Treatment of complications of cystic fibrosis

Meconial ileus

Newborns in the diagnosis of meconium ileus without perforation of the wall of the colon perform contrast enemas with a highly osmolar solution. When performing contrast enemas, you need to make sure that the solution reaches the ileum. This, in turn, stimulates the secretion of fluid into the lumen of the large intestine and the remaining meconium. In the meconic ileus, several contrast enemas should be performed, combining them with the intravenous injection of a large amount of fluid. Contrast enema is a relatively dangerous procedure, therefore they are performed only by experienced doctors and only in a hospital setting, where it is possible to perform emergency surgical intervention if necessary.

More often the neonates with a mekonial ileus perform a surgical intervention, during which:

• purify the proximal and distal parts of the intestine;
• wash out the maximum possible amount of meconium;
• Necrotic or damaged areas of the intestine are resected.

The operations are completed by the imposition of a double enterostomy or entero-entero-stoma, which is usually closed as the stable passage of stool is restored. This allows to ensure adequate washing of the intestine in the postoperative period.

The incidence of deaths in newborns with meconial ileus does not exceed 5%. Nevertheless, cystic fibrosis in these children usually proceeds quite heavily.

Obstruction of the distal small intestine

When the patient is not light, the use of lactulose or acetylcysteine can give a good effect.

Acetylcysteine is taken orally 200-600 mg 3 times a day until symptoms are eliminated.

Lactulose is taken internally until symptoms are eliminated 2 times per day from the calculation:

• children under the age of 2.5 ml;
• children 1-5 years old - 5 ml each;
• children 6-12 years old - 10 ml each.

At a serious condition of the child it is necessary:

• to treat only in a hospital and under the supervision of a surgeon;
• control the electrolyte and water balance of the patient's body;
• introduce a large number of electrolyte solutions (used for cleaning the intestine before surgery or radiography);
• perform contrast enemas with a highly osmolar solution.

When the patient is in a serious condition, two times 20-50 ml of 20% acetylcysteine solution and 50 ml of sodium chloride should be added to the contrast enemas 2 times a day.

For a complete cleansing of the intestine from the fecal masses may take several days. Adequate treatment of the patient further requires correction of the dose of pancreatic enzymes and careful monitoring of the patient's condition in dynamics. If necessary, you should take laxatives, but only for a certain time.

Surgical intervention is necessary only with irreversible obstruction. It should be remembered that, in addition to obstruction of the distal parts of the small intestine, intussusception, appendicitis and Crohn's disease may occur in patients with cystic fibrosis.

Liver disorders

Unfortunately, effective methods of treatment and prevention of liver damage in cystic fibrosis have been developed. The effectiveness of the use of ursodeoxycholic acid with the appearance of the first clinical and laboratory signs of liver damage is proved.

Ursodeoxycholic acid is taken orally before bedtime at a rate of 15-30 mg / kg of patient weight per day. The dose and duration of treatment should be determined individually for each patient.

In the syndrome of portal hypertension, which developed against cirrhosis of the liver, endoscopic sclerotherapy or ligation of varicose veins of the esophagus is performed to prevent bleeding, as well as portocaval shunting followed by liver transplantation.

Possible approaches to the treatment of liver damage in cystic fibrosis

Violation	Solutions	Attempts to correct
Disturbance of the structure of the MAPP gene, change in the structure of the MTPD protein	Introduction of a healthy gene	Gene therapy of the liver
Increased bile viscosity	Decrease in viscosity	Choleretics. Ursodeoxycholic acid
Delayed hepatotoxic bile acids	Replacing them with non-toxic bile acids	Ursodeoxycholic acid
Excess production of free radicals and lipid peroxidation	Increase in activity of the antioxidant system	Beta-carotene, vitamin E, ursodeoxycholic acid (efficacy not proven)
Severe steatosis	Replacement enzyme therapy with pancreatic exocrine pancreatic insufficiency and body weight deficiency	Pancreatic enzymes, a diet with increased energy value in comparison with the age norm
Multilobular biliary cirrhosis	Prevention of complications of portal hypertension syndrome	Ursodeoxycholic acid (efficacy not proven), palliative operations of dissociation or shunting, sclerotherapy or ligation of varicose veins
Liver failure	Liver replacement	Liver transplantation

Gastroesophageal reflux

With the development of gastroesophageal reflux, the following recommendations should be adhered to:

• organize a split meal 5-6 times a day;
• Do not lie down after eating for 1.5 hours;
• avoid tight clothing, tight belts;
• restrict the intake of drugs that depress the esophagus's motor and reduce the tone of the lower esophageal sphincter (prolonged forms of nitrates, slow calcium channel blockers, theophylline, salbutamol), as well as damaging the mucosa of the esophagus (acetylsalicylic acid and other NSAIDs);
• do not eat before going to bed;
• to sleep with the raised head end of the bed (not less than 15 cm);
• in severe cases should be abandoned positional drainage of the bronchial tree with an inclination of the head of the trunk.

