The Role of Iron Deficiency in COPD Morbidity

项目摘要 慢性阻塞性肺疾病（COPD）影响大约10%的40岁以上的成年人 是全球第三大致死原因共病通常伴随COPD， COPD结局的重要决定因素。此外，运动能力和体力活动能力强 COPD患者全因死亡率的独立预测因素。锻炼的两个重要决定因素 能力是血红蛋白水平，氧气携带能力的限制因素，和铁水平，这决定了 组织氧化能力因此，虽然缺铁和贫血是相关的，但它们是不同的条件， 病理生理学的不同机制。目前，与贫血相比，对贫血的了解较少。 铁缺乏与COPD发病率之间的关系。在有限的观察性和回顾性临床研究中， 研究表明，缺铁与自我报告的病情加重、运动不良有关。 耐受性和慢性肺病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，运动能力的改善与IV铁 在COPD患者的小队列中的补充。然而，鉴于迄今为止的研究规模较小， 尚不清楚是否所有COPD患者都受到缺铁的类似影响，以及铁补充是否会 提供平等的利益。 本提案的主要目的是了解铁含量与COPD发病率之间的关系 通过两个新的目标。首先，为了确定铁谱，特别是铁蛋白与 通过进行回顾性次要分析， 一个大型COPD患者数据登记中心，约有85，000人。第二，前瞻性地 确定铁谱与2a）医院再入院率和2b）功能性 在最近因COPD急性加重住院的患者队列中，按体力活动水平列出的状态。 第二个目标将嵌套在最近因COPD住院的患者的观察性队列研究中 加重事件的加重。我们将在索引后1周获得铁曲线 住院治疗，队列将随访12个月，定期亲自或电话随访 急性加重评估和经验证的呼吸道症状测量。体力活动水平将是 通过步数和心率监测获得。该提案为以下人员提供了出色的培训工具 通过从入组到最终的队列实践经验进行以患者为导向的临床研究 分析.我还将发展基本的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COPD发病率相关，未来的治疗研究 与铁的补充和评估的好处与伤害将是必要的，并将作为 为我未来的K级职业发展奖打下基础

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.