Small molecule inhibitors and primary airway fibroblast activation in severe asthma

对于许多人来说，哮喘是一个常见的致残问题，特别是那些患有严重的持续性疾病的人，这些疾病使他们无法正常生活。在这些患者中，这种疾病导致肺功能进行性下降，尽管进行了标准的哮喘治疗，而且呼吸道永久受损。我们的研究表明，这可能与气道壁内的疤痕有关。这种疤痕是由于被称为成纤维细胞的激活细胞中的胶原蛋白沉积造成的。这项研究还表明，实验室中从呼吸道衬里组织的小样本(活检)培养的成纤维细胞，来自重度哮喘患者志愿者，比从健康的非哮喘志愿者或轻度哮喘志愿者的呼吸道活检中生长的成纤维细胞产生更多的胶原蛋白。更多的研究表明，特定的细胞内信号通路可能参与了这种改变的反应。与UCB Celltech的这一工业合作提供了获得小分子途径抑制剂的途径，使人们能够了解这些途径与这些成纤维细胞合成功能改变的相关性。通过更好地了解这一点，将有可能针对特定的疾病过程，有望导致未来防止哮喘患者肺功能进行性下降的新疗法。

Asthma is a common and disabling problem for many, particularly those with severe persistent disease that prevents them living a normal life. In these individuals the disease leads to a progressive decline in lung function despite standard asthma therapies and the airways are left permanently impaired. Our research has shown that this can be linked to scarring within the airway wall. Such scarring is due to the deposition of collagen from activated cells called fibroblasts. This research has also demonstrated that fibroblasts, grown in the laboratory from small samples of the airway lining tissue (biopsies), from patient volunteers with severe asthma generate more collagen than do fibroblasts grown from biopsies obtained from the airways of either healthy non-asthmatic volunteers or volunteers with mild asthma. Additional studies have suggested that specific intracellular signalling pathways may be involved in this altered response. This industrial collaboration with UCB Celltech provides access to small molecule pathway inhibitors that allow the undertanding of the relevance of these pathways to the altered synthetic function of these fibroblasts. Through this better understanding it will be possible to target specific disease processes that hopefully will lead to novel therapies that in the future will prevent the progressive decline in lung function in asthma