Pediatric Medical Genetics - S.I. Smiian 2003

Congenital malformations and hereditary diseases of the bronchopulmonary system in children
Hereditary pulmonary diseases

Idiopathic diffuse pulmonary fibrosis — IDPF (idiopathic fibrosing alveolitis, Hamman-Rich syndrome). An inherited disease with an autosomal dominant pattern of inheritance.

In the acute course, edema of the interstitial Connective Tissue predominates; in the subacute course, thickening of the alveolar septa, atrophy of elastic fibers, and an increase in Collagen fibers; in the chronic course, the presence of microcystosis. The lung architecture is lost, and lung tissue is replaced by areas of fibrosis.

The cough is dry and non-productive, with minimal or absent sputum, and distinctive crackles — fine, crepitant, inconsistent, like the "crackling" of cellophane, "sclerophony". Initially, There is a discrepancy between the severity of dyspnea and minimal physical findings. Weight loss of 5-9 kg. Chest deformity (often flattening), "clubbing" (drumstick fingers), "watch-Glass Nails" — all these symptoms accompany idiopathic fibrosing alveolitis (Fig. 21). During exacerbation of the pathological process, there is an increase in body Temperature, a decrease in VC, TLC, and an increase in g-globulin levels up to 25-30 %, Ig G. Chest X-ray reveals a "ground-glass" appearance — reduced lung transparency, hilar fibrosis, increased lung markings, reticulation, and eventually nodular and focal opacities (Table 3).

Bronchography reveals bronchial narrowing, deformity, and even Bronchiectasis, while a significant number of neutrophils is found in the lavage fluid. The Diagnosis is established by intravital lung biopsy.

Due to The Development of cardiopulmonary failure, the prognosis is unfavorable. In the chronic course of IDPF, life expectancy is 4-6 years; onset of the disease in the first year of life worsens the prognosis.

We present our own clinical observation.

Excerpt from Case History No. 7783

A 12.5-year-old girl, M., was admitted to the clinic complaining of a frequent dry cough, shortness of breath, and general exhaustion.

According to her medical history, frequent respiratory episodes, recurrent Bronchitis, and Pneumonia have been observed since the second half of her first year of life. She underwent inpatient Treatment 3–4 times a year. The Effect of conventional therapy (Antibiotics, expectorants, bronchodilators) was short-lived. Progressive shortness of breath did not correlate with physical findings. Failure to thrive eventually progressed to dystrophy and general exhaustion. At the age of 11, she was diagnosed with idiopathic fibrosing alveolitis at the Moscow Research Institute of Pediatrics and Pediatric Surgery. For a year, the child received maintenance doses of corticosteroids and immunosuppressants.

The girl was born from the first full-term physiological Pregnancy, birth weight was 3600 g, and she cried immediately. The neonatal period was uneventful.

From six months of age, she experienced frequent respiratory episodes and began to lag in physical development.

There was no history of trauma or surgery.

The mother is healthy, while the father died at a young age from a pulmonary disease. The maternal grandmother has Bronchial Asthma. The mother's subsequent pregnancy ended in a Miscarriage.

The girl is allergic to dog Hair and poplar fluff.

On examination, the child's condition is severe, with severe malnutrition and a 39% weight deficit. The Skin is pale and dry, with cracks at the corners of the Mouth, perioral cyanosis, and acrocyanosis. Clubbing of the distal Phalanges is present, resembling "drumsticks" and "watch glasses". Subcutaneous fat is absent on the trunk and limbs. Tissue turgor is reduced.

The chest is keel-shaped, flattened anteroposteriorly (Fig. 21). Asymmetry of the scapulae, right-sided Scoliosis.

RR — 38 per minute, oral crepitus, inspiratory dyspnea. On lung Auscultation, there is A large number of fine, transient crepitant crackles, sclerophony. Percussion over the lower lung fields reveals a decreased percussion note.

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Fig. 21. Girl M., 12.5 years old. Idiopathic diffuse pulmonary fibrosis.

The borders of The Heart are not enlarged, Cardiac Activity is regular, and heart sounds are muffled.

The abdomen is soft, tender on deep Palpation in the right hypochondrium.

The Liver is enlarged by 2 cm, elastic. Ortner's sign is positive.

