IL-6 high phenotype in childhood asthma
儿童哮喘中 IL-6 高表型
基本信息
- 批准号:10215498
- 负责人:
- 金额:$ 24.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-13 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbsenteeismAcademic Medical CentersAddressAdipocytesAdultAffectAfrican AmericanAgeAmericanAsthmaAttenuatedBiological MarkersBody mass indexChicagoChildChildhoodChildhood AsthmaChronic DiseaseClinicalClinical DataCommunitiesDiabetes MellitusDiseaseEnzyme-Linked Immunosorbent AssayEosinophiliaExhalationGenderHealthcareHeightHigh PrevalenceHypertensionIgEInflammatoryInterleukin-6InterventionLongitudinal StudiesMeasuresMediator of activation proteinMulti-Institutional Clinical TrialNeighborhoodsNitric OxideObesityObservational StudyPatientsPediatric HospitalsPhenotypePlasmaPrevalenceProductionPublishingRaceRecording of previous eventsRegistriesResearchRiskRoleSchoolsSerumSeveritiesSideSpirometryTenuateTestingTherapeutic InterventionTherapeutic TrialsUrban HealthVulnerable PopulationsWomanWorkairway inflammationasthma exacerbationasthmatic patientatopyblack patientcohortcommunity engagementcommunity organizationscomorbidityeosinophilhigh body mass indexinner citylower income familiesmacrophagemenminority childrenmultidisciplinaryobesity in childrenprogramspulmonary functionreceptorrecruitsystemic inflammatory responsetargeted treatmenturban children
项目摘要
PROJECT SUMMARY
Asthma, now the most common chronic disease in childhood, disproportionately burdens minority children and
children from low-income families. Obesity, also a prevalent disorder in children, increases the risk of asthma
in adults. Systemic inflammation related to obesity, via production of mediators such as interleukin-6 (IL-6) by
adipocytes and macrophages, may worsen airway inflammation. Recent studies in adult patients with asthma
suggest the existence of a new “IL-6 high phenotype” characterized by high concentrations of plasma IL-6.
Adults in this phenotype have a higher body mass index (BMI), a higher prevalence of diabetes and hyperten-
sion, worse lung function, and a greater number of asthma exacerbations. We recently performed a study in
adults that corroborated the existence of the IL-6 high phenotype in both black and white patients with asthma;
our study shows that this phenotype occurs almost exclusively in the “T2-low phenotype” and correlates with
BMI. This study and other recent work clearly suggests the clinical importance of this phenotype and sets the
stage for anti-IL-6 therapeutic trials in adults with asthma. However, whether a similar IL-6 high phenotype ex-
ists in children with asthma, and particularly whether this is related to obesity, is not known. Our major objec-
tive is to determine whether an IL-6 high phenotype exists in children with asthma, and if so, whether this is
associated with obesity. Prior to embarking on major multi-center clinical trials, a clear demonstration of this
phenotype is required. We propose a single-center, observational study that focuses on children ages 6 to 17
with asthma in an urban, academic medical center and surrounding community. We will use a registry of such
children, carefully characterized for asthma severity, atopy status, BMI, co-morbidities, and key clinical param-
eters such as spirometry, serum IgE, and blood eosinophils, combined with community engagement in the
south side of Chicago to recruit 100 normal-weighted and obese children, and will recruit 50 normal-weighted
and obese children without known disease to serve as contrtols. Clinical data, BMI, spirometry, and biomarkers
such as serum IgE, blood eosinophil count and exhaled nitric oxide will be compared to plasma IL-6 concentra-
tions. Race-adjusted threshold values for plasma IL-6 will be established in the non-asthmatic children. We will
determine whether this phenotype exists in pediatric asthma and, if so, whether the children with high IL-6 are
separated from T2-high children, and whether obesity, defined as a BMI > 85th percentile for age and height, is
associated with higher IL-6 concentrations. Demonstration of a IL-6 high phenotype in children with asthma in
a single-center, observational trial will lead to larger studies that determine associations between IL-6, obesity,
and asthma control, particularly in urban and minority children. Such studies will lay the ground-work for thera-
peutic interventions that target IL-6 to attenuate airway inflammation and gain better control of poorly-controlled
asthma in a vulnerable population, thereby providing a substantial benefit to health care.
项目总结
哮喘,现在是儿童最常见的慢性病,给少数族裔儿童造成了不成比例的负担
来自低收入家庭的儿童。肥胖也是儿童中的一种普遍疾病,它增加了患哮喘的风险
在成年人身上。与肥胖相关的全身炎症,通过产生白细胞介素6(IL-6)等介质
脂肪细胞和巨噬细胞,可能会加重呼吸道炎症。成人哮喘患者的最新研究
提示存在一种新的以血浆IL-6浓度较高为特征的“IL-6高表型”。
这种表型的成年人有更高的体重指数(BMI),更高的糖尿病和高血压患病率-
锡安,肺功能变差,以及更多的哮喘恶化。我们最近进行了一项研究,
证实在黑人和白人哮喘患者中存在IL-6高表型的成年人;
我们的研究表明,这种表型几乎只出现在T2-Low表型中,并与
体重指数。这项研究和其他最近的工作清楚地表明了这种表型的临床重要性,并设置了
成人哮喘患者的抗IL-6治疗试验阶段。然而,类似的IL-6高表型是否存在于
哮喘儿童的风险,特别是这是否与肥胖有关,目前尚不清楚。我们的主要目标-
目的是确定哮喘儿童是否存在IL-6高表型,如果存在,这是否
与肥胖有关。在开始主要的多中心临床试验之前,清楚地证明这一点
表型是必填项。我们建议对6至17岁的儿童进行一项单中心观察性研究。
患有哮喘的人在城市、学术医疗中心和周围社区。我们将使用此类注册表
儿童,仔细描述哮喘严重程度、过敏状态、体重指数、合并症和关键临床参数-
肺活量、血清IgE和血嗜酸性粒细胞等指标,结合社区参与
芝加哥南区招募100名体重正常和肥胖的儿童,并将招募50名体重正常的儿童
以及没有已知疾病的肥胖儿童作为对照组。临床资料、体重指数、肺活量测定和生物标记物
如血清IgE、血嗜酸性粒细胞计数和呼出的一氧化氮将与血浆IL-6浓度进行比较。
特兹。将在非哮喘儿童中建立经种族调整的血浆IL-6阈值。我们会
确定这种表型在儿童哮喘中是否存在,如果存在,则确定高IL-6儿童是否
从高T2的儿童中分离出来,以及肥胖,定义为年龄和身高的BMI;85%,是否
与较高的IL-6浓度有关。儿童哮喘患者IL-6高表型的研究
一项单中心的观察性试验将导致更大规模的研究,确定IL-6、肥胖、
和哮喘控制,特别是在城市和少数民族儿童中。这些研究将为Thera-
针对IL-6的早期干预以减轻呼吸道炎症并更好地控制控制不良
在脆弱人群中减少哮喘,从而为卫生保健提供实质性的好处。
项目成果
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Christina Elizabeth Ciaccio其他文献
Christina Elizabeth Ciaccio的其他文献
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{{ truncateString('Christina Elizabeth Ciaccio', 18)}}的其他基金
Prenatal Fatty Acid Supplementation and Early Childhood Asthma and Atopy in Black American Families
美国黑人家庭产前脂肪酸补充剂与儿童早期哮喘和特应性
- 批准号:
10586398 - 财政年份:2023
- 资助金额:
$ 24.3万 - 项目类别:
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