Mentored Patient Oriented Research in Pulmonary Fibrosis and Lung Transplantation

指导以患者为导向的肺纤维化和肺移植研究

• 批准号: 9086954
• 负责人: David J. Lederer
• 金额: $ 11.74万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9086954
• 关键词: Abdomen; Academic Medical Centers; Acute; Acute Lung Injury; Adipocytes; Adipose tissue; Adult; Ancillary Study; Anti-Inflammatory Agents; Anti-inflammatory; Autoimmunity; Award; Bioinformatics; Biological Assay; Body Composition; Bronchiolitis Obliterans; CD8B1 gene; Cause of Death; Cells; Cessation of life; Characteristics; Chemotactic Factors; Chest; Chronic; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Cohort Studies; Critical Illness; Development; Epidemiology; Evaluation; Faculty; Fatty acid glycerol esters; Flow Cytometry; Foundations; Functional disorder; Gene Expression; Genes; Hour; IL12A gene; IL12B gene; IL6 gene; Immune; Immunophenotyping; Individual; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interleukin-10; Interstitial Lung Diseases; Knowledge; Laboratories; Lead; Leptin; Life; Lung; Lung Inflammation; Lung Transplantation; Lung diseases; Matrilysin; Measurement; Measures; Mentors; Mentorship; Methods; Mid-Career Clinical Scientist Award (K24); Modeling; Morbidity - disease rate; NCI Scholars Program; NOS2A gene; Obesity; Operative Surgical Procedures; Outcome; Outpatients; Overweight; Peripheral Blood Mononuclear Cell; Phase II Clinical Trials; Phenotype; Prevention; Preventive measure; Process; Pulmonary Fibrosis; Pulmonary artery structure; RNA; RNA Sequences; Regulatory T-Lymphocyte; Reperfusion Injury; Research; Research Methodology; Respiratory Failure; Risk; Risk Factors; Role; Serum; Severity of illness; Statistical Data Interpretation; Syndrome; T cell response; T-Lymphocyte; TNF gene; Testing; Time; Training; Transplantation; Vital capacity; Walking; Work; X-Ray Computed Tomography; adipokines; adiponectin; anakinra; cytokine; design; improved outcome; innovation; insight; lung allograft; macrophage; mortality; nonalcoholic steatohepatitis; novel; patient oriented research; pressure; programs; protein biomarkers; protein expression; public health relevance; resistin; skills; subcutaneous; success; tool; training opportunity; transcriptome; translational study

 DESCRIPTION (provided by applicant): Lung transplantation is a life-saving therapy for adults with advanced lung diseases, such as interstitial lung disease and chronic obstructive pulmonary disease. The success of lung transplantation is limited by poor early and late outcomes. Primary graft dysfunction (PGD), a form of acute lung injury (ALI) occurring within 72 hours of lung transplantation, is the leading cause of death early after lung transplantation and contributes to chronic lung allograft dysfunction. We have identified obesity as a novel risk facto for PGD. The mechanism underlying this association is not known, but obesity-related inflammation could contribute. Obesity is characterized by a chronic systemic inflammatory state due to the accumulation of pro-inflammatory adipose tissue macrophages (ATMs), T cells, and other immune cells. Adipocytes and ATMs secrete inflammatory mediators, chemoattractants, and adipokines, such as leptin, visfatin, and resistin, that could contribute to the development of ALI. The Lung Transplant Body Composition (LTBC) study is a multicenter cohort study testing the hypothesis that adipose tissue inflammation increases during lung transplant surgery and contributes to PGD, and specifically that pro-inflammatory ATMs and T cells drive this process. In this K24 Award, I propose an ancillary study to the LTBC study that will test the hypotheses that the inflammatory profile of subcutaneous adipose tissue obtained prior to lung transpalntation can (1) help identify individuals with an inflammatory profile in intrathoracic adipose tissue obtained during lung transplant surgery, and (2) is associated with greater disease severity in interstitial lung disease. With this K24 Award, I will develop additional mentorship skills and directly mentor additional trainees throughout the Award period. I also propose to develop the "Pulmonary Fibrosis Foundation Scholars Program", a multicenter mentorship program designed to train fellows and junior faculty in clinical and translational patient-oriented research methods in interstitial lung disease. The proposal is innovative in nesting a translational study examining adipose tissue inflammation in an epidemiological cohort study of lung transplant candidates with interstitial lung disease. This work will lead to phase II clinical trials to decrease PGD risk in at-risk candidates identified through an inflammatory subcutaneous adipose tissue profile.

 描述（由适用提供）：肺移植是针对患有晚期肺部疾病的成年人的救生疗法，例如间质性肺部疾病和慢性阻塞性肺部疾病。肺移植的成功受到早期和晚期不良结局的限制。原发性移植功能障碍（PGD）是一种在肺移植后72小时内发生的一种急性肺损伤（ALI），是肺移植后早期死亡的主要原因，并导致慢性肺同种异体移植功能障碍。我们已经确定肥胖症是PGD的新风险因素。该关联的基础机制尚不清楚，但与肥胖相关的炎症性可能会产生贡献。肥胖的特征是由于促炎性脂肪组织巨噬细胞（ATM），T细胞和其他免疫细胞的积累，肥胖症的特征是慢性全身性炎症状态。脂肪细胞和ATMS秘密炎症介质，化学吸引剂和脂肪因子（例如瘦素，粘蛋白和抵抗素），可能有助于发展 阿里。肺移植体组成（LTBC）研究是一项多中心队列研究，检验了脂肪组织炎症在肺移植手术过程中脂肪炎的增加的假设，并有助于PGD，特别是促炎性ATMS和T细胞驱动这一过程。在该K24奖中，我提出了一项辅助研究对LTBC研究的辅助研究，该研究将检验以下假设：在肺部转料之前获得的皮下脂肪组织的炎症性概况可以（1）帮助识别患有肺内脂肪组织在肺内脂肪组织中具有炎症性炎症性症状的患者，在肺肺内的疾病中获得了更大的疾病，并具有更大的疾病疾病（2）疾病（2）。通过此K24奖，我将在整个奖项期间发展额外的心态技能和直接心理的其他学员。我还建议开发“肺纤维化基金会学者计划”，这是一项多中心脑膜计划，旨在训练研究人员和初级教师，以临床和翻译为患者的肺部肺部疾病中的患者研究方法。该提案在筑巢的一项研究研究中，研究脂肪组织感染的翻译研究是创新的。这项工作将导致第二阶段 临床试验可降低通过炎症性皮下脂肪组织剖面鉴定出的高危候选者的PGD风险。