Airway Cellular and Cytokine Profiles in Older Patients with Asthma

老年哮喘患者的气道细胞和细胞因子谱

• 批准号: 8716660
• 负责人: PAULA J BUSSE
• 金额: $ 21.19万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-08 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8716660
• 关键词: Address; Adrenal Cortex Hormones; Adult asthma; Affect; Age; Aging; Antibody Formation; Asthma; Body Weight decreased; Breathing; Cell Count; Cell physiology; Cells; Child; Comorbidity; Data; Dendritic Cells; Dose; Elderly; Functional disorder; Generations; Goals; Health; Human; IgE; Immunophenotyping; Infection; Inflammation; Inflammatory; Inflammatory Response; Influenza; Interleukin-10; Interleukin-17; Interleukin-6; Modeling; Morbidity - disease rate; Mus; Neutrophilia; Outcome; Pathway interactions; Patients; Pattern; Phenotype; Play; Process; Recruitment Activity; Regimen; Regulation; Regulatory T-Lymphocyte; Research; Respiratory Tract Infections; Risk; Role; Severities; Severity of illness; Specificity; Sputum; Standardization; T-Cell Receptor; T-Lymphocyte; TNF gene; Testing; Translating; Vaccination; age effect; age group; age related; aged; airway hyperresponsiveness; airway inflammation; cytokine; effective therapy; ethnic minority population; high risk; immune function; indexing; innate immune function; mortality; neutrophil; normal aging; older patient; oral tolerance; peripheral blood; response; treatment response; young adult

DESCRIPTION (provided by applicant): The recognition of distinct asthma phenotypes has begun to explain differences in disease severity, persistence and response to treatment in children and younger adults. Emerging data suggest that aging also has an important effect on asthma; older asthmatics have greater morbidity and mortality, possibly reflecting distinct underlying pathophysiology and variable treatment responses. While mechanisms underlying these changes in older asthmatics are not well established, age-related alterations in immune function likely play an important role. To define the effects of age on key features of asthma, airway inflammation and airway hyperresponsiveness (AHR), we first developed a murine model of asthma using Ag sensitization and airway challenge in younger and older mice. Distinct patterns of airway inflammatory responses to Ag challenge were found in older mice characterized by increased IL-6, IL-10, IL-17, TGF-¿ expression and greater numbers of airway neutrophils and Treg cells. To translate our murine findings to humans we next generated preliminary data which suggest enhanced formation of IL-6 and neutrophilia are important to the pathophysiology of asthma in older subjects. We therefore hypothesize that, compared to younger asthmatics, older asthmatics will manifest a distinct inflammatory phenotype indexed by increased generation of IL-6, which, in turn, increases the expression of Th17 cells to induce airway neutrophilia, and also decreases Treg cell function. To test our hypothesis we will collect induced sputum and peripheral blood from 40 older (>60 years) and 40 younger adult (21-40 years) asthmatics (receiving a standardized low dose of inhaled corticosteroids) and 80 age-matched controls. We will then: a) establish the airway inflammatory (cytokine and cellular) phenotypes in the older asthmatic subjects in comparison to younger adult asthma subjects and examine association with asthma control, and b) investigate whether IL-6 contributes to the mechanisms of asthma in the older subjects by enhancing Th17 expression and decreasing Treg function.

描述（通过应用证明）：对不同的哮喘表型的识别已经解释了对儿童和年轻人的治疗的差异，这表明衰老也对哮喘具有重要的影响；以及可变的信任反应。在年轻小鼠和年龄较大的小鼠中，使用AG敏化和气道挑战开发了哮喘的鼠模型。表达和更多的嗜中性粒细胞和Treg细胞。由IL-6的产生增加的独特炎症型，可容易地表达Th17细胞诱导气道中性粒细胞，并降低Treg细胞功能，以测试我们的假设。年轻的成年人（21-40岁）吸入皮质类固醇的哮喘患者和80个年龄匹配的对照。哮喘控制和b）研究IL-6是否通过表达d降低Treg功能来促进老年受试者的哮喘机制。

项目成果

Effect of aging on sputum inflammation and asthma control.

• DOI: 10.1016/j.jaci.2016.09.015
• 发表时间: 2017-06
• 期刊: The Journal of allergy and clinical immunology
• 作者: Busse PJ;Birmingham JM;Calatroni A;Manzi J;Goryachokovsky A;Fontela G;Federman AD;Wisnivesky JP
• 通讯作者: Wisnivesky JP

The Effect of Age on T-Regulatory Cell Number and Function in Patients With Asthma.

• DOI: 10.4168/aair.2021.13.4.646
• 发表时间: 2021-07
• 期刊: Allergy, asthma & immunology research
• 作者: Birmingham JM;Chesnova B;Wisnivesky JP;Calatroni A;Federman J;Bunyavanich S;Busse PJ
• 通讯作者: Busse PJ