Някои клинични и генетични фактори за тежка астма при деца в България
Зареждане...
Дата
2021
Автори
Митева, Димитринка Събкова //
Miteva, Dimitrinka Sabkova
Заглавие на списанието
ISSN на списанието
Заглавие на тома
Издател
Медицински университет - София // Medical University - Sofia
Резюме
ЦЕЛ И ЗАДАЧИ
Цел:
Целта на настоящата дисертация е да се опишат характеристиките на тежката астма при деца в България и да се установи ролята на основните четири от единичните полиморфизми на ADAM33.
Задачи:
1. Ретроспективно определяне на честотата на тежка астма сред пациентите, лекувани в Клиника по педиатрия, УМБАЛ „Александровска“ за период от 5 години (януари 2010-декември 2014).
2. Да се оцени честотата на придружаващите заболявания, които могат да се отразят върху контрола и тежестта на бронхиалната астма в тази ретроспективна кохорта (алергичен ринит, наднормено тегло, гастро-езофагеален рефлукс).
3. Да се оптимизират праймери за T1 (rs2280091, T/C), T2 (2280090, C/T), V4 (rs2787094, C/G) и S2 (rs528557, G/C) от единичните полиморфизми на ADAM33 за RT-PCR и изработване на протокол за работа с тях.
4. Да се подберат пациенти с бронхиална астма, както и съответна контролна група пациенти, при които да се извърши генетично изследване след получаване на информирано съгласие от родителите за проспективно проучване.
5. Да се анализира как тежестта на астмата при пациентите от проспективната кохорта се отразява на резултатите от функционално изследване на дишането и лабораторните показатели (диференциална кръвна картина, назална еозинофилия, общи и специфични IgE и Th17).
6. Да се определи разпределението на посочените полиморфизми в българските пациенти.
7. Да се установи влиянието на откритите полиморфизми за клиничния ход и контрола на бронхиалната астма при изследваните деца.
8. Да се определи разпределението на изследваните полиморфизми при пациентие, които остават с клинична тежка астма и след 5 годишно проследяване (януари 2014-декември 2019).
//
SUMMARY.
Bronchial asthma (BA) affects about 15% of all children, which makes it the most common chronic lung disease in childhood, about 15-20% of asthmatics in the world have a severe clinical course. The aim of this PhD thesis is to describe the characteristics of severe asthma in Bulgarian children and to establish the role of the main four of the single polymorphisms for ADAM33. ADAM33 is the first one of the many genes connected with asthma predisposition. There are two parts of the study – retrospective and prospective. In retrospective study 1075 children (640 boys and 435 girls with average age 9,23 years) hospitalized in the ward for chronic lung diseases of the Clinic of Pediatrics, University Hospital "Alexandrovska" EAD due to exacerbation of bronchial asthma for the period from January 1, 2010 to December 31, 2014 are included. In cases with more than one hospitalization of the same patient for this period, his/her data are reported once. Retrospectively we found out that in the last decade there is a tendency for a relatively constant number of children with BA requiring hospital treatment in Bulgaria. We calculated the rate of severe bronchial asthma as 2.88% of children with asthma, requiring hospital treatment. Children with BA in Bulgaria in 20% have clinical symptoms of gastroesophageal reflux (GER). All children with severe asthma have additionally allergic rhinitis (AR). The use of LTRA as a control drug in asthma in children is prescribed mainly in children with concomitant AR. Children with BA are not in a higher percentage of overweight compared to the general population of children in Bulgaria. Additionally we have found that also accompanying AR and / or GER are more important for the severity of BA compared to overweight. Therefore, in cases with severe, non-controlled asthma sometimes adding therapy for AR and/or GER could be beneficial. Out of the children identified as one with severe asthma 20 children and their families agreed to participate in a prospective genetic study. Additionally, 59 children with bronchial asthma (not severe one) and 29 healthy children and their families were included after obtaining signed informed consent. The control group is smaller due to more difficult recruitment of children with signed informed consent, when the information obtained does not contribute directly to the children themselves. Allgroups are similar in sex and age distribution. For the genetic study we designed primers and probes for the 4 SNPs of ADAM33 (T1 (rs2280091, T/C), T2 (2280090, C/T), V4 (rs2787094, C/G) and S2 (rs528557, G/C)). During execution of this PhD thesis a protocol for each SNPs was optimized. There is a higher frequency of minor alleles for S2 (rs2787094) and V4 (rs528557) in children with asthma compared to healthy children in Bulgaria. The homozygotes on the minor allele for T2 (rs2280090) are found more in children with severe asthma than in other asthmatics. The same was noted for the minor T1 allele (rs2280091) of ADAM33. Minor alleles T2 and V4 are more common in children with a family history of asthma. Children with severe asthma have lower results in lung function test (FEV1, FVC, MMEF), higher numbers of peripheral and nasal eosinophilia, higher IgE levels and percentage of Th17, but none of these markers can serve as a prognostic factor for the persistence of the severity of bronchial asthma in children. About 40% of the children with mild to moderate asthma enter clinical remission within 5 years of follow-up, while children with severe asthma do not achieve complete clinical remission. The presence of 4 minor alleles of the studied polymorphisms is a risk factor for severe and persistent severe asthma, and four major alleles show a protective association for BA. All children with four major alleles on the studied SNPs in 5 years either enter in clinical remission or the severity of their asthma is extremely reduced. This study for the first time draws the attention of pediatricians, pediatric pulmonologists and allergists to the frequency and characteristics of severe asthma among children in Bulgaria. It further clarifies the importance and emphasizes the role of the minor alleles of ADAM33 polymorphisms in the persistence of the severity of bronchial asthma in childhood.
Описание
Ключови думи
педиатрия; деца; астма при деца; астма - генетика; белодробни болести при деца // , paediatrics; child; asthma - infancy and childhood; asthma - genetics; lung diseases - infancy and childhood