How is cystic fibrosis treated?

General principles of treatment of cystic fibrosis

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

It is preferable to treat patients with cystic fibrosis in specialized centers with the participation of nutritionists, kinesiotherapists, psychologists, nurses and social workers. It is also necessary to actively involve both parents of the patient in the treatment process and teach them the necessary skills to help a sick child.

Treatment goals for cystic fibrosis

• To ensure the highest possible quality of life for the patient.
• To prevent and treat exacerbations of chronic infectious and inflammatory processes in the bronchopulmonary system.
• Provide adequate diet and nutrition.

Essential components of cystic fibrosis treatment

• Methods of bronchial tree drainage and therapeutic exercise.
• Diet therapy.
• Mucolytic therapy.
• Antibacterial therapy.
• Replacement therapy for exocrine pancreatic insufficiency.
• Vitamin therapy.
• Treatment of complications.

Methods of bronchial tree drainage and therapeutic exercise

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 accumulations of viscous sputum that block the bronchi and predispose to the development of infectious diseases of the bronchopulmonary system. The following kinesitherapy methods are most often used:

• postural drainage;
• percussion massage of the chest;
• active breathing cycle;
• controlled coughing.

Kinesitherapy is indicated for all newborns and children in the first months of life who are sick with cystic fibrosis. In infants, passive kinesitherapy techniques are usually used, including:

• positions that improve the evacuation of mucus from the lungs;
• contact breathing;
• massage with light vibration and stroking;
• Ball exercises.

The effectiveness of certain methods varies depending on the individual characteristics of patients with cystic fibrosis. The younger the child, the more passive drainage methods should be used. Newborns are given only percussion and chest compression. As the child grows, more active methods should be gradually introduced, teaching patients the technique of controlled coughing.

Regular exercise therapy allows you to:

• effectively treat and prevent exacerbations of chronic bronchopulmonary processes;
• develop correct breathing;
• train the respiratory muscles;
• improve lung ventilation;
• improve the child's emotional status.

From early childhood, it is necessary to encourage patients to engage in any dynamic sports associated with long-term loads of medium intensity, especially those associated with being outdoors. Physical exercises facilitate the clearing of the bronchi from viscous sputum and develop respiratory muscles. Some exercises strengthen the chest and correct posture. Regular physical exercise 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 engaging in physical exercise.

Children suffering from cystic fibrosis should not engage in particularly traumatic sports (weightlifting, football, hockey, etc.), since long-term limitation of physical activity associated with recovery from injury adversely affects the drainage function of the lungs.

Diet therapy

The diet of patients with cystic fibrosis should be as close to normal as possible: the diet should contain sufficient protein, and fats and any other foods should not be limited. The energy value of the daily diet of patients with cystic fibrosis should be 120-150% of that recommended for healthy children of the same age, with fats covering 35-45% of the total energy requirement, proteins - 15%, and carbohydrates - 45-50%. The increase in the proportion of fats in the diet is due to the need to compensate for steatorrhea.

Supplementary nutrition is indicated for children with a body mass deficit of >10% and adults with a body mass index (BMI) <18.5 kg/m ². Older children and adults should additionally consume high-calorie products - milkshakes or drinks with a high glucose content. Ready-to-use dietary supplements should not be prescribed without special need. Supplementary nutrition should be prescribed according to the scheme:

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

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

Mucolytic therapy for cystic fibrosis

When symptoms of bronchial obstruction appear, in addition to kinesitherapy, mucolytic drugs and bronchodilators are prescribed. Early administration of dornase alpha, which has a pronounced mucolytic and anti-inflammatory effect and reduces the concentration of inflammation markers (neutrophil elastase, IL-8) in the bronchoalveolar fluid, is justified. Inhalations of 0.9% sodium chloride solution can be used as mucolytic therapy from the first months of a child's life.

Mucolytic drugs make bronchial secretions less viscous and provide effective mucociliary clearance, preventing the formation of mucus clots and blockage of the bronchioles. Mucolytic drugs have the most pronounced effect on the mucous membrane of the respiratory tract and the rheological properties of bronchial mucus when used by inhalation.

