The Role of Iron Deficiency in COPD Morbidity

缺铁在慢性阻塞性肺病发病中的作用

基本信息

批准号：
10750003
负责人：
Yukiko Kunitomo
金额：
$ 9.44万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750003
关键词：
Adult Affect Age Anemia Biological Biological Process Blood Banks Blood specimen Carrying Capacities Chronic Chronic Obstructive Pulmonary Disease Chronic lung disease Clinical Research Clinical Trials Complex Data Analyses Data Collection Databases Development Disease Disease Outcome Enrollment Event Exercise Tolerance Ferritin Foundations Functional disorder Future Heart failure Hemoglobin concentration result Home environment Homeostasis Hospitalization Hypoxia Immune Impairment Individual Infection Intravenous Investigation Iron Iron deficiency anemia K-Series Research Career Programs Learning Lung Measures Morbidity - disease rate Observational Study Oxygen Patient Self-Report Patients Persons Physical activity Physiological Play Population Process Pulmonary Hypertension Randomized, Controlled Trials Recurrence Research Respiratory Signs and Symptoms Respiratory Tract Infections Retrospective Studies Risk Factors Role Sample Size Severities Spirometry Symptoms Telephone Therapeutic Tissues Training Transferrin Work cohort comorbidity comparative data acquisition data management data registry data repository exercise capacity experience functional outcomes functional status heart rate monitor high risk hospital readmission hospitalization rates improved indexing iron deficiency mortality novel observational cohort study patient oriented personalized medicine precision medicine profiles in patients prospective pulmonary function readmission rates respiratory screening secondary analysis secondary outcome treatment strategy vasoconstriction

项目摘要

Project Summary Chronic obstructive pulmonary disease (COPD) affects approximately 10% of adults above the age of 40 and is the third leading cause of mortality worldwide. Comorbid diseases commonly accompany COPD and are important determinants of COPD outcomes. In addition, exercise capacity and physical activity are strong independent predictors of all-cause mortality in COPD patients. The two important determinants of exercise capacity are hemoglobin level, the limiting factor for oxygen carrying capacity, and iron level, which dictates tissue oxidative capacity. Thus, while iron deficiency and anemia are related, they are distinct conditions with differing mechanisms of pathophysiology. Currently, compared to anemia, less is known regarding the association between iron deficiency and COPD morbidity. In limited observational and retrospective clinical studies, iron deficiency has been shown to be associated with self-reported exacerbations, worse exercise tolerance, and increased severity of chronic lung disease-associated pulmonary hypertension. Regarding treatment, there have been proof-of-concept studies showing improvement in exercise capacity with IV iron repletion in small cohorts of COPD patients. However, given the small scale of the studies thus far, it remains unknown whether all COPD patients are affected similarly by iron deficiency and whether iron repletion will provide equal benefit. The main object of this proposal is to understand the association between iron profile and COPD morbidity through two novel aims. First, to determine the association between iron profile, specifically ferritin and transferrin saturation, and COPD-related hospitalization by conducting a retrospective secondary analysis of a large COPD patient data registry with approximately 85,000 individuals. Second, to prospectively determine the association between iron profile and 2a) hospital readmission rate and 2b) functional status by physical activity level, in a cohort of patients recently hospitalized for COPD exacerbations. The second aim will be nested in an observational cohort study of patients recently hospitalized for COPD exacerbations that is enriched for exacerbation events. We will obtain iron profiles at 1-week post-index hospitalization and the cohort will be followed for 12 months with regular interval in-person or telephone assessments for exacerbations and validated respiratory symptom measures. Physical activity level will be acquired through step count and heart rate monitoring. This proposal provides an excellent training vehicle for patient-oriented clinical research through hands on experience following a cohort from enrollment to final analysis. I will also develop expertise in basic large data management and physical activity data acquisition and analysis. If we find that iron deficiency is associated with COPD morbidity, future investigation of treatment with iron repletion and assessment of benefit versus harm would be warranted, and would serve as the foundation for my future K-level career development award.

项目概要慢性阻塞性肺病 (COPD) 影响约 10% 的 40 岁以上成年人是全球第三大死亡原因。合并症通常伴随慢性阻塞性肺病 (COPD)，并且是 COPD 结果的重要决定因素。另外，运动能力和体力活动都很强 COPD 患者全因死亡率的独立预测因素。运动的两个重要决定因素能力是血红蛋白水平（携氧能力的限制因素）和铁水平（它决定了组织氧化能力。因此，虽然缺铁和贫血相关，但它们是不同的病症不同的病理生理学机制。目前，与贫血相比，人们对贫血的了解还较少。铁缺乏与 COPD 发病率之间的关联。在有限的观察和回顾性临床中研究表明，缺铁与自我报告的病情恶化、运动较差有关耐受性，以及慢性肺病相关肺动脉高压的严重程度增加。关于治疗方面，已有概念验证研究表明静脉铁剂可改善运动能力一小群慢性阻塞性肺病患者的补充。但鉴于迄今为止的研究规模还较小，尚不清楚是否所有慢性阻塞性肺病患者都会受到缺铁的类似影响，以及补充铁是否会影响提供平等的福利。该提案的主要目的是了解铁含量与 COPD 发病率之间的关联通过两个新颖的目标。首先，确定铁谱（特别是铁蛋白）和通过进行回顾性二次分析来了解转铁蛋白饱和度和 COPD 相关住院情况包含大约 85,000 名患者的大型慢性阻塞性肺病 (COPD) 患者数据登记。二、要前瞻性地确定铁含量与 2a) 医院再入院率和 2b) 功能之间的关联在最近因慢性阻塞性肺病恶化住院的一组患者中，按体力活动水平划分的状态。第二个目标将嵌套在最近因慢性阻塞性肺病住院的患者的观察性队列研究中因恶化事件而丰富的恶化。我们将在指数发布后 1 周获得铁概况住院治疗和队列将定期进行面对面或电话随访 12 个月病情加重评估和经过验证的呼吸道症状测量。身体活动水平将是通过步数计数和心率监测获得。该提案为以下人员提供了一个极好的培训工具：通过对队列从入组到最终结果的实践经验进行以患者为导向的临床研究分析。我还将发展基本大数据管理和身体活动数据采集方面的专业知识和分析。如果我们发现缺铁与慢性阻塞性肺病发病有关，未来的治疗研究随着铁的补充和利益与危害的评估将是有必要的，并将作为为我未来的 K 级职业发展奖奠定了基础。