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）

• 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
• 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

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.

项目摘要 针对NOT-AI-20-031 [“特别关注通知：严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）和2019冠状病毒病（COVID-19）"]，并根据母补助金的范围， 这种补充剂的目的是确定俱乐部细胞分泌蛋白（CC 16）在提供 抵御COVID-19的能力。CC 16是由SCGB 1A 1基因编码的同源二聚体肺蛋白， 主要由远端气道中的俱乐部细胞产生，并且在循环中容易测量。 我们的母基金的中心假设是，CC 16通过调节肺组织中的细胞因子， 易感性和气道感染的炎症反应。此外，由于分泌CC 16的Club细胞 是表达血管紧张素转换酶2（ACE 2）的主要气道细胞类型之一， - 通过感染俱乐部细胞，SARS-CoV-2可以影响它们的存活和/或分泌机制，进而影响 生产CC 16。在这里，我们假设CC 16在易感性和宿主炎症中起着关键作用。 对SARS-CoV-2的反应，并提出以下具体目标： 具体目的-确定循环CC 16与以下疾病的存在和临床进展的关系： 2019冠状病毒病。 在这项试点研究中，我们将收集住院患者和门诊患者的临床数据和生物标本， 2019冠状病毒病在班纳大学医学中心-图森。根据大流行病的动态，我们 预计我们将招募75-125名住院患者和100-200名门诊患者。此外，我们将招募一名 对照组（目标病例：对照比例为2：1）。这些参与者的数据将用于比较 三组对照、COVID-19门诊患者和COVID-19患者的CC 16循环水平 住院病人此外，将检测CC 16的循环缺陷，以预测随后的临床 疾病进展。