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CC16 in Childhood and Resilience to Persistent Asthma into Adult Life

CC16 在儿童期和成年后对持续性哮喘的抵抗力

基本信息

批准号：
10224859
负责人：
Stefano Guerra
金额：
$ 72.3万
依托单位：
UNIVERSITY OF ARIZONA
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：
2017-09-25 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224859
关键词：
Address Adult Age Animals Antibodies Asthma Bacteria Biological Process Birth Blood Blood Circulation Bronchoalveolar Lavage Cells Child Childhood Childhood Asthma Chronic Chronic Obstructive Airway Disease Clara cell-specific protein Clinical Data Development Disease Distal Early identification Environmental Risk Factor Epidemiology Epithelial Cells Evaluation Genes Genetic Growth Immune response Impairment Individual Infection Inflammatory Response International Knockout Mice Life Link Lung Lung Inflammation Measures Mediating Morbidity - disease rate Mus Mycoplasma pneumonia infection Mycoplasma pneumoniae Nasal Epithelium Obstructive Lung Diseases Predisposition Property Proteins Puberty Pulmonary Function Test/Forced Expiratory Volume 1 Risk Risk Factors Role School-Age Population Serology Serum Severities Severity of illness Symptoms Term Birth Time Viral airway inflammation airway obstruction asthma exacerbation asthmatic cohort early detection biomarkers extracellular lung development mortality pathogen phenotypic data predictive modeling prevent pulmonary function resilience respiratory respiratory colonization response risk stratification young adult

项目摘要

PROJECT ABSTRACT Persistence of childhood asthma into adult life has been conclusively linked to long-term lung function deficits and an increased susceptibility to non-fully reversible airflow limitation, the hallmark of chronic obstructive pulmonary disease. Yet, at the present time there are neither established prediction models nor available biomarkers for early risk identification of long-term sequelae in childhood asthma. In preliminary studies, we found early levels of circulating CC16 – a pneumoprotein that is produced mainly by club cells in the distal airways and can be measured in circulation – to be associated with resilience to subsequent lung function deficits and persistent asthma. Of note, these effects were independent of known risk factors for persistent disease. In addition, we found CC16-/- mice to have lung function deficits, airway alterations, and susceptibility to infections by Mycoplasma pneumoniae as compared with wild-type animals. These findings support CC16 in early school age as a strong and independent factor for resilience to persistent disease and long-term sequelae in children with asthma, and suggest that CC16 may exert these effects by modulating susceptibility and responses to airway infections. The present proposal addresses 1) the identification of early determinants of circulating CC16 levels by school-age; 2) the value of levels and trajectories of circulating CC16 in childhood as predictors of persistence and severity of asthma into adult life; and 3) the evaluation of airway responses to asthma pathogens as a potential mechanism mediating CC16 effects on persistent disease.

项目摘要儿童期哮喘持续到成人期与长期肺功能缺陷有决定性的联系以及对不完全可逆的气流限制的敏感性增加，这是慢性阻塞性肺疾病的标志。肺部疾病然而，目前既没有建立的预测模型，儿童哮喘长期后遗症早期风险识别的生物标志物。在初步研究中，我们发现循环CC 16的早期水平-一种主要由远端棒状细胞产生的肺蛋白，可以在循环中测量-与随后肺功能的恢复有关缺陷和持续性哮喘。值得注意的是，这些影响独立于已知的持续性风险因素。疾病此外，我们发现CC 16-/-小鼠具有肺功能缺陷、气道改变和易感性。与野生型动物相比，肺炎支原体感染。这些发现支持CC 16，学龄早期是抵抗持续性疾病和长期性疾病的一个强大和独立的因素，提示CC 16可能通过调节易感性发挥这些作用以及对呼吸道感染的反应。本建议涉及1）早期决定因素的识别循环CC 16水平的学龄; 2）循环CC 16在儿童时期的水平和轨迹的价值作为哮喘持续性和严重程度的预测因子; 3）评估气道对哮喘病原体作为一种潜在的机制，介导CC 16对持续性疾病的影响。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CC16 drives VLA-2-dependent SPLUNC1 expression.

CC16驱动VLA-2依赖性Splunc1表达。

DOI：
10.3389/fimmu.2023.1277582
发表时间：
2023
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
通讯作者：

Club cell secretory protein and lung function in children with cystic fibrosis.

DOI：
10.1016/j.jcf.2022.03.007
发表时间：
2022-09
期刊：
JOURNAL OF CYSTIC FIBROSIS
影响因子：
5.2
作者：
Zhai, Jing;Emond, Mary J.;Spangenberg, Amber;Stern, Debra A.;Vasquez, Monica M.;Blue, Elizabeth E.;Buckingham, Kati J.;Sherrill, Duane L.;Halonen, Marilyn;Gibson, Ronald L.;Rosenfeld, Margaret;Sagel, Scott D.;Bamshad, Michael J.;Morgan, Wayne J.;Guerra, Stefano
通讯作者：
Guerra, Stefano

The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells.

DOI：
10.3390/cells12151984
发表时间：
2023-08-01
期刊：
CELLS
影响因子：
6
作者：
Iannuzo, Natalie;Dy, Alane Blythe C.;Guerra, Stefano;Langlais, Paul R. R.;Ledford, Julie G. G.
通讯作者：
Ledford, Julie G. G.

COPD: To Be or Not to Be, That is the Question.