Clinical and pathogenetic features of the formation of pulmonary hypertension and cardiovascular complications in patients with bronchial asthma

The dissertation is devoted to the study of clinical and pathogenetic features of the formation of pulmonary hypertension and associated cardiovascular complications in patients with bronchial asthma. Based on a retrospective analysis of medical records of the pulmonology center of Samara for the period from 1995 to 2005, the author establishes the prevalence of pulmonary hypertension among patients with bronchial asthma and compares its severity with the severity of the underlying disease. The work investigates the role of endothelial dysfunction, the state of vascular tone, acid-base balance, vasomotor and hemostatic functions of the endothelium, as well as the activity of antiprotease protection of the lungs according to the level of α1-antitrypsin in the pathogenesis of pulmonary hypertension and cardiovascular complications. On the basis of the data obtained, prognostic signs have been formulated that make it possible to identify groups of patients with a high risk of development of pulmonary hypertension and cardiovascular complications, and recommendations have been proposed for monitoring the functional state of the endothelium to improve the management of patients with bronchial asthma.

Relevance of the topic

Despite considerable advances in the treatment of pulmonary pathology, bronchial asthma (BA) continues to be among the most common therapeutic diseases. Epidemiological studies conducted in Western Europe in recent years indicate that in the general population bronchial asthma occurs in more than 5% of cases, and in some regions of the world, for example in Australia, these figures reach 10%. At the same time, according to data from many countries of the world, the morbidity and mortality from BA are not decreasing, despite the unification of methods of treatment of the disease. An increase in the prevalence of the disease is noted in the USA, England, New Zealand, and Austria.

One of the characteristic complications in broncho-obstructive pathology is an increase in pressure in the pulmonary artery system (PH). At present, pulmonary arterial hypertension (PAH) is defined as a progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular failure and premature death. Pulmonary hypertension (PH) is one of the main factors of unfavorable outcome of BA, contributing to the progression of heart failure and disorders of intracardiac hemodynamics. At the same time, data on the prevalence of PH among patients with BA, the patterns of its occurrence and development are scattered and do not allow judging the frequency of its occurrence, as well as the degree of its influence on the course of the underlying pathology and the features of the formation of cardiovascular complications in this group of patients. Despite the widespread view that the leading cause of disability and mortality among patients with broncho-obstructive pathology is progressive respiratory failure (RF), data from recent statistical studies indicate an increased role of cardiovascular complications in this process, which may be due to the introduction into medical practice of new standards of treatment and the development of modern bronchodilator drugs. However, the prevention of complications on the part of the cardiovascular system in this group of patients has not so far received due attention. The role of PH in the progression of heart failure has not been fully studied, and there is no unified point of view on the tactics of management and methods of treatment of patients with BA against the background of increased pressure in the pulmonary artery.

At the same time, these questions are decisive for planning the organization and development of new methods of rendering medical care to patients with respiratory pathology against the background of PH.

Aim of the work: to establish the prevalence of pulmonary hypertension among patients with bronchial asthma (according to a retrospective analysis of case histories), as well as the role of endothelial dysfunction and disorders in antiprotease protection of the lungs in the genesis of pulmonary hypertension, progression of pulmonary-heart failure, and development of cardiovascular complications for determining prognostic criteria of the course of bronchial asthma.

Objectives of the study:

1. To study the prevalence of pulmonary hypertension among patients with BA according to a retrospective analysis of medical records of patients of the pulmonology city center of Samara for the period from 1995 to 2005, as well as the level of pulmonary hypertension in patients with varying severity of BA.

2. To identify the features of the course, prognosis and prevalence of cardiovascular complications in patients with BA against the background of PH compared with BA without PH.

3. To establish the role of endothelial disorders and hereditary factors in the pathogenesis of progression of PH, pulmonary-heart failure, as well as in the development of cardiovascular complications in patients with BA.

4. To determine the state of antiprotease protection of the lungs in patients with bronchial asthma with and without pulmonary hypertension by the level of α1-antitrypsin in blood serum and the role of α1-antitrypsin in the genesis of PH.

5. To evaluate the role of endothelial disorders and antiprotease protection of the lungs as a marker of predisposition to the development of PH, as well as a prognostic criterion of increased risk of development of cardiovascular complications in this group of patients.

Scientific novelty

1. The features of prevalence and severity of PH in patients with varying severity of BA, as well as the degree of influence of PH on the severity of the course, prognosis and character of complications in patients with this pathology, have been studied.

2. The levels of pressure in PH correlating with a high risk of development of fatal cardiovascular complications have been determined.

3. The role of endothelial dysfunction in the progression of broncho-obstructive pathology, the development of cardiovascular and thrombotic complications, and the occurrence of irreversible pulmonary hypertension has been identified and evaluated.

4. The interrelation between genetically determined activity of α1-antitrypsin in patients with BA, the rate of formation of PH, and the occurrence of cardiovascular complications in different variants of the course of bronchial asthma has been established.

Practical significance

On the basis of the refined pathogenesis of PH in patients with bronchial asthma, criteria have been developed for the formation of groups of patients with a high risk of development of cardiovascular complications.

Regular monitoring of the functional state of the endothelium in them will improve control over the symptoms of the disease and the effectiveness of the treatment being carried out.

Establishment of the role of endothelial disorders in the pathogenesis of PH and cardiovascular complications in patients with BA will make it possible to develop additional individual recommendations for the treatment of patients with this pathology.

Methods for predicting the course of BA do not require special equipment and can be used in the presence of a standard clinical laboratory in the practice of pulmonologists, therapists, and cardiologists.

Implementation of the results of the study

The developed criteria, which make it possible to identify a risk group for the early formation of PH and cardiovascular complications in young patients with bronchial asthma, have been introduced into the practice of therapists of the polyclinic of the Samara Pulmonology Center at MMU MSCh No. 12.

The main provisions of the dissertation are used in teaching at the Department of Internship of the Samara Military Medical Institute, in the course of training interns in the specialties "Therapy" and "General Practice" in the cycles "Pulmonology" and "Cardiology" and residents of the Samara Military Medical Institute and GIUV MO RF.

Main provisions of the dissertation submitted for defense

The addition of PH leads to a change in the clinical course and severity of BA, an increase in the number of exacerbations, and a worsening of its prognosis, which is associated with a disorder of central hemodynamics and the formation of chronic hypoxia.

The basis of the pathogenesis and progression in patients with PH is formed by genetic factors (decreased production of α1-antitrypsin, polymorphism of the ACE gene) and endothelial disorders manifested by pathological changes in the vasomotor and hemostatic functions of the endothelium.

Pulmonary hypertension and the factors contributing to its formation underlie the early occurrence of cardiovascular complications, including fatal ones, in patients with BA.

The level of PH, the degree of severity of endothelial disorders, and the antiprotease protection of the lungs can be used as prognostic criteria of the course of BA and for the formation of groups of patients with a high risk of development of cardiovascular complications.

Approval of the dissertation

The materials of the dissertation were presented at the XXXVIII Final Scientific Conference of the Faculty of the Military Medical Faculty under the Samara State Medical University (Samara, 2005); the XXXX and XXXXII Final Scientific Conferences of the Faculty of the Samara Military Medical Institute (Samara, 2007 and 2009).

Publications

On the topic of the dissertation 5 scientific works have been published, of which 1 in the central press (according to the VAK list); 2 rationalization proposals have been defended.

Scope and structure of the dissertation