Kim Woo Jin, Oh Yeon-Mok, Sung Joohon, Kim Tae-Hyung, Huh Jin Won, Jung Hoon, Lee Ji-Hyun, Kim Eun-Kyung, Lee Jin Hwa, Lee Sang-Min, Lee Sangyeub, Lim Seong Yong, Shin Tae Rim, Yoon Ho Il, Kwon Sung-Youn, Lee Sang Do
Department of Internal Medicine, College of Medicine, Kangwon National University, Chuncheon, South Korea.
Lung. 2008 Nov-Dec;186(6):381-6. doi: 10.1007/s00408-008-9103-9. Epub 2008 Aug 29.
Recent reports suggest that beta(2)-adrenergic receptor (ADRB2) genotypes are associated with therapeutic responses to beta(2) agonists in asthmatics. However, few studies have investigated therapeutic responses to beta(2) agonists in chronic obstructive pulmonary disease (COPD) patients. This study investigated immediate bronchodilator response and lung function responses following a 12-week treatment with a long-acting beta(2) agonist combined with a steroid inhaler in patients with COPD with various ADRB2 genotypes. One hundred four patients with chronic obstruction were genotyped for codon 16 and 27 polymorphisms of the ADRB2 gene. The immediate bronchodilator response to beta(2)-agonist treatment was evaluated after inhalation of 400 microg salbutamol. In addition, long-term response was evaluated using observed change in spirometric values before and after the treatment with salmeterol (50 microg) combined with fluticasone propionate (500 microg) inhalation twice daily for 12 weeks. In terms of codon 16 variants, the immediate bronchodilator response to salbutamol was 6.4 +/- 0.8% (% predicted value) in Arg/Arg patients, 4.9 +/- 0.7% in Arg/Gly patients, and 5.8 +/- 1.2% in Gly/Gly patients (p = 0.418). The FEV(1) changes following the 12-week treatment were 7.0 +/- 1.2% in Arg/Arg patients, 3.0 +/- 1.5% in Arg/Gly patients, and 7.2 +/- 1.2% in Gly/Gly patients (p = 0.229). Similarly, there was no difference between codon 27 variants in terms of immediate bronchodilator response or FEV1 changes after 12 weeks of treatment. We were unable to demonstrate an association between ADRB2 genotype and the effect on lung function of 12-week treatment with combined long-acting beta(2) agonist and glucocorticoid inhalation or on the immediate bronchodilator response to a short-acting beta(2) agonist in patients with COPD.
近期报告表明，β₂肾上腺素能受体（ADRB2）基因型与哮喘患者对β₂激动剂的治疗反应相关。然而，很少有研究调查慢性阻塞性肺疾病（COPD）患者对β₂激动剂的治疗反应。本研究调查了不同ADRB2基因型的COPD患者在接受长效β₂激动剂联合类固醇吸入剂治疗12周后的即时支气管扩张反应和肺功能反应。对104例慢性阻塞性患者进行了ADRB2基因第16和27密码子多态性的基因分型。吸入400微克沙丁胺醇后评估对β₂激动剂治疗的即时支气管扩张反应。此外，使用每日两次吸入沙美特罗（50微克）联合丙酸氟替卡松（500微克）治疗12周前后肺活量测定值的观察变化来评估长期反应。就第16密码子变体而言，Arg/Arg患者对沙丁胺醇的即时支气管扩张反应为6.4±0.8%（预测值百分比），Arg/Gly患者为4.9±0.7%，Gly/Gly患者为5.8±1.2%（p = 0.418）。12周治疗后，Arg/Arg患者的FEV₁变化为7.0±1.2%，Arg/Gly患者为3.0±1.5%，Gly/Gly患者为7.2±1.2%（p = 0.229）。同样，在治疗12周后的即时支气管扩张反应或FEV₁变化方面，第27密码子变体之间没有差异。我们无法证明ADRB2基因型与长效β₂激动剂和糖皮质激素联合吸入治疗12周对COPD患者肺功能的影响或对短效β₂激动剂的即时支气管扩张反应之间存在关联。
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