How is cystic fibrosis treated?

General principles of treatment of cystic fibrosis

A patient with cystic fibrosis should be treated immediately after diagnosis. The amount of medication interventions depends on the clinical manifestations of this patient and the results of laboratory and instrumental studies.

To treat patients with cystic fibrosis preferably in specialized centers with the participation of dieticians, kinesitherapists, psychologists, nurses and social workers. It should also be actively involved in the treatment of both parents of the patient and teach them the necessary skills to help the sick child.

Objectives of cystic fibrosis

• Provide the highest quality of life for the patient.
• To prevent and treat exacerbations of a chronic infectious-inflammatory process in the bronchopulmonary system.
• Provide adequate diet and diet.

Mandatory components of cystic fibrosis treatment

• Methods of drainage of the bronchial tree and therapeutic exercise.
• Dietotherapy.
• Mucolytic therapy.
• Antibacterial therapy.
• Replacement therapy of insufficiency of exocrine pancreatic function.
• Vitaminotherapy.
• Treatment of complications.

Methods of drainage of the bronchial tree and exercise therapy

Kinesitherapy is one of the important components of the complex treatment of cystic fibrosis. The main goal of kinesitherapy is to cleanse the bronchial tree from clumps of viscous sputum, blocking the bronchi and predisposing to the development of infectious diseases of the bronchopulmonary system. The following methods of kinesitherapy are most often used:

• postural drainage;
• percussion chest massage;
• active breathing cycle;
• controlled cough.

Kinesitherapy is indicated for all newborns and children of the first months of life, with cystic fibrosis. Infants usually use passive kinesitherapy techniques, which include:

• positions in which evacuation of mucus from the lungs is improved;
• contact breathing;
• massage with light vibration and stroking;
• lessons on the ball.

The effectiveness of these or those methods varies depending on the individual characteristics of patients with cystic fibrosis. The younger the child, the more passive drainage techniques should be used. The newborn perform only percussion and compression of the thorax. As the child grows, more active methods should be gradually introduced, teaching patients the technique of controlled coughing.

Regular sessions of physiotherapy exercises allow:

• effectively treat and prevent exacerbations of chronic bronchopulmonary process;
• form the right breath;
• to train the respiratory musculature;
• improve ventilation of the lungs;
• increase the emotional status of the child.

From early childhood, it is necessary to encourage the desire of patients to engage in any dynamic sports associated with long-term loads of moderate intensity, especially those associated with outdoor activities. Physical exercises make it easier to cleanse the bronchi from viscous sputum and develop respiratory musculature. Some exercises strengthen the chest and correct the posture. Regular physical activity improves the well-being of sick children and facilitates communication with peers. In rare cases, the severity of the patient's condition completely excludes the possibility of exercising.

Children suffering from cystic fibrosis should not be engaged in especially traumatic sports (weightlifting, football, hockey, etc.), since the prolonged restriction of physical activity associated with recovery after trauma adversely affects the drainage function of the lungs.

Dietotherapy

Nutrition of patients with cystic fibrosis should be as close as possible to normal: the diet should contain a sufficient number of proteins, should not limit the consumption of fats and any products. The energy value of the daily diet of patients with cystic fibrosis should be 120-150% recommended for healthy children of the same age, while fats should cover 35-45% of the total energy needs, proteins - 15%, carbohydrates - 45-50%. The increase in the proportion of fats in the diet is due to the need to compensate for steatorrhea.

Additional nutrition is indicated for children with a body weight deficit> 10% and an adult with a body mass index (BMI) <18.5 kg / m ². Older children and adults should additionally consume high-calorie foods - milkshakes or high glucose drinks. Ready-to-eat biologically active food supplements should not be prescribed without special need. Additional power should be assigned according to the scheme:

• Children 1-2 years give an additional 200 kcal / day;
• 3-5 years - 400 kcal / day;
• 6-11 years - 600 kcal / day:
• over 12 years old - 800 kcal / day.

Prolonged food (via the nasogastric tube, ejno or gastrostomy) is used in the absence of the effect of diet therapy for 3 months (in adults - 6 months) or with a body weight deficit> 15% in children and 20% in adults (against the background of optimal replacement enzyme therapy and elimination of all possible psychological stress). Only in severe cases it is necessary to switch to partial or complete parenteral nutrition.

