Enterolactone and asthma

肠内酯与哮喘

• 批准号: 10091388
• 负责人: Juan Carlos Cardet
• 金额: $ 19.28万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091388
• 关键词: A549; Adrenal Cortex Hormones; Adult; Affect; American; Anti-Inflammatory Agents; Antiinflammatory Effect; Antioxidants; Area; Asthma; Attenuated; Award; B-Lymphocytes; Basic Science; Biochemical; Biological; Biological Markers; Biometry; Bronchial Spasm; Bronchoscopy; Cell model; Cells; Cellular Structures; Chemicals; Clinical; Clinical Research; Data; Data Analyses; Data Set; Dietary Intervention; Dietary Lignans; Disease; Emergency department visit; Enrollment; Environment; Epithelial Cells; Exposure to; Extrinsic asthma; F2-Isoprostanes; Funding; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Healthcare; Histologic; Hospitalization; Human; In Vitro; Inbred BALB C Mice; Inflammation; Interleukin-6; Interleukin-8; Intervention Trial; Israel; Lead; Lignans; Longitudinal cohort; Measures; Mentors; Mentorship; Morbidity - disease rate; National Health and Nutrition Examination Survey; National Heart, Lung, and Blood Institute; Nature; Outcome; Oxidants; Oxidative Stress; Participant; Patients; Phenotype; Physicians; Physiological; Plants; Population; Positioning Attribute; Prevalence; Property; Public Health; Publishing; Reporting; Research; Research Design; Research Personnel; Role; Sampling; Scientist; Serum amyloid A protein; Severities; Structure; Techniques; Time; Training; Translational Research; Translations; United States National Institutes of Health; Urine; Work; airway epithelium; airway inflammation; asthma model; bacterial metabolism; career; career development; cohort; cost; design; dietary; enterolactone; experience; experimental study; follow-up; gut microbiome; in vivo; laboratory experiment; microbiome composition; mortality; mouse model; novel; nutrition; oxidation; patient oriented research; pediatric patients; programs; prospective; public health relevance; research and development; skills; systemic inflammatory response; translational scientist

Project Summary/Abstract 1  This proposal details a 5-yr plan to prepare the candidate, Juan C. Cardet MD, for a career as an 2  independent, translational investigator positioned to impact our understanding of asthma. The aim is to clarify 3  the relationship between enterolactone and asthma through complementary clinical and basic strategies. 4  Lignans are dietary, plant-derived chemicals with anti-inflammatory and antioxidant properties. Enterolactone 5  is the end product of human gut bacterial metabolism of lignans. Differences in gut microbiome composition 6  categorize patients into high- vs. low-enterolactone producers. This group reported concentration-dependent 7  inverse associations between enterolactone and asthma in a nationally-representative cohort (NHANES); but 8  this study is limited by its cross-sectional design and incomplete clinical characterization. We hypothesize 9  that enterolactone's inverse relationship with asthma is driven by its anti-inflammatory and anti- 10  oxidative properties. The candidate will clarify whether enterolactone has a clinically-evident relationship 11  with asthma by analyzing data from the NHLBI Severe Asthma Research Program's (SARP) prospective 12  study. As a founding partnership in SARP, our group has access to stored biospecimens and participants' 13  clinical, biochemical, and physiological data collected during 3 years of follow-up. Further, the candidate 14  will employ in vitro and in vivo approaches to determine enterolactone's effects on human airway structural 15  cells and murine models of asthma. Preliminary data by Cardet et al suggest that enterolactone may have 16  anti-inflammatory effects on A549 human airway epithelial cells, observations this group will extend through 17  this proposal. Clinical findings will steer the focus of laboratory experiments, and reversely, discoveries at the 18  bench will generate clinical questions. At this project's conclusion, the candidate will be skillful with (1) 19  sophisticated biostatistical analyses on clinical datasets such as SARP's; and with designing, conducting, and 20  interpreting experiments on (2) airway structural cells (3) and murine models of asthma. 21  During the award period, the candidate will leverage his clinical experience with asthma, regular exposure to 22  NIH research networks, and structured academics at the HSPH's MPH program. This training will allow him to 23  transition to independence during the 4-5th years of the award. Dr. Cardet will work under the 1° mentorship of 24  Dr. Elliot Israel, an expert in translation asthma research with an excellent mentoring record. He will have as 25  co-mentors Drs. Quan Lu and Stephanie Shore, who will train Dr. Cardet to master the basic experiments 26  described herein (see `Research Strategy, Aim 2'). Further, Dr. Cardet has assembled a team of 27  extraordinary physician-scientists (Drs. Joshua Boyce, Bruce Levy, and Wanda Phipatanakul), who have 28  committed their time and expertise to assist his career development and research goals. Their mentorship, the 29  scientific-clinical environment at BWH and HSPH, and the proposed research goals and career development 30  plan will position the candidate to establish himself as an independent translational asthma researcher.

