Cystic fibrosis is a severe congenital disease manifested by tissue damage and violation of the secretory activity of the exocrine glands, as well as functional disorders, primarily from the respiratory and digestive systems. Separately, the pulmonary form is isolated. In addition to it, there are intestinal, mixed, atypical forms and mekonivaya intestinal obstruction. Pulmonary form manifests itself in childhood with a paroxysmal cough with thick sputum, obstructive syndrome, repeated prolonged bronchitis and pneumonia, progressive respiratory function disorder leading to chest deformity and signs of chronic hypoxia. The diagnosis is established according to anamnesis, lung radiography, bronchoscopy and bronchography, spirometry, molecular genetic testing.
ICD 10
E84 Cystic fibrosis
Information
Changes in cystic fibrosis affect the pancreas, liver, sweat, salivary glands, intestines, bronchopulmonary system. The disease is hereditary, with autosomal recessive inheritance (from both parents-carriers of the mutant gene). Disorders in the organs with disease occur already in the intrauterine phase of development, and progressively increase with the age of the patient. The earlier cystic fibrosis appears, the more severe the course of the disease, and the more serious its prognosis may be. Due to the chronic course of the pathological process, patients need constant treatment and supervision by a specialist.
Causes of cystic fibrosis
In the development of cystic fibrosis, three main points are leading: damage to the glands of external secretion, changes in connective tissue, water-electrolyte disorders. The cause of disease is a gene mutation, as a result of which the structure and functions of the MBTR protein (transmembrane regulator of cystic fibrosis) involved in the water-electrolyte metabolism of the epithelium lining the bronchopulmonary system, pancreas, liver, gastrointestinal tract, organs of the reproductive system are disrupted.
With this disease, the physico-chemical properties of the secretion of exocrine glands (mucus, lacrimal fluid, sweat) change: it becomes thick, with an increased content of electrolytes and protein, and is practically not evacuated from the excretory ducts. The retention of viscous secretions in the ducts causes their expansion and the formation of small cysts, to the greatest extent in the bronchopulmonary and digestive systems.
Electrolyte disturbances are associated with high concentrations of calcium, sodium and chlorine in secretions. Stagnation of mucus leads to atrophy (shrinkage) of glandular tissue and progressive fibrosis (gradual replacement of gland tissue with connective tissue), early appearance of sclerotic changes in organs. The situation is complicated by the development of purulent inflammation in the case of secondary infection.
The defeat of the bronchopulmonary system in disease occurs due to difficulty in the discharge of sputum (viscous mucus, impaired function of the atrial fibrillation), the development of mucostasis (mucus stagnation) and chronic inflammation. Violation of the patency of small bronchi and bronchioles is the basis of pathological changes in the respiratory organs in cystic fibrosis. Bronchial glands with mucopurulent contents, increasing in size, protrude and block the lumen of the bronchi. Baggy, cylindrical and “teardrop-shaped” bronchiectasis are formed, emphysematous areas of the lung are formed, with complete obstruction of the bronchi by sputum, atelectasis zones, sclerotic changes in lung tissue (diffuse pneumosclerosis).
With cystic fibrosis, pathological changes in the bronchi and lungs are complicated by the addition of bacterial infection (Staphylococcus aureus, Pseudomonas aeruginosa), abscessing (lung abscess), the development of destructive changes. This is due to disturbances in the local immunity system (a decrease in the level of antibodies, interferon, phagocytic activity, a change in the functional state of the bronchial epithelium).
In addition to the bronchopulmonary system, with cystic fibrosis, there is a lesion of the stomach, intestines, pancreas, liver.
Symptoms of cystic fibrosis
Cystic fibrosis is characterized by a variety of manifestations that depend on the severity of changes in certain organs (glands of external secretion), the presence of complications, the age of the patient. There are the following forms of cystic fibrosis:
- pulmonary;
- intestinal;
- mixed (respiratory organs and digestive tract are affected simultaneously);
- meconium intestinal obstruction;
- atypical forms associated with isolated lesions of individual glands of external secretion (cirrhotic, edematous – anemic), as well as erased forms.
The division of cystic fibrosis into forms is conditional, since with a predominant lesion of the respiratory tract, digestive disorders are also observed, and with the intestinal form, changes develop from the bronchopulmonary system.
