DISEASE MODIFYING GENES IN SEVERE ASTHMA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 哮喘是成人的一种异质性疾病，有些表现为轻度疾病，而另一些则表现为严重症状。一些成人哮喘患者进展为严重的不可逆转的呼吸道阻塞，而另一些人则维持呼吸道功能。研究人员在他们城市诊所的成人哮喘患者中发现了大量特应性和持续性呼吸道阻塞患者。因此，问题出现了，在患有哮喘的特应性受试者中，是否存在易于发生不可逆转的呼吸道阻塞的疾病修饰基因。这项提议的总体目标将是检验这一假设，即在易感宿主中，存在调节对反复过敏性炎症损伤的反应的疾病修饰基因。重点将是确定重症哮喘的确切生理表型，并测试气道/基质重塑基因的等位基因变异与已定义的严重表型之间的关联。更具体地说，这项研究的目的如下：1)通过肺活量测定法、体积描记术和测量肺的弹性反冲特性来确定“严重哮喘”的特定生理表型。2.检验以总IgE和过敏原特异性IgE测定的哮喘易感性区分重度哮喘生理表型的假设。3)验证基质重塑基因多态性与重症哮喘生理表型(疾病修饰基因)相关的假说。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is a heterogeneous disease in adults, with some expressing mild disease, whereas others have severe symptoms. Some adults with asthma progress to severe irreversible airway obstruction, whereas other maintain airway function. The investigators have identified a large cohort of patients with atopy and persistent airway obstruction in their urban clinic of adult patients with asthma. The question arises, therefore, whether in the atopic subject with asthma, there are disease modifying genes that predispose to the development of irreversible airway obstruction. The global aim of this proposal will be to test the hypothesis that in a susceptible host, there are disease-modifying genes that modulate the response to the repetitive allergic inflammatory injury. The focus will be to define precise physiologic phenotypes of severe asthma and to test the association between allelic variants in airway/matrix remodeling genes and the defined severe phenotypes. More specifically, the study's aims are as follows: 1) To identify specific physiologic phenotypes of "severe asthma" defined by spirometry, plethysmography and measurement of elastic recoil properties of the lung. 2.)To test the hypothesis that asthma susceptibility as determined by IgE (total and allergen-specific) discriminates the physiologic phenotypes of severe asthma. 3) To test the hypothesis that polymorphisms of matrix remodeling genes are associated with physiologic phenotypes of severe asthma (disease-modifying genes).