项目概要/摘要 1 该提案详细介绍了一个 5 年计划，旨在帮助候选人 Juan C. Cardet MD 为职业生涯做好准备 2 独立的转化研究者旨在影响我们对哮喘的理解。 3 通过补充临床和基本策略来了解肠内酯与哮喘之间的关系。 4 木酚素是一种膳食植物来源的化学物质，具有抗炎和抗氧化特性。 图5是人体肠道细菌代谢木脂素的终产物肠道微生物组成的差异。 6 类患者分为高肠内酯生产者和低肠内酯生产者。该组报告了浓度依赖性。 7 在全国代表性队列 (NHANES) 中，肠内酯与哮喘之间呈负相关； 8 这项研究因其横断面设计和不完整的临床特征而受到限制。 9 肠内酯与哮喘的反比关系是由其抗炎和抗炎作用驱动的 10 氧化特性。考生将阐明肠内酯是否具有临床上明显的关系。 通过分析 NHLBI 严重哮喘研究计划 (SARP) 前瞻性数据，发现 11 例哮喘患者 12 研究作为 SARP 的创始合作伙伴，我们的团队可以访问存储的生物样本和参与者的数据。 13 3 年随访期间收集的临床、生化和生理数据。 14 将采用体外和体内方法来确定肠内酯对人体气道结构的影响 Cardet 等人的 15 细胞和小鼠哮喘模型的初步数据表明肠内酯可能具有 16 对 A549 人气道上皮细胞的抗炎作用，该小组的观察结果将延伸至 17 该提案将引导实验室实验的重点，反之亦然。 18 台将提出临床问题，在该项目结束时，候选人将熟练掌握 (1)。 19 对临床数据集（例如 SARP）进行复杂的生物统计分析，并进行设计、实施和分析； 20 解释 (2) 气道结构细胞 (3) 和小鼠哮喘模型的实验。 21 在奖励期间，候选人将利用他的哮喘临床经验、定期接触 22 美国国立卫生研究院 (NIH) 研究网络以及 HSPH 公共卫生硕士项目的结构性学者 这次培训将使他能够 23 在获奖的 4-5 年期间，Cardet 博士将在 1° 的指导下过渡到独立。 24 埃利奥特·伊斯雷尔 (Elliot Israel) 博士是转化性哮喘研究专家，拥有出色的指导记录。 25 位联合导师 Quan Lu 博士和 Stephanie Shore 博士将培训 Cardet 博士掌握基本实验 26 此处描述（参见“研究策略，目标 2”）。此外，Cardet 博士还组建了一个团队。 27 位杰出的医学科学家（Joshua Boyce 博士、Bruce Levy 博士和 Wanda Phipatanakul 博士）， 28 投入了时间和专业知识来协助他的职业发展和研究目标。 29 BWH 和 HSPH 的科学临床环境，以及拟议的研究目标和职业发展 30 计划将使候选人成为一名独立的转化性哮喘研究者。

项目成果

Hormonal Effects on Asthma, Rhinitis, and Eczema.

• DOI: 10.1016/j.jaip.2022.04.002
• 发表时间: 2022-08
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
• 影响因子: 9.4
• 作者: Weare-Regales, Natalia;Chiarella, Sergio E.;Cardet, Juan Carlos;Prakash, Y. S.;Lockey, Richard F.
• 通讯作者: Lockey, Richard F.

Socioeconomic impact of COVID-19 and willingness to be vaccinated in African American/Black and Hispanic/Latinx adults.

• DOI: 10.1016/j.jnma.2021.12.010
• 发表时间: 2022-04
• 期刊: Journal of the National Medical Association
• 影响因子: 3.3
• 作者: Carroll JK;Arias Hernandez P;Brooks-Greisen A;Carlos Cardet J;Cui J;Ericson B;Fagan M;Fajt ML;Forth VE;Fuhlbrigge AL;Lorenzi M;Rodriguez-Louis J;Maher NE;Manning BK;Pace WD;Shields JB;Israel E
• 通讯作者: Israel E

Reply.

回复。

• DOI: 10.1002/art.40923
• 发表时间: 2019
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Kim,AlfredHJ;Strand,Vibeke;Atkinson,JohnP
• 通讯作者: Atkinson,JohnP

A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial.

• DOI: 10.1016/j.cct.2020.106246
• 发表时间: 2021-03
• 期刊: Contemporary clinical trials
• 影响因子: 2.2
• 作者: Israel E;Cardet JC;Carroll JK;Fuhlbrigge AL;Pace WD;Maher NE;She L;Rockhold FW;Fagan M;Forth VE;Hernandez PA;Manning BK;Rodriguez-Louis J;Shields JB;Coyne-Beasley T;Kaplan BM;Rand CS;Morales-Cosme W;Wechsler ME;Wisnivesky JP;White M;Yawn BP;McKee MD;Busse PJ;Kaelber DC;Nazario S;Hernandez ML;Apter AJ;Chang KL;Pinto-Plata V;Stranges PM;Hurley LP;Trevor J;Casale TB;Chupp G;Riley IL;Shenoy K;Pasarica M;Calderon-Candelario RA;Tapp H;Baydur A
• 通讯作者: Baydur A

"As-Needed" Inhaled Corticosteroids for Patients With Asthma.

哮喘患者“按需”吸入皮质类固醇。

• DOI: 10.1016/j.jaip.2023.01.010
• 发表时间: 2023
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Cardet,JuanCarlos;Papi,Alberto;Reddel,HelenK
• 通讯作者: Reddel,HelenK