Stool and urination are normal.

Chest X-ray shows bilateral loss of the bronchovascular pattern due to overlying fibrotic Changes in the hilar region. The hila are poorly defined, infiltrated, with fibrotic streaking in the lower zones.

Cor — bulging of the II-III arches on the left.

The spirogram shows a significant mixed-type impairment of pulmonary ventilation. Grade II-III ventilatory insufficiency.

ECG: sinus tachycardia. Impaired repolarization in the ventricular myocardium.

Allergy tests: sensitization to house dust and dog hair.

Immunogram: grade II cellular immunodeficiency (total T-Cells — 36 %, active T-cells — 16 %, increased O-cells — 52 %), allergic predisposition manifested by a low count of T-suppressor cells (7 %), elevated level of CIC (220 arb. units), hyperimmunoglobulinemia.

Complete Blood count: grade I deficiency anemia (erythrocytes 3.02І,І10¹²/L, Hb — 98 g/L, CI 0.8).

Abdominal ultrasound: liver — +2 cm, homogeneous parenchyma.

Gallbladder is oval-shaped, walls are 3 mm.

Pancreas and Kidneys are unremarkable.

The child was consulted by a thoracic surgeon, geneticist, ENT specialist, and orthopedist.

Clinical diagnosis: Idiopathic fibrosing alveolitis (Hamman-Rich syndrome); chronic pulmonary insufficiency (respiratory failure grade II). Chronic cholecystocholangitis of moderate severity, sluggish course. Grade I deficiency anemia. Grade II right-sided scoliosis.

Prescribed treatment: 1) ward regimen; 2) Pevzner diet No. 5; 3) prednisolone at a dose of 0.8 mg/kg; 4) expectorants: ambropuren 1 capsule in the morning; 5) Vitamins: aevit 1 dragee 3 times daily, Vitamin C 0.25 1 tab. three times daily; 6) riboxin 0.2 1 tab. 3 times daily; 7) iron supplements at a dose of 5 mg/kg: hemofer 1 tab. 3 times daily; 8) allochol 1 tab. 3 times daily; 9) tubage with sorbitol.

For the Second Stage of treatment, the child was transferred to the local sanatorium 'Berezhany'. Detailed recommendations for maintenance therapy were provided, taking into account immunological changes.

Given the early onset of the disease (During the first year of life) and its continuously relapsing course, the prognosis for this girl's life is unfavorable.

Corticosteroids and immunosuppressants are used in the treatment of IFA.

Kartagener syndrome (Fig. 22) has an Autosomal Recessive Inheritance pattern with 50% penetrance (frequency of 1:50,000) of the pathological Gene. It occurs more frequently in consanguineous marriages.

This syndrome is characterized by a triad: 1) situs viscerum inversus; 2) bronchiectasis; 3) sinusitis. Kartagener syndrome is a form of ciliary dyskinesia — the defect in ciliary Structure is considered a genetically determined pathology. In 90% of patients, the chronic bronchopulmonary process develops during the first or second year of life, and its activity in the bronchopulmonary system and nasopharynx determines the severity of the disease.

Fig. 22. Diagram of pathological changes in Kartagener syndrome.

Clinical Features. A characteristic cough with purulent sputum production and multiple physical findings: mixed moist crackles and dullness to percussion. Dextrocardia, left-sided liver position, obstructed nasal breathing, and purulent nasal discharge are observed. Otitis media is common, leading to Hearing loss, and signs of blepharoconjunctivitis may occur. Subsequently, Cor Pulmonale develops. Physical findings in the Lungs are identical to those found in patients with chronic pneumonia. The diagnosis is confirmed by X-ray Examination, which reveals diffuse changes predominantly localized in the basal segments. Bronchoscopy shows signs of purulent endobronchitis and a reversed bronchial tree; bronchography reveals cylindrical and saccular bronchiectasis, bilateral bronchial deformity, and sometimes polycystic disease.

Treatment is conservative, using anti-inflammatory drugs to clear the lungs and nasopharynx. Postural drainage and inhalations that facilitate sputum expectoration are indicated. Surgical treatment is of low efficacy because the pathological process is associated with a ciliary defect.

The prognosis for recovery is unfavorable.

