Mechamisms of death from asthma-basic and clinical approach-

我们最近报道，近致死性哮喘患者缺氧呼吸反应降低，呼吸困难感觉减弱，提示这两个因素是哮喘发作死亡的易感因素。我们推测这些因素可能是由于外周（颈动脉）化学感受器功能障碍。在本研究中，我们探讨了哮喘死亡、缺氧呼吸反应和颈动脉体功能之间的关系。我们的研究结果如下：(1)利用正电子发射断层扫描，我们证明了健康受试者在吸气阻力负荷呼吸时扣带皮层、丘脑和前运动皮层被激活，而这些区域在几乎致命的哮喘患者中被激活较少。(2)采用原位杂交和免疫组化方法，在缺氧、高碳血症或呼吸阻力大鼠的扣带皮层、丘脑、下丘脑和脑桥中发现C-fos癌原的表达。这些结果表明，这些脑区可能参与呼吸困难的发生和/或负荷呼吸时呼吸的行为控制。(3)观察多西普兰对7例正常人呼吸困难及缺氧通气反应的影响。Doxapram增加呼吸困难的感觉以及低氧通气反应。呼吸困难与低氧通气反应能力有一定关系，提示颈动脉化学感受器可能在呼吸困难感觉的发生中起一定作用。

We have recently reported that patients with near-fatal asthma have lowered hypoxic respiratory response as well as blunted perception of dyspnea, suggesting that these two factors are predisposing factors to death from asthma attacks. We speculate that these factors may be due to dysfunction of peripheral (carotid) chemoreceptors. In this study, we have examined the relationships among death from asthma, hypoxic respiratory responses and the function of carotid body.Our results were as follows,(1) Using positron emission tomography, we have demonstrated that cingulate cortex, thalamus and premoter cortex were activated during inspiratory resistive loaded breathing in healthy subjects and that these areas were less activated in patients with nearfatal asthma.(2) We have found expression of C-fos oncogen in the cingulate cortex, thalamus, hypothalamus, and pons of rats, which were exposed to hypoxia, hypercapnia or inspiratory resistance by using in situ hybridization and immunohistochemistry.. These results suggest that these area of the brain may be involved in the genesis of dyspnea and/or behavioral control of breathing during loaded breathing.(3) The effects of doxapram on dyspnea and ventilatory response to hypoxia were examined in 7 normal subjects. Doxapram increased dyspnea snsation as well as hypoxic ventilatory response. There was a relationship dyspnea and the ablity of hypoxic ventilatory response, suggesting that carotid chemoreceptor may play some role in the genesis of dyspnea sensation.