Treatment of complications of cystic fibrosis

Meconium ileus

In newborns, when diagnosing meconium ileus without perforation of the colon wall, contrast enemas with a high-osmolar solution are administered. When performing contrast enemas, it is necessary to ensure that the solution reaches the ileum. This, in turn, stimulates the release of fluid and remaining meconium into the lumen of the colon. In case of meconium ileus, several contrast enemas should be administered, combining them with intravenous administration of a large amount of fluid. A contrast enema is a relatively dangerous procedure, so they are performed only by experienced doctors and only in a hospital setting, where it is possible to perform emergency surgery if necessary.

Most often, newborns with meconium ileus undergo surgical intervention, during which:

• cleanse the proximal and distal parts of the intestine;
• wash out as much meconium as possible;
• resect necrotic or damaged areas of the intestine.

The operations are completed by the placement of a double enterostomy or entero-enterostomy, which is usually closed as stable passage of feces is restored. This allows for adequate intestinal lavage in the postoperative period.

The mortality rate in newborns with meconium ileus does not exceed 5%. However, cystic fibrosis in these children is usually quite severe.

Distal small bowel obstruction

In mild cases, the use of lactulose or acetylcysteine can have a good effect.

Acetylcysteine is taken orally at 200-600 mg 3 times a day until symptoms disappear.

Lactulose is taken orally until symptoms disappear, 2 times a day, at the rate of:

• children under one year old - 2.5 ml;
• children 1-5 years old - 5 ml;
• children 6-12 years old - 10 ml.

If the child's condition is serious, it is necessary:

• carry out treatment only in a hospital setting and under the supervision of a surgeon;
• monitor the electrolyte and water balance of the patient's body;
• administer large amounts of electrolyte solutions (used to cleanse the intestines before surgery or X-rays);
• perform contrast enemas with a high-osmolar solution.

In severe cases of the patient's condition, 20-50 ml of 20% acetylcysteine solution and 50 ml of sodium chloride should be added to contrast enemas twice a day.

It may take several days for the intestines to be completely cleared of fecal matter. Adequate treatment of the patient in the future requires adjustment of the dose of pancreatic enzymes and careful monitoring of the patient's condition over time. If necessary, laxatives should be taken, but only for a certain period of time.

Surgery is only necessary if the obstruction is irreversible. It should be remembered that in addition to distal small bowel obstruction, patients with cystic fibrosis may also experience intussusception, appendicitis, and Crohn's disease.

Liver damage

Unfortunately, effective methods of treatment and prevention of liver damage in cystic fibrosis have been developed. The effectiveness of using ursodeoxycholic acid when the first clinical and laboratory signs of liver damage appear has been proven.

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

In case of portal hypertension syndrome that developed against the background of liver cirrhosis, endoscopic sclerotherapy or ligation of varicose veins of the esophagus, as well as portocaval shunting with subsequent liver transplantation are performed to prevent bleeding.

Possible approaches to the treatment of liver damage in cystic fibrosis

Violation	Solutions	Attempts at correction
Disruption of the structure of the MVTP gene, change in the structure of the MVTP protein	Introducing a healthy gene	Liver gene therapy
Increased viscosity of bile	Decrease in viscosity	Choleretics. ursodeoxycholic acid
Retention of hepatotoxic bile acids	Replacing them with non-toxic bile acids	Ursodeoxycholic acid
Excessive production of free radicals and lipid peroxidation	Increased activity of the antioxidant system	Beta-carotene, vitamin E, ursodeoxycholic acid (efficacy not proven)
Severe steatosis	Enzyme replacement therapy for exocrine pancreatic insufficiency and underweight	Pancreatic enzymes, diet with increased energy value compared to age norm
Multilobular biliary cirrhosis	Prevention of complications of portal hypertension syndrome	Ursodeoxycholic acid (efficacy not proven), palliative operations of disconnection or bypass, sclerotherapy or ligation of varicose veins
Liver failure	Liver replacement	Liver transplant

Gastroesophageal reflux

If gastroesophageal reflux develops, the following recommendations should be followed:

• organize fractional meals 5-6 times a day;
• do not lie down for 1.5 hours after eating;
• avoid tight clothing and tight belts;
• limit the intake of drugs that inhibit esophageal motility and reduce the tone of the lower esophageal sphincter (prolonged forms of nitrates, calcium channel blockers, theophylline, salbutamol), as well as those that damage the esophageal mucosa (acetylsalicylic acid and other NSAIDs);
• do not eat before bed;
• sleep with the head of the bed raised (at least 15 cm);
• In severe cases, positional drainage of the bronchial tree with tilting of the head of the body should be abandoned.

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

• Antacids.
• Sucralfate is taken orally, 1-2 tablets 4 times a day for 6-8 weeks.
• _{Histamine H2} -receptor blockers.
• Ranitidine is taken orally at 5-6 mg/kg of the patient's body weight per day (up to 10 mg/kg of body weight per day) for 6-8 weeks, dividing the total dose into 2 doses.
• Famotidine is taken orally at 10-40 mg/kg of the patient's body weight per day for 6-8 weeks, dividing the total dose into 2 doses.
• Proton pump inhibitors.
• Omeprazole is taken orally at a rate of 1-2 mg/kg of the patient's body weight (up to 20 mg/day) once a day for 6-8 weeks.
• Antiemetic drugs.
• Metoclopramide is taken orally at 5-10 mg 3 times a day for 1-2 days (to relieve acute symptoms).
• Domperidone is taken orally at 0.25 mg/kg of the patient's body weight per day (up to 5-10 mg/day) for 6-8 weeks, dividing the total dose into 3-4 doses.