The main risk factor in the development of cystic fibrosis is heredity (transmission of a defect in the MBTR protein – cystic fibrosis transmembrane regulator). The initial manifestations of this disease are usually observed in the earliest period of a child’s life: in 70% of cases, detection occurs in the first 2 years of life, at an older age much less often.
Pulmonary form of cystic fibrosis
The respiratory form of cystic fibrosis manifests itself at an early age and is characterized by pallor of the skin, lethargy, weakness, small weight gain with normal appetite, frequent acute respiratory viral infections. In children, there is a constant paroxysmal, whooping cough with thick mucopurulent sputum, repeated prolonged (always bilateral) pneumonia and bronchitis, with pronounced obstructive syndrome. Breathing is hard, dry and wet wheezes are heard, with obstruction of the bronchi – dry whistling wheezes. There is a possibility of developing infectious-dependent bronchial asthma.
Respiratory function disorders can steadily progress, causing frequent exacerbations, an increase in hypoxia, pulmonary symptoms (shortness of breath at rest, cyanosis) and heart failure (tachycardia, “pulmonary heart“, edema). There is a deformation of the chest (keeled, barrel-shaped or funnel-shaped), a change in the nails in the form of watch glasses and the terminal phalanges of the fingers in the form of drumsticks. With a prolonged course of cystic fibrosis in children, inflammation of the nasopharynx is detected: chronic sinusitis, tonsillitis, polyps and adenoids. With significant violations of the function of external respiration, there is a shift in the acid-base balance towards acidosis.
If pulmonary symptoms are combined with extrapulmonary manifestations, then they speak of a mixed form. It is characterized by a severe course, occurs more often than others, combines pulmonary and intestinal symptoms of the disease. From the first days of life, severe recurrent pneumonia and bronchitis of a prolonged nature, persistent cough, indigestion are observed.
The criterion of the severity of the course of cystic fibrosis is considered to be the nature and degree of damage to the respiratory tract. In connection with this criterion, four stages of respiratory system damage are distinguished in cystic fibrosis:
- Stage I is characterized by unstable functional changes: dry cough without sputum, slight or moderate shortness of breath during exercise.
- Stage II is associated with the development of chronic bronchitis and is manifested by coughing with sputum separation, moderate shortness of breath, which increases with tension, deformation of the phalanges of the fingers, wet wheezing, heard against the background of hard breathing.
- Stage III is associated with the progression of lesions of the bronchopulmonary system and the development of complications (limited pneumosclerosis and diffuse pneumofibrosis, cysts, bronchiectasis, severe respiratory and heart failure of the right ventricular type (“pulmonary heart”).
- Stage IV is characterized by severe cardiopulmonary insufficiency, leading to a fatal outcome.
Complications
The course of cystic fibrosis can be aggravated by complications:
- from the respiratory tract – sinusitis, pleurisy, hemoptysis and pulmonary bleeding, pneumothorax, “pulmonary heart”, destruction of the lungs, empyema of the pleura, etc.
- in the case of intestinal form – diabetes mellitus, gastric bleeding, cirrhosis of the liver, celiac syndrome, intestinal obstruction, rectal prolapse, edematous syndrome, secondary pyelonephritis and urolithiasis on the background of metabolic disorders, etc.
Diagnostics
A timely diagnosis of cystic fibrosis is very important in terms of predicting the life of a sick child. The pulmonary form of cystic fibrosis is differentiated with obstructive bronchitis, whooping cough, chronic pneumonia of a different genesis, bronchial asthma; the intestinal form – with intestinal absorption disorders that occur with celiac disease, enteropathy, intestinal dysbiosis, disaccharidase deficiency.
The diagnosis of cystic fibrosis involves:
- The study of family and hereditary history, early signs of the disease, clinical manifestations;
- Blood test and urinalysis;
- Coprogram – examination of feces for the presence and content of fat, fiber, muscle fibers, starch (determines the degree of enzymatic disorders of the glands of the digestive tract);
- Microbiological examination of sputum;
- Bronchography (detects the presence of characteristic “teardrop-shaped” bronchiectasis, bronchial defects)
- Bronchoscopy (reveals the presence of thick and viscous sputum in the bronchi in the form of filaments);
- Lung x-ray (reveals infiltrative and sclerotic changes in the bronchi and lungs);
- Spirometry (determines the functional state of the lungs by measuring the volume and velocity of exhaled air);
- Sweat test – the study of sweat electrolytes is the main and most informative analysis for cystic fibrosis (it allows you to identify a high content of chlorine and sodium ions in the sweat of a patient with cystic fibrosis);
- Molecular genetic testing (analysis of blood or DNA samples for the presence of mutations of the cystic fibrosis gene);
- Prenatal diagnostics – examination of newborns for genetic and congenital diseases.
