The Role of Iron Deficiency in COPD Morbidity

缺铁在慢性阻塞性肺病发病中的作用

• 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
• 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

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.

项目摘要 慢性阻塞性肺疾病（COPD）影响了40岁以上的成年人的10％ 这是全球死亡率的第三大主要原因。合并症通常伴随COPD，是 COPD结果的重要决定因素。此外，运动能力和体育锻炼很强 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 容量是血红蛋白水平，这是氧气承载能力的限制因素，铁水平决定了 组织氧化能力。因此，尽管铁缺乏症和贫血是相关的，但它们是不同的条件 病理生理的不同机制。目前，与贫血相比，关于 铁缺乏和COPD发病率之间的关联。在有限的观察和回顾性临床中 研究，铁缺乏症已被证明与自我报告的恶化有关，运动较差 耐受性和慢性肺相关肺动脉高压的严重程度增加。关于 治疗，有概念验证研究表明，用静脉铁铁提高了运动能力 少数COPD患者的补充。但是，鉴于到目前为止的研究量很小，它仍然是 尚不清楚所有COPD患者是否受到铁缺乏症的影响以及铁的补充是否会 提供同等的好处。 该提案的主要目的是了解铁概况与COPD发病率之间的关联 通过两个小说的目标。首先，确定铁概况之间的关联，特别是铁蛋白和 通过进行回顾性二级分析，转铁蛋白饱和和与COPD相关的住院 大约有大约85,000名个人的大型COPD患者数据注册中心第二，前瞻性 确定铁概况和2A）医院再入院率和2B）功能 在最近住院的COPD加重的患者中，体育锻炼水平的状态是按身体活动水平进行的。 第二个目标将嵌套在最近住院的COPD的患者的观察队列研究中 加剧因加剧事件而富裕的加剧。我们将在1周后获得铁剖面 住院和队列将进行12个月的时间，并定期面对面或电话 评估加重和验证呼吸道症状措施。体育锻炼水平将是 通过步骤计数和心率监测获得。该建议为 从入学到最终的队列之后，通过手动经验进行了以患者为导向的临床研究 分析。我还将在基本的大数据管理和体育活动数据获取方面发展专业知识 和分析。如果我们发现铁缺乏症与COPD发病率有关，则对治疗的未来研究 随着铁的补充和对利益与伤害的评估，将有必要作为 我未来K级职业发展奖的基础。