are able to lead full lives.

The life expectancy of such patients is on average twenty to thirty years.

How is diagnostics carried out?

Diagnosis of cystic fibrosis includes several important steps. Preventing severe complications of the disease and taking measures to improve the living conditions of a sick child will allow early detection of pathology, which is based on clinical signs of chronic inflammation in the bronchopulmonary system or corresponding symptoms of gastrointestinal damage.

Thus, the diagnosis of the disease in question includes:

• carrying out laboratory tests: sweat test based on determining the amount of chlorine ions in sweat after administration of pilocarpine, coprogram, general blood test, sputum analysis;
• radiography;
• spirometry;
• molecular genetic research;
• measurement of anthropometric data;
• Ultrasound – is prescribed for severe damage to the heart, gallbladder and liver.

The capabilities of modern medicine also make it possible to carry out prenatal diagnostics - identifying cystic fibrosis and other genetically determined diseases in the prenatal period. If the disease is detected on early, the question of artificial termination of pregnancy is raised.

As already mentioned, cystic fibrosis is an incurable disease, but competent supportive therapy can significantly facilitate and prolong the life of patients.

Note! Treatment for cystic fibrosis is symptomatic, and it should be carried out throughout life. Interruption of therapy is fraught with rapid progression of the disease with the development of severe complications.

It is extremely important for all patients to make it a rule:

• regularly cleanse the bronchi from viscous secretions;
• carry out prophylaxis that will protect the bronchi from the proliferation of pathogenic microorganisms in them;
• constantly strengthen the immune system;
• fight the stress that inevitably arises as a result of a grueling fight against the disease.

Carrying out therapeutic measures is necessary both during acute periods and during periods of remission.

For inflammatory processes in the organs affected by the disease, the following are prescribed:

• drugs from the group;
• glucocorticosteroids are hormone-based drugs (prednisolone) that help cope with infectious processes and inflammation. They are prescribed only in the most severe cases, when the patient has a blockage of the respiratory tract;
• oxygen therapy;
• physiotherapy and inhalations.

If disorders of the digestive tract are identified, therapy is necessary aimed at improving the process of food absorption. Patients are prescribed a special high-calorie diet. For children under one year of age, special nutritional supplements. Drugs are also prescribed to improve liver function.

Important! In case of cystic fibrosis, all chronic infectious foci must be treated, be it a common runny nose or caries.

And although medical scientists have not found an effective medicine that can completely cure cystic fibrosis, they have developed special techniques that significantly improve their well-being and can be performed even by the patients themselves. The most significant way to treat cystic fibrosis has become the so-called kinesitherapy, which consists of regularly performing a series of exercises and procedures that improve lung ventilation. Kinesitherapy includes postural and vibration massage, as well as the practice of an active breathing cycle with positive exhalation pressure.

The most radical treatment method is lung transplant surgery. Transplantation can stabilize the patient's condition only when other organs and systems have not been affected by the lesion. After surgery, medications that suppress the immune system are prescribed, which helps avoid rejection of the transplanted organ. The surgery itself is very complex and lengthy, and its successful implementation does not eliminate the need for lifelong treatment for cystic fibrosis.

Prevention

As for the prevention of cystic fibrosis, prenatal diagnosis is considered one of the most important measures to prevent the disease, with the help of which it is possible to identify the presence of a defect in the seventh gene even before birth. To strengthen the immune system and improve living conditions, all patients need careful care, good nutrition, personal hygiene, moderate physical activity and the provision of the most comfortable living conditions.

Chumachenko Olga, pediatrician

This disease leaves its mark on the child’s entire life, starting from infancy. Over time, cystic fibrosis damages almost every organ system (intestinal, respiratory, reproductive, etc.), to a greater or lesser extent. Even 40 years ago, this pathology was considered exclusively for children, since young patients did not live to reach adolescence, and even more so older age. However, thanks to the modern level of medicine, such a statement has remained in history. Currently, patients reach 30-45 years of age, with adequate therapy.

Why does cystic fibrosis occur?

