Increased levels of angiopoietin-2 in induced sputum from smoking asthmatic patients
Increased levels of angiopoietin-2 in induced sputum from smoking asthmatic patients
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DOI：
10.1111/j.1365-2222.2009.03262.x
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发表时间：
2009-09-01
影响因子：
6.1
通讯作者：
Hirata, K.
中科院分区：
文献类型：
--
作者：
Kanazawa, H.;Asai, K.;Hirata, K.
研究背景主动吸烟对哮喘的发病率和严重程度有不利影响.已显示血管生成素-1保护微血管免受血浆渗漏，而血管生成素-2增强血管通透性并随后诱导气道粘膜水肿。因此，我们认为，血管生成素-2（Angiopoietin-2，Angiopoietin-2）可能参与哮喘的病理生理过程。目的探讨Angiopoietin-2在吸烟哮喘患者气道中的表达水平与临床表现的关系。方法检测35例正常人诱导痰中Angiopoietin-1和Angiopoietin-2的表达水平（18名非吸烟者和17名吸烟者）和49名哮喘患者（24名非吸烟者和25名吸烟者）吸入二丙酸倍氯米松前后结果哮喘患者诱导痰中Angiopoietin-1和Angiopoietin-2水平明显高于正常对照组。此外，血管生成素-2水平显着高于吸烟哮喘患者比非吸烟哮喘患者（P=0.0001）。吸烟哮喘患者的气道血管通透性指数也高于非吸烟哮喘患者。哮喘患者血清促血管生成素-2水平与气道血管通透性指数呈正相关（不吸烟组r=0.87，P < 0.001;吸烟组r=0.64，P=0.002）。BDP治疗后，非吸烟哮喘患者、戒烟哮喘患者和活动性吸烟哮喘患者的血管生成素-1水平显著降低。相反，在非吸烟哮喘患者和活动性吸烟哮喘患者中，BDP治疗前后血管生成素-2水平没有差异。而BDP治疗后，其水平明显下降（P=0.002）。尽管BDP治疗前1秒用力呼气容积（FEV 1）/用力肺活量（FVC）在所有亚组中相当，但BDP治疗后，主动吸烟哮喘患者的该参数显著低于非吸烟和戒烟哮喘患者。此外，BDP治疗后戒烟哮喘患者的血管生成素-2水平的降低与FEV 1/FVC的改善显著相关。结论吸烟哮喘患者气道中血管生成素-2水平升高，其水平与气道反应受损相关。
P>BackgroundActive cigarette smoking has detrimental effects on asthma morbidity and severity. Angiopoietin-1 has been shown to protect the microvessels against plasma leakage, whereas angiopoietin-2 enhances vascular permeability and subsequently induces airway mucosal oedema. Therefore, it is recently thought that angiopoietin-2 may contribute to the pathophysiology of asthma.ObjectiveTo determine whether angiopoietin-2 levels in the airways are associated with clinical profiles in smoking asthmatics.MethodsWe measured angiopoietin-1 and -2 levels in induced sputum in 35 normal controls (18 non-smokers and 17 smokers) and 49 asthmatics (24 non-smokers and 25 smokers) before and after inhaled beclomethasone dipropionate (BDP: 800 mu g/day) therapy for 12 weeks.ResultsAngiopoietin-1 and -2 levels in induced sputum were significantly higher in asthmatics than in normal controls. Moreover, angiopoietin-2 levels were significantly higher in smoking asthmatics than in non-smoking asthmatics (P=0.0001). The airway vascular permeability index was also higher in smoking asthmatics than in non-smoking asthmatics. Moreover, the angiopoietin-2 level was positively correlated with the airway vascular permeability index (non-smoking asthmatics: r=0.87, P < 0.001, smoking asthmatics: r=0.64, P=0.002). After BDP therapy, angiopoietin-1 levels were significantly decreased in non-smoking asthmatics, smoking-cessation asthmatics, and active-smoking asthmatics. In contrast, angiopoietin-2 levels did not differ from before to after BDP therapy in non-smoking asthmatics and active-smoking asthmatics. However, its levels were significantly decreased from before to after BDP therapy in smoking-cessation asthmatics (P=0.002). Although forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) before BDP therapy was comparable in all subgroups, this parameter after BDP therapy was significantly lower in active-smoking asthmatics than in non-smoking and smoking-cessation asthmatics. Moreover, the reduction in angiopoietin-2 levels after BDP therapy in smoking-cessation asthmatics was significantly correlated with an mprovement in FEV1/FVC.ConclusionAngiopoietin-2 levels were elevated in the airways of smoking asthmatics, and its levels were associated with impaired airway responses.