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

Nasal polyps

This is a typical complication of cystic fibrosis, often asymptomatic. In case of nasal obstruction, glucocorticoids are administered through the nose.

Pneumothorax

Spontaneous pneumothorax significantly worsens the patient's condition, worsening respiratory failure. In addition, it can become a serious threat to the patient's life. After confirming the diagnosis, it is necessary to aspirate air from the pleural cavity and establish drainage. To treat frequently recurring pneumothorax, sclerosing agents can be introduced into the pleural cavity.

Hemoptysis

Bronchiectasis can contribute to the development of pulmonary hemorrhages, which are usually small (no more than 25-30 ml/day) and do not cause much harm to the health of patients. In case of episodic or repeated heavy (>250 ml of blood) bleeding caused by rupture of varicose collateral bronchial blood vessels, emergency medical care is required, consisting of embolization and occlusion of the damaged vessel. If this method is ineffective or unavailable, surgery is indicated, during which ligatures are applied and, if necessary, the affected segment or lobe of the lung is excised. Such care for a patient with cystic fibrosis can only be provided in specialized centers.

Cholelithiasis

In 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 the patient's 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 treatment techniques are used.

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Diabetes mellitus

In the case of diabetes mellitus, patients should be consulted and observed by an endocrinologist. Insulin is required to treat diabetes mellitus that has developed against the background of cystic fibrosis.

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Chronic pulmonary heart disease

When this complication develops, drug therapy is aimed at:

• treatment and prevention of exacerbations of chronic infectious and inflammatory processes in the bronchopulmonary system;
• elimination of respiratory failure;
• reduction of pressure in the pulmonary circulation;
• reduction of the degree of circulatory failure.

Allergic bronchopulmonary aspergillosis

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

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

For the treatment and prevention of frequent exacerbations, prednisolone is taken (orally) at a rate of 0.5-1 mg/kg of body weight per day for 2-3 weeks. With a decrease in respiratory failure, improvement in FVD indicators and positive radiological dynamics, prednisolone intake is reduced: 0.5-1 mg/kg of the patient's 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 a rate of 2 mg/kg of the patient's body weight per day for 1-2 weeks. After a decrease in the IgE concentration, the dose of prednisolone is gradually reduced by 5-10 mg/week until complete withdrawal over the next 8-12 weeks.

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

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

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Evaluation of the effectiveness of treatment for cystic fibrosis

The effectiveness of treatment is assessed by the degree to which treatment goals are achieved.

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Antibacterial therapy

The reason for stopping antibacterial therapy is the abatement of the exacerbation of the chronic infectious and inflammatory process in the bronchopulmonary system, manifested by the normalization of the main indicators of the patient's condition (body weight, respiratory function, the nature and amount of sputum secreted, etc.).

Pancreatic enzyme replacement therapy

The dose of enzymes is selected until the disappearance (maximum possible) of signs of malabsorption syndrome based on clinical manifestations (normalization of frequency and nature of stool) and laboratory parameters (disappearance of steatorrhea and creatorrhea, normalization of the concentration of triglycerides in the lipidogram of feces).

Treatment of allergic bronchopulmonary aspergillosis

Remission of bronchopulmonary aspergillosis is indicated by:

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

To confirm the regression of radiographic changes characteristic of aspergillosis, a control chest radiography is performed 1-2 months after the start of treatment. This study is repeated after 4-6 months to confirm the absence of new infiltrates in the lungs.

After starting to reduce the dose of prednisolone, it is necessary to monitor the content of total IgE in the blood plasma monthly for a year. A sharp increase in the content of IgE in the blood plasma is a sign of a relapse of allergic bronchopulmonary aspergillosis, indicating the need to increase the dose of prednisolone.

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Side effects

When pancreatic enzymes are used in doses exceeding 6,000 U/kg of patient body weight per meal or 18-20,000 U/kg of patient body weight per day, the risk of developing colon stricture increases. Surgical intervention is necessary to treat this complication of drug therapy.

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

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

Errors and unjustified appointments

Patients with cystic fibrosis are contraindicated to use cough suppressants, in particular those containing codeine. Two antimicrobial drugs of the beta-lactam group should not be combined in one course of antibacterial therapy. To avoid their inactivation, aminoglycosides and penicillins (or cephalosporins) should not be mixed in the same vial or syringe; intravenous administration (jet or drip) of antibacterial drugs of these groups should be carried out separately.

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Active dispensary observation

Patients with cystic fibrosis should be under active dispensary observation. Upon 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 correction of therapy.

List of laboratory and instrumental studies performed during outpatient examination of a patient with cystic fibrosis.

Research that must be carried out at each patient visit (once every 3 months)	Mandatory annual examination
Anthropometry (height, body weight, body mass deficit)	Blood biochemistry (liver enzyme activity, protein fraction ratio, electrolyte composition, glucose concentration)
General urine analysis	Chest X-ray in frontal 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 - a smear from the back wall of the pharynx) for microflora and sensitivity to antibiotics	Fibroesophagogastroduodenoscopy
FVD study	Examination by an otolaryngologist
Determination of SaO2	Glucose tolerance test

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Prognosis for cystic fibrosis

Cystic fibrosis is a chronic incurable disease, so patients need active follow-up and continuous treatment. In some patients, despite timely diagnosis and adequate therapy, the damage to the bronchopulmonary system progresses rapidly, while in others the dynamics of changes are more favorable. Many patients survive to adulthood and even adulthood. It is impossible to accurately assess the prognosis of the disease even in cases where the type of mutation is precisely determined. Factors influencing the prognosis of the disease:

• quality of the therapy provided;
• compliance with the prescribed treatment regimen;
• lifestyle;
• number of viral, bacterial and fungal infections suffered;
• diet;
• the environmental conditions in which the patient lives.