Cystic fibrosis: treatment

Cystic fibrosis is a common monogenic disease caused by the mutation of the gene of the transmembrane cystic fibrosis regulator (CFTR), characterized by the defeat of the exocrine glands of vital organs and systems and usually having a severe course and prognosis.

The disease occurs at a frequency of 7-8: 100,000 population. In 1989, the cystic fibrosis gene was isolated and then its structure was deciphered: it contains 27 exons, covers 250,000 nucleotide pairs, located in the middle of the long arm of the autosome 7. Due to the mutation of the cystic fibrosis gene, the structure and function of the CFTR protein, which acts as a chloride channel and regulates water Electrolyte exchange of epithelial cells of the respiratory tract, pancreas, intestine, liver, sweat glands of the reproductive system. In connection with the violation of the function of the protein MVTR chloride ions inside the apical part of the cell membrane. As a result, the electrical potential in the lumen of the excretory ducts changes, which promotes increased clearance of the sodium and water ions from the lumen into the cell.

As a result of these disorders, there is a thickening of the secrets of the above-mentioned external secretion glands, a difficulty in their isolation and secondary changes in these organs, most pronounced in the bronchopulmonary system.

The defeat of the bronchopulmonary system in cystic fibrosis is expressed in the following clinical variants.

• bronchitis (acute, recurrent, chronic);
• pneumonia (repeated, relapsing).

The disease as progressing is complicated by atelectasis, lung abscesses, pyopneumothorax, development of bronchiectasis, pulmonary heart.

Treatment of cystic fibrosis includes the following activities:

1. Improving the drainage function of the bronchi, the release of the bronchial tree from viscous sputum:
   • application of mucolytic expectorants;
   • treatment with bronchodilators;
   • kinesitherapy (positional drainage, klopfmassazh and vibrating massage of the chest, special cough exercises, active breathing cycles and forced exhalation, positive exhalation pressure using flutter or special mask.
2. Fighting the infection of the bronchopulmonary system.

Chronic and recurrent respiratory tract infection is the main cause of morbidity and mortality in patients with cystic fibrosis.

The main causative agent of infection is Pseudomonas aeruginosa, which is found in 70-90% of patients. According to Ficlc (1989), the Pseudomonas aeruginosa almost constantly persists in the sputum of patients. Quite often, at the same time, there is a golden staphylococcus, a hemophilic rod.

Pseudomonas aeruginosa develops various factors that damage lung tissue (exotoxins A and S, alkaline protease, elastase, leucocidin, pigments), and also synthesizes a mucoid membrane consisting of an alginic acid polymer. This membrane combines with a viscous bronchial secretion, strengthens obstruction and makes it difficult for antibiotics to act on the pathogen. Pseudomonas aeruginosa is extremely resistant to beta-lactam antibiotics.

For the treatment of Pseudomonas aeruginosae, penicillins, aminoglycosides, fluoroquinolones, monobactams, carbapenems, anti-synergic cephalosporins of the third (cefoperazone, ceftazidime) and the fourth (cefpyr, cefsulodin and cefepime) are used for the treatment of Pseudomonas aeruginosa. Cefsulodin is a specific anti-synergic antibiotic, it acts weakly on other microorganisms. Cefoperazone is inferior to the rest of the anti-synergic antibiotics. The most effective against pseudomonas aeruginosa infection is ceftazidime. Cefoperazone and ceftazidime affect not only the Pseudomonas aeruginosa, but also the majority of Gram-negative bacteria. Cephir and cefepime are active not only against Pseudomonas aeruginosa, but also against nonpositive flora, as well as Enterobacter, Citrobacter, Klebsiella and Escherichia coli.

3. Correction of exocrine insufficiency of the pancreas is performed using medicines containing pancreatic enzymes. The most effective are microspherical preparations covered with an acid-resistant coating (kreon, lancitrate, prolipase, pancreatic).

In recent years, the possibility of treating cystic fibrosis with omyloride, sodium adenosine triphosphate, opening alternative chloride channels, is being discussed; the possibilities of treatment with anticytokines, anti-interleukins (anti-IL-2, anti-IL-8); Genetic engineering approaches to the correction of a genetic defect in cystic fibrosis are being developed.

[1], [2], [3], [4], [5], [6], [7], [8]