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SPIROMICS II: Biological underpinnings of COPD heterogeneity and progression

SPIROMICS II：COPD 异质性和进展的生物学基础

基本信息

批准号：
10178075
负责人：
PRESCOTT G WOODRUFF
金额：
$ 358.92万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10178075
关键词：
Airway Disease Anatomy Biochemical Biological Biological Factors Biology Blood Bronchoscopy Cause of Death Characteristics Chronic Bronchitis Chronic Obstructive Airway Disease Clinical Data Development Diagnostic radiologic examination Disease Disease Progression Enrollment Event Goals Gold Heterogeneity Immune response Individual Inflammation Inflammatory Inflammatory Response Interleukin-17 Lesion Link Longitudinal Studies Lung Lung diseases MUC5AC gene MUC5B gene Measurement Measures Medical Metabolism Methods Modification Mucins Mucous body substance Natural History Nucleosides Nucleotides Osmotic Pressure Outcome Measure Participant Pathway interactions Patients Pattern Phenotype Physiological Process Publishing Pulmonary Emphysema Risk Sampling Smoker Solid Source Spirometry Sputum Subgroup Symptoms Syndrome Testing Transcript Vascular Diseases Viral X-Ray Computed Tomography associated symptom base biophysical properties clinical phenotype disease heterogeneity disease phenotype extracellular follow-up former smoker lung microbiome molecular phenotype mortality never smoking next generation novel novel strategies pathogen patient subsets preservation pulmonary function respiratory microbiome respiratory pathogen small airways disease targeted treatment therapeutic development therapeutic target transcriptome sequencing treatment guidelines treatment trial

项目摘要

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. No medical therapies reduce mortality or slow disease progression, in part because COPD is a heterogeneous syndrome, which hinders the development of targeted therapies. The SPIROMICS study enrolled 2,982 participants into a 3-year longitudinal study of current and former smokers and never-smoking controls, phenotyping them clinically, radiographically and biologically to identify sources of heterogeneity in COPD. This new project will extend follow-up of participants enrolled in SPIROMICS, perform a bronchoscopy substudy and perform an exacerbation substudy to test three specific aims. The overarching premise underlying these aims is that COPD is a consequence of a heterogeneous group of molecular phenotypes that underlie distinct radiographic (anatomic) and clinical (physiologic) phenotypes; and that linking molecular phenotypes to specific radiographic and clinical phenotypes will identify key biological factors associated with disease exacerbation and progression. The first aim is to define the natural history of “Smokers with symptoms despite preserved spirometry” and characterize the airway mucus abnormalities underlying this condition. Patients with this newly recognized condition do not meet current criteria for COPD but nonetheless have symptoms, exacerbation-like events, activity limitations and airway wall thickening and they may have a precursor condition to bona fide COPD. The second aim is to determine the radiographic precursor lesion(s) for emphysema, and identify the molecular phenotypes underlying progression of chronic bronchitis, radiographic airway disease and emphysema. This aim will leverage several novel radiographic methods for measurement of lung disease and new approaches to phenotyping based on inflammatory pathways and the lung microbiome that we developed in SPIROMICS. The third aim is to advance our understanding of the biology of COPD exacerbations through analysis of predisposing baseline phenotypes, exacerbation triggers and host inflammatory response. This aim will leverage RNA sequencing methods to simultaneously measure respiratory pathogens and the host inflammatory response in an exacerbation substudy. Our ultimate goal is to enable targeted approaches to COPD treatment and disease modification that are based on the heterogeneous biological pathways that underlie COPD progression and exacerbations.

项目总结

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Wouldn't you like to know: are tertiary lymphoid structures necessary for lung defence?

您不想知道：三级淋巴结构对于肺部防御来说是必需的吗？

DOI：
10.1183/13993003.04352-2020
发表时间：
2021
期刊：
The European respiratory journal
影响因子：
0
作者：
Curtis,JeffreyL
通讯作者：
Curtis,JeffreyL

Novel Respiratory Disability Score Predicts COPD Exacerbations and Mortality in the SPIROMICS Cohort.

新型呼吸功能障碍评分可预测 SPIROMICS 队列中的 COPD 恶化和死亡率。

DOI：
10.2147/copd.s250191
发表时间：
2020
期刊：
International journal of chronic obstructive pulmonary disease
影响因子：
2.8
作者：
Cooper,ChristopherB;Paine,Robert;Curtis,JeffreyL;Kanner,RichardE;Martinez,CarlosH;Meldrum,CatherineA;Bowler,Russell;O'Neal,Wanda;Hoffman,EricA;Couper,David;Quibrera,Miguel;Criner,Gerald;Dransfield,MarkT;Han,MeiLanK;Hans
通讯作者：
Hans

Should the number of acute exacerbations in the previous year be used to guide treatments in COPD?