Mucolytic therapy of cystic fibrosis

When symptoms of bronchial obstruction appear, mucolytics and bronchodilators are prescribed in addition to kinesi therapy. Justified early assignment of dornase alpha, which has a pronounced mucolytic and anti-inflammatory effect and reduces the concentration of markers of inflammation (neutrophil elastase, IL-8) in the bronchoalveolar fluid. As mucolytic therapy from the first months of life, you can use inhalation 0.9% solution of sodium chloride.

Mucolytic drugs make the bronchial secret less viscous and provide effective mucociliary clearance, preventing the formation of clots of mucus and clogging of bronchioles. The maximum effect on the mucosa of the respiratory tract and the rheological properties of bronchial mucus mucolytic drugs have an inhaled use.

The most effective drugs and regimens

• Ambroxol should be taken internally at 1-2 mg / kg body weight per day in 2-3 doses, or administered intravenously at 3-5 mg / kg body weight per day.
• Acetylcysteine is taken internally at 30 mg / kg body weight per day in 2-3 doses, or administered intravenously from the calculation of 30 mg / kg body weight per day in 2-3 injections, or inhaled 20% solution of 2-5 ml of 3- 4 times a day.
• Dornase alpha is inhaled through the nebulizer at 2.5 mg once a day.

With the regular use of dornase alpha, the incidence and severity of exacerbations of the chronic infectious inflammatory process in the bronchopulmonary system is reduced, and the degree of colonization of S. Aureus and P. Aeruginosa pulmonary tissue is reduced. In children younger than 5 years, dornase alpha is effective only if the proper techniques of inhalation through a mask are strictly observed.

The appointment of mucolytic agents must be combined with drugs and methods that accelerate the evacuation of bronchial mucus and sputum from the respiratory tract. To restore and improve mucociliary clearance and accelerate the excretion of bronchial mucus, various methods of drainage of the bronchial tree and therapeutic exercise are used.

Antibiotic therapy

Recently, antibiotic therapy in cystic fibrosis is recommended:

• begin when the first signs of exacerbation of the infectious and inflammatory process in the bronchopulmonary system;
• spend for a sufficiently long period of time;
• appoint with a preventive purpose.

This tactic allows to prevent or slow down the rate of development of a chronic infection of the lower respiratory tract and the progression of changes in the pulmonary tissue.

Antibacterial drugs for cystic fibrosis should be administered in high single and daily doses, which is due to some features of the disease:

• due to high systemic and renal clearance and accelerated hepatic metabolism, the concentration of antimicrobial drugs in the blood serum in patients with cystic fibrosis remains relatively low;
• pathogenic microorganisms are located intrabronchially, which together with the rather poor ability of most antimicrobial drugs to accumulate in sputum prevents the creation of bactericidal concentrations of the active substance in the source of infection;
• resistant strains of microorganisms (multiresistant microflora) are increasingly encountered in many antimicrobial preparations.

The choice of antimicrobial drugs depends on the type of microorganisms isolated from the sputum of a patient with cystic fibrosis and their sensitivity to antimicrobial drugs, the condition of the patient and the presence of complications.

Antibacterial therapy for detection in sputum S. Aureus

The detection of S. Aureus in phlegm allows us to assert that this exacerbation of the infectious inflammatory process in the bronchopulmonary system is caused precisely by this type of microorganism. Preventive courses of antimicrobials acting on S. Aureus should be carried out at least 1-2 times per year. Sometimes the course of the disease requires very frequent repeated courses with short intervals between them. Unfortunately, the expediency of carrying out preventive courses of antimicrobials in cystic fibrosis is not recognized by all specialists.

For the prevention and treatment of non-severe exacerbations, the following drugs and regimens are most effective:

Azithromycin is taken orally once a day for 3-5 days from the calculation:

• children older than 6 months - 10 mg / kg body weight of the child;
• children with a body weight of 15-25 kg - 200 mg each;
• children with a body weight of 26-35 kg - 300 mg;
• children with a body weight of 36-45 kg - 400 mg;
• adults - 500 mg each.