Idiopathic pulmonary hemosiderosis (IPH) was first described by Virchow in 1864 under the name 'Brown Induration of the lungs'. This pathological process is characterized by lung damage with iron deposition in them, as well as anemia. The disease is rare; by 1968, 200 cases had been described. It is inherited in a dominant pattern, and the penetrance of the pathological gene is low.

It is suggested that an anomaly in the development of pulmonary arteriolovenular anastomoses and an abnormal structure of mucopolysaccharides in the pulmonary connective tissue are inherited. These changes lead to increased blood congestion in the lung tissue, significant extravasation of erythrocytes into the lung tissue (per diapedesis), and gradual sensitization of the body to them. Iron from hemolyzed erythrocytes forms a stable bond with pathological mucopolysaccharides and does not enter the bloodstream, failing to participate in metabolic processes and Hemoglobin synthesis. Therefore, the anemia accompanying IPH is classified as iron-deficiency anemia. Iron deposition, hemorrhages, and inflammatory flare-ups lead to pulmonary fibrosis, pulmonary Hypertension, and Chronic cor pulmonale. Allergic lesions of the joints, skin, heart, and kidneys may also develop.

Clinical features. The disease more commonly develops in school-aged children and has a fluctuating course. The onset is usually gradual, with weakness, lethargy, fatigue, pallor, dizziness, moderate dyspnea, subicterus, sometimes icteric sclerae, hypochromic anemia, and a mild cough in some children. During an exacerbation (crisis), sudden weight loss, severe weakness, sharp headache, acrocyanosis, fever up to 39-40 °C, dyspnea, tachycardia, retrosternal and abdominal pain, cough with sputum production (sometimes rusty), and hemoptysis are noted; physical examination reveals dullness to percussion and multiple mixed moist crackles. The hemogram shows anemia and an increased ESR. The chest X-ray reveals cloud-like small focal opacities, 1-2 cm in diameter, which sometimes coalesce. The involvement is usually bilateral; less frequently, a segment or lobe is involved. An increased bronchovascular marking is also observed. The severity of pulmonary fibrosis and emphysema depends on the severity and duration of the disease. Small focal lesions, similar to Miliary tuberculosis, are noted, especially after the I and II crises. With each crisis, respiratory failure and clinical manifestations progress.

Diagnosing the disease is difficult. The main diagnostic criteria are the combination of lung lesions with hypochromic anemia, hemoptysis, chest pain, and allergic manifestations. Siderophages and hemosiderin-laden macrophages are found in the sputum and bronchial washings, and the iron content in the sputum is increased. Lung tissue examination is of great importance.

Prognosis. Previously, the life expectancy of patients was about 3 years. Thanks to The Use of hormonal drugs, particularly prednisolone (2 mg per 1 kg of body weight), immunosuppressants, and, if ineffective, splenectomy, the prognosis has become more favorable. The combination of hemosiderosis and Glomerulonephritis forms The basis of Goodpasture's syndrome (up to 1973, 220 cases had been described). This condition is considered an immune complex disease.

Primary pulmonary hypertension is associated with increased pressure in the pulmonary artery and isolated Hypertrophy of the right ventricular myocardium. These changes are unrelated to congenital or acquired Pathology of the lungs or heart. There are about 20 names for the disease — idiopathic right ventricular hypertrophy, primary pulmonary artery sclerosis, isolated pulmonary hypertension, Ayerza's disease, and others. The inheritance pattern varies — dominant or recessive.

Pathomorphology: pathomorphological changes in primary pulmonary hypertension are distinct. Right ventricular hypertrophy, dilation of the large Branches of the pulmonary artery with layered fibroelastosis of the intima, the presence of arteriovenous anastomoses, thrombosis, and fibrinoid necrotic arteritis of the small branches of the pulmonary artery are observed.

