Clinical prediction and epigenetic regulation of asthma and rhinitis

哮喘和鼻炎的临床预测和表观遗传调控

• 批准号: 10559562
• 负责人: Alberta L. Wang
• 金额: $ 19.51万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-10 至 2023-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10559562
• 关键词: 6 year old; Advisory Committees; Affect; Allergic; Allergic Disease; Applications Grants; Asthma; Biological; Biological Markers; Biological Process; Characteristics; Child; Childhood; Childhood Asthma; Clinical; Clinical Data; Computer Analysis; Data; Development; Development Plans; Disease; Disease Progression; Early identification; Epidemiology; Epigenetic Process; Functional disorder; Future; GAB2 gene; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Goals; Grant; Hospitals; Household; Hypersensitivity; IgE; Immune signaling; Income; Individual; Institution; Intervention; Investigation; Knowledge; Life; Link; Longitudinal Studies; Low Birth Weight Infant; Manuscripts; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Messenger RNA; MicroRNAs; Monitor; Multiomic Data; Nasal Epithelium; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pediatric cohort; Peripheral; Persons; Positioning Attribute; Preparation; Prognostic Marker; Regulation; Research; Research Personnel; Research Proposals; Resources; Respiratory Disease; Rhinitis; Risk; Risk Factors; Role; Scientist; Serum; Severity of illness; Statistical Data Interpretation; Symptoms; T-Cell Development; TCF7L2 gene; Testing; Therapeutic Intervention; Tissues; Vitamin D; Whole Blood; Woman; Work; antenatal; asthma exacerbation; asthma model; asthmatic; atopy; candidate identification; career; career development; chronic respiratory disease; circulating microRNA; clinical phenotype; clinical predictive model; clinical predictors; clinical prognostic; clinical risk; cohort; comorbidity; differential expression; early childhood; epigenetic regulation; experience; high risk; improved; insight; machine learning classification; new therapeutic target; patient oriented research; peripheral blood; predictive marker; preventive intervention; prognostic tool; programs; prospective; recruit; research and development; skills; supervised learning; symposium; therapeutic miRNA; transcriptome; unsupervised learning

Asthma and rhinitis share a strong genetic component and are the most common chronic respiratory diseases worldwide affecting 339 million and 500 million people, respectively. Both allergic and non-allergic rhinitis are well-studied risk factors for the development of asthma, independent of atopy and IgE sensitization, and up to 80% of asthmatics have concomitant rhinitis. Conversely, asthma is also a risk factor for the development of rhinitis suggesting a common pathophysiological link between the upper and lower airways. Individuals with comorbid asthma and rhinitis are more likely to experience frequent and severe asthma exacerbations. Currently, an unmet need exists in the understanding of the comorbid development of asthma and rhinitis, including which patients are at risk and why patients with comorbid disease have increased disease severity. microRNAs (miRNAs) have emerged as important predictive biomarkers and regulators of the pathogenesis of asthma and rhinitis. However, the role of miRNA-messenger RNA (mRNA) regulatory networks in asthma with comorbid rhinitis is not known. The overall hypothesis of this K23 award proposal is that the comorbid development of asthma and rhinitis can be predicted by clinical factors and is regulated by miRNA-mRNA networks. Specific Aim 1 will evaluate the early childhood clinical prediction of the development of comorbid disease in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohorts and create a validated clinical prognostic tool to identify high-risk children who may benefit from early monitoring and interventions. Specific Aim 2 will identify the unique miRNA-mRNA pathways and regulatory networks in the peripheral blood that regulate asthma with comorbid rhinitis in children from the VDAART, BAMSE, and Childhood Asthma Management Program (CAMP) cohorts to identify candidate miRNAs and biological pathways that may serve as future targets of miRNA-based therapies and biomarkers. Specific Aim 3 will prospectively validate the miRNA-mRNA signature of asthma with comorbid rhinitis across the peripheral whole blood and local nasal epithelium in subjects recruited from Brigham and Women’s Hospital to identify the shared and tissue-specific pathogenic pathways in the peripheral blood and local primary airway tissue. Through this K23 award proposal, the candidate will complete an integrated plan of mentorship, coursework, conferences, patient-oriented research, statistical and computational analyses, manuscript submissions, and R01 grant preparation. She will develop new knowledge and skills in clinical, translational, and computational research and generate new hypotheses and data that will provide the basis for future independent lines of investigation. With the support of her division, mentors, and scientific advisory committee and the resources available at her institution, the candidate is ideally positioned to achieve her goal of becoming a successful independent investigator in the epidemiology and epigenetics of asthma and allergic diseases.

哮喘和鼻炎有很强的遗传成分，是最常见的慢性呼吸道疾病 全球分别有3.39亿人和5亿人受到影响。过敏性鼻炎的危害有哪些？ 研究充分的哮喘发生的危险因素，独立于特应性和IgE致敏， 80%的哮喘患者伴有鼻炎。相反，哮喘也是发展成 鼻炎表明上呼吸道和下呼吸道之间存在共同的病理生理学联系。人士 哮喘和鼻炎共病更可能经历频繁和严重的哮喘恶化。 目前，在理解哮喘和鼻炎的共病发展方面存在未满足的需求， 包括哪些患者处于风险中以及为什么患有共病的患者具有增加的疾病严重性。 microRNAs（miRNAs）已成为重要的预测性生物标志物和调节剂的发病机制， 哮喘和鼻炎。然而，miRNA-信使RNA（mRNA）调控网络在哮喘中的作用， 共病鼻炎尚不清楚。这项K23奖励提案的总体假设是， 哮喘和鼻炎的发生可通过临床因素预测，并受miRNA-mRNA的调节 网络.具体目标1将评估儿童早期临床预测共病的发展， 维生素D治疗哮喘减少试验（VDAART）和儿童，过敏，环境， 斯德哥尔摩，流行病学（BAMSE）队列，并创建一个有效的临床预后工具，以确定高风险 可能受益于早期监测和干预的儿童。具体目标2将确定独特的 外周血中的miRNA-mRNA通路和调节网络调节哮喘与共病 VDAART、BAMSE和儿童哮喘管理项目（CAMP）队列中儿童的鼻炎 鉴定候选miRNAs和生物学途径，这些可能作为基于miRNAs的 治疗和生物标志物。特异性目标3将前瞻性验证哮喘的miRNA-mRNA特征 在招募的受试者中，外周全血和局部鼻上皮共病鼻炎 布里格姆妇女医院，以确定共同的和组织特异性的致病途径，在 外周血和局部主要气道组织。通过K23奖项提案，候选人将 完成导师，课程，会议，以病人为导向的研究，统计和 计算分析、手稿提交和R 01资助准备。她将发展新的知识 临床，转化和计算研究的技能，并产生新的假设和数据， 为今后的独立调查提供基础。在她所在部门、导师和 科学咨询委员会和她所在机构的可用资源，候选人是理想的定位 为了实现她的目标，成为一个成功的独立调查员在流行病学和表观遗传学的， 哮喘和过敏性疾病。

项目成果

Assessment of the quality of mobile apps for food allergy.

• DOI: 10.1016/j.jaip.2022.02.015
• 发表时间: 2022-06
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
• 影响因子: 9.4
• 作者: Wu, Allison C.;Walsh, Ryan;Wang, Alberta L.
• 通讯作者: Wang, Alberta L.

Preventing Anaphylaxis in College Students With Food Allergies.

预防食物过敏大学生的过敏反应。

• DOI: 10.1016/j.jaip.2023.02.004
• 发表时间: 2023
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Wu,AllisonC;Wang,AlbertaL
• 通讯作者: Wang,AlbertaL