Pathophysiological Basis of Laser Stimulation of Acupoints in the Treatment of Bronchial Asthma

The dissertation is devoted to the pathophysiological justification of laser stimulation of acupoints in the treatment of bronchial asthma. The investigation was conducted using a helium-neon laser with low-intensity radiation and encompasses a comprehensive study of clinical, functional, biochemical, and immunological indicators in patients with bronchial asthma of exogenous, endogenous, and mixed forms of varying degrees of severity. The central direction of the work is the luminescent-histochemical determination of the content of biogenic amines — histamine, serotonin, and catecholamines — in plasma and formed elements of capillary and venous blood. The dynamics of these indicators during monolaser and complex therapy have been studied, and the interrelationship between the levels of biogenic amines and indicators of external respiration function, sensitivity and reactivity of the bronchi, and laboratory parameters has been established. Data have been obtained on the possibility of reducing histamine and serotonin content and increasing catecholamine content under the influence of laser stimulation, which testifies to the activation of the functions of formed elements of blood and the normalization of pathogenetic mechanisms of bronchospastic reactions.

The Relevance of the Problem. Bronchial asthma (BA) is one of the most prevalent and severe diseases of the respiratory organs. In various countries, it affects from 4 to 18% of the population (Khaityov R.M. et al., 1998; Chuchalin A.G., 1994, 2002; Woolcock A.J. et al., 1997; Mannino D.M., Nota D.M., Pertowski S.A. et al., 1998). In our country, BA afflicts approximately 7 million people (Chuchalin A.G., Mednikov B.L., Belevsky A.S. et al., 1999). An especially high increase in morbidity has been noted in large industrial cities (Ilyina N.I., 2002). In some countries, BA ranks among the leading causes of temporary disability, invalidism, and mortality of the population (Jarvis D et al., 1997; Stout J.W., White L.C., Redding G.J. et al., 2001).

Pharmacological and economic aspects of BA also constitute a growing problem of healthcare, which requires increased expenditures on pharmacotherapy, provision of emergency urgent care, payment for prolonged periods of disability, and disease prevention (Gamkrelidze A.G., Gotua M.A., Rukhadze M.T. et al., 2004; Segura N. et al., 1994; Serra-Batlles J., Plasa V., Morejon E. et al., 1998; Gergen P.J., 2001; Global Initiative for Asthma, 1995, 2003; Dolan C.M., Fraher K.E., Bleecker E.R. et al., 2004). Medications prescribed to BA patients include maintenance drugs (anti-inflammatory agents and long-acting bronchodilators), which allow control of the disease course (Fedoseev G.B., 2001; Lasitsa O.I. et al., 2001; Chuchalin A.G., 2002; Clinical Recommendations, 2002; Ogorodova L.M. et al., 2002; Avdeev S.N., 2005). The most effective anti-inflammatory agents are inhaled glucocorticosteroids (IGCS). For patients with severe BA, when IGCS are ineffective, systemic glucocorticoids are administered. For the treatment of patients with mild persistent BA, as well as prophylactically to prevent bronchospasm, cromones are prescribed. Recently, antileukotriene agents have been widely used. For the prevention of suffocation attacks, inhaled beta2-agonists of long and short action are widely applied. Their mechanism of action is associated with relaxation of bronchial smooth muscle, reduction of vascular permeability, and inhibition of mediator release from mast cells (MC) and basophils (B). Muscarinic antagonists are also employed. For relief of BA attacks, methylxanthines: theophylline, eufyllin, are prescribed. Specific immunotherapy is successfully applied in exogenous BA.

