Gender-based precision care for asthma

基于性别的哮喘精准护理

• 批准号: 10223404
• 负责人: Joe Zein
• 金额: $ 13.41万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-07 至 2023-06-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223404
• 关键词: 5q31; Adrenal Cortex Hormones; Adult; Affect; Age; American; Area; Asthma; Award; Biochemical Pathway; Biological; Body mass index; Candidate Disease Gene; Characteristics; Child; Childhood Asthma; Cilia; Clinic; Clinical; Clinical Research; Data; Data Set; Databases; Development; Development Plans; Dose; Drug Targeting; Education; Endocrinology; Environment; Epidemiology; Epithelial Cells; Estradiol; European; Exhibits; Female; Foundations; GTP-Binding Protein alpha Subunits, Gs; Gender; Genes; Genetic; Genetic Risk; Genetic Transcription; Genomics; Glucocorticoids; Glutamine; Goals; Gonadal Steroid Hormones; Hormonal; IRF1 gene; Immunity; Incidence; Inhalation; Interferons; Isoleucine; Knowledge; Laboratories; Life Cycle Stages; Linear Regressions; Longevity; Menopause; Mentors; Mucociliary Clearance; National Heart, Lung, and Blood Institute; Natural History; Outcome; Participant; Pathogenesis; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Physicians; Predisposition; Prevalence; Productivity; Progesterone; Proteins; Puberty; Pulmonary Function Test/Forced Expiratory Volume 1; Reporting; Research; Research Institute; Research Proposals; Risk; Role; Scientist; Severities; Sex Differences; Single Nucleotide Polymorphism; Subgroup; Testing; Testosterone; Time; Ubiquitin; Variant; Vocational Guidance; Woman; activating transcription factor 1; airway obstruction; asthmatic; base; boys; career; career development; cohort; epidemiology study; experience; female sex hormone; gender difference; genetic association; genetic epidemiology; genetic variant; genome wide association study; genome-wide; genomic locus; girls; improved; innovation; male; men; middle age; patient oriented; personalized care; programs; pulmonary function; response; risk variant; sex; success; tiotropium bromide; whole genome

ABSTRACT Asthma affects boys more than girls, but gender-switch occurs after puberty and asthma is more common in women than men. This research proposal investigates gender effect(s) on asthma severity. The long-term goal of our studies is to identify sex related differences in genetic risks and biological pathways of severe asthma. Our analyses of large databases reveal that severe asthma exhibits a bimodal peak in young boys and middle age women [1, 2], which pointes to sex hormones in mechanisms of asthma severity [1]. Preliminary data of sex hormone levels in participants with asthma from the Severe Asthma Research Program (SARP Iⅈ 2001- 2012) shows that men with both low progesterone and low testosterone and women with low testosterone and high estradiol have the most severe airflow limitation. Additionally, our genome-wide association analyses of single nucleotide polymorphism (SNP) x sex interaction and candidate gene analyses of European American adults with asthma in SARP I & II shows sex-specific genetic associations with percent predicted FEV1, a marker of severe asthma. Based on the findings, we hypothesize that risk of severe asthma is gender dependent due to variation in levels of male and/or female sex hormones over the lifecourse and the consequent interactions of sex hormones with asthma risk variants that result in a bimodal peak of severe asthma in boys and women. In aim 1, we will assess SNP × sex interactions across the whole genome using genome wide interaction study (GWIS). We will also use a candidate gene approach, which will determine SNP x sex interactions in previously described asthma severity gene loci, such as lung function and immunity pathway genes. In aim 2, we investigate the effect of variations in sex hormone levels on the risk for severe asthma differentially in males and females. Equally important and parallel to the research plan, the career development plan is constructed for didactic coursework, one-on-one education and career guidance from strong mentors and collaborators expert in asthma, endocrinology, and analytical genetics. This research will be performed in the laboratory of Dr. Erzurum, Lerner Research Institute (LRI), Cleveland Clinic, and will be advised by experts in genomics and biochemical pathways unique to asthma. The LRI offers the ideal intellectual and research environment for success. The proposed research is innovative and significant as it may lay the groundwork for the care of patients with severe asthma in a personalized, gender specific way. Altogether the award will provide the candidate the knowledge, hands-on experience, expertise and productivity to develop into an independent physician-scientist focused on patient-centered mechanistic research.

摘要

项目成果

Beyond tobacco - the secondary impact of substance misuse in chronic obstructive lung disease.

• DOI: 10.1080/02770903.2020.1847932
• 发表时间: 2022-03
• 期刊: The Journal of asthma : official journal of the Association for the Care of Asthma
• 作者: Macmurdo M;Lopez R;Udeh BL;Zein J
• 通讯作者: Zein J

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19.

• DOI: 10.1371/journal.pbio.3000970
• 发表时间: 2020-11
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Zhou Y;Hou Y;Shen J;Mehra R;Kallianpur A;Culver DA;Gack MU;Farha S;Zein J;Comhair S;Fiocchi C;Stappenbeck T;Chan T;Eng C;Jung JU;Jehi L;Erzurum S;Cheng F
• 通讯作者: Cheng F

Alcohol use disorder and healthcare utilization in patients with chronic asthma and obstructive lung disease.

• DOI: 10.1016/j.alcohol.2021.03.002
• 发表时间: 2021-06
• 期刊: Alcohol (Fayetteville, N.Y.)
• 作者: MacMurdo M;Lopez R;Udeh BL;Zein JG
• 通讯作者: Zein JG

Eosinophilia Is Associated with Improved COVID-19 Outcomes in Inhaled Corticosteroid-Treated Patients.

• DOI: 10.1016/j.jaip.2021.12.034
• 发表时间: 2022-03
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Zein JG;Strauss R;Attaway AH;Hu B;Milinovich A;Jawhari N;Chamat SS;Ortega VE
• 通讯作者: Ortega VE

Dietary patterns in patients with asthma and their relationship with asthma-related emergency room visits: NHANES 2005-2016.

哮喘患者的饮食模式及其与哮喘相关急诊室就诊的关系：NHANES 2005-2016。

• DOI: 10.1080/02770903.2021.1984529
• 发表时间: 2022
• 期刊: The Journal of asthma : official journal of the Association for the Care of Asthma
• 作者: Zhang,Peng;Lopez,Rocio;Arrigain,Susana;Rath,Mary;Khatri,SumitaB;Zein,JoeG
• 通讯作者: Zein,JoeG