Amoxicillia is taken orally for 3-5 days from the calculation:

• children - 50-100 mg / kg of the child's body weight per day in 3-4 sessions;
• adults - 1,0 g 4 times a day.

Clarithromycin is taken orally for 3-5 days from the calculation:

• children with a body weight <8 kg - 7.5 mg / kg body weight of the child 2 times a day;
• children 1-2 years - 62.5 mg 2 times a day:
• children 3-6 years - 125 mg,
• children 7-9 years - 187.5 mg 2 times a day;
• children over 10 years - 250 mg twice a day;
• adults - 500 mg 2 times a day.

Clindamycin taken inside for 3-5 days from the calculation:

• children - 20-30 mg / kg body weight of the child per day in 3-4 receptions;
• adults - 600 mg 4 times a day.

Co-trimoxazole is taken orally 2 times a day for 3-5 days from the calculation:

• children 6 weeks - 5 months - 120 mg;
• children 6 months - 5 years - 240 mg;
• children 6-12 years old - 480 mg each;
• adults - 960 mg.

Oksatsillin taken inside for 3-5 days from the calculation:

• children - 100 mg / kg of the child's body weight per day in 4 sessions;
• adults - 2.0 grams 3-4 times a day.

Rifampicin is taken orally for 3-5 days from the calculation:

• children - 10-20 mg / kg of the child's body weight per day in 1-2 receptions;
• adults - on 0,6-1,2 g / day in 2-4 receptions.

Flukloxacillin inside 50-100 mg / kg / day in 3-4 sessions 3-5 days (children); on 1.0 g 4 times a day for 3-5 days (adults).

Fusidic acid is taken orally for 3-5 days from the calculation:

• children - 40-60 mg / kg body weight per day in 3 sessions;
• adults - on 0,75 g 3 times a day.

Cefaclor is taken orally for 3-5 days 3 times a day from the calculation:

• children under the age of 1 year - 125 mg;
• children 1-7 years - 250 mg;
• children over 7 years and adults - 500 mg.

Cefixime is taken orally for 3-5 days in 1-2 doses from the calculation:

• children aged 6 months - 1 year - 75 mg / day;
• children 1-4 years - 100 mg / day;
• children 5-10 years - 200 mg / day;
• children of 11-12 years - 300 mg / day;
• adults - 400 mg / day.

Erythromycin is taken orally for 3-5 days from the calculation:

• children - 30-50 mg / kg of the child's body weight per day, dividing the dose by 2-4 receptions;
• adults - 1.0 g 2 times a day.

With severe exacerbation of chronic infectious and inflammatory process in the bronchopulmonary system, the following drugs and regimens are most effective.

Vancomycin is administered intravenously within 14 days from the calculation:

• children - 40 mg / kg of the child's body weight per day, dividing the total dose by 4 injections;
• adults - 1.0 g 2-4 times a day.

Cefazolin is administered intravenously or intramuscularly for 14 days from the calculation:

• children - 50-100 mg / kg of child body weight per day, dividing the total dose by 3-4 injections;
• adults - 4.0 g / day, dividing the total dose into 4 injections.

Ceftriaxone is administered intravenously or intramuscularly for 14 days from the calculation:

• children - 50-80 mg / kg of the child's body weight per day, dividing the total dose by 3-4 injections;
• adults - 4.0 g / day, dividing the total dose into 4 injections.

Cefuroxime is administered intravenously or intramuscularly for 14 days from the calculation:

• children - 30-100 mg / kg of the child's body weight per day, dividing the total dose by 3-4 injections;
• adults - 750 mg 3-4 times a day.

Flukloxacillin IV in 100 mg / kght in 3-4 injections of 14 days (children); 1,0-2,0 g 4 r / day 14 days (adults).

Vancomycin is prescribed in cases when the exacerbation of the infectious inflammatory process in the bronchopulmonary system is caused by infection of the patient with methicillin-resistant strains of S. Aureus.