Despite the fact that the first symptoms of cystic fibrosis in children may appear only at 6-7 months, this pathology is considered congenital. The reason for its development is a change in one of the chromosomes, which is responsible for the creation of an important regulatory protein. Without it, the composition of all fluids secreted by the glands (pancreas, sweat, liver, etc.) is disrupted.

This genetic defect is quite rare - in one child out of 3 thousand. However, once a mutation has occurred, it cannot be corrected. That is why cystic fibrosis is considered an incurable disease, but not fatal. With the help of properly prescribed therapy, it is possible to maintain the quality of life of patients at a decent level for a long time (several decades).

How does cystic fibrosis develop?

Each person has organs whose purpose is to produce special fluids (secrets) for the normal functioning of all systems: respiratory, digestive, excretory and others. They are designated by one term - “exocrine glands”. Why "external"? Because biologically active substances do not enter the blood, but are ultimately released into the environment. It is these organs that are primarily affected by cystic fibrosis.

All symptoms of the disease arise for one reason - a change in the composition of the fluids secreted by the glands. They become much thicker than they should normally be. Because of this, the secretion stagnates in the ducts, damages the organ and does not fulfill its function.

Taking into account the mechanism of development of the disease, we can say exactly what symptoms it will manifest. This point is very important for timely diagnosis and successful treatment of pathology.

Symptoms of cystic fibrosis

To a greater or lesser extent, the disease affects almost all exocrine glands. Therefore, its symptoms can be very diverse - from diarrhea to asthma attacks. It is this range of symptoms that should alert parents and doctors. The first signs of cystic fibrosis usually appear in the first year of a baby’s life. In rare cases (up to 10%) - in the first days after birth.

Neonatal cystic fibrosis

As you know, the first bowel movements of a child are different from all subsequent ones. A baby's poop is mostly made up of partially digested amniotic fluid that was swallowed in the womb. Pediatricians and neonatologists call it “meconium.” Unlike regular stool, it has no odor (since it contains virtually no bacteria), is more viscous (the consistency is similar to resin), and has a characteristic brown-yellow color.

Cystic fibrosis in newborns can manifest itself as intestinal obstruction due to blockage with original feces. Due to the fact that the secretion of the digestive glands is much thicker than it should be normally, the normal passage of meconium is disrupted. It stagnates at a certain level and does not allow digested milk and gases to pass through.

Why is this dangerous? Above the level of fecal stagnation, the intestines begin to stretch and become damaged, which can allow toxins to enter the baby's bloodstream. If the obstruction is not identified in a timely manner, the wall of the organ may rupture and cause the development of peritonitis (inflammation of the peritoneum). The level of harmful substances in the blood, in this case, reaches a critical value and often leads to the death of a small patient.

How does meconium ileus manifest? A child cannot say that he has a stomach ache, so the pathology can be diagnosed only by external data and his behavior:

• The newborn does not have stool or pass gas for a long time;
• Characteristic is hysterical crying, which intensifies when palpating the tummy. The child tries to lie still, as movements cause him pain;
• If you examine the abdominal area, you can note the presence of bloating, sometimes you can see a thickening of the wall and even the outline of the intestine;
• When palpating, it is quite easy to determine the area where the obstruction is located - with your fingers you can feel the dense, swollen intestinal wall. Below the level of stagnation, the diameter and density of the organ become normal.

Even at the slightest suspicion of this pathology, you should urgently call a doctor (preferably a neonatologist or pediatrician). He will be able to objectively assess the child’s condition and confirm/refute the presence of intestinal obstruction.

Cystic fibrosis in young children

Most often, children with cystic fibrosis are diagnosed at 5-7 months of life. Pathology can manifest itself in different ways, but two signs are most typical for young patients - decreased weight gain and damage to the respiratory tract.

In the first six months after birth, the child must gain at least 500 g in weight every month. By 6 months, the baby should weigh about 8 kg, and by 12 months - at least 9.5 kg. Developmental delay can be caused by various reasons: an unbalanced diet, previous intestinal infections, the presence of endocrine diseases, etc.

