Mechanisms of Air Pollution Health Effects in Subjects with Heart Failure

描述（由申请人提供） 博士Gregory Wellenius的长期职业目标是成为一名能够领导环境心脏病学以患者为导向的研究工作的独立调查员。 在该职业发展奖的指导（K99）阶段，候选人将获得在综合临床研究中心开展以患者为导向的机制研究，评估血管内皮功能，统计方法和暴露评估方面的专业知识。候选人还将建立自己的实验室，收集初步数据，并在此阶段完善功率计算。 博士候选人目前的博士后导师Murray Mittleman将担任主要导师，并监督候选人培训的各个方面。 此外，一个由三名具有互补专业领域的共同导师组成的团队将补充Wellenius博士在特定领域的培训。导师和共同导师共同致力于帮助候选人实现他的研究培训和职业发展目标，并确保候选人从博士后研究员成功过渡到独立研究员。 在该奖项的独立（R00）阶段，候选人将进行前瞻性，重复测量研究，以评估颗粒空气污染影响充血性心力衰竭患者的自主神经功能，炎症和血管内皮功能的机制。 这些假定的机制已经在许多正常和易感人群中进行了评估，但从未专门在充血性心力衰竭受试者中进行过评估。 相关性：充血性心力衰竭患者的住院率极高。流行病学研究表明，环境空气污染的短期增加与该人群住院风险的增加有关，但这种影响的机制尚未得到研究。了解潜在的机制可能会导致新的预防策略，新的治疗方法或改善空气质量。

DESCRIPTION (provided by applicant) Dr. Gregory Wellenius's long-term career goal is to be become an independent investigator capable of leading patient-oriented research efforts in environmental cardiology. During the mentored (K99) phase of this career development award, the candidate will gain expertise in conducting patient-oriented mechanistic research in the setting of the General Clinical Research Center, assessment of vascular endothelial function, statistical methodology, and exposure assessment. The candidate will also establish his own laboratory, collect preliminary data, and refine power calculations during this phase. Dr. Murray Mittleman, the candidate's current post-doctoral mentor, will serve as primary mentor and oversee all aspects of the candidate's training. In addition, a team of three co-mentors with complimentary areas of expertise will supplement Dr. Wellenius's training in specific areas. Together, the mentor and co-mentors are committed to assisting the candidate reach his research training and career development goals and to ensuring the candidate's successful transition from postdoctoral fellow to independent researcher. During the independent (R00) phase of this award, the candidate will conduct a prospective, repeated-measures study to evaluate the mechanisms by which particulate air pollution affects autonomic function, inflammation, and vascular endothelial function in a cohort of patients with congestive heart failure. These putative mechanisms have been evaluated in a number of normal and susceptible populations, but never specifically in subjects with congestive heart failure. Relevance: Hospitalization rates among patients with congestive heart failure are extremely high. Epidemiologic studies suggest that short-term increases in ambient air pollution are associated with increased risk of hospitalization in this population, but the mechanisms of this effect have not been investigated. Understanding the underlying mechanisms may lead to new preventative strategies, new treatments, or improved air quality.