Pharmacotherapy of gastroesophageal reflux should be carried out according to generally accepted principles. The following drugs and regimens are most effective:

• Antacids.
• Sucralfate is taken orally 1-2 tablets 4 times a day for 6-8 weeks.
• H ₂ blockers of histamine.
• Ranitidine is taken internally at 5-6 mg / kg body weight per day (up to 10 mg / kg body weight per day) for 6-8 weeks. Dividing the total dose by 2 doses.
• Famotidine is taken internally for 10-40 mg / kg of patient's body weight per day for 6-8 weeks, dividing the total dose by 2 doses.
• Proton pump inhibitors.
• Omeprazole taken internally from the calculation of 1-2 mg / kg body weight of the patient (up to 20 mg / day) once a day for 6-8 weeks.
• Antiemetic drugs.
• Metoclopramide is taken orally 5-10 mg 3 times a day for 1-2 days (for relief of acute symptoms).
• Domperidone is taken internally at 0.25 mg / kg of patient's body weight per day (up to 5-10 mg / day) for 6-8 weeks, dividing the total dose by 3-4 doses.

In severe esophagitis, as well as for the treatment of Barrett's esophagus, the inhibitors of the proton pump (omeprazole) are most effective.

Nasal polyps

This is a typical complication for cystic fibrosis, often asymptomatic. With obstruction of the nasal passages, inhalations through the nose of glucocorticoids are prescribed.

Pneumothorax

Spontaneous pneumothorax significantly increases the patient's condition, aggravating respiratory failure. In addition, it can become a serious threat to the life of the patient. After confirming the diagnosis, it is necessary to aspirate air from the pleural cavity and establish drainage. Sclerosing substances can be injected into the pleural cavity to treat a recurrent pneumothorax.

Hemoptysis

Bronchiectasis can promote the development of pulmonary hemorrhages, which are often small (not more than 25-30 ml / day) and do not cause great harm to the health of patients. With occasional or repeated heavy (> 250 ml blood) bleeding due to rupture of varicose dilated collateral bronchial blood vessels, emergency medical care is required, consisting in embolization and occlusion of the damaged vessel. If this method is ineffective or unavailable, a surgical operation is shown, during which ligatures are applied and, if necessary, the affected segment or lobe of the lung is excised. Such assistance to a patient with cystic fibrosis can be provided only in specialized centers.

Chololithiasis

With the development of chronic gallstone disease, not accompanied by cholecystitis, the use of ursodeoxycholic acid is effective.

Ursodeoxycholic acid is taken orally before bedtime at a rate of 15-30 mg / kg of patient body weight per day. The duration of treatment is determined individually in each case.

To reduce the number and severity of postoperative complications from the bronchopulmonary system, laparoscopic surgical procedures are used.

[1], [2], [3]

Diabetes

When developing diabetes patients should consult and observe the endocrinologist. For the treatment of diabetes mellitus, developed against cystic fibrosis, insulin is needed.

[4], [5], [6], [7], [8],

Chronic Pulmonary Heart

With the development of this complication, drug therapy is aimed at:

• treatment and prevention of exacerbations of a chronic infectious and inflammatory process in the bronchopulmonary system;
• elimination of respiratory failure;
• decrease in pressure in a small circle of blood circulation;
• decrease in the degree of circulatory failure.

Allergic bronchopulmonary aspergillosis

It is necessary to limit as much as possible the possibility of contact with mold fungus A. Fumigatus, which should be avoided:

• stay in damp rooms with a mold deposit on the walls, haylofts;
• consumption of food containing mold (for example, cheese), etc.

For treatment and prevention of frequent exacerbations, prednisolone (oral) is taken from the calculation of 0.5-1 mg / kg of body weight per day for 2-3 weeks. With decreasing respiratory insufficiency, improvement in FVD indices and with a positive X-ray dynamics, the intake of prednisolone is reduced: 0.5-1 mg / kg of patient body weight every other day for 2-3 months.

If clinical symptoms persist against the background of a high concentration of total IgE in the blood plasma, prednisolone is taken orally at the rate of 2 mg / kg of the patient's body weight per day for 1-2 weeks. After lowering the IgE concentration, the dose of prednisolone is gradually reduced by 5-10 mg / week until complete withdrawal within the next 8-12 weeks.

The effectiveness of antifungal drugs in cystic fibrosis has not been studied enough. With frequent relapses of allergic bronchopulmonary aspergillosis in combination with glucocorticoids, itraconazole can be used.