Antibacterial therapy for H. Influenzae sputum . Antibacterial therapy with antimicrobials active against H. Influenzae is prescribed for prophylaxis (in ARVI, detection of this microorganism in sputum) and treatment of exacerbations of the chronic infectious inflammatory process in the bronchopulmonary system caused by H. Influenzae . The duration of the standard course of antibiotic therapy is 14 days. More commonly prescribed azithromycin, amoxicillin, clarithromycin, co-trimoxazole, cefaclor, cefixime. If signs of exacerbation of the infectious inflammatory process persist in the bronchopulmonary system and the repeated detection of H. Influenzae, an intravenous route of administration of antimicrobials (ceftriaxone, cefuroxime) should be used.

Antibacterial therapy for detection in sputum H. Aeruginosa Indications for prescribing antimicrobial drugs against H. Aeruginosa detection in sputum:

• exacerbation of a chronic infectious-inflammatory process in the bronchopulmonary system;
• prevention of the development of chronic infection (in patients without signs of exacerbation with H. Aeruginosa for the first time sown ) and the progression of the infectious inflammatory process in the bronchopulmonary system (patients with chronic colonization of the lower respiratory tract H. Aeruginosa).

With exacerbation, antibiotic therapy begins with intravenous antimicrobial drugs in a hospital setting. With positive clinical dynamics, treatment can be continued in outpatient settings. The duration of antibiotic therapy should not be less than 14 days.

For the eradication of H. Aeruginosa, the following drugs and regimens are most effective.

Azlocillin is administered intravenously, dividing the daily dose by 3-4 injections, from the calculation:

• children - 300 mg / kg body weight per day;
• adults - 15 g / day.

Amicacin is administered intravenously from the calculation:

• children - 30-35 mg / kg body weight of the child 1 time per day;
• adults - 350-450 mg 2 times a day.

Gentamicin.

• Applied in the form of intravenous injections, administered once a day, from the calculation:
  • children - 8-12 mg / kg of the child's body weight;
  • adults - 10 mg / kg body weight of the patient.
• In inhalations, conducted 2 times a day, from the calculation:
  • children under 5 years - 40 mg;
  • children 5-10 years - 80 mg;
  • children over 10 years and adults - 160 mg.

Colistin.

• Apply in the form of intravenous injections, dividing the total dose into 3 injections, from the calculation:
  • children - 50 000 U / kg of child's body weight per day;
  • adults - 2 000 000 units.
• In inhalations, conducted 2 times a day, from the calculation:
  • Infant-children - 500 000 units;
  • children 1-10 years old - 1 000 000 units each;
  • children over 10 years and adults - 2 000 000 units.

Meropenem is administered intravenously, dividing the total dose into 3 injections, from the calculation:

• children - 60-120 mg / kg of the child's body weight per day;
• adults - 3-6 g / day.

Piperacillin is administered intravenously, dividing the total dose into 3 injections, based on:

• children - 200-300 mg / kg body weight per day;
• adults - 12.0-16.0 g / day.

Piperacillin with tazobactam is administered intravenously, dividing the total dose into 3 injections, based on:

• children - 90 mg / kg body weight of the child per day;
• adults - 2.25-4.5 g / day.

Tobramycin.

• Applied in the form of intravenous injections, administered once a day, from the calculation:
  • children - 8.0-12.0 mg / kg of the child's body weight per day;
  • adults - 10 mg / kg body weight per patient per day.
• In inhalations, conducted 2 times a day, from the calculation:
  • children under 5 years - 40 mg,
  • children 5-10 years - 80 mg:
  • children over 10 years and adults - 160 mg.

Cefepime is administered intravenously, dividing the total dose into 3 injections, based on:

• children - 150 mg / kg body weight of the child per day;
• adults - to 6.0 g / day.

Ceftazidime.

• o Apply in the form of intravenous injections, dividing the total dose into 2 injections, based on:
  • children - 150-300 mg / kg of the child's body weight;
  • adults - 6-9 g / day.
• In inhalations of 1.0-2.0 g 2 times a day.

Ciprofloxacin.

• Take inside, dividing the daily dose into 2 doses, from the calculation:
  • children - 15-40 mg / kg body weight of the child per day;
  • adults - 1,5-2,0 g / day.
• Enter intravenously, dividing the total dose into 2 injections, from the calculation:
  • children - 10 mg / kg of the child's body weight per day;
  • adults - 400 mg / day.