The Clinical presentation of primary pulmonary hypertension is characterized by dyspnea on exertion, and later at rest, weakness, fatigue, eventually cyanosis appears, pain in the heart region and retrosternal pain are observed; dizziness and loss of consciousness as a consequence of Hypoxia; hemoptysis, which is associated with vasculitis. Initially, there are no changes in the lungs, but later a secondary inflammatory process develops. There is an increased systolic pulsation in the epigastric region, and sometimes in the II-III intercostal spaces on the left, accentuation of the second heart sound (S2) over the pulmonary artery, sometimes splitting of the heart sounds, and a systolic murmur of various locations as a sign of right ventricular hypertrophy. Among the radiological changes, dilation of the right heart chambers, pulmonary roots and their pulsation, bulging of the pulmonary artery segment, and diminished peripheral vascular markings of the lungs should be noted. Electrocardiographic examination reveals right ventricular overload, sometimes rhythm and conduction disturbances; phonocardiography shows a high-frequency, high-amplitude second sound and a systolic murmur over the pulmonary artery. The definitive diagnosis is verified after catheterization of the heart chambers and pulmonary artery. Echocardiographic examination shows increased pressure in the pulmonary artery and the absence of cardiac and pulmonary diseases.

The course varies: rapid, moderate, and slowly progressive. The prognosis is unfavorable. Life expectancy ranges from several months to 10 years from the onset of clinical manifestations.

Treatment is ineffective.

The most common forms of Congenital Malformations of bronchopulmonary asthma that any physician may encounter, and the Prevention of which any healthcare worker may face, are presented.

Among inherited diseases characterized by multi-organ involvement with leading clinical manifestations in the bronchopulmonary system, cystic fibrosis is the most common and well-studied.

Cystic fibrosis (mucoviscidosis) is a universal genetically determined exocrinopathy, manifested primarily by damage to the bronchopulmonary system and the digestive tract, inherited in an autosomal recessive manner.

This disease was first described by Fanconi in 1936. In 1986, the localization of its gene on chromosome 7 was determined, and in 1989, the gene itself was identified. In 1993, using an adenovirus, the CFTR gene of the regulator protein was first implanted via inhalation into a 23-year-old man (USA), opening up the prospect of introducing effective Introduction/32.html">Genetic Engineering into the treatment of cystic fibrosis in the coming years.

Relevance. 1. Among Hereditary diseases, cystic fibrosis is the most common. The prevalence of cystic fibrosis in newborns ranges from 1:1000 to 1:9000. 2. Among children with chronic and recurrent respiratory diseases, according to various authors, the condition occurs in 10-75 % of cases. Thus, about 4000-5000 such patients are born annually in the USA, and 400-500 in France. 3. Practically all patients with cystic fibrosis have a disability and receive free treatment. 4. Every second child suffering from cystic fibrosis survives to school age (N.I. Kapryanov, 1987). Modern medical achievements make it possible to extend their life to 18 years of age. However, recent data (WHO, 1994) indicate an average life expectancy of up to 30 years for these patients.

The following links can be distinguished in the Pathogenesis of cystic fibrosis: a) damage to the exocrine glands, which leads to changes in the secretion, namely: an increase in its viscosity, protein content, and concentration of certain electrolytes, and a decrease in enzymatic properties; b) electrolyte imbalance and connective tissue damage; in the sweat, saliva, and tears of patients, an increased content of sodium and chlorine is observed, in the hair and nails — The amount of sodium, and in bronchial and pancreatic secretions — the amount of calcium; c) the presence of Spock's factor in the saliva and urine of patients.

It is believed that increased excretion of sodium and chloride is associated with impaired autonomic nervous Regulation of the exocrine glands. A protein substance has been found in the blood of patients that disrupts Cell membrane function and affects their permeability, and experiments have identified a substance that inhibits sodium reabsorption in the excretory ducts of the glands.

Excessive viscosity of the secretion of exocrine mucous glands leads to obstruction of the excretory ducts, The formation of cystic dilations, and promotes infection, inflammation, and secondary sclerosis of the organ. In the lungs, sputum stasis is associated not only with its increased viscosity but also with impaired ciliary epithelial function. These impairments occur under METABOLISM/18.html">The Influence of Spock's factor. In addition to cystic changes in the bronchial glands, obstructive emphysema develops, and Atelectasis, inflammatory processes, secondary pulmonary fibrosis, bronchial deformity, and bronchiectasis often occur. A decrease in The activity of pancreatic, liver, and intestinal Enzymes leads to impaired Digestion AND ABSORPTION in the intestines, accompanied by Clinical symptoms of malabsorption syndrome of varying severity.