• Itraconazole is taken orally 100-200 mg 2 times a day for 4 months.

[9], [10], [11], [12]

Evaluation of the effectiveness of cystic fibrosis

The effectiveness of treatment is assessed by the degree of achievement of treatment goals.

[13], [14], [15], [16], [17], [18], [19]

Antibiotic therapy

The reason for the cessation of antibacterial therapy is the stunning of the exacerbation of the chronic infectious and inflammatory process in the bronchopulmonary system, which is manifested by the normalization of the main indicators of the patient's condition (body weight, FVD, the nature and quantity of sputum recovered, etc.).

Substitution therapy with pancreatic enzymes

The dose of enzymes is selected before the disappearance (as much as possible) of signs of malabsorption syndrome according to clinical manifestations (normalization of the frequency and character of the stool) and laboratory indicators (disappearance of steatorrhea and creatorrhea, normalization of triglyceride concentration in the fecal lipidogram).

Treatment of allergic bronchopulmonary aspergillosis

On the remission of bronchopulmonary aspergillosis:

• elimination of clinical symptoms;
• restoration of FHD indicators to the level that preceded its development;
• regress of radiological changes;
• decrease in the concentration of total IgE in the blood plasma by more than 35% within 2 months, while maintaining the stability of this indicator during the period of decreasing the dose of glucocorticoids.

To confirm the regression of radiologic changes characteristic of aspergillosis 1-2 months after the start of treatment, a chest X-ray is performed. Repeatedly this research is performed after 4-6 months to confirm the absence of new infiltrates in the lungs.

After the start of reducing the dose of prednisolone during the year, it is necessary to monitor the total IgE content in the blood plasma on a monthly basis. A sharp increase in IgE in the blood plasma is a sign of a relapse of allergic bronchopulmonary aspergillosis, indicating the need to increase the dose of prednisolone.

[20], [21], [22], [23], [24], [25]

Side effects

When using pancreatic enzymes at doses exceeding 6000 U / kg body weight of the patient for food intake or 18-20 000 units / kg body weight of the patient per day, the risk of developing stricture of the large intestine increases. To treat this complication of drug therapy, surgical intervention is necessary.

Laryngitis, pharyngitis and bronchospasm are the most frequent undesirable drug reactions that develop with the use of dornase alpha. These side effects are rare and do not have a serious impact on the patient's health.

Aminoglycosides have a nephro- and ototoxic effect. When using inhalation forms of this group of drugs in high doses, pharyngitis can develop.

Errors and unreasonable appointments

Patients with cystic fibrosis are contraindicated with suppressive cough medications, in particular containing codeine. In a single course of antibiotic therapy should not combine the intake of two antimicrobial agents of the beta-lactam group. In order to avoid their inactivation, aminoglycosides and penicillins (or cephalosporins) can not be mixed in one vial or syringe, intravenous administration (jet or drip) of antibacterial drugs of these groups should be done separately.

[26], [27]

Active dispensary observation

Patients with cystic fibrosis should be on active dispensary observation. After reaching the age of 1 year, patients with cystic fibrosis should be examined once every 3 months, which allows monitoring the dynamics of the disease and timely correcting the therapy.

A list of laboratory and instrumental studies conducted during an outpatient examination of a patient with cystic fibrosis.

Studies that need to be done with each patient's admission (1 time per 3 months)	Mandatory annual examination
Anthropometry (height, body weight, body weight deficit)	Biochemical blood test (activity of liver enzymes, ratio of protein fractions, electrolyte composition, glucose concentration)
General urine analysis	Chest X-ray in the straight and right lateral projections
Coprological examination	Ultrasound examination of abdominal organs
Clinical blood test	ECG
Bacteriological examination of sputum (if it is impossible to collect sputum smear from the back wall of the pharynx) to microflora and sensitivity to antibiotics	Fibroesophagogastroduodenoscopy
FVD investigation	Inspection by an otolaryngologist
Determination of SaO2	Glucose Tolerance Test

[28], [29]

Prognosis for cystic fibrosis

Cystic fibrosis is a chronic incurable disease, therefore patients need active dispensary observation and continuous treatment. In some patients, despite timely diagnosis and adequate therapy, the bronchopulmonary system lesion progresses rapidly, in others the dynamics of changes are more favorable. Many patients live to an adult and even a mature age. It is impossible to accurately assess the prognosis of the disease, even in cases when the type of mutation has been determined exactly. Factors affecting the prognosis of the disease:

• quality of the therapy;
• compliance with the prescribed treatment regimen;
• Lifestyle;
• number of viral, bacterial and fungal infections transferred;
• diet;
• the ecological situation in which the patient lives.