The most effective drugs and dosage regimens

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

With regular use of dornase alfa, the frequency and severity of exacerbations of chronic infectious and inflammatory processes in the bronchopulmonary system decrease, and the degree of contamination of lung tissue with S. aureus and P. aeruginosa decreases. In children under 5 years of age, dornase alfa is effective only with strict adherence to the correct inhalation technique through a mask.

The use of mucolytic agents should 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 removal of bronchial mucus, various methods of bronchial tree drainage and therapeutic exercise are used.

Antibacterial therapy

Recently, antibacterial therapy for cystic fibrosis has been recommended:

• start when the first signs of exacerbation of the infectious and inflammatory process in the bronchopulmonary system appear;
• to be carried out over a sufficiently long period of time;
• prescribe for prophylactic purposes.

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

Antibacterial drugs for cystic fibrosis must 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 of 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 at the site of infection;
• Strains of microorganisms that are resistant to many antimicrobial drugs (polyresistant microflora) are increasingly encountered.

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

Antibacterial therapy when S. aureus is detected in sputum

The detection of S. aureus in sputum allows us to state that this exacerbation of the infectious and inflammatory process in the bronchopulmonary system is caused by this type of microorganism. Preventive courses of antimicrobial drugs that act on S. aureus should be administered at least 1-2 times a year. Sometimes the course of the disease requires very frequent repeated courses with short intervals between them. Unfortunately, not all specialists recognize the advisability of conducting preventive courses of antimicrobial drugs in cystic fibrosis.

For the prevention and treatment of mild exacerbations, the following drugs and regimens are most effective:

Azithromycin is taken orally once a day for 3-5 days at the rate of:

• children over 6 months - 10 mg/kg of the child's body weight;
• children weighing 15-25 kg - 200 mg;
• children weighing 26-35 kg - 300 mg;
• children weighing 36-45 kg - 400 mg;
• adults - 500 mg.

Amoxicillium is taken orally for 3-5 days at the rate of:

• children - 50-100 mg/kg of the child's body weight per day in 3-4 doses;
• adults - 1.0 g 4 times a day.

Clarithromycin is taken orally for 3-5 days at the rate of:

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

Clindamycin is taken orally for 3-5 days at the rate of:

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

Co-trimoxazole is taken orally 2 times a day for 3-5 days at the rate of:

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

Oxacillin is taken orally for 3-5 days at the rate of:

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

Rifampicin is taken orally for 3-5 days at the rate of:

• children - 10-20 mg/kg of the child's body weight per day in 1-2 doses;
• adults - 0.6-1.2 g/day in 2-4 doses.

Flucloxacillin orally 50-100 mg/kg/day in 3-4 doses for 3-5 days (children); 1.0 g 4 times a day for 3-5 days (adults).

Fusidic acid is taken orally for 3-5 days at the rate of:

• children - 40-60 mg/kg of body weight per day in 3 doses;
• adults - 0.75 g 3 times a day.

Cefaclor is taken orally for 3-5 days, 3 times a day at the rate of:

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

Cefixime is taken orally for 3-5 days in 1-2 doses at the rate of:

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

Erythromycin is taken orally for 3-5 days at the rate of:

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

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

Vancomycin is administered intravenously for 14 days at the rate of:

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

Cefazolin is administered intravenously or intramuscularly for 14 days at the rate of:

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

Ceftriaxone is administered intravenously or intramuscularly for 14 days at the rate of:

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

Cefuroxime is administered intravenously or intramuscularly for 14 days at the rate of:

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

Flucloxacillin intravenously 100 mg/kg/day in 3-4 doses for 14 days (children); 1.0-2.0 g 4 times a day for 14 days (adults).

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

Antibacterial therapy when H. influenzae is detected in sputum Antibacterial therapy with antimicrobial drugs active against H. influenzae is prescribed for the prevention (in acute respiratory viral infections, detection of this microorganism in sputum) and treatment of exacerbations of chronic infectious and inflammatory processes in the bronchopulmonary system caused by H. influenzae. The duration of the standard course of antibacterial therapy is 14 days. Azithromycin, amoxicillin, clarithromycin, co-trimoxazole, cefaclor, cefixime are most often prescribed. If signs of exacerbation of the infectious and inflammatory process in the bronchopulmonary system persist and H. influenzae is detected again, intravenous administration of antimicrobial drugs (ceftriaxone, cefuroxime) should be used.

