The Role of Bioamines in Chronic Gastritis Combined with Chronic Bronchitis and Their Correction by Ozone Therapy

The dissertation is devoted to the study of the role of bioamines—histamine, serotonin, and catecholamines—in the pathogenesis of the combined course of chronic gastritis and chronic bronchitis. The work examines the clinical and morphological interrelations between the gastroduodenal zone and the respiratory organs, as well as the possible common pathogenetic links mediated by inflammatory mediators in the mucosal membranes of the stomach and bronchi. Using luminescent histochemical methods, a comparative study was carried out of bioamine levels in healthy individuals and in patients with combined pathology, taking into account sex, age, duration of disease, gastric secretory activity, degree of infection with pyloric helicobacteria, character of endobronchitis, and activity of bronchial inflammation. Special attention is paid to evaluating the clinical effectiveness of including infusion ozone therapy in standard treatment and its influence on the bioamine status of the mucosal membranes. The data obtained broaden the understanding of the pathogenesis of combined diseases and substantiate the pathogenetic orientation of ozone therapy as a component of complex treatment.

The relevance of the problem of combined pathology is determined, first of all, by the opinion currently accepted by clinicians and morphologists that two or more diseases that mutually aggravate the prognosis quite frequently occur simultaneously in one patient. In this respect, considerable interest is attracted by the possibility of the combined development and manifestation of such widespread diseases as gastroduodenitis and chronic lung diseases, in particular chronic bronchitis (CB). This is associated with the continuing unabated increase in each of the diseases under consideration and with data on their more frequent combination (Chuchalin A.G., Belevsky A.S., Chernyak B.A. et al., 2005; Tsimmerman Ya.S., 2006; Pleshko R.I., Ogorodova L.M., Sukhodolo I.V., Gereng E.A., 2006; Riccioni G., Delia Vecchia R., Menna V., et al., 2004; etc.).

The practical significance of this problem is also determined by the fact that many causes of the rather frequent tendency toward such a combination have not been fully elucidated, the features of the clinical course have been insufficiently studied, and comprehensive therapy has not actually been developed. Preventive measures carried out without taking into account the specific mechanisms of such combined pathology are still insufficiently effective. Interest in the problem of combined pathology was undeservedly lost in recent decades, apparently due to the intensified development of narrow specialization in the field of internal medicine. However, the emerging concept of family medicine with the creation of a wide network of general practitioner offices is reactivating scientific research in this area.

In recent years, notable advances have been achieved in studying many aspects of the problem of each of the two associated diseases. Achievements in gastroenterology have made it possible to reconsider and shed new light on the issues of chronicity of gastroduodenitis; in particular, the special role of gastroduodenal zone infection with pyloric helicobacteria has been established.

Until recently, the statements made by V.Kh. Vasilenko (1970) have not lost their relevance, according to which there is still "… no unified theory of the origin of chronic gastritis and peptic ulcer disease, and very much still needs to be clarified. Although there are many reliable facts, the main thing remains unknown." Many issues in the therapy of chronic gastritis, despite the tangible successes achieved in this area in recent years, are still far from final resolution. The developed therapeutic measures in most cases only allow achieving a temporary short-term remission, but they do not always eliminate the causes and conditions that contribute to the occurrence of disease exacerbation.

Certain achievements are known in studying the etiology and pathogenesis of chronic bronchitis. At the same time, the successes in developing and implementing effective methods for the prevention and therapy of CB that meet the current requirements of practical public health are less tangible (Aisanov Z.R., Kokosov A.N., 2001; Kokosov A.N., 2000; 2002; Ovcharenko S.I., Litvinova I.V., 2004; Dvoretsky L.I., Dubrovskaya N.V. et al., 2004, etc.).

It is quite understandable that the existing difficulties in studying each of the diseases under consideration—chronic gastritis and chronic bronchitis separately—increase and become even more complex when they occur simultaneously.

The digestive and bronchopulmonary systems, as is known, have close anatomical and functional interrelations, which are realized through the commonality of innervation and blood supply. The embryological kinship of these organs, which develop together from the embryonic digestive tube, should also be pointed out. Therefore, it is entirely possible to expect the occurrence of more or less pronounced accompanying functional and structural changes in one of these organs when the other is affected. It is obvious that in combined diseases of the stomach, duodenum, bronchi, and lungs, the probability of a more persistent course, serious functional disorders, and complications on the part of each of these organs significantly increases due to the mutually aggravating influence.