At the same time, 2-3 antimicrobial preparations from different groups are prescribed, which prevents the development of H. Aeruginosa resistance and helps to achieve the maximum clinical effect. The most commonly used combinations of aminoglycosides with cephalosporins are 3-4 generations. It is advisable periodically to change combinations of antibiotics effective against Pseudomonas aeruginosa. It should be remembered that the laboratory definition of the sensitivity of a microorganism to antibiotics does not always fully coincide with the clinical response to ongoing therapy.

48 hours after the first administration of aminoglycosides, it is advisable to determine their concentration in the blood. When using high doses of aminoglycosides, this test should be repeated 1-2 times a week. Special interest in anti-vomicrobial agents of the aminoglycoside class is also due to the fact that they are able to restore the defective protein function in some mutations of the gene of the cystic fibrosis transmembrane conduction regulator.

Antimicrobials in the form of aerosols until recently used only as a supplement to the main enteral and parenteral antibacterial therapy. It should be noted that such a method of administration of drugs is essentially alternative to systemic, as it allows you to quickly create the necessary concentration of antimicrobial agent in the focus of the infectious process, and also minimize the risk of developing toxic systemic effects of the drug. At the same time, experimental data indicate that only 6-10% of the antibiotic used reaches the distal parts of the lungs, therefore, increasing the doses of antibiotics for inhalations is not only safe for the patient, but it is also advisable to achieve the maximum therapeutic effect. For inhalation of antibiotics, it is necessary to use jet nebulizers, as well as special preparations and their medicinal forms (Tobi, Bramitob).

Preventive courses of antibacterial therapy for chronic colonization of the lower respiratory tract H. Aeruginosa increase the life expectancy of patients. At the same time, the provision of preventive courses of antibacterial therapy has practically no effect on the stability of strains of microorganisms, but only with the timely change of the drugs used. Unfortunately, the cost of such courses is quite high, so the indication for their conduct is the progressive deterioration of HPF.

It is widespread to carry out antibiotic therapy in outpatient settings (at home) in connection with the significant advantages of this tactic:

• absence of risk of cross infection and development of superinfection;
• elimination of psychoemotional problems caused by staying in a medical institution;
• economic feasibility.

To assess the possibility of conducting a course of antibiotic therapy at home, it is necessary to take into account:

• the state of the child;
• place and conditions of residence of the family;
• the possibility of constant consultation of the patient with specialists; o the family's ability to provide proper patient care;
• level of communication and education of the child's parents. Basic principles of preventive courses of antibacterial therapy for chronic colonization of the lower respiratory tract H. Aeruginosa;
• every 3 months should be a 2-week course of antibiotic therapy, using an intravenous route of administration of antimicrobials;
• it is necessary to take 2-3 antimicrobial preparations in combination with sensitivity of microflora;
• permanent inhalation use of antimicrobial agents.

With frequent exacerbations of the infectious inflammatory process in the bronchopulmonary system, the course duration of antibiotic therapy should be increased to 3 weeks, using the intravenous route of administration, and / or to reduce the intervals between courses, and (or) between courses to ingest ciprofloxacin.

In case of sputum smearing from H. Aeruginosa:

• at the first seeding, it is necessary to perform inhalations with colistin for 1 000 000 units 2 times a day, together with ingestion of ciprofloxacin from the calculation of 25-50 mg / kg of the patient's body weight per day, dividing the total dose by 2 doses;
• at repeated sowing it is necessary to conduct inhalations with colistin 2 000 000 units 2 times a day, together with ingestion of ciprofloxacin from the calculation of 25-50 mg / kg of patient's body weight per day, dividing the total dose by 2 doses;
• more than 3 times in 6 months should be inhaled for 2 weeks with colistin 2,000,000 units 2 times a day, together with ingestion of ciprofloxacin from the calculation of 25-50 mg / kg of patient's body weight per day, dividing the total dose by 2 doses.

If H. Aeruginosa is detected in the sputum after receiving negative bacteriological test results for several months. Patients who had previously received antimicrobial therapy courses using an intravenous route of administration should undergo inhalations with 2,000,000 units of colistin 2 times a day, together with ingestion of ciprofloxacin, at a rate of 25-50 mg / kg of patient body weight day, dividing the total dose by 2 doses.