Antibacterial therapy when H. aeruginosa is detected in sputum Indications for prescribing antimicrobial drugs when H. aeruginosa is detected in sputum:

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

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

The following drugs and regimens are most effective for eradication of H. aeruginosa.

Azlocillin is administered intravenously, dividing the daily dose into 3-4 administrations, based on the calculation:

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

Amikacin is administered intravenously at the rate of:

• children - 30-35 mg/kg of the child's body weight once a day;
• adults - 350-450 mg 2 times a day.

Gentamicin.

• It is used in the form of intravenous injections, administered once a day, at the rate of:
  • children - 8-12 mg/kg of the child's body weight;
  • adults - 10 mg/kg of the patient's body weight.
• In inhalations carried out 2 times a day, at the rate of:
  • children under 5 years old - 40 mg;
  • children 5-10 years old - 80 mg;
  • children over 10 years old and adults - 160 mg.

Colistin.

• It is used in the form of intravenous injections, dividing the total dose into 3 injections, based on the calculation:
  • children - 50,000 IU/kg of the child's body weight per day;
  • adults - 2,000,000 IU.
• In inhalations carried out 2 times a day, at the rate of:
  • infants - 500,000 IU;
  • children 1-10 years old - 1,000,000 IU;
  • children over 10 years old and adults - 2,000,000 IU each.

Meropenem is administered intravenously, dividing the total dose into 3 administrations, based on 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 the calculation:

• 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 the calculation:

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

Tobramycin.

• It is used in the form of intravenous injections, administered once a day, at the rate of:
  • children - 8.0-12.0 mg/kg of the child's body weight per day;
  • adults - 10 mg/kg of the patient's body weight per day.
• In inhalations carried out 2 times a day, at the rate of:
  • children under 5 years old - 40 mg,
  • children 5-10 years old - 80 mg:
  • children over 10 years old and adults - 160 mg.

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

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

Ceftazidime.

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

Ciprofloxacin.

• Take orally, dividing the daily dose into 2 doses, based on the calculation:
  • children - 15-40 mg/kg of the child's body weight per day;
  • adults - 1.5-2.0 g/day.
• It is administered intravenously, dividing the total dose into 2 injections, based on the calculation:
  • children - 10 mg/kg of the child's body weight per day;
  • adults - 400 mg/day.

Simultaneously, 2-3 antimicrobial drugs from different groups are prescribed, which prevents the development of resistance of H. aeruginosa and helps to achieve the maximum clinical effect. Most often, combinations of aminoglycosides with cephalosporins of the 3rd-4th generation are used. It is advisable to periodically change the combinations of antibiotics effective against Pseudomonas aeruginosa. It should be remembered that laboratory determination of the sensitivity of the microorganism to antibiotics does not always fully coincide with the clinical response to the therapy.

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

Until recently, antimicrobial drugs in the form of aerosols were used only as an addition to the main enteral and parenteral antibacterial therapy. It should be noted that this method of drug administration is, in fact, an alternative to the systemic one, since it allows for the rapid creation of the necessary concentration of the antimicrobial agent in the focus of the infectious process, as well as minimizing 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 inhalation is not only safe for the patient, but also advisable to achieve the maximum therapeutic effect. For inhalation of antibiotics, jet nebulizers should be used, as well as special drugs and their dosage forms (Tobi, Bramitob).

Preventive courses of antibacterial therapy for chronic colonization of the lower respiratory tract by H. aeruginosa increase the life expectancy of patients. At the same time, conducting preventive courses of antibacterial therapy has virtually no effect on the resistance of microorganism strains, but only with a timely change in the drugs used. Unfortunately, the cost of such courses is quite high, so the indication for their implementation is a progressive deterioration in FVD.

