INTRODUCTION

Problem urgency

The bronchial asthma is one of the most widespread hroniyocheskih diseases at children. According to researches within the limits of the international program of studying of prevalence of an asthma and an allergy (ISAAO, real prevalence of a bronchial asthma at children in the various countries znachitelyono varies, reaches 5-10 % and repeatedly exceeds digits of official statistics.

Concerning epidemiological researches of prevalence bronyohialnoj asthmas at children of inhabitants of village in Russia are available only individual works [29, 51, 52, 92]. Besides, it is obviously important to investigate national features and their potential influence on prevalence of disease.

At teenage age in connection with hormonal reorganisation of an organism disease quite often undergoes changes, and as aside uluchsheyonija, and towards deterioration. At a part of children prevalence growth bronhiyoalnoj asthmas at teenage age and to increase of gravity of a current zabolevayonija can be promoted by the smoking beginning [129, 181, 278]. However in Russia dokayozatelnye scientific researches concerning a tobacco smoking role at bronhiyoalnoj to an asthma at teenagers are individual [40, 42, 56, 114]. The problem gets osoyobuju the importance still because working out and improvement reabiyolitatsionnyh programs with including antismokingovogo formations among children and teenagers represents a special urgency for pediatrists, lung specialists, in connection with realisation of the National project confirmed by the Government «nation Health», creation of a network of the Centers of Health and clinics, friendly to youth [18].

The bronchial asthma is hereditary multifactorial zaboyolevaniem [4, 34, 88] which clinical manifestation occurs owing to interaction of genetic factors to corresponding conditions okruzhayojushchej medium and a way of life, including a tobacco smoking. By present time isyosledovana association of a bronchial asthma with polymorphic variants of hundreds genes. It is identified more than 150 genes-candidates: genes of cytokines and their yard
tseptorov (TNFA, CCL5, IL4, IL4RA, IL12B, IL13); genes _{of v2-adrenoreceptors} (ADRB2); IgE-receptor genes (FCERI, FCERII); genes No-sintaz (NOS3, NOS2и NOS1); genes of II phase of a biotransformation of xenobiotics (GSTM1, GSTP1и GSTT1); the genes localised in area 17q12-q21 (ORMDL3, GSDMB, ZPBP2и IKZF3). For different races, the people, nationalities of frequency of alleles and a spectrum of genes-candidates essentially differ. As a result polnogenomnogo the analysis (GWAS), proveyodennogo in 19 countries odnonukleotidnyh poliyomorfizmov (ONP), localised in area 17q12-q21 (genes ORMDL3и GSDMB), with a bronchial asthma the accurate association is found out in children [293]. Their ethnic differences at evropeoidov, the Afro-Americans, Japanese, Chineses, Koreans, and also at inhabitants of the Volgo-Ural region [53, 209, 293, 348, 366] are taped.

From the data published to the present time by means of GWAS vyyojavleno some locuses bound to development HOBL, settling down on 4th and 15th chromosomes in area 15q25.1 - CHRNA3, CHRNA5 (cholinergic nikoyotinovye receptors an alpha 3 and 5).

Despite large number of genetic researches concerning the bronchial asthma, the received results are inconsistent enough and harakyoterizujutsja presence of the expressed interethnic differences. In this connection aktuyoalna identification of ethnospecific risk factors of development of the bronchial asthma, allowing with high accuracy to judge probability of development and tjazheyosti disease currents, influence on it of a tobacco smoking, to estimate the forecast foryomirovanija HOBL and purposefully to carry out rehabilitational programyomy taking into account specific features and racial differences. The aforesaid defines an urgency of the present research.

The purpose: definition clinico-epidemiological, genetic and etnicheyoskih features of a bronchial asthma and influence of a tobacco smoking on its current at teenagers of Transbaikalia for working out of the differentiated approaches to profiyolaktike and to treatment.

Research problems:

1. To define prevalence of a bronchial asthma and its symptoms among teenagers of the Buryat and Russian ethnogroups living in a countryside of Transbaikalian edge.

2. To estimate prevalence of a tobacco smoking among the teenagers sick bronyohialnoj of an asthma, to compare it with frequency of respiratory symptoms and kliniyocheskimi features of disease.

