LONGITUDINAL EXACERBATION STUDY OF COPD (LES COPD)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要 与烟草相关的肺部疾病，包括伴有和不伴有肺气肿的慢性阻塞性肺疾病（COPD），是全世界与肺相关的残疾和死亡的主要原因。 COPD患者呼吸系统症状恶化的病因学以及需要特殊医疗关注的这些受试者的表型可能是异质性的，并且肯定知之甚少。 在一项纵向队列研究中，我们发现，在23个月内，大约一半的重度COPD（GOLD III期和IV期）受试者至少有一次急诊中心访视和/或因呼吸衰竭住院，而正常对照或轻度COPD（GOLD 0-11期）受试者无需紧急医疗护理。 然而，令人惊讶的是，我们发现与对照组相比，重度COPD受试者的年度症状性呼吸道病毒感染率相似。 因此，尽管严重COPD患者有类似的病毒感染记录，但他们仍然比对照组使用更多的医疗护理资源。 一种可能的解释是COPD患者对病毒感染的免疫反应与对照组不同。 为了支持这一观点，我们的研究小组已经正确地表明，患有COPD和肺气肿的稳定的前吸烟者的肺特异性免疫表型偏向于T辅助细胞1型（Th 1）免疫失调，这在那些没有疾病的人中是看不到的。 我们的建议将前瞻性地确定两个患者队列：1）根据COPD急性加重的操作定义，处于稳定状态和COPD急性加重期间的COPD各阶段的非卧床患者，如通过存在鼻炎或咽炎症状定义的上呼吸道疾病和/或通过咳嗽增加、呼吸短促定义的下呼吸道疾病，在存在或不存在发热（体温>37.7度）的情况下痰液产生和/或痰液颜色的变化;其中将基于经验证的St乔治呼吸问卷对恶化的严重程度进行分级; 2）患有COPD恶化的德克萨斯医学中心医院收治的患者。 我们还将研究正常对照组（吸烟者和非吸烟者）。 在本提案的目的之一中，我们将描述我们的COPD队列，并将前瞻性地确定受试者的表型，以确定是否可以使用一组特定的身体和功能特征来区分频繁COPD急性加重的受试者。 在我们的研究对象中，将特别强调那些将确定并发肺气肿的作用的研究。 将研究充血性心力衰竭和肝肾功能不全作为频繁加重受试者的潜在促成因素的作用。 在该提案的第二和第三个目标中，我们将确定可能导致该队列肺功能频繁加重和下降的病毒和非病毒介导的T细胞应答的机制。

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. ABSTRACT Tobacco related lung diseases, including chronic obstructive pulmonary disease (COPD) with and without emphysema, are major causes of lung-related disability and death worldwide. The etiology of worsening of respiratory sumptoms in patients with COPD, and the phenotype of these subjects that require special medical attention, are probably heterogeneous and certainly poorly understood. In a longitudinal cohort study, we have shown that approximately one half of subjects with severe COPD (GOLD stage III, and IV), had at least one emergency center visit and/or hospital admission for respiratory failure as compared to no need for urgent medical care in normal controls or subjects with mild COPD (GOLD stage 0-11) in 23 months. Surprisingly however, we found similar annual symptomatic respiratory virus infection rates in severe COPD subjects as compared to controls. Thus, although patients with severe COPD have comparable documented viral infections, they still utilize more medical care resources than controls. One possible explanation is that the immune response to the viral infection in patients with COPD differs fromthat of control groups. In support of this idea, our group has rectntly shown that the lung-specific immune phenotype of stable ex-smokers with COPD and emphysema is biased towards T helper type 1 (Th1) immune dysregulation that is not seen in those without the disease. Our proposal will prospectively identify two cohorts of patients 1) ambulatory patients with various stages of COPD, during stable condition and during COPD exacerbation as defined byour operational definition of COPD exacerbation, as upper respiratory tract illness defined by the presence of symptoms of rhinitis or pharyngitis, and/or lower respiratory tract illness defined by increase cough, shortness of breath, sputum production and/or change in sputum color in the presence or absence of fever (temperature >37.7 degrees); where the severity of exacerbation will be graded based on the validated St George's Respiratory Questionnaire; 2) patients admitted to the Texas Medical Center hospitals with COPD exacerbation. We will also study normal controls (smokers and non-smokers). In aim one of this proposal we will characterize our COPD cohort and will prospectively determine the phenotype of subjects to determine if a specific set of physical and functional characteristics can be used to distinguish sujbects with frequent COPD exacerbation. A special emphasis will be placed on studies that willdefine the role of concurrent emphysema, in our study subjects. The role of congestive heart failure, and liver and kidney dysfunction will be investigated as potential contributing factors in subjects with frequent exacerbation. In the second and third aims of the proposal we will determine the mechanisms for the viral and non-viral mediated T cell responses that may contribute to frequent exacerbation and decline in lung function of this cohort.