Antibacterial therapy is widely used in outpatient settings (at home) due to the significant advantages of this tactic:

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

To assess the possibility of conducting a course of antibacterial therapy at home, it is necessary to consider:

• the child's condition;
• place and conditions of family residence;
• the possibility of constant consultation of the patient with specialists; the possibility of the family to provide proper care for the patient;
• the level of communication skills and education of the child's parents. Basic principles of conducting preventive courses of antibacterial therapy for chronic colonization of the lower respiratory tract with H. aeruginosa;
• Every 3 months, a 2-week course of antibacterial therapy should be administered using the intravenous route of administration of antimicrobial drugs;
• it is necessary to take 2-3 antimicrobial drugs in combination, taking into account the sensitivity of the microflora;
• continuous inhalation use of antimicrobial drugs.

In case of frequent exacerbations of the infectious and inflammatory process in the bronchopulmonary system, the duration of courses of antibacterial therapy should be increased to 3 weeks, using the intravenous route of administration, and (or) the intervals between courses should be reduced, and (or) ciprofloxacin should be taken orally between courses.

In case of H. aeruginosa culture from sputum:

• at the first sowing, it is necessary to carry out inhalations with colistin for 3 weeks at 1,000,000 IU 2 times a day together with oral administration of ciprofloxacin at the rate of 25-50 mg/kg of the patient's body weight per day, dividing the total dose into 2 doses;
• when re-seeding, it is necessary to carry out inhalations with colistin for 3 weeks at 2,000,000 IU 2 times a day together with oral administration of ciprofloxacin at the rate of 25-50 mg/kg of the patient's body weight per day, dividing the total dose into 2 doses;
• more than 3 times in 6 months, inhalations with colistin should be carried out for 12 weeks at 2,000,000 IU 2 times a day together with oral administration of ciprofloxacin at the rate of 25-50 mg/kg of the patient's body weight per day, dividing the total dose into 2 doses.

If H. aeruginosa is detected in sputum after negative results of bacteriological examination for several months, patients who have previously undergone courses of antibacterial therapy using the intravenous route of administration of drugs should undergo inhalations with colistin at 2,000,000 IU 2 times a day for 12 weeks together with oral administration of ciprofloxacin at the rate of 25-50 mg / kg of the patient's body weight per day, dividing the total dose into 2 doses.

Antibacterial therapy when B. cepacia is detected in sputum

Patients with B. cepacia detected in sputum should be isolated from other patients with cystic fibrosis, due to the lack of ability to predict cases of severe and rapid development of B. cepacia infection, due to the resistance of this pathogen to most antimicrobial drugs.

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

Doxycycline for children over 12 years of age and adults should be taken orally at 100-200 mg once a day for 14 days.

Co-trimoxazole is taken orally 2 times a day for 14 days at the rate of:

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

Chloramphenicol is taken orally at 25 mg/kg of the patient's body weight 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 drugs in combination (fluoroquinolones, 3rd-4th generation cephalosporins, carbapenems, chloramphenicol).

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

• 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 g/day of ceftazidime and 400 mg/day of ciprofloxacin.

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

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

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

In case of exacerbation caused by other microorganisms, the combination of antibacterial drugs and the regimen are selected based on the data of the antibiogram or drugs are prescribed that are traditionally effective for these forms of infection.

Anti-inflammatory therapy

Antibacterial therapy for chronic colonization of the lower respiratory tract by P. aeruginosa only leads 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 the 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 indicators. Most often, prednisolone is prescribed for maintenance therapy at 0.3-0.5 mg/kg of the patient's body weight per day. It should be taken orally every other day (constantly). When using inhaled forms of glucocorticoids, side effects develop more slowly and in smaller quantities.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have a fairly pronounced anti-inflammatory effect, but with their long-term use, serious complications often develop. The possibility of long-term use of NSAIDs that selectively inhibit cyclooxygenase-2 in cystic fibrosis is discussed, but their anti-inflammatory activity is lower than that of earlier analogues.

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

• in chronic colonization of the lower respiratory tract by H. aeruginosa;
• with low FVD values.

