Chronopathophysiological Mechanisms of Gastroduodenal Pathology in Children. Chronotherapy of the Pathological Process

The dissertation is devoted to the study of chronopathophysiological mechanisms of gastroduodenal pathology in children and the development of chronotherapeutic approaches to the treatment of the pathological process. The research focuses on the analysis of the temporal organization of physiological functions in children with chronic diseases of the upper digestive tract, including those associated with Helicobacter pylori.

The work addresses relevant issues of the etiopathogenesis of gastroduodenal pathology, including the role of Helicobacter pylori, acid-peptic, and alimentary factors. Special attention is given to pathological desynchronosis of biological rhythms in children with chronic gastroduodenal pathology, its seasonal features, and its significance in the pathogenesis of the disease. Group and individual recommendations for comprehensive chronotherapy have been proposed, including a chronotherapeutic approach to the prescription of eradication therapy, correction of metabolic disturbances in the mucous membrane of the gastroduodenal zone, and chronocorrection of pathological desynchronosis through the use of phytadaptogens, aromatherapy, and music therapy.

Chronic diseases of the digestive organs are widespread, and their incidence has been increasing in recent years.

The leading place in the structure of diseases of the digestive system in children is occupied by pathology of the upper gastrointestinal tract (UGIT). According to P.L. Shcherbakov (1997), it has a combined character in 53.1% of children. Isolated lesions of the digestive tract are considerably less common: gastritis — in 29.4%, duodenitis — in 16.2%, esophagitis — in 16.2% of children. Duodenal ulcer disease (DUD) is diagnosed in 8% [10, 97, 137, 168]. Diseases of the stomach and duodenum are the most prevalent among digestive diseases in children, their frequency is increasing and accounts for 58–65% of the spectrum of pediatric gastroenterological pathology. Over the past decades, the frequency of ulcer disease has increased 2.5-fold. The disease occurs with equal frequency in boys and girls. In the structure of ulcer disease, DUD predominates — 81% of all cases, gastric ulcer (GU) — 13%, and a combination of DUD and GU is observed in 6% of cases [7, 24].

The relapsing nature of the disease course, with a tendency toward progression of morphofunctional changes and combined involvement of the digestive organs, along with insufficient effectiveness of the therapy administered and early disability of children in certain cases, determines heightened attention to gastrointestinal pathology [57, 97, 128, 166].

At present, extensive material has been accumulated concerning clinical, instrumental diagnosis, and treatment of UGIT pathology in adults and children [34, 100, 168].

For many years, the etiopathogenetic factors of chronic UGIT diseases were considered to be genetic, acid-peptic, alimentary, as well as impairment of gastric and duodenal motility, the pathogenetic mechanisms of which have been studied in sufficient detail. However, recent conceptions of the etiopathogenesis of gastroduodenal pathology have changed, primarily due to the discovery of Helicobacter pylori (Hp). According to the latest scientific data, Hp is associated with 70–80% of chronic gastritis, 100% of DUD, and 85% of cancerous diseases. Invasion of Hp has been demonstrated in over 80% of children with chronic UGIT diseases. A familial pattern of Hp infection has been noted [6, 32, 80, 168, 188].

The pathogenesis of ulcer disease continues to be regarded as the result of a disbalance, a conflict between local factors of "aggression" and "defense," with the decisive role nonetheless being attributed to the "aggressive" factors [34]. Such factors as alimentary and ecological retain their significance in the pathogenesis of gastroduodenal diseases, but in most cases serve as aggravating factors.

The peak of morbidity falls on children aged 8 to 13 years, indicating a dependence of the occurrence and development of chronic pathology of the digestive organs on the functional state of the neuroendocrine system and the mechanisms of regulation of adaptive processes during this age period.

The question of treatment of UGIT diseases remains relevant. Modern therapy of chronic UGIT diseases, including GU and DUD, encompasses basic therapy, influence on the psychoemotional sphere, and the temporal organization of vital systems. The necessity of influencing the temporal organization of vital systems has determined heightened interest in recent decades in studying the rhythmic organization of processes in the body, both under normal conditions and in pathology, in particular, in the digestive system. The chronomedical approach to studying gastroenterological problems opens up new mechanisms of development of digestive organ diseases and necessitates a new approach to investigating their etiology, pathogenesis, treatment, and prevention [70, 111, 153].

Basic therapy of UGIT diseases associated with Hp is primarily directed at eradication of the microorganism through the prescription of a triple therapy regimen, either with bismuth preparations or with an antisecretory drug in combination with two antibiotics or an antibiotic and an antibacterial drug (macmiror, furazolidone, etc.). In the presence of a history of unsuccessful prior treatment, antibiotic resistance, or inability to determine antibiotic sensitivity — quadruple therapy is prescribed.

Eradication therapy is highly toxic and may cause a number of side effects (dispeptic disorders, allergic reactions, disturbances of the intestinal biocenosis, etc.). In this regard, the question arises of developing optimal doses, frequency, and timing of drug administration.