Antibacterial therapy for detection in sputum B. Cepacia

Patients who have B. Cepacia found in sputum should be isolated from other patients with cystic fibrosis, which is due to the lack of ability to predict cases of severe and transient development of B. Cepacia infection , due to the resistance of this pathogen to most antimicrobial agents.

In the case of a mild exacerbation, the following drugs and regimens are most effective:

Doxycycline for children older than 12 years and adults should be taken orally 100-200 mg once a day for 14 days.

Co-trimoxazole is taken orally 2 times a day for 14 days from the calculation:

• children 6 weeks - 5 months - 120 mg; about children 6 months - 5 years - 240 mg;
• children 6-12 years old - 480 mg each;
• adults - 960 mg.

Chloramphenicol is taken internally at 25 mg / kg body weight of the patient 4 times a day for 14 days.

Ceftazidime is used in the form of inhalations of 1.0-2.0 g 2 times a day for 14 days.

In case of severe exacerbation of the infectious and inflammatory process in the bronchopulmonary system caused by B. Cepacia, it is necessary to take 2 or 3 antimicrobial preparations (fluoroquinolones, 3-4 generation cephalosporins, carbapenems, chloramphenicol).

Ceftazidime with ciprofloxacin is administered intravenously for 14 days, dividing the daily dose into 2 injections, based on:

• children - 150-300 mg / kg of the child's body weight per day of ceftazidime and 10 mg / kg per day of ciprofloxacin;
• adults - 6-9 r / day ceftazidime and 400 mg / day ciprofloxacin.

Meropenem is administered intravenously for 14 days, dividing the total dose into 3 injections, based on:

• children - 60-120 mg / kg of the child's body weight per day;
• adults - 3-6 g / day.

Chloramphenicol is taken internally at 25 mg / kg body weight of the patient 4 times a day for 14 days.

When exacerbation caused by other microorganisms, a combination of antibacterial drugs and a regimen are selected on the basis of antibioticogram data or prescribe medications that are traditionally effective in these forms of infection.

Anti-inflammatory therapy

Antibacterial therapy for chronic colonization of the lower respiratory tract P. Aeruginosa leads only to clinical improvement and a decrease in the degree of microbial contamination, but does not suppress the excessive immune response of the patient's body, which prevents eradication of the infection.

Long-term use of systemic glucocorticoids in small doses helps not only to stabilize the patient's condition, but also to improve functional and clinical parameters. Most often for maintenance therapy, prednisolone is prescribed at 0.3-0.5 mg / kg of patient's body weight per day. It should be taken within a day (permanently). When using inhalation forms of glucocorticoids, side effects develop more slowly and in lesser amounts.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a pronounced anti-inflammatory effect, but with their long-term use, serious complications often develop. The possibility of prolonged use of NSAIDs selectively inhibiting cyclooxygenase-2 in cystic fibrosis is discussed, but their anti-inflammatory activity is lower than in the case of earlier analogs.

Macrolides have not only an antimicrobial effect, but also anti-inflammatory, as well as immunomodulating. With long-term administration of these drugs, the progression of the chronic infectious-inflammatory process in the bronchopulmonary system in cystic fibrosis slows down. These drugs should be prescribed as an addition to basic therapy:

• with chronic colonization of the lower respiratory tract H. Aeruginosa;
• at low FVD values.

The following drugs and regimens are most effective:

• Azithromycin is taken orally 250 mg / day 2 times a week for 6 months or more.
• Clarithromycin is taken internally at 250 mg / day every other day for 6 months or more.

Replacement therapy for pancreas function deficiency

Substitution therapy with microspherical pancreatic enzymes should be administered to all newborns with cystic fibrosis having clinical manifestations of intestinal syndrome (49%) or a low concentration of elastase-1 in stool. When conducting substitution therapy, it is necessary to monitor:

• indicators of the coprogram; o The frequency and nature of the stool;
• monthly weight gain and growth dynamics of the patient.

To restore adequate assimilation of fat should be used highly effective pancreatic enzymes. With this application, in most cases, it is possible to compensate for steatori and reduce body mass deficit without the use of specialized biologically active food additives.

