MYCOPLASMA INFECTIONS AND CHILDHOOD ASTHMA

支原体感染和儿童哮喘

• 批准号: 6184720
• 负责人: THOMAS PRESCOTT ATKINSON
• 金额: $ 25.11万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184720
• 关键词: Mycoplasma pneumoniae; asthma; clinical research; host organism interaction; human subject; immunopathology; laboratory mouse; middle childhood (6-11); pathologic process; preschool child (1-5); respiratory hypersensitivity; respiratory infections

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 Recent unpublished data has identified a subset of adult asthmatics who have experienced exacerbations of their asthma associated with M pneumoniae infection which was both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.

哮喘是一种慢性呼吸道疾病，影响8- 13%的人， 美国人群，并以气道高反应性为特征。慢性 越来越多的感染被确定为 人类发病率和死亡率。 支原体致肺部感染 肺炎与哮喘恶化有关， 感染后肺功能长期异常。 最近未发表的数据已经确定了一个成年哮喘患者的子集， 发生了与M相关的哮喘恶化 肺炎感染，这是长期的，并未能引起 可检测的抗体反应。 一些慢性支原体感染病例 感染，包括肺内和肺外感染，在成人中也有发生 和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，本发明还 支原体在HIV晚期患者中非常普遍 感染，这表明免疫反应的细胞臂可能 同样也能控制这些感染。 我们假设 一个哮喘患者亚组对哮喘的治疗不充分或不适当， 对支原体的免疫应答，导致慢性/复发性 感染 我建议研究支原体感染的发病率 在慢性哮喘儿童中， 感染，以确定是否存在差异， 一般人口。我将研究这种生物体 在体外改变细胞信号和激活。 最后，我打算 研究感染对哮喘小鼠模型的影响， 将允许在研究中使用缺失突变株 致病机制。