Genetic Epidemiology of Respiratory Function in Former Preterm Children

早产儿呼吸功能的遗传流行病学

• 批准号: 10318563
• 负责人: Lystra P. Hayden
• 金额: $ 19.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318563
• 关键词: 4 year old; Adult; Affect; Age-Months; Air; Area; Asthma; Biology; Birth Rate; Boston; Bronchopulmonary Dysplasia; Candidate Disease Gene; Caring; Child; Childhood; Childhood Asthma; Chronic Obstructive Pulmonary Disease; Clinic Visits; Clinical; Clinical Research; Complex; DNA Library; Data; Development Plans; Diagnosis; Doctor of Philosophy; Enrollment; Epidemiology; Fetal Lung; Future; Gene Expression Profiling; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genomics; Genotype; Gestational Age; Goals; Growth; Height; Heritability; Hospitals; Incidence; Infant; Investigation; Low Birth Weight Infant; Lung; Lung diseases; Measures; Medical; Medicine; Mentors; Morbidity - disease rate; Obstruction; Obstructive Lung Diseases; Outcome; Pathway Analysis; Pathway interactions; Patients; Pediatric Hospitals; Pediatrics; Physicians; Pneumonia; Population; Populations at Risk; Positioning Attribute; Predisposition; Premature Birth; Premature Infant; Prognosis; Prospective cohort; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Pulmonology; Records; Registries; Research; Research Design; Research Personnel; Research Project Grants; Respiratory Disease; Respiratory physiology; Risk; Sampling; Science; Single Nucleotide Polymorphism; Smoke; Smoking; Specimen; Steroids; Surveys; Swab; Training; Translations; Variant; Weight; Woman; Work; asthmatic; biobank; biomedical informatics; career; career development; chronic airflow obstruction; clinical epidemiology; clinical practice; clinical predictors; cohort; developmental disease; genetic epidemiology; genetic predictors; genetic variant; genome-wide; improved; instructor; interest; lung development; medical schools; patient oriented research; patient registry; premature; pulmonary function; recruit; research and development; respiratory; skills; standard of care; statistics; surfactant; treatment response; ventilation; young adult

PROJECT SUMMARY/ABSTRACT RESEARCH: The goal of this proposal is to investigate the clinical and genetic predictors of childhood respiratory disease in former preterm infants. We hypothesize that bronchopulmonary dysplasia (BPD), poor somatic growth, smoke exposure, and genetic variants will be associated with reduced lung growth and obstructive lung disease in former preterm infants. Furthermore, network analysis will reveal shared biology between BPD, chronic obstructive pulmonary disease (COPD), and asthma. The specific aims expand an existing patient registry, including over 780 former preterm infants with and without BPD who are followed at the Center for Healthy Infant Lung Development at Boston Children’s Hospital. This will include obtaining longitudinal lung function measures and survey data on smoke exposure, as well as initiating a DNA bank of buccal swab specimens. We will perform genome-wide genotyping, and examine specific associations with 48 single nucleotide polymorphisms (SNPs) known to be associated with COPD and lung function. We will leverage existing data from other populations with poor lung growth, and respiratory diseases including BPD, asthma, and COPD, to identify networks and pathways that may define lifelong susceptibility to reduced lung growth and obstructive lung disease, ultimately influencing prognosis, outcomes, and treatment response. This work will stimulate basic discoveries about the causes of BPD and COPD, and enable the translation of these discoveries into clinical practice. CANDIDATE: Lystra P. Hayden, MD, MMSc is a pediatric pulmonologist, Instructor of Pediatrics at Harvard Medical School (HMS) in the Division of Respiratory Disease of Boston Children’s Hospital (BCH) and an Associate Physician at the Channing Division of Network Medicine (CDNM) at Brigham and Women’s Hospital (BWH). She received a Master’s of Medical Science in Biomedical Informatics from HMS. At the CDNM she has been pursing epidemiologic and genomic investigations into the early origins of complex respiratory diseases, specifically COPD, with particular interest in the influences of smoke exposure, pneumonia, asthma and prematurity. Dr. Hayden plans to develop her career in the field of academic pediatric pulmonology as an independent researcher using genomics to elucidate the early origins of pulmonary disease with a focus on BPD, a population which may progress to future COPD patients. ENVIRONMENT: Dr. Hayden will perform her research and career development at the CDNM of BWH, and her clinical work, including subject recruitment, at The Center for Healthy Infant Lung Development in the Division of Respiratory Diseases at BCH. She will be mentored by Craig P. Hersh, MD, MPH, and Edwin K. Silverman, MD, PhD, both leaders in the field of COPD genetic epidemiology and experts in clinical research with excellent track records of mentoring young investigators towards independent research careers.