The problem of treatment, prevention of complications, prevention of severe disease course, and invalidization of working-age patients remains far from resolved, as the number of BA patients has been steadily increasing in recent years. Over the last 20 years, according to data from various authors, BA morbidity has increased by 2 to 2.5 times (Hershey G.K.K. et al., 1997; Sibbald W., 1997). An increase in severe cases has been noted (Chuchalin A.G., Ogorodova L.M., Petrovsky F.I. et al., 2005). Mortality during severe BA exacerbations, according to various literary sources, reaches 1-10% (Georgopoulos D. et al., 1998). Despite the successes achieved in pharmacotherapy of BA, questions regarding therapy in the presence of adverse reactions and resistance to medicinal agents remain unresolved. In this regard, the selection of non-pharmacological treatment methods based on activation of the body's own protective forces and its functional reserves has become relevant. Such properties are possessed by low-intensity laser (LIL) radiation, which provides a wide spectrum of effects: anti-inflammatory, immunomodulatory, desensitizing, spasmolytic, antihypoxic, vasodilating, improvement of microcirculation and blood rheology, stimulation of metabolic processes and factors of nonspecific protection and humoral immunity (Inyushin V.M., 1976; Kozlov V.I., Bulylin V.A., Samoilov N.G. et al., 1993; Skobeikin O.K., Gordon D.S., Sapelov V.N. et al., 1993; Ananchenko V.G., Sergeev V.A., Vinogradov D.L. et al., 1994; Samoilov N.G., 2000; Bulylin V.A. et al., 2001, 2003; Azizov G.A., 2003; Mantsova L.I., 2003; Geints A.V. et al., 2004; Baibekov I.M. et al., 2004; Brill G.E. et al., 2004; Kozlov V.I., 2004; Rubert N., 1983; Ismailov D.A., Khoroshaev V.A., Shishkin M.A. et al., 1993). Significant experience has been accumulated in the application of LIL in the complex treatment of various pathologies (Nogaller A.M. et al., 1986). Laser therapy is widely and successfully used in cardiology (Lyusov V.A. et al., 1996; Vasilyev A.P. et al., 1999; Korochkin I.M., 2001), gastroenterology (Rapoport S.I. et al., 1999), pulmonary tuberculosis (Dityatkov A.E. et al., 2001; Zhilin Yu.N., 2003); pulmonology (Kurochkin A.A., 1996; Osin A.Ya. et al., 1999; Kumeyko O.V., Khazov S.V., Krasnoshekov A.A. et al., 2000; Shchegolkov A.M., Klyachkin L.M., Yaroshenko V.P. et al., 2000; Alexandrova O.Yu., 2001; Mantsova L.I., 2003; Moskalenko I.T. et al., 2003; Khan M.A., Chernysheva L.A., Konova O.M. et al., 2003; Sorokin G.N., Bakhtin V.I., Pochivalov A.V. et al., 2004).

According to contemporary views, in the development of inflammatory and allergic processes in BA, biologically active substances (BAS), in particular histamine (H), serotonin (5-HT), and catecholamines (CA), play an important role (Freidin I.S. et al., 1996; Gordon D.S. et al., 1982; Smerdova V.V., 1989; Gushchin I.S., 1997). The role of heparin, a recognized inhibitor of BAS, is also great (Gordon D.S., 1994). In the mechanisms of development of inflammatory and bronchospastic reactions, various cellular elements take an active part, most notably mast cells and eosinophils (E), capable of secreting a number of inflammatory mediators (Fedoseev G.B. et al., 1980; Zhikharev S.S., Fedoseev G.B., Kachanova T.P. et al., 1990; Fedoseev G.B., 1995; Bochkarev V.A. et al., 1991; Chuchalin A.G., 1997, 2003; Johnson P.R.A., Ammit A.J., Carlin S.M. et al., 1997; Brightling C.E., Ward R., Woltmann G. et al., 2000; Johnson P.R., Roth M., Tamm M. et al., 2001; Marguet C. et al., 2002). N.G. Carroll et al. (2002) discovered the largest number of mast cells in the smooth muscles of the respiratory passages. The number of degranulated mast cells was the highest among patients who died of asthma. S.E. Brightling, P. Bradding, F.A. Symon et al. (2002) report that comparison of immunohistochemical analyses of biopsy specimens from asthmatic patients with control patients showed a striking increase in mast cells in the ligaments of smooth muscles of the respiratory passages. The number of mast cells correlates with asthmatic signs — airway hyperresponsiveness, which was revealed by means of the methacholine inhalation test.

Despite the significance of the participation of biogenic amines in the inflammatory and allergic processes playing a substantial role in the development of BA, we have not found information in the available literature on the dynamics of their content under acupoint impact of LIL in patients with BA. In our opinion, many questions concerning this problem remain unresolved to this day. This information would allow a deeper understanding of the pathophysiological mechanisms of laser stimulation and the correct selection of pathogenetic therapy of such a prevalent and severe disease as BA. The great medical and social significance and the necessity of a scientific-practical solution of existing problems have determined the need for the present investigation.

OBJECTIVE OF THE INVESTIGATION: Pathophysiological justification of the mechanism of laser stimulation of acupoints in patients with bronchial asthma from the standpoint of clinical, histochemical, functional, biochemical, and immunological indicators.

TASKS:

1. To conduct a comparison of the clinical effectiveness of laser stimulation of acupoints in patients with bronchial asthma during monolaser therapy and complex therapy (combination of laser stimulation of acupoints with traditional pharmacotherapy).