Cystic fibrosis should be suspected as a factor in reducing the child's weight in combination with respiratory disorders and constant stool disorders. Feces may be liquid, or its consistency may change - it becomes “greasy”, smears heavily and is difficult to wash off from diapers. Its color remains unchanged or becomes yellow. In some cases, it takes on a shiny appearance.

Typical respiratory symptoms of cystic fibrosis in infants include:

• A persistent dry cough, which subsides somewhat after treatment, but reoccurs a few weeks after “recovery.” More often, attacks intensify at night, due to the infant’s lying static position;
• Episodes of suffocation - the child coughs and suffocates due to blockage of part of the respiratory tract with a mucus plug. If he coughs, a small amount of thick, sticky mucus comes out. The liquid may be clear or dirty green (if it is infected with bacteria);
• Frequent repeated respiratory tract infections (rhinitis, pharyngitis, bronchitis, etc.). It is not uncommon for cystic fibrosis to be hidden under the guise of “chronic bronchitis,” which is difficult to treat and occurs with frequent exacerbations.

Let us note once again that this disease is very characterized by a combination of symptoms from the digestive and respiratory tracts. Over time and without adequate therapy, they will only develop, taking a chronic relapsing course.

Symptoms of damage to various systems

As the child grows up, this pathology will develop with him. If the correct therapy has been prescribed since childhood, the disease can be partially controlled and most relapses can be prevented. However, regardless of treatment, the symptoms of cystic fibrosis in adults may be supplemented by new signs of system damage:

Modern medicine can cope with most of these symptoms with the help of drugs, but some changes in the internal organs become irreversible. Therefore, it is important to promptly identify the disease and prevent its development. severe forms pathology

Cardiopulmonary failure

Although this condition is not directly related to cystic fibrosis, it can occur with the disease. The reason lies in a serious obstruction of the respiratory tract. Over time, most of the small bronchi become closed with mucus and stop carrying oxygen. Due to the fact that the remaining respiratory tract cannot deliver the same volume of air for gas exchange, the heart has to “pump” blood to the lungs much more intensely.

For several years, these processes may not manifest themselves in any way, as the organs cope with increased load. Gradually, the right side of the heart begins to increase in size, as it can no longer perform the “work” assigned to it. Quite quickly, its compensatory capabilities expire, and the blood begins to stagnate in the organ cavity and pulmonary vessels. It is at this stage that cardiopulmonary failure (CPF) develops.

How does it manifest itself? It is quite easy to suspect it without special research. The following signs are characteristic of SLS:

• Shortness of breath. At the very beginning of the process, the symptom can occur only after mental/physical stress (severe stress, climbing stairs, etc.). However, the process progresses and in severe cases, shortness of breath begins to appear spontaneously, without any provoking factors;

• Moist cough . It occurs due to stagnation of blood in the pulmonary vessels and sweating of its liquid part into the intercellular space;

• Pale skin. A typical manifestation of a lack of oxygen for tissues;

• « Drumsticks". This is a characteristic change in the fingers, manifested by thickening of the nail (end) phalanges. Characteristic of severe SHF, in which the functioning of not only the right, but also the left parts of the heart is disrupted;

• "Watch glasses". Changes in fingernails such as thickening, protrusion, and receding round shape. As a rule, it occurs together with the symptom of “drumsticks”.

The presence of this condition is an unfavorable prognostic sign, since pulmonary heart failure significantly worsens the patient’s quality of life. It is impossible to get rid of it.

Diagnosis of cystic fibrosis

It is important to detect the relationship between the symptoms of cystic fibrosis as early as possible in order to make a correct diagnosis, and not to treat “false” bronchitis, dysbiosis, lactase deficiency and other pathologies that the child has never had. First of all, the doctor and parents should be alerted to the range of symptoms that occurs in a young patient almost simultaneously.

In addition to the characteristic clinical picture, it is important to use special laboratory techniques. Classic blood and urine tests will not give a clear picture. The diagnosis can be confirmed using a simple but unusual method - examining the patient's sweat. In case of cystic fibrosis, the content of electrolytes (chlorine and sodium) should exceed the norm by 3-5 times.

