Mechamisms of death from asthma-basic and clinical approach-

我们最近报道，几乎致命的哮喘患者缺氧呼吸反应降低，以及迟钝的感觉呼吸困难，这表明这两个因素是诱发因素死于哮喘发作。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。本研究探讨了哮喘死亡与低氧呼吸反应和颈动脉体功能的关系，结果表明：（1）应用正电子发射断层扫描（PET）技术，发现正常人在吸气阻力负荷呼吸时，扣带皮层、丘脑和前运动皮层激活，而哮喘患者在吸气阻力负荷呼吸时，扣带皮层、丘脑和前运动皮层的激活减弱。(2)应用原位杂交和免疫组织化学方法，在低氧、高碳酸血症和吸气阻力大鼠的扣带回皮质、丘脑、下丘脑和脑桥中发现了C-fos癌基因的表达。这些结果表明，大脑的这些区域可能参与呼吸困难和/或负荷呼吸期间呼吸行为控制的发生。(3)本文观察了多沙普仑对7名正常人呼吸困难和低氧反应的影响。多沙普仑可增加呼吸困难和低氧缓解反应。呼吸困难与低氧缓解反应能力有关，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.