Siberian State Medical University, Tomsk, Russian Federation.
Siberian State Medical University, Tomsk, Russian Federation.
Ann Allergy Asthma Immunol. 2012 Jan;108(1):39-43. doi: 10.1016/j.anai.2011.10.002. Epub 2011 Nov 2.
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.
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.
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.
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.
The results of the study suggest that the differential expression of the ADRB2 and CHRM3 genes is associated with asthma and COPD clinical subtypes.
支气管扩张剂是支气管哮喘和慢性阻塞性肺疾病(COPD)联合治疗的首选药物。然而,患者之间的治疗敏感性存在差异,这可能是由于调节分子的结构特征或关键基因表达的变化。
本研究旨在评估 COPD 患者和不同严重程度哮喘患者支气管黏膜中β2-肾上腺素能受体(ADRB2)和 M3-胆碱能受体(CHRM3)基因的表达。
从 59 例哮喘患者(10 例严重脆性表型、14 例持续气流受限的严重哮喘、27 例中度哮喘和 8 例轻度哮喘)和 10 例 COPD 患者(伴或不伴支气管高反应性(BHR))中获取右中叶支气管活检标本。使用定量逆转录聚合酶链反应(RT-PCR)揭示支气管黏膜中 ADRB2 和 CHRM3 基因的信使 RNA(mRNA)水平,并在组间进行比较。
与轻度和中度疾病患者相比,严重哮喘和 COPD 患者的 ADRB2 基因表达增加。持续气流受限的严重哮喘患者的 ADRB2 mRNA 水平显著升高。与哮喘患者相比,COPD 患者的 CHRM3 mRNA 水平显著降低。此外,与无 BHR 的患者相比,COPD 患者伴有 BHR 时 CHRM3 基因表达显著升高。
研究结果表明,ADRB2 和 CHRM3 基因的差异表达与哮喘和 COPD 的临床亚型有关。