If the doctor doubts the results of the study or the symptoms do not allow a clear conclusion, the child undergoes a genetic examination. If a defect in the regulatory protein gene is found, there is no doubt about the presence of the disease.

As additional methods to assess the condition of the body and its individual systems, you can use:

As a rule, the listed studies are sufficient to make a final diagnosis and determine the amount of treatment required.

Modern treatment of cystic fibrosis

Since it is impossible to restore the damaged chromosome and completely get rid of this pathology, treatment should be aimed at restoring the functions of individual organs. In cystic fibrosis, the main burden, as a rule, falls on the digestive and respiratory systems, so correcting their work is the primary goal of therapy.

Therapeutic nutrition for infants

It is very important to organize nutrition for an infant with cystic fibrosis. This will help prevent developmental delays in the child that occur due to lack of nutrients, and strengthen his body from harmful external influences. Let us note the most important points:

1. If the child's mother does not suffer infectious diseases, including chronic ones (HIV, hepatitis, etc.), breastfeeding is always better than synthetic formulas. It is optimally absorbed in the child’s intestines, as it is created only for him. It also contains substances (antibodies) that protect the baby’s body from pathological microorganisms;
2. If it is not possible to feed the baby with mother’s milk, special “adapted” formulas should be used, which are easier to digest in conditions of impaired digestion. These include: Humana LP + MCT, Alfare, Nutrilon Pepti TSC, Pregestimil and others. Your attending pediatrician will help you choose the best option;
3. If a child has a confirmed lack of pancreatic enzymes, it is necessary to compensate for their deficiency, starting from an early age. For this purpose, there are modern preparations in the form of microgranules, which are enclosed in one capsule: Creon, Ermital or Panzinorm. The dose should be selected individually. As a rule, 1/3 or 1/2 of one capsule is enough for children under one year of age;
4. Feeding should be done at the baby's request. The signal for this is “hungry” crying. Most often, it looks like this - the baby screams invitingly for a certain time, after which it calms down for a few minutes, waiting for the result. If he is not fed, he continues to cry.

Each of these points is explained to the parents of a small patient by neonatologists/pediatricians immediately after the disease is diagnosed. It is important to approach the issue of feeding responsibly, as this will have big influence on the future quality of life of the child.

Medical nutrition for adolescents and adults

For older patients, proper nutrition does not lose its relevance, but the requirements for it are much easier to fulfill. There are only three of them:

1. The diet should be dominated by high-calorie foods - the daily intake in patients with cystic fibrosis should be 1.5-2 times higher than in healthy people. Calories should be distributed evenly throughout the day over 4-5 meals;
2. If the patient has proven insufficiency of digestive enzymes, adequate doses of replacement medications must be selected. The drugs used are the same as for infants;
3. The patient's body must receive vitamins A, D, E, and K. As a rule, regular multivitamin complexes are prescribed for this purpose.

Such simple nutritional correction will significantly improve the quality of life with this disease, maintaining physical development at the proper level and maintaining immune function.

Treatment of respiratory disorders

Medication methods

The second, most common group of symptoms, along with digestive disorders, are signs of damage to the respiratory tract. The biggest role in this pathological process is the blockage of small bronchi with mucus, which makes normal breathing impossible. Taking this point into account, you can decide on treatment tactics - you should constantly dilute the thickened secretion of the glands and expand the airways (if necessary).

This can be done using two groups of drugs:

• “Thinning” medications (Ambroxol, Acetylcysteine, Carcysteine ​​and their analogues) - thanks to this therapy, in patients with cystic fibrosis it is possible to reduce the density of the mucous fluid in the bronchi, so that they can expectorate it and independently restore the patency of the respiratory tract. For this purpose, you can also use a regular solution of Sodium Chloride (recommended 7%) for inhalation;
• Therapy that dilates the bronchi (Salbutamol, Berodual, Formoterol, Fenoterol) - the need for these drugs is determined individually. Most often, they are not used for continuous use, but only during attacks of suffocation/shortness of breath.