The chronomedical aspect remains relevant, as the literature insufficiently reflects changes in biological rhythms in children with chronic gastroduodenal pathology associated with Hp; signs of disturbances in the temporal organization of vital systems in children with this pathology have not been described; and treatment schemes for gastroduodenal pathology that take into account disturbances of biological rhythms and periods of activity of the digestive system have not been developed.

In light of the above, the relevance of the studied problem is evident.

The aim of the present work is to comprehensively study the features of the temporal organization of physiological systems in children with various pathologies of the gastroduodenal zone; to pathophysiologically substantiate, develop, and implement methods of chronotherapy and chronoprophylaxis of exacerbations of the pathological process capable of improving the results of standard treatment.

In accordance with this aim, the following tasks were set:

1. To assess the features of the temporal organization of main physiological functions in healthy children of the control group and to identify characteristic disturbances of biological rhythms in children with chronic gastroduodenal pathology in the form of pathological desynchronosis, determining its role in the pathogenesis of the disease.

2. To pathophysiologically substantiate, pilot, and implement recommendations for chronotherapy of gastroduodenal pathology, individual and group chronocorrection, and chronoprophylaxis of pathological desynchronoses in children.

3. To compare the therapeutic and economic effects of standard and chronomedical treatment schemes.

Scientific novelty

1. For the first time, a comparative analysis of the state of biological rhythms of indicators of main physiological systems in healthy children and children with chronic gastroduodenal pathology has been conducted, and the role of identified dysregulatory disturbances of biological rhythms in the pathogenesis of upper digestive tract diseases has been determined.

2. For the first time, the features of pathological desynchronosis in children with gastroduodenal pathology associated with Hp have been described according to the spectrum of periodicities and their parameters — mesor, amplitude, and acrophase.

3. Group and individual recommendations for comprehensive chronotherapy of the studied pathological process have been developed and pathophysiologically substantiated, taking into account the features of vital functions (VFF), the chronotype of patients, parametric shifts, and chronosensitivity to drugs.

Theoretical and practical significance

The work has theoretical significance, as it formulates and argues conceptions regarding changes in the temporal organization of physiological systems in the form of pathological desynchronosis in children with chronic gastroduodenal pathology associated with Hp. Its characteristic features, seasonal peculiarities, and role in the pathogenesis of gastroduodenal diseases have been determined.

The practical significance of the results of the work lies in the fact that, based on new knowledge of pathogenesis, they allow the development and pathophysiological substantiation of a complex of chronomedical therapeutic measures that improve the results of treatment of gastroduodenal pathology in children, including a chronotherapeutic approach to the prescription of eradication therapy, correction of metabolic disturbances in the mucous membrane of the gastroduodenal zone, and correction of the important pathogenetic link of gastroduodenal pathology — pathological desynchronosis — through the inclusion in the complex of therapeutic measures of internal administration of phytadaptogens, aromatherapy, and music therapy.

Recommendations for medical and preventive institutions regarding chronotherapy of gastroduodenal pathology in children associated with Helicobacter pylori, as well as aromatherapy, music therapy, and chronophytocorrection of disturbances in the temporal organization of physiological functions, have been developed, pathophysiologically substantiated, and piloted at the gastroenterology department of the Republican Scientific Center of Pediatrics (РДКБ).

The implementation of the recommendations has led to optimization of treatment and rehabilitation of patients with gastroduodenal pathology in terms of quality of recovery and increased duration of disease remission, thereby ensuring a positive medical-social and economic effect.

Main provisions for defense.

1. The temporal organization of physiological functions in children with chronic gastroduodenal pathology associated with Hp is in a state of pathological desynchronosis that impedes mechanisms of successful adaptation and has seasonal features.

2. The application of combined chronotherapy in children with chronic gastroduodenal pathology associated with Hp leads to improved results of standard treatment and prolonged remission periods.

3. The inclusion in the comprehensive chronotherapeutic scheme of chronocorrection of metabolic disturbances in the mucous membrane of the gastroduodenal zone, chronocorrection of pathological desynchronosis impeding chronoadaptation, internal administration of phytadaptogens, aromatherapy, and music therapy improves clinical-endoscopic, biorhythmological, and psychoemotional indicators, normalizes sleep and appetite in sick children, improves the results of the SAN test, normalizes clinical-laboratory and histomorphological features of pathology, and prolongs remission periods to a greater extent than standard treatment.

Pilot testing.

The main provisions and results of the research were discussed at a session of the regional branch of the Union of Pediatricians of Russia (Vladikavkaz, 2004); the third, fifth, and sixth scientific conferences of young scientists "Young Scientists — Medicine" (Vladikavkaz, 2004, 2006, 2007); the VI International Conference "Innovative Technologies for Sustainable Development of Mountain Territories" (Vladikavkaz, 2007); and the IV Regional Scientific and Practical Conference "New Technologies in Health Recreation of the Population" (Vladikavkaz, 2007).

Publications.

Fragments of the work have been published in 12 printed works, including one article in a peer-reviewed journal recommended by VAK for publication of dissertation materials.