项目摘要/摘要 研究：这项建议的目标是调查儿童的临床和遗传预测因素 先前早产儿的呼吸系统疾病。我们假设支气管肺发育不良(BPD)， 躯体生长、烟雾暴露和基因变异将与肺生长减慢和 既往早产儿的阻塞性肺病。此外，网络分析将揭示共享的生物 BPD、慢性阻塞性肺疾病(COPD)和哮喘之间的关系。具体目标是扩大和 现有患者登记，包括780多名患有和不患有BPD的前早产儿，他们在 波士顿儿童医院的健康婴儿肺发育中心。这将包括获得 纵向肺功能测量和吸烟暴露的调查数据，以及启动 口腔拭子样本。我们将进行全基因组基因分型，并检查与48个 已知的单核苷酸多态(SNPs)与COPD和肺功能相关。我们会 利用来自其他肺生长不良人群和包括BPD在内的呼吸系统疾病的现有数据， 哮喘和慢性阻塞性肺病，以确定可能定义终身肺部易感性的网络和途径 生长和阻塞性肺疾病，最终影响预后、结果和治疗反应。这 这项工作将促进对BPD和COPD病因的基本发现，并使这些发现得以转化 将这些发现转化为临床实践。 候选人：Lystra P.Hayden，医学博士，医学硕士，儿科肺病专家，哈佛大学儿科学讲师 波士顿儿童医院(BCH)呼吸科医学院(HMS) 布里格姆妇女医院网络医学部(CDNM)钱宁科副医生 (BWH)。她获得了HMS的生物医学信息学医学硕士学位。在CDNM她 一直在寻求对复杂呼吸道疾病早期起源的流行病学和基因组研究 疾病，特别是慢性阻塞性肺病，特别关注烟雾暴露、肺炎、哮喘的影响 和早产儿。海登医生计划在儿科肺病学术领域发展她的职业生涯 独立研究人员使用基因组学阐明肺部疾病的早期起源，重点是 BPD，这一人群可能会发展为未来的COPD患者。 环境：海登博士将在BWH的CDNM进行她的研究和职业发展 她的临床工作，包括受试者招募，在健康的婴儿肺发育中心 英国皇家儿科医院呼吸科。她的导师是克雷格·P·赫什，医学博士，公共卫生硕士和埃德温·K。 Silverman，医学博士，COPD遗传流行病学领域的领导者和临床研究的专家 在指导年轻研究人员走向独立研究事业方面有着良好的记录。

项目成果

Obstructive sleep apnea is associated with use of assisted ventilation among children with bronchopulmonary dysplasia hospitalized with respiratory illness: A nationwide inpatient cohort.

阻塞性睡眠呼吸暂停与因呼吸系统疾病住院的支气管肺发育不良儿童使用辅助通气相关：全国住院患者队列。

• DOI: 10.1016/j.sleep.2023.06.030
• 发表时间: 2023
• 期刊: Sleep medicine
• 影响因子: 4.8
• 作者: Tsou,Po-Yang;Hayden,LystraP
• 通讯作者: Hayden,LystraP

Comparison of Pneumotachometer and Portable Digital Turbine Spirometry for Field-Based Assessment: An Air Quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia Study.

用于现场评估的呼吸速度计和便携式数字涡轮肺量计的比较：支气管肺发育不良研究中的空气质量、环境和呼吸结果。

• DOI: 10.1089/ped.2023.0046
• 发表时间: 2023
• 期刊: Pediatric allergy, immunology, and pulmonology
• 作者: Mukharesh,Lana;Ryan,Morgan;Hayden,LystraP;Dahlberg,SuzanneE;Gaffin,JonathanM
• 通讯作者: Gaffin,JonathanM

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study.

• DOI: 10.1186/s12931-018-0890-0
• 发表时间: 2018-10-29
• 期刊: Respiratory research
• 影响因子: 5.8
• 作者: Hayden LP;Cho MH;Raby BA;Beaty TH;Silverman EK;Hersh CP;COPDGene Investigators
• 通讯作者: COPDGene Investigators

Characteristics of infants or children presenting to outpatient bronchopulmonary dysplasia clinics in the United States.

• DOI: 10.1002/ppul.25332
• 发表时间: 2021-06
• 期刊: Pediatric pulmonology
• 影响因子: 3.1
• 作者: Collaco JM;Agarwal A;Austin ED;Hayden LP;Lai K;Levin J;Manimtim WM;Moore PE;Sheils CA;Tracy MC;Alexiou S;Baker CD;Cristea AI;Fierro JL;Rhein LM;Villafranco N;Nelin LD;McGrath-Morrow SA
• 通讯作者: McGrath-Morrow SA

Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia.

• DOI: 10.1016/j.jpeds.2022.06.037
• 发表时间: 2022-10
• 期刊: JOURNAL OF PEDIATRICS
• 影响因子: 5.1
• 作者: McGrath-Morrow, Sharon A.;Agarwal, Amit;Alexiou, Stamatia;Austin, Eric D.;Fierro, Julie L.;Hayden, Lystra P.;Lai, Khanh;Levin, Jonathan C.;Manimtim, Winston M.;Moore, Paul E.;Rhein, Lawrence M.;Rice, Jessica L.;Sheils, Catherine A.;Tracy, Michael C.;Bansal, Manvi;Baker, Christopher D.;Cristea, A. Ioana;Popova, Antonia P.;Siddaiah, Roopa;Villafranco, Natalie;Nelin, Leif D.;Collaco, Joseph M.
• 通讯作者: Collaco, Joseph M.