As a rule, inhalation is considered the optimal method of drug delivery for patients with cystic fibrosis. It allows you to achieve better effect from a smaller dose of medication. Therefore, patients (or their parents) are recommended to purchase a nebulizer - this is a small device with which you can carry out therapy at home.

The best drug for normalizing breathing. In addition to nonspecific drugs (Ambroxol, Acetylcysteine, etc.), which are used for any bronchitis, pneumonia and other respiratory tract diseases, a special medicine has been developed for cystic fibrosis - DNase (synonyms Silex, Pulmozyme). It is aimed at destroying mucus in the lumen of the bronchi and improving its discharge. Comparing the effect of Ambroxol and Pulmozyme, it was proven that the second drug is much more effective in this pathology. The disadvantage of DNase is its price - on average, 7,500 rubles. for 2.5 ml of solution.

Kinesiotherapy

In addition to the use of medications to restore breathing, a certain effect can be achieved from a non-drug technique called “Kinesiotherapy”. Literally, this term means “motion therapy.” This is a set of measures that mechanically affect the chest and improve the movement of mucus in the respiratory tract.

What is kinesiotherapy? Currently, the following methods are distinguished:

• Percussion massage - with the patient sitting, rhythmic tapping blows are performed on the chest. As a rule, they start from the front surface and then move to the back. To perform it, it is not necessary to involve a specialist - after simple training from a doctor, even members of the patient’s family can perform it;
• Active breathing - normal deep breathing movements that cause the bronchi to periodically expand/contract, which improves the passage of fluid through them;
• Postural drainage is performed by the patient independently. To do this, you need to put your feet on an elevated surface and actively cough up sputum while lying down, turning from your stomach to your side. It has been proven that thanks to this simple manipulation, the effect of medications can be significantly improved;
• Devices for compression-vibration effects - at present, special equipment has been developed that applies vibration to the chest, breaking up solid mucous formations into separate parts. However, these devices are not common in the Russian Federation.

It is very important that treatment of cystic fibrosis in children and adults is carried out using all available techniques until the patient’s well-being improves. Since this is a serious incurable disease with constant exacerbations, you should not neglect the doctor’s recommendations, even if they seem insignificant (regarding diet, kinesiotherapy, etc.).

Latest developments in the treatment of cystic fibrosis

Currently, the search for a gene treatment for the disease has almost reached a dead end. Therefore, scientists decided to influence not the very cause of the pathology, but the mechanism of development of cystic fibrosis. It was determined that the thickening of the secretions of the glands occurs due to a lack of one microelement (chlorine) in them. Accordingly, by increasing its content in these fluids, the course of the disease can be significantly improved.

For this purpose, the drug VX-770 was developed, which partially restores the normal chlorine ratio. During clinical trials, doctors were able to reduce the frequency of exacerbations by almost 61%, improve respiratory function by 24% and achieve weight gain by 15-18%. This is a significant success and suggests that in the foreseeable future, cystic fibrosis can be successfully treated, rather than just eliminating its symptoms. On this moment, The VX-770 is undergoing additional testing and will not go on sale until 2018-2020.

Forecast

In most cases, patients with cystic fibrosis live to an older age (about 45 years) with adequate treatment. Their quality of life is somewhat lower than that of healthy people due to regular exacerbations of pathology and the constant need for medications. The patient is registered all his life in medical institutions (usually regional or regional centers), where he needs to be observed every six months if the course of the disease is stable.

FAQ

Question:
If the parents are healthy, can the child develop this pathology?

Yes, since the parents may be carriers of the damaged gene.

Question:
How to prevent cystic fibrosis?

To do this, you need to undergo a medical genetic consultation. Several years ago, according to a government program, such centers were created in every region. However, each analysis there is carried out for a fee, even if the parents are at risk.

Question:
Is it necessary to use antibiotics to treat this disease?

Only in case of infectious complications (pneumonia, purulent bronchitis, abscesses, etc.)

Question:
Does this disease affect mental development?

No, as a rule, children with this pathology do not lag behind their peers in mental development.