Connective tissue damage is associated with the accumulation of acid mucopolysaccharides in cells and changes in fibroblasts, which are an active component of connective tissue. These changes are genetically determined by connective tissue insufficiency and manifest as the development of connective tissue in the interalveolar septa, subalveolar areas of the lung, peribronchially, perivascularly, in the pancreas, and in the liver. Pulmonary fibrosis and hypoxia cause pulmonary hypertension and cor pulmonale.

Thus, the pathogenesis of cystic fibrosis is associated with a defect in the gene that regulates the Synthesis of the protein responsible for the Transmembrane Transport of Cl^- ions in epithelial cells; it decreases chloride ion secretion and increases sodium ion absorption. All this reduces the Water content on the lung surface, leading to dehydration of the mucous secretion, decreased clearance, and consequently, increased bacterial colonization → chronicity of the inflammatory process → obstruction of the bronchopulmonary system → respiratory failure, disability → mortality.

The clinical presentation of cystic fibrosis is diverse and depends on the severity of involvement of certain exocrine glands, sclerosis, and the onset of complications. There are 3 forms of cystic fibrosis: mixed (pulmonary-intestinal) — which accounts for 80 % of the cases; respiratory (15 %), and intestinal (5 %). Meconium ileus (7-8 % of cases) and atypical forms (2-5 %) — which represent isolated involvement of exocrine glands such as the Salivary Glands or liver, or mild/subclinical forms that become typical with age — are also encountered. This Classification is arbitrary, as patients with the respiratory form may experience decreased intestinal enzymatic activity, while those with the intestinal form may develop pulmonary fibrosis and pulmonary syndrome.

The disease usually manifests in infancy. The first respiratory episodes of cystic fibrosis are observed before 6 months of age in 60 % of cases, before one year in 80 %, and before 2 years in 91 %. In 14 % of cases, the disease presents with diarrheal syndrome, most often when transitioning to mixed or formula feeding.

The characteristic appearance of a child with cystic fibrosis includes: a "doll-like" face, a distended, often deformed chest, a bloated abdomen, often an umbilical hernia, thin, wasted limbs, clubbing of the fingers (drumstick fingers), dry, grayish-earthy skin, cyanosis, dyspnea, an unbearable cough with viscous, purulent sputum that is difficult to clear from the mucous membranes, numerous moist and dry rales on both sides, tachycardia, hepatomegaly, and characteristic greasy, putty-like, voluminous, frequent, foul-smelling stools.

Bronchopulmonary changes prevail in the clinical picture, determining the prognosis in more than 90 % of patients. Respiratory symptoms in the form of a constant cough, bronchorrhea, and characteristic physical findings are not the result of antenatal damage but are associated with inflammatory changes, primarily in the bronchial mucosa. Excessive viscosity of sputum complicates its clearance and promotes bacterial colonization of the bronchial tree, followed by the expected edema and infiltration of the bronchial wall. All these factors lead to a sharp impairment of mucociliary clearance. The resulting cough becomes unbearable, often paroxysmal, pertussis-like, unproductive, and constant. Sputum is viscous and difficult to separate from the mucous membranes.

Dullness to percussion (shortening of the percussion sound) is noted paravertebrally, over areas of pneumonia and atelectasis. Areas with hyperresonant (box-like) percussion sounds are possible. On auscultation, multiple dry and variable moist rales are heard on both sides.

The evolution of clinical and radiological findings in the bronchopulmonary system follows this pattern: after a latent or zero stage, the disease progresses to stage I — the stage of recurrent bronchitis with persistent functional changes, which in some patients lasts up to 10 years. Chronic bronchitis forms the basis of subsequent bronchopulmonary lesions, representing Stage II of the disease. Its course is accompanied by periodic coughing fits (usually in the morning and during exertion) with the expectoration of mucopurulent sputum, moderate dyspnea that worsens on exertion, and often crackles against a Background of harsh breathing. The duration of stage II is from 1 to 15 years. The stage of diffuse pulmonary fibrosis (stage III) with areas of localized pulmonary fibrosis, bronchiectasis, cysts, and severe respiratory failure is often combined with right-sided Heart Failure. The course of stage III lasts up to 3-5 years. Stage IV is characterized by the development of severe cardiopulmonary failure against the background of these bronchopulmonary changes, which ends fatally within a few months.