2. To study the level of histamine, serotonin, and catecholamines in plasma and formed elements of capillary and venous blood in patients with bronchial asthma by luminescent-histochemical methods.

3. To reveal features of the effect of laser stimulation of acupoints on the dynamics of histamine, serotonin, and catecholamine content in plasma and formed elements of capillary and venous blood in patients with bronchial asthma depending on the clinical variant, phase, and degree of severity.

4. To study the effect of laser stimulation of acupoints in patients with bronchial asthma on the capillary-venous difference of histamine, serotonin, and catecholamines in plasma and formed elements of blood.

5. To evaluate the therapeutic effectiveness of laser stimulation of acupoints in patients with bronchial asthma by indicators of external respiration function, sensitivity, and reactivity of the bronchi.

6. To determine the character of the effect of laser stimulation of acupoints in patients with bronchial asthma on clinical-laboratory indicators, the number of eosinophils of nasal secretion, cortisol level, blood immunoglobulins, specific cutaneous reactivity, and to reveal the correlation relationship of these indicators with the content of biogenic amines in plasma and formed elements of blood.

7. To reveal the correlation relationship between the dynamics of histamine, serotonin, and catecholamine levels in plasma and formed elements of peripheral blood and the dynamics of external respiration function indicators, sensitivity, and reactivity of the bronchi during laser stimulation of acupoints.

8. To justify the pathogenetic mechanism of laser stimulation of acupoints based on analysis of clinical, histochemical, functional, biochemical, and immunological indicators.

9. To justify the possibility of using luminescent-histochemical methods for determination of biogenic amines in plasma and formed elements of peripheral blood in monitoring the effectiveness of monolaser and complex therapy.

10. To develop recommendations for the application of monolaser and complex therapy for the treatment and rehabilitation of patients with bronchial asthma in ambulatory-polyclinic conditions.

SCIENTIFIC NOVELTY:

For the first time, a pathophysiological justification of the effectiveness of laser stimulation of acupoints by a helium-neon laser in the treatment of patients with bronchial asthma is provided, with the application of luminescent-histochemical methods of investigation of plasma and formed elements of capillary and venous blood. It has been demonstrated that the positive effects of low-intensity laser radiation are explained by its ability to reduce the initially elevated content of histamine and serotonin and to increase the initially decreased content of catecholamines in the formed elements of capillary and venous blood in patients with bronchial asthma.

Acupoint impact of low-intensity laser radiation activates the functions of formed elements of blood in patients with bronchial asthma, leading to active binding of biogenic amines and normalization of the capillary-venous difference.

The work has demonstrated the interrelationship between the content of histamine, serotonin, and catecholamines in plasma and formed elements of venous and capillary blood and indicators of external respiration function, hypersensitivity and hyperreactivity of the bronchi, specific cutaneous reactivity, as well as laboratory tests (formula of peripheral blood, number of eosinophils of nasal secretion, cortisol level, immunoglobulins, fibrinogen, prothrombin index) during laser stimulation of acupoints.

Within separate clinical groups, the advantage of monolaser therapy over traditional pharmacotherapy in patients with bronchial asthma of mild degree, and complex therapy — in moderate and severe degrees, has been demonstrated.

It has been shown that with early initiation of treatment, timely repetition of courses of laser therapy, not only are clinical, functional, and laboratory indicators normalized, but also the number of exacerbations and frequency of hospitalization, emergency calls, temporary and persistent loss of working capacity are reduced, pharmacological dependence is decreased, economic efficiency is increased, and the quality of life of patients is improved.

SCIENTIFIC-PRACTICAL SIGNIFICANCE:

High effectiveness of monolaser therapy in patients with exogenous and endogenous bronchial asthma of mild degree has been demonstrated, which allows its application in ambulatory-polyclinic conditions. Indications for complex therapy in patients with exogenous, endogenous, and mixed bronchial asthma of moderate and severe degrees have been formulated. Practical recommendations on laser stimulation of acupoints for the optimization of treatment and rehabilitation of patients with bronchial asthma in ambulatory-polyclinic conditions have been developed and implemented. A design for remote control of a laser unit has been proposed (rationalization proposal No. 671 dated 27.05.87).