The following medications and regimens are the most effective:

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

Replacement therapy for pancreatic exocrine insufficiency

Replacement therapy with microsphere pancreatic enzymes should be administered to all neonates with cystic fibrosis who have clinical manifestations of the intestinal syndrome (49%) or low concentrations of elastase-1 in the feces. During replacement therapy, it is necessary to monitor:

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

To restore adequate fat assimilation, highly effective pancreatic enzymes should be used. In most cases, this application allows to compensate for steatorrhea and reduce body weight deficit without the use of specialized biologically active food supplements.

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). Weight deficit develops as a result of:

• disturbances in the digestion and absorption of fats and proteins caused by insufficiency of the exocrine function of the pancreas;
• insufficient food consumption when patients feel unwell;
• relatively high rates of energy utilization, which is due to the increased load on the respiratory organs;
• chronic infectious and inflammatory process in the lungs with frequent exacerbations.

When the body mass deficit is eliminated, the prognosis of the disease as a whole significantly improves. Patients become more active, have a desire to exercise, and their appetite improves.

In case of malabsorption syndrome in patients with cystic fibrosis, modern preparations of pancreatic enzymes should be prescribed. Modern preparations for enzyme replacement therapy, widely used in medical practice, are microgranules or minispheres containing pancreatic enzymes [the dose of the preparation is usually expressed in lipase activity - in action units (AU)], coated and placed in gelatin capsules. Such dosage forms dissolve only in the alkaline environment of the duodenum, without being destroyed in the acidic environment of the stomach, which ensures maximum effectiveness of the preparation.

Enzymes should be taken with meals in 2 possible options:

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

Pancreatic enzymes should not be taken after meals. Capsules with small, coated microgranules or minispheres can be opened and their contents taken simultaneously with a small amount of food, and if the patient with cystic fibrosis is already old enough, they can be swallowed whole without opening. The dose of enzyme preparations for replacement therapy of exocrine pancreatic insufficiency should be selected individually. When selecting a dose of microsphere pancreatic enzymes for cystic fibrosis, it is advisable to adhere to the following recommendations:

• infants should take about 4000 IU per 100-150 ml of milk;
• for children over one year old:
• 2000-6000 U/kg of the child’s body weight per day;
• 500-1000 U/kg of the child’s body weight before (or during) the main meal;
• 250-500 U/kg of the child’s body weight before (or during) additional meals.

Increased acidity of gastric or pancreatic juices may cause the absence of a clinical effect from taking enzyme replacement therapy (doses of drugs taken during meals that exceed 3000 U/kg of the patient's body weight are ineffective). In this case, the shell of microgranules or minispheres does not dissolve in the acidic environment of the duodenum and small intestine and the enzyme does not work. In this case, drugs that inhibit the secretion of hydrochloric acid in the gastric mucosa should be taken for a long time: histamine H2-receptor antagonists _or proton pump inhibitors.

Unfortunately, modern drug therapy cannot completely eliminate the signs of pancreatic insufficiency in cystic fibrosis; it is inappropriate and even dangerous to constantly increase the dose of enzymes if only steatorrhea persists. If enzyme replacement therapy is ineffective and pronounced clinical signs of malabsorption syndrome persist for a long time, a thorough additional examination is necessary.

Along with pancreatic enzyme preparations, 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 levels of vitamin E in plasma may not manifest clinically for a long time. Vitamin K should be prescribed to patients when signs of liver damage appear and with long-term use of antimicrobial drugs. When selecting a daily dose of fat-soluble vitamins for patients with cystic fibrosis, it should be taken into account that it should exceed the standard age dose by 2 times or more.

Recommended Daily Intakes of Fat-Soluble Vitamins for People with Cystic Fibrosis

Vitamin	Age	Daily dose
A	-	5000-10 000 U
D	-	400-800 U
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 Over a year old	2-5 mg 5-10 >mg

Gene therapy

Research into the use of gene therapy in cystic fibrosis is ongoing. Vectors containing the intact gene of the cystic fibrosis transmembrane conductance regulator have already been developed. Unfortunately, dose-dependent inflammatory and immunological side effects have occurred during studies of the administration of these drugs. It may take another 5-10 years before these methods of treating the disease are practically applied.

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