Novel Quantitative Emphysema Subtypes in MESA and SPIROMICS

MESA 和 SPIROMICS 中新的定量肺气肿亚型

基本信息

批准号：
10453736
负责人：
R Graham BARR
金额：
$ 72.83万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10453736
关键词：
Airway Fibrosis Algorithms Angiography Apical Bayesian learning Biological Blood Vessels Cause of Death Characteristics Chronic Obstructive Pulmonary Disease Clinic Clinical Computed Tomography Scanners Data Diffuse Disease Dose Endothelium Funding Genetic Genotype Histologic Histology Image Impairment Learning Lung Machine Learning Malignant neoplasm of lung Molecular Molecular Target Morbidity - disease rate Participant Pathway interactions Patients Pattern Pharmaceutical Preparations Phenotype Physiology Pulmonary Emphysema Pulmonary Fibrosis Rare Diseases Reproducibility Research Scanning Smoker Smoking Structure Symptoms Techniques Testing Text Translating X-Ray Computed Tomography alpha 1-Antitrypsin Deficiency clinical care clinical practice computed tomography screening contrast enhanced computed tomography deep learning disorder control follow-up genetic variant genome sequencing genome wide association study genome-wide improved innovation lung cancer screening lung histology microCT mortality novel population based recruit success symptomatology unsupervised learning whole genome

项目摘要

Chronic obstructive pulmonary disease (COPD) and emphysema, jointly, are the fourth leading cause of death in the US and globally. Decades of research have not found disease-modifying therapies except for a1 antitrypsin deficiency, a rare disease found by improved phenotyping, characterized by a specific emphysema subtype and caused by gene variants in SERPINA1. This renewal builds on the successful discovery of six new quantitative emphysema subtypes (QES), which were associated independently with greater symptoms, impaired function and increased mortality in addition to several genome-wide significant associations for gene variants. In the renewal, we propose to leverage over 27,000 CTs acquired over 5-7 years of follow-up from 4,500 highly phenotyped and genotyped participants to test if deep and unsupervised learning on new state-of- the-art CTs and CT angiograms will reveal additional deep-learned and molecular QES that suggest mechanistic pathways to treatment. Further, we will collect 60 explanted lungs and use state-of-the art microCT to test if QES have distinct histology and structure. Finally, we will recruit 100 patients undergoing lung cancer CT screening to test if QES will be translatable to clinical low-dose lung cancer screening CT scans acquired on contemporary scanners. Successful completion of these aims will discover new deep QES and molecular QES and validate and translate QES to further subphenotype emphysema and facilitate testing of personalize molecular therapies and, hopefully, replicate the success of therapy for a1-antitrypsin deficiency for more common emphysema subtypes.

共同的慢性阻塞性肺疾病（COPD）和肺气肿是第四大死亡原因在美国和全球。数十年的研究还没有发现疾病改良的疗法，除了A1 抗胰蛋白酶缺乏症，一种通过改进的表型发现的罕见疾病，其特征是特定的肺气肿亚型和由serpina1中的基因变异引起的。这种更新是基于成功发现的六个新的定量肺气肿亚型（QES），与更大的症状相关，除了几个基因组的显着关联外，功能受损和死亡率增加了变体。在续签中，我们建议利用超过27,000个CTS从超过5 - 7年的随访中获得 4,500个高度表型和基因分型参与者，以测试对新的最新态度的深入和无监督的学习 ART CT和CT血管造影将揭示其他深入学习和分子QE的表明治疗的机械途径。此外，我们将收集60种外植的肺并使用最先进的 Microct测试QES是否具有不同的组织学和结构。最后，我们将招募100名正在进行的患者肺癌CT筛查以测试QE是否可以翻译成临床低剂量肺癌筛查CT 在当代扫描仪上获得了扫描。这些目标的成功完成将发现新的深QE 和分子QE，并验证和翻译QE，以进一步亚型肺气肿并促进测试个性化分子疗法，并希望复制A1-抗抑制剂缺乏症的疗法的成功对于更常见的肺气肿亚型。