3. To carry out the analysis of associations of polymorphic variants of genes-candidates razyovitija a bronchial asthma (FCER2, ADRB2, TNFA, GSTM1, NOS2, NOS3и GSDMB) and predispositions to a tobacco smoking (THOI, CHRNA5) with formiroyovaniem diseases at teenagers to identify markers raised risyoka and interethnic differences.

4. To establish value of intergene interactions of the investigated genes - of candidates at a bronchial asthma at teenagers Buryat and Russian etnoyogrupp.

5. To define communication investigated polimofnyh variants of genes-candidates of formation of a bronchial asthma and predisposition to nicotinic zaviyosimosti with features of a current, age of a manifestation of disease, level of the general IgE in blood serum and a floor taking into account an ethnic accessory.

6. To estimate the contribution sochetannogo influences genetic and outwardly-sredovyh (an exposition to a tobacco smoke) factors on development of a bronchial asthma.

7. Scientifically to prove directions complex treatment-and-reabilitation meyoroprijaty, including educational programs, therapy by modern Mucolyticums and vegetative inhibitors lejkotrienov.

Scientific novelty:

Epidemiological data about prevalence bronhialyonoj an asthma and its symptoms among teenagers Russian and Buryat natsionalnoyosti, living in a countryside of Transbaikalian edge are obtained. RasprostranenYOnost the verified bronchial asthma (BA) between Buryats and Russian
Does not differ. In structure of gravity of a bronchial asthma at teenagers preoblayodajut easy forms of disease.

Negative influence of a tobacco smoking on a current of disease at podyorostkov is proved, the most significant risk factors of formation bronhialyonoj an asthma and an accompanying chronic bronchitis of the smoker are taped. The last in a larger measure prevail at the Buryat. As a whole, the tobacco smoking enlarges risk of development of a bronchial asthma at teenagers by 30,4 %. Influence of passive smoking is elderly till 6 years enlarged risk of an early debut bronchial astyomy at children by 22 %. At smoking teenagers the bronchial asthma has neyokontroliruemoe a current is more often, attacks differ larger gravity and vyrazhennoyostju clinical symptoms.

Are taped as the general for both ethnoses, and ethnospecific genetiyocheskie markers of the raised risk of formation of a bronchial asthma at podyorostkov. The association of development of a bronchial asthma at the Buryat with genes NOS3 (VNTR) and GSDMB (rs7216389), at Russian - with NOS2 (CCTTT) n, GSDMB (rs7216389) and CHRNA5 (rs16969968) is established. The polymorphism association rs7216389 gene GSDMBу the Buryat and gene THOI (STR) at Russian a disease debut is defined with the years; association of genes FCER2 (T2206C) and THOI (STR) with level of the general IgE in blood at Russian patients BA.

Gender and ethnic differences of the intergene interactions contributing to development of disease are taped. The association of development BA with a floor at girls the Buryat with locuses of genes GSDMB (rs7216389), NOS3 (VNTR) and TNFA (-308G> A), at young men the Buryat - with GSDMB (rs7216389) is established; at Russian girls - with CHRNA5 (rs16969968), NOS3 (VNTR) and GSDMB (rs7216389), at Russian young men - with CHRNA5 (rs16969968) and NOS2A (CCTTT) n.

Bronchial asthma at smoking patients assotsiirovana with genes GSDMB (rs7216389), NOS3 (VNTR) and ADRB2 (Gln27Glu), at non-smoking - with GSDMB (rs7216389), CHRNA5 (rs16969968), ADRB2 (Gln27Glu) and TH0I (STR). Markers of the raised risk of disease at smokers is the carriage of genotypes 4/4 or 4/5 genes NOS3 (VNTR), genotypes GG or CG gene ADRB2 (Gln27Glu); at nekuyo
rjashchih patients - a carriage of genotype CC of gene ADRB2 (Gln27Glu), allelja G and genotype G/G of gene CHRNA5 (rs16969968), a carriage of alleles and genotypes, soyoderzhashchih short repetitions (6-9), gene TH0I (STR). A carriage allelja T and goyomozigotnogo genotype T/T of polymorphism rs7216389 GSDMBявляется a risk factor of formation of a bronchial asthma as at smokers, and non-smoking.