One of the most difficult issues is that of establishing the existence of common pathogenetic links in the combined diseases, chronic gastritis (CG) and CB, taking into account the etiological significance of various kinds of infections in the formation of these diseases. It would be logical to assume that the connecting link may be the mediator supply of individual tissue structures as a marker of infectious lesions of the gastric and bronchial mucosae, which constitute a kind of "arena" of pathological reactions in CG and CB. The existence of an interconnection between individual fragments of the pathogenesis of CG and CB would broaden our understanding of combined diseases and make it possible to determine the tactics of more effective therapy and prevention.

The polysystemic character of the pathological manifestations in the combination of CG with CB requires the simultaneous prescription of many medications, which contributes to sensitization and immunodestabilization. A reasonable limitation of pharmacotherapy is necessary, along with the use of methods and agents with diverse effects, when the maximum clinical effect is achieved with minimal load, including drug load, on the patients' organism. In recent years, interest in the use of non-pharmacological methods of treatment, in particular ozone therapy (OT), has been revived in the therapeutic clinic. The therapeutic prerequisites for the use of medical ozone (Karataev S.D. et al., 2000; Zmyzgova A.V., Maksimov V.A., 2003; Peretyagan S.P., 2003) are based on the nonspecific sanogenic action of ozone, which can be used at all levels of pathogenetic therapy as a supplement or replacement for traditional methods (Chernekhovskaya N.E., Andreev V.G. et al., 2003; Maslennikov O.V., Kontorshchikova K.N., 2005; Fedorov A.A. et al., 2005).

There are few works devoted to studying the effect of infusion ozone therapy on combined gastroduodenal and bronchopulmonary pathology, and their results do not always have an unambiguous interpretation. The study of the clinical effectiveness of ozone therapy and the development of a scientifically grounded approach to its use in the treatment of combined diseases requires further research in this area. The use of ozone therapy in the combined treatment of CG and CB could possibly solve the problem of more effective and safer treatment, as well as the prevention of this pathology.

Despite the large number of experimental and clinical studies proving the participation of bioamines as mediators of inflammatory and allergic processes, there are few works devoted to the comprehensive study of histamine, serotonin, and catecholamine levels in CG combined with CB, and their results are highly contradictory. Moreover, they are based on the study of neurotransmitters in blood, gastric juice, and gastric mucosa by spectrofluorimetric methods (Birg N.A., 1981, 1982). The few works contain brief information on the role of bioamines in the body (Artemyeva E.G., Batrakov S.N., 2005, 2006), which is insufficient to characterize their participation in the pathogenesis of combined pathology.

In the domestic and foreign literature, there are few works devoted to the parallel study of histamine, serotonin, and catecholamine levels in the tissues of the stomach and bronchi by luminescent histochemical methods in patients with CG combined with CB.

The need for an in-depth study of the fine pathogenetic mechanisms of the parallel development of the named diseases, which are important for pathogenetically substantiated treatment using ozone therapy, determines the scientific and practical relevance of this study.

Aim of the study. To investigate the role of bioamines in the structures of the gastric and bronchial mucosae in chronic gastritis combined with chronic bronchitis as one of the pathogenetic mechanisms of the development of this combined pathology, as well as to evaluate the effect of ozone therapy on the levels of histamine, serotonin, and catecholamines in the structures of the gastric and bronchial mucosae in combined diseases.

Tasks of the study:

1. To study the levels of bioamines in the structures of the gastric and bronchial mucosae in patients with chronic gastritis combined with chronic bronchitis.

2. To determine the dependence of histamine, serotonin, and catecholamine levels on the sex and age of patients, the duration of the disease, the level of gastric secretion and the degree of infection of the gastric mucosa with pyloric helicobacteria, the character of endobronchitis, and the degree of activity of the inflammatory process in the bronchi.

3. To carry out a comparative analysis of the dynamics of bioamine levels in the structures of the gastric and bronchial mucosae of patients with chronic gastritis combined with chronic bronchitis under different treatment methods and, on the basis of their comparison, to evaluate the effectiveness of ozone therapy.

Scientific novelty of the work

1. Based on the analysis of the results of the comprehensive study, the role of changes in the levels of serotonin, histamine, and catecholamines in the structures of the gastric and bronchial mucosae in the pathogenesis of combined pathology—chronic gastritis and chronic bronchitis—has been shown.

2. For the first time, in patients with chronic gastritis combined with chronic bronchitis, the dependence of the bioamine status of the structures of the gastric and bronchial mucosae on the sex and age of patients, the duration of the disease, the level of gastric secretion, the degree of infection of the gastric mucosa with pyloric helicobacteria, the character of endobronchitis, and the degree of activity of the inflammatory process in the bronchi has been established.

