CC16 in Childhood and Resilience to Persistent Asthma into Adult Life (Supplement)

CC16 在童年和成年生活中对持续性哮喘的抵抗力（补充）

基本信息

批准号：
10189106
负责人：
Stefano Guerra
金额：
$ 14.92万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-06 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10189106
关键词：
2019-nCoV Academic Medical Centers Address Adhesions Adult Adult Respiratory Distress Syndrome Affect Age Ambulatory Care Facilities Anti-Inflammatory Agents Arizona Asthma Blood Blood Circulation COVID-19 Cells Childhood Clinical Clinical Data Colonoscopy Control Groups Data Development Disease Disease Progression Distal Employee Health Endothelial Cells Frequencies Funding Genes Goals Health Personnel Hospitalization Immune response Individual Infection Infiltration Inflammation Inflammatory Inflammatory Response Inpatients Leukocytes Life Lung Lung infections Measures Medical Molecular Outpatients Participant Pathway interactions Patients Peptidyl-Dipeptidase A Pilot Projects Play Population Predisposition Procedures Production Property Proteins Proteomics Reporting Rhinovirus Risk stratification Role Sampling Schedule Secretory Cell Severity of illness Swab Symptoms Testing Time Viral Virus antimicrobial base case control cell type coronavirus disease cost insight interest metabolomics novel pandemic disease parent grant prevent prospective protective effect receptor recruit resilience response screening secretory protein sex

项目摘要

PROJECT SUMMARY In response to NOT-AI-20-031 [“Notice of Special Interest: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19)”] and in line with the scope of the parent grant, the goal of this supplement is to determine the role of Club cell secretory protein (CC16) in providing resilience to COVID-19. CC16 is a homodimeric pneumoprotein that is encoded by the SCGB1A1 gene, mainly produced by Club cells in the distal airways, and readily measured in circulation. The central hypothesis of our parent grant is that CC16 exerts protective effects in the lungs by modulating susceptibility and inflammatory responses to airway infections. In addition, because CC16-secreting Club cells are among the main airway cell types expressing Angiotensin-Converting Enzyme 2 (ACE2), it is plausible that – by infecting Club cells – SARS-CoV-2 can affect their survival and/or secretory machinery, and in turn impact production of CC16. Here, we postulate that CC16 plays a critical role in susceptibility and host inflammatory responses to SARS-CoV-2 and propose the following specific aim: Specific Aim - To determine the relation of circulating CC16 to the presence and clinical progression of COVID-19. In this pilot study, we will collect clinical data and biospecimens from both inpatients and outpatients with COVID-19 at Banner University Medical Center – Tucson. Depending on the dynamics of the pandemic, we estimate that we will recruit between 75-125 inpatients and 100-200 outpatients. In addition, we will recruit a group of controls (with a target case:control ratio of 2:1). Data from these participants will be used to compare circulating levels of CC16 across the three groups of controls, COVID-19 outpatients, and COVID-19 inpatients. In addition, circulating deficits of CC16 will be tested for prediction of subsequent clinical progression of disease.

项目概要回应 NOT-AI-20-031 [“特别关注通知：严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2）和 2019 年冠状病毒病（COVID-19）”]并根据家长补助金的范围，该补充剂的目标是确定 Club 细胞分泌蛋白 (CC16) 在提供 CC16 是一种由 SCGB1A1 基因编码的同型二聚体肺炎蛋白，主要由远端气道中的俱乐部细胞产生，并且易于在循环中测量。我们的母基金的中心假设是 CC16 通过调节对肺部发挥保护作用此外，由于分泌 CC16 的 Club 细胞对气道感染的易感性和炎症反应。是表达血管紧张素转换酶 2 (ACE2) 的主要气道细胞类型之一，这似乎是合理的 – 通过感染 Club 细胞 – SARS-CoV-2 可以影响它们的生存和/或分泌机制，进而影响在这里，我们假设 CC16 在易感性和宿主炎症中发挥着关键作用。应对 SARS-CoV-2 并提出以下具体目标：具体目标 - 确定循环 CC16 与以下疾病的存在和临床进展的关系新冠肺炎。在这项试点研究中，我们将从住院患者和门诊患者收集临床数据和生物样本图森班纳大学医学中心的 COVID-19，我们根据大流行的动态。预计我们将招募75-125名住院患者和100-200名门诊患者。此外，我们还将招募1名住院患者。对照组（目标案例：对照比例为 2:1）将用于比较这些参与者的数据。三组对照、COVID-19 门诊患者和 COVID-19 的 CC16 循环水平此外，还将测试CC16的循环缺陷以预测后续临床。疾病的进展。