Are defined significant for formation of a bronchial asthma a gene - sredovye interactions for locuses of various genes at smoking and non-smoking. Thus at smoking risk of formation of a bronchial asthma above on znachiyotelno to a larger combination of didymous genotypes. On the basis of their analysis in mul - tilokusnyh models at smokers the genetic attributive risk (AR) is defined and the contribution of a tobacco smoking to development of a bronchial asthma is proved.

The practical importance

The obtained data about prevalence of a bronchial asthma and tabakokuyorenija at teenagers will allow to plan rationally the organisation spetsializiyorovannoj medical aid to children with a bronchial asthma in region, to introduce group and individual treatment-and-prophylactic actions for preyoduprezhdenija formations of a chronic pulmonary pathology, and the account of risk factors will allow differentsirovanno to approach to aftertreatment.

The taped genetic markers of a bronchial asthma and their association at aginskih the Buryat and the Russian living in Transbaikalian edge, allow opreyodelit group of the raised risk of development of disease, formation at them a chronic bronchitis of the smoker with an outcome in HOBL.

Introduction of non-invasive methods of definition monooksida Carboneum in vyyodyhaemom air and kotinina in urine obektiviziruet revealing of smokers that allows adresno to carry out antismokingovye programs.

The basic directions of rehabilitational actions in komyoplekse antitobacco programs for the teenagers, including modern mukoyoreguljatory and natural antagonists lejkotrienov are offered. Necessity of a concentration of attention not on treatment of nicotinic dependence at smokers is proved
Teenagers, and, mainly, on realisation of educational programs and education of a healthy way of life.

The substantive provisions which are taken out on protection

1. Prevalence of a bronchial asthma at teenagers, prozhiyovajushchih in a countryside of Transbaikalia is defined. It above at smokers, than at nekurjayoshchih, that proves the importance of a tobacco smoking as a risk factor formiyorovanija a bronchial asthma and the accompanying phenomena of a chronic bronchitis. At smoking teenagers the bronchial asthma has uncontrollable techeyonie is more often; attacks differ larger gravity and expression of clinical symptoms, appointment of antibacterial therapy, owing to an exacerbation of a purulent bronchitis of the smoker is more often demand. At subject passive kureyoniju in house conditions of teenagers the bronchial asthma debuts at earlier age, than at not exhibited to tobacco.

2. Development of a bronchial asthma in the Buryat assotsiirovano c polymorphic vayoriantami genes GSDMB (rs7216389) and NOS3 (VNTR), at Russian teenagers - with poyolimorfnymi variants of genes GSDMB (rs7216389), NOS2A (CCTTT) n and CHRNA5 (rs16969968). Ethnospecific markers of the raised risk foryomirovanija diseases are defined: a carriage allelja S, containing short tandemnye repetitions, gene NOS2A (CCTTT) n and homozygous genotype G/G of polymorphism CHRNA5 (rs16969968) at teenagers of Russian ethnogroup; allelja 4 and genotypes 4/4 and 4/5 NOS3 (VNTR) at teenagers of the Buryat nationality. A marker povyyoshennogo risk of development of a bronchial asthma at teenagers of the Buryat and Russian nationalities were allele T and homozygous genotype T/Т of polymorphism GSDMB (rs7216389). The association of alleles of investigated genes with klinikoyolaboratornymi indicators is shown: with an early debut of a bronchial asthma (about 6 years are elderly) - allelja rs7216389*C gene GSDMBу the Buryat; allelja L, containing tanyodemnye repetitions 9.3, gene THOI (STR) at Russian patients; with raised level IgE in blood serum - minor allelja C gene FCER2 (T2206C) and alleles and genotype S, containing short tandemnye repetitions, gene THOI (STR) - at rusyo
skih. Gender differences of association of polymorphic locuses of genes - of candidates with development of a bronchial asthma are taped. At girls of both ethnic groups it is defined more associations of development of a bronchial asthma with genes, than at young men.

