ENDOTOXIN AND ASTHMA PREVENTION IN YOUNG CHILDREN

幼儿的内毒素和哮喘预防

• 批准号: 6749011
• 负责人: ANDREW H LIU
• 金额: $ 12.24万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-10 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6749011
• 关键词: airborne allergen; antibiotics; asthma; atopy; blood chemistry; child (0-11); cytokine; disease /disorder prevention /control; endotoxins; environmental exposure; eosinophil; flow cytometry; home health care; human subject; human therapy evaluation; hypersensitivity desensitization; immediate hypersensitivity; immunoglobulin E; immunologic skin test; interferons; lipopolysaccharides; longitudinal human study; patient oriented research; respiratory disorder diagnosis; statistics /biometry

The primary objective of this research is to investigate the potential role of chronic environmental endotoxin exposure in asthma prevention in young children. Since asthma generally begins in early childhood, interventions and exposures that lessen the atopic immune development that underlies asthmatic inflammation may have their greatest efficacy in young children, prior to the advent of pathologic lung processes typical of the intractable disease state. Although endotoxin exposure has been shown, in adult asthmatics, to be pro-inflammatory and augment asthma, it is also well known to be a potent inducer of IFN-gamma or "Type 1" immune responses, that are counter-regulatory to atopic "Type 2" immune development. Therefore, the main hypothesis of this proposal is that chronic endotoxin exposure in young children will prevent asthma by enhancing Type 1 immunity, thereby inhibiting atopic immune development and airways inflammation. A recently funded NIH study, entitled the "Childhood Asthma Prevention Study" (CAPS), provides an outstanding opportunity to explore this hypothesis in a supplemental manner. CAPS is a nurse home visitation intervention study that is enrolling 180 Inner-city infants with at least 3 previous episodes of wheezing, and following them until age 4 years for the development of asthma. Pilot studies supplemental to CAPS have demonstrated that, in these asthma-prone infants, increased house dust endotoxin levels are associated with less allergen sensitization and enhanced Type 1 immune responses. By continuing to study this CAPS study cohort, we propose to determine if chronic endotoxin exposure further reduces the prevalence of asthma at ages 6-7 years, by enhancing Type 1 immunity and thereby inhibiting allergen sensitization and Type 2 immune development. As well, several factors contributing to variations in immune responses to endotoxin will be studied. Ultimately, this research may serve to define the potential of augmenting Type 1 immunity in early life as a primary prevention strategy for asthma and allergy. New diagnostic tools to follow pro-asthmatic immune progression or resolution have been developed and will be tested in the process. This K23 Mentored Patient-Oriented Research Career Development Award will provide the Candidate, a Pediatric Asthma, Allergy & Immunology specialist, with the skills, experience, mentorship, and knowledge needed to be a productive and independent investigator in patient-oriented research. A specific Research Career Development Plan has been designed by the Candidate that includes the research described above in order to accomplish the goals of this Award.

这项研究的主要目的是调查慢性环境内毒素暴露在幼儿哮喘预防中的潜在作用。由于哮喘通常始于儿童早期，在顽固性疾病状态典型的病理肺过程出现之前，减轻哮喘炎症背后的特应性免疫发展的干预和暴露可能对幼儿具有最大的疗效。尽管在成人哮喘患者中，内毒素暴露已被证明是促炎和加重哮喘的，但众所周知，它也是干扰素-伽马或“1型”免疫反应的有效诱因，后者对特应性“2型”免疫发展具有反调节作用。因此，这一建议的主要假设是，幼儿长期暴露内毒素将通过增强1型免疫功能，从而抑制特应性免疫发育和呼吸道炎症来预防哮喘。美国国立卫生研究院最近资助的一项名为“儿童哮喘预防研究”(CAPS)的研究为以补充方式探索这一假说提供了一个绝佳的机会。CAPS是一项疗养院探视干预研究，该研究招募了180名有至少3次喘息史的内城婴儿，并对他们进行跟踪调查，直到他们4岁时出现哮喘。补充CAPS的初步研究表明，在这些易患哮喘的婴儿中，室内粉尘内毒素水平增加与过敏原敏感度降低和1型免疫反应增强有关。通过继续研究CAPS研究队列，我们建议确定慢性内毒素暴露是否通过增强1型免疫从而抑制过敏原致敏和2型免疫发展来进一步降低6-7岁儿童哮喘的患病率。此外，还将研究导致内毒素免疫反应变化的几个因素。最终，这项研究可能有助于确定在生命早期增强1型免疫作为哮喘和过敏的主要预防策略的潜力。已经开发了跟踪哮喘前期免疫进展或消退的新诊断工具，并将在此过程中进行测试。这项K23指导的以患者为导向的研究职业发展奖将为候选人，一名儿科哮喘、过敏和免疫学专家，提供所需的技能、经验、指导和知识，以成为面向患者的研究中高效和独立的研究员。候选人已经设计了一份具体的研究职业发展计划，其中包括上述研究，以实现该奖项的目标。