IL-6 high phenotype in childhood asthma

儿童哮喘中 IL-6 高表型

• 批准号: 10043029
• 负责人: Christina Elizabeth Ciaccio
• 金额: $ 20.25万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-13 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043029
• 关键词: Absenteeism; Academic Medical Centers; Address; Adipocytes; Adult; Affect; African American; Age; American; Asthma; Attenuated; Biological Markers; Body mass index; Chicago; Child; Childhood; Childhood Asthma; Chronic Disease; Clinical; Clinical Data; Communities; Diabetes Mellitus; Disease; Enzyme-Linked Immunosorbent Assay; Eosinophilia; Exhalation; Gender; Healthcare; Height; High Prevalence; Hypertension; IgE; Inflammation; Inflammatory; Interleukin-6; Intervention; Longitudinal Studies; Measures; Mediator of activation protein; Multi-Institutional Clinical Trial; Neighborhoods; Nitric Oxide; Obesity; Observational Study; Patients; Pediatric Hospitals; Phenotype; Plasma; Prevalence; Production; Publishing; Race; Recording of previous events; Registries; Research; Respiratory physiology; Risk; Role; Schools; Serum; Severities; Side; Spirometry; Tenuate; Testing; Therapeutic Intervention; Therapeutic Trials; Urban Health; Vulnerable Populations; Woman; Work; airway inflammation; asthma exacerbation; asthmatic patient; atopy; cohort; community organizations; comorbidity; eosinophil; inner city; lower income families; macrophage; men; minority children; multidisciplinary; obesity in children; programs; receptor; recruit; targeted treatment; urban children

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.

项目摘要 哮喘，现在是童年时期最常见的慢性疾病，伯恩斯少数儿童和 来自低收入家庭的孩子。肥胖症，也是儿童普遍存在的疾病，增加了哮喘的风险 在成年人中。与肥胖有关的系统性炎症，通过产生介体（例如白介素6（IL-6）） 脂肪细胞和巨噬细胞可能会炎症。最近对成年患者哮喘的研究 表明存在一种新的“ IL-6高表型”，其特征是高浓度的血浆IL-6。 该表型中的成年人的体重指数（BMI）较高，糖尿病患病率更高 sion，肺功能较差，哮喘发作更多。我们最近进行了一项研究 在黑人和白人哮喘患者中证实了IL-6高表型的存在的成年人。 我们的研究表明，这种表型几乎完全出现在“ T2-low表型”中，并且与 BMI。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，并设定了 哮喘成人抗IL-6治疗试验的阶段。但是，是否相似的IL-6高表型可以 尚不清楚哮喘儿童，尤其是与肥胖有关的儿童。我们的主要objec- Tive是确定哮喘儿童中是否存在IL-6高表型，如果是这样，是否是 与肥胖有关。在进行主要的多中心临床试验之前，明确证明了这一点 需要表型。我们提出了一项单一中心的观察性研究，该研究的重点是6至17岁的儿童 在城市，学术医疗中心和周边社区中哮喘。我们将使用此类注册表 儿童，以哮喘的严重程度，特温状态，BMI，合并症和关键的临床参数为特征 肺活量测定法，血清IgE和血液嗜酸性粒细胞等ETER，结合社区参与 芝加哥南侧招募100个正常加权和肥胖的孩子，并将招募50个正常加权 肥胖的儿童没有已知疾病作为对照。临床数据，BMI，肺活量测定法和生物标志物 例如血清IgE，血液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 tions。血浆IL-6的种族调整后阈值值将在非心脏儿童中建立。我们将 确定这种表型是否存在于小儿哮喘中，如果是的，则IL-6的孩子是否是 与T2高的儿童分开，是否肥胖定义为年龄和身高的BMI> 85％ 与较高的IL-6浓度相关。哮喘儿童中IL-6高表型的演示 单中心的观察性试验将导致更大的研究，以确定IL-6，肥胖症，肥胖症之间的关联 和哮喘控制，特别是在城市和少数民族儿童中。这样的研究将为thera奠定基础 靶向IL-6的精力干预措施可减弱气道注入并更好地控制不良控制 脆弱人群的哮喘，从而为医疗保健带来了可观的好处。