At the beginning of antibacterial therapy, the course of the disease is interrupted, but subsequently, acute respiratory viral infections lead to the development of chronic purulent obstructive bronchitis. Quite often in young children, the acute onset of cystic fibrosis is associated with the development of pneumonia, which, in turn, may be accompanied by abscess formation (18 %).

Severe complications of the pathological process include pneumothorax, hemoptysis, and fibroplastic Pleurisy. Emphysematous changes in the lung tissue play a role in the development of pneumothorax As a result of a pertussis-like cough, which leads to increased intrapulmonary pressure and even pleural rupture. Chest deformity is observed, becoming barrel-, keel-, or funnel-shaped. The development of cardiopulmonary failure is accompanied by clubbing of the fingers ('drumsticks') and watch-glass nails. Children lag in physical development, showing pronounced dystrophic changes in the skin, hair, and nails as a consequence of chronic hypoxia and constant intoxication. Practically all patients have sinusitis.

Pancreatic enzyme insufficiency with the absence of all enzymes (Trypsin, lipase, amylase) is observed in 80 % of patients, and partial insufficiency (dyspancreatism) — in 10 %. The latter tends to progress, while in approximately 10 % of patients, pancreatic function is preserved. The main intestinal manifestations are associated with impaired breakdown and absorption of fats, Proteins, and CARBOHYDRATES. In children, flatulence, frequent (4-6 times a day) and voluminous stools are observed; the feces are greasy, foul-smelling, and putty-like. Symptoms of multivitamin deficiency (atrophic glossitis, angular stomatitis) and anemia as a result of iron and vitamin deficiency are detected. Mood lability, excitability, and irritability are observed. In parallel with exocrine pancreatic insufficiency, hyperglycemia, glucosuria, and polyuria may occur. Ketoacidosis is usually absent. In addition to Diabetes Mellitus, rare manifestations include retinopathy and optic neuritis.

Pancreatic insufficiency and small intestinal gland dysfunction play a significant role in the development of meconium ileus and its equivalents in older children. Meconium ileus develops in utero or within the first 48 hours after birth as a small bowel obstruction. Antenatal perforation may occur, leading to meconium Peritonitis. In diagnosing this disease, it should be noted that distal intestinal obstruction syndrome (a meconium ileus equivalent) is observed in 20-40 % of newborns with cystic fibrosis and presents as recurrent abdominal pain. Rectal prolapse, which does not require surgical treatment, is observed in 15 % of patients.

Hepatic changes appear later, depend on the severity of the process, and present as fatty degeneration, chronic hepatitis, and biliary cirrhosis. Despite a good appetite, malnutrition develops, and jaundice, ascites, hematemesis due to esophageal varices, and signs of hypersplenism may occur. Older school-age patients may experience biliary colic as a consequence of cholelithiasis.

Sexual development is delayed. Secondary sexual characteristics are poorly developed, and menstruation starts later. Pulmonary exacerbations can lead to secondary Amenorrhea and cervicitis due to the accumulation of viscous mucus in the cervical canal. Only 3-5 % of males retain reproductive function, while the rest present with azoospermia due to the underdevelopment of Wolffian duct structures. Some women remain fertile. The risk of a mother with cystic fibrosis giving birth to an affected child when the father's genetic status is unknown is 1:40-1:50 births.

Cystic fibrosis can be suspected upon reviewing chest radiographs. The radiological findings in this pathological process are polymorphic, with emphysema being a constant feature due to the thickening and obstruction of bronchioles. As a result of sternal deformity, retrosternal space widening, flattening of the diaphragmatic domes, and widening of the intercostal spaces are observed. Thoracic Kyphosis, increased and deformed bronchovascular markings in the form of linear or rounded shadows caused by bronchial wall thickening are frequently seen. Additionally, nodulocystic changes, multiple small (up to 0,5 см) round opacities and lucencies representing filled or drained parabronchial abscesses, segmental or lobular atelectasis, pneumonic infiltrates, and prominent, blurred hilar markings are detected; in older children, diffuse pansinusitis is observed.

Impairment of pulmonary function is manifested by obstructive and restrictive changes. Viral antibody levels decrease. While staphylococci were previously isolated from sputum, bronchial washings, and throat swabs, Pseudomonas aeruginosa (in 70 %) and microbial associations (in 30 %) are now commonly cultured.