3. Reliable data have been obtained on changes in the levels of histamine, serotonin, and catecholamines in the structures of the gastric and bronchial mucosae depending on the therapy performed (standard or standard combined with infusion ozone therapy), which allows them to be used for a comparative assessment of the effectiveness of the treatment methods applied.

4. It has been proven that ozone therapy is a pathogenetic component in the treatment of combined pathology—chronic gastritis and chronic bronchitis.

Practical significance of the work

The established dependence of the bioamine status of the gastric and bronchial mucosae on the sex and age of patients, the duration of the disease, the level of gastric secretion, the degree of infection of the gastric mucosa with pyloric helicobacteria, the character of endobronchitis, and the degree of activity of the inflammatory process in the bronchi testifies to a certain role of these changes in the pathogenesis of combined pathology—chronic gastritis combined with chronic bronchitis.

Reliable data have been obtained on the interrelation of the dynamics of bioamine levels in the structures of the gastric and bronchial mucosae in chronic gastritis combined with chronic bronchitis, which refine and supplement the existing understanding of the pathogenesis of combined diseases.

It has been proven that infusion ozone therapy is a pathogenetic component of the therapeutic complex and increases the effectiveness of the treatment of combined diseases, improves the regeneration of the gastric mucosa, exerts an anti-helicobacter effect, improves bronchial patency, reduces the activity of the inflammatory process in the bronchi, and has a positive effect on the bioamine status of the structures of the gastric and bronchial mucosae.

The dynamics of bioamine levels in the structures of the gastric and bronchial mucosae reflects new pathogenetic mechanisms of the development of combined pathology—chronic gastritis combined with chronic bronchitis. The features of the dynamics of these indicators against the background of different therapeutic methods (standard or standard combined with infusion ozone therapy) can be used to assess the effectiveness of treatment in outpatient-polyclinic practice and in inpatient settings, as well as in the educational process of a medical university.

Statements for defense

1. In patients with chronic gastritis combined with chronic bronchitis, an increase in the levels of bioamines—histamine, serotonin, catecholamines—has been established in the structures of the gastric mucosa: endocrine and enterochromaffin cells, macrophages, glandular epithelium, connective tissue and intercellular space, as well as in the structures of the bronchial mucosa: alveolar macrophages, lymphocytes, neutrophils, mast cells, and mucus.

2. Changes in the levels of bioamines in the structures of the gastric and bronchial mucosae depend on the age and sex of patients, the duration of the disease, the level of gastric secretion, the degree of infection of the gastric mucosa with pyloric helicobacteria, the character of endobronchitis, and the degree of activity of the inflammatory process in the bronchi.

3. Ozone therapy is a pathogenetic component of the treatment of patients with chronic gastritis combined with chronic bronchitis. The use of infusions of ozonized physiological solution contributes to a significant change in the levels of histamine, serotonin, and catecholamines in the structures of the gastric and bronchial mucosae in this category of patients.

Implementation of the work

Infusion ozone therapy has been introduced at the Republican Medical Center of the Ministry of Health of the Chuvash Republic; at the Republican Clinical Hospital No. 1 of the Ministry of Health of the Chuvash Republic, at the Municipal Healthcare Institution "Central City Hospital," at the Municipal Healthcare Institution "City Hospital No. 4," at the Municipal Healthcare Institution "City Hospital No. 8," at the Municipal Healthcare Institution "City Hospital No. 9," at the Novocheboksarsk City Hospital, at the Morgaush Central District Hospital, and at the Shumerlya City Hospital of the Chuvash Republic.

Approbation of the work

The materials of the dissertation were reported and discussed at the scientific seminars of the Department of Internal Diseases of the Stomatological and Pediatric Faculties (2002; 2003; 2004; 2005; 2006), at the meetings of the Scientific Medical Society of Therapists of the Chuvash Republic (2004; 2005), at the scientific-practical conference of therapists and endoscopists of the Chuvash Republic (2003), at the interregional scientific-practical conference of young scientists, interns, and students (Cheboksary, 2004, 2005), at the republican scientific-practical conference of therapists (2004), at the V International Congress "Rehabilitation in Medicine and Immunorehabilitation" (Thailand, 2004), and at the interregional scientific-practical conference of the Volga Federal District "Ozone in Biology and Medicine" (Nizhny Novgorod, 2005).

Publications

Thirteen works have been published on the topic of the dissertation.

Scope of the work

The dissertation consists of a table of contents, an introduction, five chapters, a conclusion, conclusions, practical recommendations, an appendix, and a list of references.