Lesions of lungs with deficiency of α1-inhibitor of proteases
The hereditary deficit of α1-inhibitors of proteases is a congenital pathology of enzymes, which is characterized by a primary lesion of the respiratory part of the lung tissue in the form of early developing primary emphysema( increased airiness of the lung tissue).
The existence of family forms of emphysema was described back in the XIX century. However, it was only in 1963 that the work was published whose authors, on the basis of biochemical and genetic studies, linked some obstructive pulmonary diseases, in particular early developing emphysema, with congenital insufficiency in the serum of a certain enzyme, and established that this insufficiency is inherited in an autosomal recessive type. Further work confirmed these data and showed that the lack of enzyme is relevant to some other forms of pulmonary pathology.
Protease inhibitors are proteins that have the property of inactivating proteolytic enzymes formed in the body itself or coming into it from the outside( endo- and exogenous origin).They represent the third largest group of functionally active proteins( after albumins and immunoglobulins) and constitute up to 10% of the total protein content in the serum.
There are 7 inhibitors of proteolysis contained in human blood plasma. The first place among them by the number and importance is occupied by a1-protease inhibitor, belonging to the globulin fraction and accounting for 75% of its total number. This enzyme is synthesized in liver cells.
Exogenous factors, in particular smoking products, air pollutants, xenobiotics, contribute to the manifestation of the disease. Expressed clinical manifestations of the deficiency of this enzyme, associated with the homozygous carrier of the corresponding gene, are usually formed by 30-35 years. Manifestations of the disease are associated with a developing at a relatively young age progressive pulmonary emphysema. The main symptom is shortness of breath, which occurs initially with minor, and then with more severe physical exertion. Quite typical is a gradual decrease in body weight. Cough is most often absent or slightly expressed. Usually it is dry, less sparse mucous sputum is separated. The body weight is reduced, the chest becomes barrel-shaped. When percussion( tapping) of the chest, a "boxed" sound is detected( indicating increased airiness of the lungs), a reduction in the boundaries of the heart or a complete disappearance of them( as a result of an increase in lung volume that is full of air).The lower limit of the lungs shifts downward, which is also explained by the increase in their volume due to excess air. When listening to the lungs( auscultation), breathing noises are barely audible.
Radiography of chest organs reveals an increase in the transparency of lung tissue( due to excess air), in some cases more pronounced in the lower parts of the lungs.
The study of the α1-inhibitor content of proteases in serum is crucial in establishing the diagnosis of pulmonary disease associated with a hereditary enzyme deficiency.
Until recently, the treatment of congenital deficiency of α1-protease inhibitor was considered to be unpromising. Substitution therapy can be carried out by intravenous injection of α1-inhibitor proteases. Significantly less effective, although more accessible, are intravenous injections of donor human plasma.
Some authors recommend the use of well-known agents that inhibit proteolysis( for example, repeated intravenous courses of contrikal or gordox).For the same purpose, a 5% E-aminocaproic acid of 100 ml is used.
Antioxidants are of particular importance.
Primary prophylaxis of enzyme deficiency has not yet been developed sufficiently. Theoretically, the carriage of the deficit gene causes a marked decrease in the content of α1-inhibitor proteases in the blood serum of both spouses. For the early diagnosis and timely implementation of preventive measures, it is recommended that the content of the α1-inhibitor of proteases be determined in all children and boys suffering from frequently recurring respiratory diseases, especially those with dyspnoea. In the case of an established diagnosis, regardless of the presence and intensity of clinical manifestations, and also to family members suffering from this disease, smoking is categorically contraindicated, as well as work in conditions of polluted air. It is necessary to prevent respiratory viral diseases.
Early detection and timely implementation of preventive measures and treatment allow prolonging the life of people suffering from cystic fibrosis.