Pancreatic insufficiency is detected by Quantitative determination of trypsin and Chymotrypsin activity in stool samples and the presence of steatorrhea. As a rule, serum isoamylase is absent or significantly reduced. Pancreatic enzymes are also measured in duodenal contents and urine, and their levels are likewise altered.

The diagnosis of cystic fibrosis is also based on sweat test results. Sweat is collected from the skin of the upper back using pilocarpine iontophoresis (the sample weight must be at least 100 мг) from the skin of the upper back. The chloride concentration is determined in the sweat. The sodium chloride content in a healthy child under 7 years of age is 23 ммоль/л, and in those over 7 years of age, it is 28 ммоль/л. A sweat chloride concentration equal to or exceeding 60 ммоль/л confirms the diagnosis of cystic fibrosis. The combination of respiratory and intestinal syndromes with a typical radiological presentation and a 2-5-fold increase in sweat electrolyte levels allows for the diagnosis of cystic fibrosis.

Treatment extends life, improves general well-being, and enhances social adaptation. When long-term, adequate, and initiated early, it yields positive results. Thanks to therapy, the patient's condition remains stable over a long period. It is managed on an outpatient basis, or in a hospital Setting if outpatient treatment fails to achieve the desired effect. Maintenance therapy is aimed at normalizing respiratory and gastrointestinal function.

The primary goal is to clear secretions from the Airways and prevent infection. Restoration of drainage function is achieved by improving the clearance of bronchial secretions. For this purpose, inhalations (preferably ultrasonic) are used to thin the sputum and facilitate its expectoration. Mucolytics are used for inhalation, with a 20 % solution of acetylcysteine being considered the best option, along with its analogues: mucosolvan, mucomyst, fluimucil, broncholysin, and mucisol. The single dose of acetylcysteine, regardless of the route of administration, is 15-20 мг per 1 kg of body weight; during exacerbations, the drug is prescribed three times a day, and during remission, 1 time. This agent is used for bronchial lavage, intramuscularly, and orally. In early childhood, in extremely severe cases, mucolytics are administered intravenously, transitioning to intramuscular and oral administration as the condition improves. In older children, mucolytics are administered intramuscularly alongside oral intake and inhalations. In the intestinal form of cystic fibrosis, when there is no bowel movement for two days, colonic irrigation with mucolytics, such as a 10 % acetylcysteine solution, is prescribed. This Procedure is also performed for meconium ileus. Postural drainage should be scheduled before or after aerosol inhalations. Inhalations are also combined with physical therapy, chest percussion, and general body massage. In some cases, mist tent therapy in a special room where the patient sleeps overnight is beneficial. Whenever possible, swimming, running, horseback riding, and cycling are recommended.

Antibiotic therapy reduces the intensity of pulmonary infection, inflammation, and disease progression in the lungs. When indicated, tobramycin, kanamycin, oxacillin, methicillin, lincomycin, or cephalothin are administered at standard doses for at least 2 weeks. Pseudomonas aeruginosa is targeted with tobramycin, amikacin, carbenicillin, azlocillin, and mezlocillin; in severe Pseudomonas infections, amikacin is combined with azlocillin, or gentamicin with mezlocillin, or newer Cephalosporins are used: ceftazidime, cefsulodin, cefoperazone. If H. Influenzicae is detected, Aminoglycosides, chloramphenicol, tetracycline, or erythromycin are indicated. Some patients require courses of antibiotic therapy every one and a half to two months; indications for their use include cough and isolation of pathogens from sputum. The treatment course lasts two weeks. In a hospital setting, antibiotics can be administered directly into the bronchial tree via lavage, allowing for high local concentrations in the Bronchi. Isotonic sodium chloride solution and mucolytics are used concurrently during bronchopulmonary lavage.

Practically all patients require dietary correction, which consists of increasing the caloric value of food by 15-30 % by increasing the amount of proteins and fats (40 % of the total energy requirement), while the amount of carbohydrates remains unchanged or is even slightly reduced. This is necessary to compensate for increased nutritional needs and losses. During hot weather and in cases of hyperthermia, up to 1 г of sodium chloride is added to the diet of young children, and 2-3 г per day for older patients.