3. The genetic predisposition structure at formation bronyohialnoj asthmas differs at smoking and non-smoking teenagers. The carriage allelja 4 genes NOS3 (VNTR) is a marker of the raised risk of development zayobolevanija at smoking teenagers, and a carriage of homozygous genotype G/G CHRNA5 (rs16969968) and homozygous genotype S/S of microsatellite THOI (STR) - at non-smoking. The carriage of homozygous genotype T/T GSDMB (rs7216389) at smoking and non-smoking teenagers is the general risk factor of formation of a bronchial asthma. At the same time concerning gene ADRB2 (Gln27Glu) vyjavleyony raznonapravlennye interactions of genotypes. So, homozygous genotype C/C ADRB2 (Gln27Glu) is a risk factor of formation of a bronchial asthma at non-smoking, and presence allelja G ADRB2 (Gln27Glu) - at smokers.

4. At a bronchial asthma between formation genes-candidates bronyohialnoj an asthma and a tobacco smoking exist mezhallelnye and intergene vzaiyomodejstvija, characterised by a synergy and antagonism in fenotipicheskom implication of effects of separate genes concerning risk of development of disease. Character of intergene interactions of the investigated polymorphic locuses of geyonov-candidates of formation of a bronchial asthma and predisposition to tayobakokureniju varies depending on an ethnic accessory, a floor and the smoking status.

5. In a complex of treatment-and-reabilitation actions at smokers podrostyokov with a bronchial asthma it is expedient to use modern mukoreguyoljatory and vegetative inhibitors lejkotrienov. Working out of antitobacco programs is necessary For preventive maintenance tabakokuyorenija at teenagers, opirajushchajayosja, first of all, on psychological and pedagogical aspects of struggle against this habit as nicotinic dependence prevails only at a small part of smoking teenagers.

Introduction in practice. Results of dissertational work are introduced in clinical practice GUZ «Mogojtujsky central regional hospital», GUZ «Aginsky district hospital», GUZ «Duldurginsky central rajonyonaja hospital», GUZ «Regional children's advisory-diagnostic the centre» and the Center of health of of Chita, GUZ «the City children's out-patient department №2» by of Chita and Clinic Friendly to youth «Your individual direction», isyopolzujutsja in educational process for students, interns and interns GBOU VPO «the Chita state medical academy» the Ministries zdravoyoohranenija the Russian Federation, GBOU DPO «Irkutsk state meyoditsinskaja academy poslediplomnogo formations» the Ministries zdravoohrayonenija the Russian Federation, in work Children's scientifically-practical pulmoyonologicheskogo the centre of Ministry of Health of the Russian Federation. Work materials are used at razyorabotke the National program «the Bronchial asthma at children. Strategy lecheyonija and preventive maintenance »(2012).

Approbation of materials of the dissertation. Results of research and osnovyonye positions of dissertational work are reported on exit nauchnoyoprakticheskih conferences (Aginsk, 2006, 2007); Regional scientifically-practical conferences (Chita, 2007, 2008, 2010); II regional scientifically-practical conference «aftertreatment Pressing questions in the XXI-st century» (Kaluga, 2009); I congress of pediatrists of the Far East (Khabarovsk, 2010); Russian nauchnoyoprakticheskoj pediatric pulmonologicheskoj conferences (Ufa, 2010); XX Russian congress by illnesses of organs of breath (Moscow, 2010); the European respiratory congress (Spain, Barcelona, 2010); IX, XI, XII Russian konyogressah «Innovative technologies in pediatrics and children's surgery» (Moscow, 2010, 2012, 2013); IX Far East congress «the Person and a medicine» (VladiYOvostok, 2012). The dissertation is approved at session of the problem commission on pediatrics FGBU «the Moscow scientific research institute of pediatrics and children's surgery» Ministry of Health of the Russian Federation 27.09.2013.

Publications on a work theme. On a dissertation theme 56 works in domestic and a foreign press are published, including 19 articles in the leading reviewed
The scientific magazines recommended VAK the Russian Federation. By results of work the information-methodical letter (utv is published. Ministry of Health of Zayobajkalsky edge, 2012).

Work is executed in FGBU «the Moscow scientific research institute of pediatrics and a nursery hiruryogii» Ministry of Health of the Russian Federation (the director - zasl. The doctor of the Russian Federation, the doctor of medical sciences, prof. Tsaregorodtsev A.D.).