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：
9426640
负责人：
Stefano Guerra
金额：
$ 72.76万
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 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9426640
关键词：
Address Adult Age Animals Antibodies Asthma Bacteria Biological Markers 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 Employee Strikes 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 Modeling Morbidity - disease rate Mus Mycoplasma pneumonia infection Mycoplasma pneumoniae Nose Predisposition Property Proteins Pulmonary Function Test/Forced Expiratory Volume 1 Respiratory physiology Risk Risk Factors Risk stratification Role School-Age Population Serological Serum Severities Severity of illness Symptoms Term Birth Time Viral airway inflammation asthmatic cohort extracellular lung development mortality pathogen phenotypic data prevent resilience respiratory response 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年已明确与长期肺功能缺陷有关以及对非完全可逆气流受限的敏感性增加，这是慢性阻塞性肺疾病的标志然而，目前还没有建立的预测模型，也没有可用的预测模型。在初步研究中，我们使用生物标志物来早期识别儿童哮喘长期后遗症。发现循环 CC16 的早期水平——一种主要由远端球杆细胞产生的肺蛋白气道，可以在循环中测量——与随后的肺功能恢复能力相关值得注意的是，这些影响与已知的持续性哮喘危险因素无关。此外，我们发现 CC16-/- 小鼠存在肺功能缺陷、气道改变和易感性。与野生型动物相比，这些发现支持 CC16 对肺炎支原体感染的影响。早期学龄是抵抗持续性疾病和长期疾病的一个强大而独立的因素哮喘儿童的后遗症，并表明 CC16 可能通过调节易感性发挥这些作用以及对气道感染的应对措施本提案涉及 1) 早期决定因素的识别。学龄期 CC16 循环水平；2) 儿童时期 CC16 循环水平和轨迹的值；作为成年期哮喘持续性和严重程度的预测因素；3) 评估气道反应哮喘病原体作为介导 CC16 对持续性疾病影响的潜在机制。