Pancreatic insufficiency is managed with pancreatin or other combination preparations containing, alongside pancreatin, intestinal enzymes, Bile enzymes, and lipotropic substances. Pancreatin is prescribed in individualized doses; the indicator of dosage adequacy is the complete normalization of stools and the absence of neutral fat in the stool test. Daily doses range from 2-3 to 10 г of pancreatin.

Pathogenetic Therapy requires the use of B-group vitamins, Fat-soluble vitamins A, E, Д, iron supplements, anabolic Hormones, and antioxidants. Cell membrane stabilization is achieved by prescribing vitamin E; during exacerbations, the drug is administered parenterally at a dose of 5-7 мг/кг once daily for three weeks. For the same purpose, a 0,25 % solution of cytochrome С is administered intravenously once daily for 10 days at 0,2-0,3 г/кг. During remission, vitamin E is used in capsules at 3-5 мг/кг per day for a month, and Essentiale Forte at 1-2 capsules per day for 30 days.

The onset of hepatitis, cirrhosis, cor pulmonale, and other complications requires appropriate therapy.

The developments of Saint Petersburg researchers deserve commendation (А.В. Орлов et al., 1994; Tables 4, 5).

Prognosis. Cystic fibrosis remains a life-limiting disease. The median survival has increased to 30 years, especially for those patients diagnosed before the development of significant pulmonary changes. The vast majority of children attend school, and their physical activity is not restricted. In homozygous twins, the course of the disease is severe, while in heterozygous ones, it is mild and atypical. Severe cases ending in death do occur, particularly in children with severe pulmonary manifestations.

Table 5 Treatment regimen for cystic fibrosis

Note: 1. PEP - exercises with a special mask that creates positive expiratory pressure within 10-20 mm of water Column; 2. The course of intravenous antibiotics is 14-20 days, and their doses are 2-3 times higher than usual; 3. Enzyme doses are adjusted so that with a normal diet, bowel movements occur 1 time daily.

CONTROL QUESTIONS

1. Relevance of studying congenital Anomalies of the bronchopulmonary system.

2. What general classifications of bronchopulmonary system diseases do you know?

3. What classifications of bronchopulmonary malformations do you know?

4. Provide a general characterization of congenital lung anomalies.

5. Substantiate the clinical manifestations, treatment, and prevention of pulmonary agenesis, hypoplasia, and aplasia.

6. Explain the Clinical Presentation and management of polycystic lung disease.

7. Explain the clinical presentation and management of pulmonary sequestration.

8. Provide a General Overview of congenital Malformations of the bronchopulmonary system.

9. Explain the clinical presentation, treatment, and prevention of branching anomalies of the tracheobronchial tree.

10. Explain the clinical presentation, treatment, and prevention of congenital lobar emphysema.

11. Explain the clinical presentation, treatment, and prevention of Williams-Campbell syndrome

12. Explain the clinical presentation, treatment, and prevention of Mounier-Kuhn syndrome

13. Explain the clinical presentation, treatment, and prevention of tracheo- and bronchoesophageal fistulas.

14. What is your understanding of inherited Diseases of the bronchopulmonary system?

15. What do you know about idiopathic diffuse pulmonary fibrosis?

16. What do you know about Kartagener's syndrome?

17. What do you know about idiopathic pulmonary hemosiderosis?

18. What do you know about primary pulmonary hypertension?

19. Define cystic fibrosis.

20. Relevance and Clinical significance of cystic fibrosis.

21. Etiology AND PATHOGENESIS of cystic fibrosis.

22. Provide two Examples of cystic fibrosis diagnoses According to the classification.

23. Describe the MAIN CLINICAL MANIFESTATIONS of cystic fibrosis.

24. The Importance of Additional Diagnostic Methods in confirming the diagnosis of cystic fibrosis.

25. What are the main approaches to the treatment of cystic fibrosis?

26. Explain the principles of dietary management in cystic fibrosis.

27. Explain the rationale for antibiotic therapy.

28. Explain the rationale for enzyme therapy.

29. Is there a need to prescribe bacterial preparations in the treatment of cystic fibrosis?

30. What is The Role of physical therapy and physiotherapy in the treatment of cystic fibrosis?