The role of FIZZ-2/RELM-beta in airways remodelling in asthma: from mouse to man

在今天英国患有哮喘的600万成年人和儿童中，许多人通过药物得到了很好的控制，例如吸入性类固醇（预防剂），可以减少导致哮喘的气道炎症，支气管扩张剂如沙丁胺醇（ventolin）（缓解剂）和白三烯阻断药物如孟鲁司特（Singulair）。然而，成千上万的人没有，几乎总是有严重的症状，使他们的生活变得痛苦。这些患者最终可能会出现气道阻塞，这似乎对目前的抗哮喘药物反应不佳。这种阻塞被认为至少部分是由炎症引起的气道不可逆转的疤痕以及目前抗哮喘药物无法逆转的其他变化引起的。关于这些变化的原因知之甚少，但最近的证据表明，在哮喘患者的发炎气道中释放了一个新的蛋白质家族，其不寻常的名称为FIZZ。在这项研究中，我们计划研究这些蛋白质之一，FIZZ-2，在哮喘患者气道中造成不可逆阻塞的作用。如果FIZZ被发现是重要的，这将为开发新的哮喘药物提供动力，这些药物可以阻断FIZZ的作用，从而不可逆转地阻塞气道：一种全新的哮喘治疗方法，有利于慢性患者。

Of the 6 million adults and children in the UK today suffering from asthma, many are well controlled with medicines such as inhaled steroids (preventers), which reduce the inflammation in the airways which causes asthma, bronchodilators such as salbutamol (ventolin) (relievers) and leukotriene blocking drugs such as montelukast (Singulair). Many thousands, however, are not and have severe symptoms almost constantly, making their lives a misery. These patients may eventually develop blockage of the airways, which seems not to respond very well to current anti-asthma medicines. This blockage is thought to be caused, at least partly, by irreversible scarring of the airways caused by the inflammation, and other changes which cannot be reversed by current anti-asthma medicines. Very little is known about what causes these changes, but recent evidence implicates a new family of proteins released in the inflamed airways of asthmatics with the unusual name of FIZZ. In this study we plan to investigate the role of one of these proteins, FIZZ-2, in bringing about irreversible blockage in the airways of asthmatics. If FIZZ is found to be important, this will provide the impetus to develop new drugs for asthma which block the action of FIZZ, and therefore irreversible blockage of the airways: a totally new approach to asthma treatment for the benefit of chronic sufferers.