Treatment for cystic fibrosis
Since cystic fibrosis, as a hereditary disease, cannot be avoided, timely diagnosis and compensatory therapy are of paramount importance. The earlier adequate treatment of cystic fibrosis is started, the more chances a sick child has to survive.
Intensive therapy is carried out in patients with respiratory failure of II-III degree, lung destruction, decompensation of the “pulmonary heart”, hemoptysis. Surgical intervention is indicated for severe forms of intestinal obstruction, suspected peritonitis, pulmonary bleeding.
Treatment of cystic fibrosis is mostly symptomatic, aimed at restoring the functions of the respiratory and gastrointestinal tract, is carried out throughout the patient’s life. With the predominance of the intestinal form of cystic fibrosis, a diet with a high protein content (meat, fish, cottage cheese, eggs) is prescribed, with a restriction of carbohydrates and fats (only easily digestible). Coarse fiber is excluded, with lactase deficiency – milk. It is always necessary to add salt to food, consume an increased amount of liquid (especially in the hot season), take vitamins.
Substitution therapy for the intestinal form includes taking medications containing digestive enzymes: pancreatin, etc. (the dosage depends on the severity of the lesion, it is prescribed individually). The effectiveness of treatment is judged by the normalization of stool, the disappearance of pain, the absence of neutral fat in the feces, normalization of weight. To reduce the viscosity of digestive secretions and improve their outflow, acetylcysteine is prescribed.
Treatment of the pulmonary form of cystic fibrosis is aimed at reducing the viscosity of sputum and restoring the patency of the bronchi, eliminating the infectious and inflammatory process. Mucolytic agents (acetylcysteine) are prescribed in the form of aerosols or inhalations, sometimes inhalations with enzyme preparations (chymotrypsin, fibrinolysin) daily throughout life. In parallel with physiotherapy, physical therapy, chest vibration massage, positional (postural) drainage are used. For therapeutic purposes, bronchoscopic sanitation of the bronchial tree is carried out using mucolytic agents (bronchoalveolar lavage).
In the presence of acute manifestations of pneumonia, bronchitis, antibacterial therapy is performed. Metabolic drugs that improve myocardial nutrition are also used: cocarboxylase, potassium orotate, glucocorticoids, cardiac glycosides are used.
Patients with cystic fibrosis are subject to dispensary observation by a pulmonologist and a district therapist. Relatives or parents of the child are trained in vibration massage techniques, rules of patient care. The issue of preventive vaccinations for children suffering from cystic fibrosis is decided individually.
Children with mild forms of cystic fibrosis receive sanatorium treatment. It is better to exclude the stay of children with cystic fibrosis in preschool institutions. The possibility of attending school depends on the condition of the child, but he is given an additional day of rest during the school week, time for treatment and examination, exemption from examination tests.
Prognosis and prevention
The prognosis of cystic fibrosis is extremely serious and is determined by the severity of the disease (especially the pulmonary syndrome), the time of the appearance of the first symptoms, the timeliness of diagnosis, and the adequacy of treatment. There is a large percentage of deaths (especially in sick children of the 1st year of life). The earlier a child is diagnosed with cystic fibrosis, targeted therapy is initiated, the more likely a favorable course is. In recent years, the average life expectancy of patients suffering from cystic fibrosis has increased and in developed countries is 40 years.
Family planning issues, medical and genetic counseling of couples with cystic fibrosis, medical examination of patients with this serious illness are of great importance.
Literature
- Cystic fibrosis. Elborn JS. Lancet. 2016 Nov 19;388(10059) link
- New treatments targeting the basic defects in cystic fibrosis. Fajac I, Wainwright CE. Presse Med. 2017 Jun;46(6 Pt 2) link
- Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis. Skilton M, Krishan A, Patel S, Sinha IP, Southern KW. Cochrane Database Syst Rev. 2019 Jan 7;1(1) link
- What’s new in cystic fibrosis? From treating symptoms to correction of the basic defect. Proesmans M, Vermeulen F, De Boeck K. Eur J Pediatr. 2008 Aug;167(8) link
- Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis. Patel S, Sinha IP, Dwan K, Echevarria C. Cochrane Database Syst Rev. 2015 Mar 26;(3) link
