Natural History of Viral Induced Airway Dysfunction and Asthma in Minority Children

少数民族儿童病毒引起的气道功能障碍和哮喘的自然史

基本信息

批准号：
10369849
负责人：
Esteban Gonzalez Burchard
金额：
$ 8.61万
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：
2018
资助国家：
美国
起止时间：
2018-09-24 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369849
关键词：
3 year old Address Affect African American Age Asthma Birth Bronchiolitis Child Childhood Childhood Asthma Clinical Data Collaborations Data Development Diagnosis Disease Environment Ethnic Origin Ethnic group Etiology Exhibits Functional disorder Gene Expression Gene Expression Profile Genes Genetic Genetic Determinism Genetic Predisposition to Disease Health Policy Human Incidence Infant Infection Infrastructure Life Longitudinal Studies Metagenomics Mexican Americans Minority Molecular Monitor Morbidity - disease rate Natural History Newborn Infant Nose Participant Plant Roots Population Prevalence Prospective Studies Public Health Publications Puerto Rican Puerto Rico Race Recurrence Reporting Research Respiratory Signs and Symptoms Respiratory Syncytial Virus Infections Respiratory syncytial virus Rhinovirus Risk Risk Factors Seasons Seminal Severities Standardization Swab Testing Variant Viral Viral Respiratory Tract Infection Virus Virus Diseases Wheezing Work airway epithelium base case control clinical practice cohort design early childhood epidemiology study gene environment interaction genome-wide health care service utilization high risk population injured longitudinal analysis minority children minority subjects mortality nasal swab novel racial and ethnic recruit respiratory respiratory infection virus response risk variant social transcriptome transcriptomics virus genetics

项目摘要

PROJECT SUMMARY/ABSTRACT Asthma prevalence in Puerto Ricans is 37% versus 12% for whites yet most studies have been conducted among the latter. This asthma burden extends to asthma morbidity and mortality, which are 2.4- and 4-fold higher among Puerto Ricans compared to whites, respectively. There is a strong association between severe, early-life viral respiratory illnesses and development of childhood recurrent wheeze and asthma. However, little is known about the mechanisms underlying these associations. Does airway dysfunction exist at birth and first manifest in early life as a severe illness in response to viral respiratory infections, and later as childhood asthma? Or does a severe, early-life respiratory illness injure a normal airway and precipitate asthma later in childhood? We will study Puerto Rican children to address these questions via three Specific Aims. Aim 1: Recruit a cohort of 3,000 newborns to longitudinally study the effects of early-life viral respiratory illnesses on nasal airway molecular endotype and risk for recurrent wheeze. We will collect yearly environmental, social, and clinical data on each participant and track all respiratory illnesses from birth to age 3. We will record severity and presence of wheezing in each child's illnesses and collect nasal swabs to determine the presence/type of virus associated with these illnesses. Aim 2: Identify viral and genetic determinants of severe early-life respiratory illnesses and whether the molecular state of the nasal airway epithelium at birth is predictive of these severe illnesses. We will perform transcriptomic and viral analyses on nasal airway swabs from subjects at birth and during respiratory illness. We will test if severe respiratory illnesses are associated with viral infection in general and/or infection with a specific viral species. We will use genome-wide genetic data to identify risk variants for severe early-life respiratory illnesses and variants influencing airway gene expression at birth and during illness (eQTLs). We will test for GxE interactions between top risk variants/eQTLs and infection with different viral species. We will also identify gene expression response to mild vs. severe early-life respiratory illnesses and determine if airway gene expression at birth is predictive of severe respiratory illness in early childhood. Aim 3: Determine the relationship between severity of early-life respiratory illness and post-illness but pre-asthma nasal airway gene expression profiles. We will perform transcriptomic and viral metagenomic analysis of nasal swabs collected from subjects at age 3. We will determine how severe respiratory illnesses affect the trajectory of airway gene expression profiles from birth to early childhood. Finally, we will determine if mild or severe respiratory illness in early life is predictive of recurrent wheeze at age 3. Our longitudinal birth cohort will [1] be the largest prospective study of minority infants, [2] provide novel and seminal information on genetic/viral risk factors for severe respiratory illnesses, and [3] identify airway endotypes that high-risk groups exhibit at birth and after respiratory illness, but prior to asthma onset. Our study will help to elucidate the relationship between early-life respiratory illness and asthma.

项目摘要/摘要波多黎各人的哮喘患病率为37％，而白人为12％，但大多数研究已经进行在后者中。这种哮喘负担扩展到哮喘发病率和死亡率，为2.4倍和4倍与白人相比，波多黎各人之间的更高。严重之间有很强的联系早期病毒呼吸道疾病以及儿童复发性喘息和哮喘的发展。但是，很少关于这些关联的基础机制已知。气道功能障碍在出生时是否存在在早期生命中表现为病毒呼吸道感染的严重疾病，后来是童年哮喘？或造成严重的早期呼吸系统疾病会伤害正常的气道并在以后沉淀哮喘童年？我们将通过三个特定目标来研究波多黎各儿童，以解决这些问题。目标1：招募一组3,000名新生儿，以纵向研究早期病毒呼吸道疾病的影响鼻气道分子内型和反复喘息的风险。我们将收集年度环境，社会，以及每个参与者的临床数据，并跟踪从出生到3岁的所有呼吸道疾病。我们将记录严重性和每个孩子病中喘息的存在并收集鼻拭子以确定与这些疾病相关的病毒的存在/类型。目标2：确定严重的病毒和遗传决定因素早期生命的呼吸道疾病以及出生时鼻气道上皮的分子状态是否为预测这些严重疾病。我们将对鼻气道拭子进行转录组和病毒分析来自出生时和呼吸系统疾病时的受试者。我们将测试是否有严重的呼吸系统疾病一般具有病毒感染和/或特定病毒物种感染。我们将使用全基因组遗传数据以识别严重早期生命呼吸系统疾病的风险变异和影响气道基因的变体出生时和疾病时表达（eqtls）。我们将测试最高风险之间的GXE相互作用变体/eqtls和不同病毒物种感染。我们还将确定基因表达对温和的反应与严重的早期生命呼吸道疾病，并确定出生时气道基因表达是否可以预测幼儿时期严重的呼吸道疾病。目标3：确定早期生命的严重程度之间的关系呼吸道疾病和胸膜后，但质子前鼻气道基因表达谱。我们将表演 3岁受试者收集的鼻拭子的转录组和病毒核分析。我们将确定从出生到气道基因表达谱的严重呼吸道疾病如何影响幼儿。最后，我们将确定早期的轻度或严重呼吸道疾病是否可以预测 3岁时的经常性喘息。我们的纵向出生队列将[1]是最大的前瞻性研究婴儿[2]提供有关严重呼吸系统疾病的遗传/病毒危险因素的新颖和开创性信息， [3]确定高危人群在出生时和呼吸道疾病后表现出的气道内型，但哮喘发作。我们的研究将有助于阐明早期呼吸系统疾病与哮喘之间的关系。