DISEASE MODIFYING GENES IN SEVERE ASTHMA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。哮喘在成人中是一种异质性疾病，一些人表现为轻度疾病，而另一些人则有严重的症状。有些成年哮喘患者会发展为严重的不可逆性气道阻塞，而另一些则保持气道功能。研究者在他们的城市成人哮喘门诊中确定了一个大的特应性和持续性气道阻塞患者队列。因此，问题出现了，在特应性哮喘患者中，是否存在易导致不可逆气道阻塞发展的疾病修饰基因。该提案的总体目标是检验以下假设：在易感宿主中，存在调节对重复性过敏性炎症损伤的反应的疾病修饰基因。重点将是定义严重哮喘的精确生理表型，并测试气道/基质重塑基因的等位基因变异与定义的严重表型之间的关联。更具体地说，该研究的目的如下：1）通过肺量测定法、体积描记法和肺的弹性回缩特性的测量来确定“严重哮喘”的特定生理表型。2.）的情况。检验通过IgE（总IgE和过敏原特异性IgE）确定的哮喘易感性可区分重度哮喘的生理表型的假设。3)验证基质重塑基因（疾病修饰基因）多态性与重度哮喘生理表型相关的假设。

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).