MYCOPLASMA INFECTIONS AND CHILDHOOD ASTHMA

哮喘是一种慢性呼吸道疾病，8%-13%的人患有哮喘 美国人群，以呼吸道高反应性为特征。慢性 感染越来越频繁地被确定为 人类发病率和死亡率。支原体所致肺部感染 肺炎与哮喘的恶化和 感染后肺功能长期异常。 最近未发表的数据表明，成年哮喘患者中有一部分人 曾经历过与M相关的哮喘加重 肺炎感染，既延长，又未能引起 可检测的抗体反应。若干慢性支原体感染病例 感染，包括肺部和肺外感染，都发生在成年人身上。 以及患有低丙种球蛋白血症的儿童表明体液免疫 在解决这些微生物的感染方面很重要。此外， 支原体在艾滋病毒晚期患者中非常普遍。 感染，这表明免疫反应的细胞臂可能 同样，在控制这种感染方面也起到了作用。我们假设 哮喘患者的一小部分患者没有足够的或不适当的 对导致慢性/复发的支原体的免疫应答 感染。我建议研究支原体感染的发病率 对慢性哮喘儿童以及宿主免疫反应的影响 感染，以确定是否存在差异 广大的人口。我将研究生物体通过哪些机制 在体外改变细胞信号和激活。最后，我计划 研究感染对哮喘小鼠模型的影响 将允许在调查中使用缺失突变菌株 致病机制的研究。

Asthma is a chronic respiratory disease affecting 8-13 percent of the U.S. population and characterized by airway hyperreactivity. Chronic infections are being identified with increasing frequency as causes of human morbidity and mortality. Pulmonary infection due to Mycoplasma pneumoniae has been associated with exacerbations of asthma and prolonged abnormalities in pulmonary functions following infection. Recent unpublished data has identified a subset of adult asthmatics who have experienced exacerbations of their asthma associated with M pneumoniae infection which was both prolonged and failed to elicit a detectable antibody response. A number of cases of chronic mycoplasmal infection, both pulmonary and extrapulmonary, have been seen in adults and children with hypogammaglobulinemia indicating that humoral immunity is important in resolving infection with these organisms. Further, mycoplasmas are highly prevalent in patients in the late stages of HIV infection, suggesting that the cellular arm of the immune response may likewise function in controlling such infections. We hypothesize that a subgroup of patients with asthma have inadequate or inappropriate immune responsiveness to mycoplasmas which results in chronic/recurrent infection. I propose to study the incidence of mycoplasmal infection in children with chronic asthma as well as the host immune response to the infection in order to determine whether differences exist from the population at large. I will examine the mechanisms by which the organism alters cell signaling and activation in vitro. Finally, I plan to investigate the effects of infection in a mouse model of asthma, which will permit the use of deletional mutant strains in the investigation of pathogenic mechanisms.