The ability of laser stimulation of acupoints in patients with bronchial asthma to: reduce the content of histamine, serotonin, and increase the content of catecholamines in plasma and formed elements of capillary and venous blood; activate the functions of formed elements of blood; restore bronchial sensitivity to sympathomimetics and xanthine derivatives; normalize clinical-laboratory indicators; improve flow indicators of external respiration function; reduce hypersensitivity and hyperreactivity of the bronchi; activate adrenal function and increase cortisol levels; exert an immunomodulatory effect; and reduce specific cutaneous reactivity has been established. These observations have important theoretical and practical significance for the study of pathophysiological mechanisms of laser stimulation of acupoints in patients with bronchial asthma and for new approaches to monolaser and complex therapy, rehabilitation of patients, and prevention of the disease.

POSITIONS SUBMITTED FOR DEFENSE:

1. Laser stimulation of acupoints in bronchial asthma substantially improves the results of treatment and rehabilitation of patients, facilitates the clinical course, restores bronchial sensitivity to sympathomimetics, allows reduction of the dose of glucocorticosteroids, reduces the frequency of hospitalization and duration of temporary disability, decreases the incidence of invalidism, which leads to a significant economic effect.

2. An important factor in the mechanism of laser stimulation of acupoints is the reduction of histamine and serotonin content and the increase of catecholamine content in plasma and formed elements of capillary and venous blood, activation of the function of formed elements of blood, which contributes to improvement of external respiration function, reduction of hypersensitivity and hyperreactivity of the bronchi, and decrease in the intensity of inflammatory and allergic manifestations.

3. Laser stimulation of acupoints contributes to activation of adrenal function and increase of cortisol blood levels.

4. Laser stimulation of acupoints normalizes clinical-laboratory blood indicators (leukocyte count, eosinophil count, erythrocyte sedimentation rate), hemostasis indicators (fibrinogen, prothrombin index), and immune reactivity (specific cutaneous reactivity and immunoglobulin levels).

5. Functional improvement and improvement of laboratory indicators during laser stimulation of acupoints in patients with bronchial asthma reliably correlate with the dynamics of histamine, serotonin, and catecholamine content in plasma and formed elements of capillary and venous blood.

6. Monolaser therapy is effective in the treatment of patients with exogenous and endogenous bronchial asthma of mild degree. Combination of laser stimulation of acupoints with traditional pharmacotherapy is indicated for patients with exogenous, endogenous, and mixed bronchial asthma of moderate and severe degrees.

IMPLEMENTATION OF RESEARCH RESULTS

The results of the scientific investigation: methods of cytofluorescent determination of biogenic amines in formed elements of blood and bronchoprovocation tests with inhalation of oxisatromide have been introduced into the work of pulmonology and traditional medicine departments of Cheboksary city hospitals — MUZ No. 4, No. 5, the polyclinic of the Cheboksary Machine-Building Plant, the 'Chuvashkabel' Plant, and the Cheboksary City Mud Bath Dispensary, for the purpose of diagnosing the form, phase, and degree of severity of bronchial asthma and objective assessment of the effectiveness of treatment with low-intensity laser radiation.

The materials of the work are included in the methodological recommendations 'Educational-Research Work in Bronchial Asthma.' The obtained data are used in the educational process at the departments of faculty therapy and internal diseases, in the course of polyclinic therapy, pathological physiology of the medical faculty of the Chuvash State University during seminar and practical classes, as well as in the scientific-practical work of therapists of the city of Cheboksary and the Chuvash Republic.

VALIDATION OF THE WORK. The work was validated at scientific-practical conferences (Cheboksary, 1978-2005; Kaluga, 2002), at scientific conferences of the medical faculty of the Chuvash State University (Cheboksary, 1979-2005), at all-Union scientific conferences (Kuibyshev, 1979; Barnaul, 1989; Riga, 1992), at national congresses on diseases of the respiratory organs (Kiev, 1990; Moscow, 2002), at international conferences on laser medicine (Moscow, 1990, 1992, 1994, 1996, 1999, 2005; Saint Petersburg, 1993, 2001; Kazan, 1995), at international congresses on immune rehabilitation (Antalya, 1996; Singapore, 2002).

PUBLICATIONS. Thirty-one works have been published on the dissertation topic, including 12 in peer-reviewed journals. Based on the results of the scientific investigations, rationalization proposal No. 671 dated 27.05.87 has been obtained, entitled: 'Design for Remote Control of a Laser Unit.'

STRUCTURE AND SCOPE OF THE DISSERTATION. The dissertation consists of an introduction, a literature review, a methodological chapter, 5 chapters — results of the author's investigations, discussion of the obtained results, conclusions, practical recommendations, and a list of references. The dissertation is presented on 267 pages of typed text, illustrated with 71 tables and 70 figures, and contains a bibliography of 307 domestic and 132 foreign sources.