Polina A Selivanova1, Evgeny S Kulikov2, Olga V Kozina3, Irina N Trofimenko4, Maxim B Freidin5, Boris A Chernyak4, Ludmila M Ogorodova2. 1. Siberian State Medical University, Tomsk, Russian Federation. Electronic address: p.selivanova@mail.ru. 2. Siberian State Medical University, Tomsk, Russian Federation. 3. Regional Centre of AIDS and infectious diseases prevention, Petropavlovsk-Kamchatsk, Russian Federation. 4. Irkutsk State Institute for Postgraduate Medical Education, Irkutsk, Russian Federation. 5. Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russian Federation.
Abstract
BACKGROUND: Bronchodilators are drugs of choice in the combined therapy of bronchial asthma and chronic obstructive pulmonary disease (COPD). However, the therapeutic sensitivity is variable between patients, probably because of structural features of regulating molecules or variation in key genes' expression. OBJECTIVES: The aim of this study was to evaluate the β2-adrenoceptor (ADRB2) and M3-cholinoreceptor (CHRM3) gene expression in bronchial mucosa in patients with COPD and different severity of asthma. METHODS: Biopsy specimens of right middle lobar bronchus were obtained from 59 asthma patients (10 patients with severe brittle phenotype, 14 patients with severe asthma with persistent airflow limitation, 27 patients with moderate asthma, and 8 patients with mild asthma) and 10 COPD patients with or without bronchial hyperresponsiveness (BHR). The messenger RNA (mRNA) levels for the ADRB2 and CHRM3 genes in bronchial mucosa were revealed using quantitative reverse transcription polymerase chain reaction (RT-PCR) and compared between groups. RESULTS: An increase of the ADRB2 genes expression was demonstrated in patients with severe asthma and COPD as compared with patients with mild and moderate disease. Significantly higher levels of ADRB2 mRNA were observed in patients with severe asthma with persistent airflow limitation. Significantly lower levels of the CHRM3 mRNA were observed in patients with COPD as compared with asthma patients. Also, CHRM3 gene expression was significantly elevated in COPD patients with BHR as compared with patients without BHR. CONCLUSIONS: The results of the study suggest that the differential expression of the ADRB2 and CHRM3 genes is associated with asthma and COPD clinical subtypes.
BACKGROUND: Bronchodilators are drugs of choice in the combined therapy of bronchial asthma and chronic obstructive pulmonary disease (COPD). However, the therapeutic sensitivity is variable between patients, probably because of structural features of regulating molecules or variation in key genes' expression. OBJECTIVES: The aim of this study was to evaluate the β2-adrenoceptor (ADRB2) and M3-cholinoreceptor (CHRM3) gene expression in bronchial mucosa in patients with COPD and different severity of asthma. METHODS: Biopsy specimens of right middle lobar bronchus were obtained from 59 asthmapatients (10 patients with severe brittle phenotype, 14 patients with severe asthma with persistent airflow limitation, 27 patients with moderate asthma, and 8 patients with mild asthma) and 10 COPDpatients with or without bronchial hyperresponsiveness (BHR). The messenger RNA (mRNA) levels for the ADRB2 and CHRM3 genes in bronchial mucosa were revealed using quantitative reverse transcription polymerase chain reaction (RT-PCR) and compared between groups. RESULTS: An increase of the ADRB2 genes expression was demonstrated in patients with severe asthma and COPD as compared with patients with mild and moderate disease. Significantly higher levels of ADRB2 mRNA were observed in patients with severe asthma with persistent airflow limitation. Significantly lower levels of the CHRM3 mRNA were observed in patients with COPD as compared with asthmapatients. Also, CHRM3 gene expression was significantly elevated in COPDpatients with BHR as compared with patients without BHR. CONCLUSIONS: The results of the study suggest that the differential expression of the ADRB2 and CHRM3 genes is associated with asthma and COPD clinical subtypes.
Authors: J M Gaffin; B A Raby; C R Petty; E B Hoffman; A A Baccarelli; D R Gold; W Phipatanakul Journal: Clin Exp Allergy Date: 2014 Impact factor: 5.018
Authors: Philippa R Dale; Hana Cernecka; Martina Schmidt; Mark R Dowling; Steven J Charlton; Michael P Pieper; Martin C Michel Journal: Curr Opin Pharmacol Date: 2014-03-27 Impact factor: 5.547