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: 9337490
• 负责人: David J. Lederer
• 金额: $ 11.72万
• 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/9337490
• 关键词: Abdomen; Academic Medical Centers; Acute; Acute Lung Injury; Adipocytes; Adipose tissue; Adult; Ancillary Study; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Autoimmunity; Award; Bioinformatics; Biological Assay; Body Composition; Bronchiolitis Obliterans; CD8-Positive T-Lymphocytes; 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; 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; Organ; Outcome; Outpatients; Overweight; Peripheral Blood Mononuclear Cell; Phase II Clinical Trials; Phenotype; Prevention strategy; Preventive measure; Process; Pulmonary Fibrosis; Pulmonary artery structure; RNA Sequences; Regulatory T-Lymphocyte; Reperfusion Injury; Research; Research Methodology; Respiratory Failure; Risk; Risk Factors; Role; Savings; 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（由申请人提供）：肺移植是治疗患有晚期肺病（例如间质性肺病和慢性阻塞性肺病）的一种挽救生命的疗法。肺移植的成功受到早期和晚期移植功能障碍的影响。 (PGD) 是肺移植后 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，并导致慢性同种异体肺移植功能障碍。这种关联的潜在机制尚不清楚，但肥胖相关的炎症可能是由于促炎脂肪组织巨噬细胞 (ATM)、T 细胞的积累而导致的慢性全身炎症状态。和其他免疫细胞会分泌炎症介质、趋化剂和脂肪因子，例如瘦素、内脂素和抵抗素，这些可能有助于脂肪细胞的形成。 ALI。肺移植身体成分 (LTBC) 研究是一项多中心队列研究，测试肺移植手术期间脂肪炎症增加并导致 PGD 的假设，特别是促炎 ATM 和 T 细胞驱动这一过程。 ，我提出了一项 LTBC 研究的辅助研究，该研究将检验以下假设：肺移植前获得的皮下脂肪组织的炎症特征可以 (1) 帮助识别具有炎症特征的个体肺移植手术期间获得的胸腔内脂肪组织，以及（2）与间质性肺疾病的严重程度相关，通过这个 K24 奖项，我将培养额外的指导技能，并在整个奖励指导期间直接培养更多的学员。 “肺纤维化基金会学者计划”是一项多中心指导计划，旨在培训研究员和初级教师进行间质性肺疾病的临床和转化性研究方法。在患有间质性肺病的肺移植候选者的流行病学队列研究中检查脂肪组织炎症的转化研究这项工作将进入第二阶段。 通过炎症性皮下脂肪组织图谱确定的高危候选人降低 PGD 风险的临床试验。