One of the important indicators of the adequacy of treatment and compensation of the patient's condition is the dynamics of weight gain (in children) and BMI (in adults). Deficiency of body weight develops due to:

• violation of digestion and assimilation of fats and proteins due to insufficiency of the exocrine function of the pancreas;
• Inadequate food intake in case of poor health of patients;
• relatively high rates of energy utilization, which is caused by increased pressure on the respiratory system;
• chronic infectious-inflammatory process in the lungs with frequent exacerbations.

When the body mass deficit is eliminated, the prognosis of the disease as a whole is significantly improved. In patients, the activity increases, there is a desire to exercise, and appetite improves.

In the syndrome of malabsorption in patients with cystic fibrosis, modern preparations of pancreatic enzymes should be prescribed. Modern drugs for substitution enzyme therapy, widely used in medical practice, are microgranules or minispheres containing pancreatic enzymes [the dose of the drug is usually expressed in lipase activity - in units of action (ED)], coated and encapsulated in gelatin capsules. Such dosage forms dissolve only in the alkaline medium of the duodenum, not breaking down in the acidic environment of the stomach, which ensures the maximum effectiveness of the drug.

Enzymes should be taken with food in 2 possible versions:

• the entire dose of the drug is taken immediately before meals;
• the total dose is divided into 2 parts - one part is taken before meals, the other - between the first and second course.

Pancreatic enzymes should not be taken after a meal. Capsules with small, coated microgranules or minispheres can be opened and taken at the same time with a small amount of food, and if the patient with cystic fibrosis is already old enough to swallow whole without opening it. To select a dose of enzyme preparations for replacement therapy of insufficiency of exocrine pancreatic function should be individualized. When choosing a dose of microspherical pancreatic enzymes in cystic fibrosis, it is advisable to adhere to the following recommendations:

• Infants should take about 4000 units per 100-150 ml of milk;
• children over the year:
• 2000-6000 units / kg of child's body weight per day;
• 500-1000 units / kg of baby's body weight before (or during) the main meal;
• for 250-500 units / kg body weight of the child before (or during) an additional meal.

The increased acidity of gastric or pancreatic juices can cause a lack of clinical effect from taking substitution enzyme therapy (ineffective doses taken during meals, exceeding 3000 units / kg body weight of the patient). In this case, the shell of microgranules or minispheres in the acid medium of the duodenum and small intestine does not dissolve and the enzyme does not act. In this case, for a long time should take drugs that inhibit the secretion of hydrochloric acid in the gastric mucosa: antagonists of H ₂ -receptor histamine or proton pump inhibitors.

Unfortunately, modern drug therapy can not completely eliminate the signs of pancreatic insufficiency in cystic fibrosis, it is inappropriate and even dangerous to constantly increase the dose of enzymes while preserving only steatorrhoea. If the substitution enzyme therapy is ineffective and the long-lasting persistent clinical signs of malabsorption syndrome, a thorough additional examination is necessary.

Together with preparations of pancreatic enzymes it is necessary to constantly take fat-soluble vitamins (A, D, E and K). In patients with cystic fibrosis who do not take vitamins, hypovitaminosis A often develops. Low content of vitamin E in the plasma can not be clinically manifested for a long time. Vitamin K should be administered to patients with signs of liver damage and long-term use of antimicrobial drugs. When selecting a daily dose of fat-soluble vitamins, patients with cystic fibrosis should take into account that it should exceed the standard age dose in 2 times or more.

Recommended daily doses of fat-soluble vitamins for patients with cystic fibrosis

Vitamin	Age	Daily dose
A	-	5000-10 000 units
D	-	400-800 IU
E	0-6 months 6-12 months 1-4 years 4-10 years 10 years	25 mg 50 mg 100 mg 100-200 mg 200-400 mg
TO	0-1 year Senior of the year	2-5 mg 5-10> mg

Gene therapy

Studies on the use of gene therapy in cystic fibrosis are continuing. Vectors containing the intact gene of the cystic fibrosis transmembrane conduction regulator have already been developed. Unfortunately, in the course of studies on the administration of these drugs, dose-related adverse inflammatory and immunological reactions occurred. Perhaps, 5-10 years will pass before the practical application of these methods of treatment of the disease.

[1], [2], [3]