Progression of Airway Obstruction in Childhood Asthma

儿童哮喘气道阻塞的进展

• 批准号: 7672230
• 负责人: Stanley J Szefler
• 金额: $ 19.5万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672230
• 关键词: Address; Adolescence; Adolescent; Air; Airway Resistance; Asthma; Biological Markers; Blood; Bronchodilator Agents; Caring; Characteristics; Child; Childhood; Childhood Asthma; Complex; Data; Densitometry; Development; Elastases; Enrollment; Eosinophil-Derived Neurotoxin; Exhalation; Frequencies; Gelatinase B; Guidelines; Hospitalization; Image; Inflammation; Lead; Lung; Measurement; Measures; Methods; Monitor; Morbidity - disease rate; National Health and Nutrition Examination Survey; National Heart, Lung, and Blood Institute; Obstruction; Oral; Outcome; Participant; Pattern; Peptide Hydrolases; Phenotype; Physiological; Physiology; Plasma; Population Programs; Populations at Risk; Proteins; Proteolysis; Randomized; Refractory; Reporting; Research; Research Design; Respiratory physiology; School-Age Population; Secondary to; Sputum; Steroid therapy; Steroids; Structure; Thick; Time; Tissue Inhibitor of Metalloproteinase-1; Urine; Visit; Work; airway inflammation; airway obstruction; base; cohort; early childhood; emerging adult; falls; follow-up; improved; inflammatory marker; insight; prevent; programs; public health relevance; pulmonary function; response; urinary; young adult

DESCRIPTION (provided by applicant): The course of persistent asthma in childhood is highly variable and incompletely understood. The NHLBI Childhood Asthma Management Program (CAMP) and CAMP Continuation Studies (CAMPCS) afford a unique opportunity to evaluate continuing asthma progression in over 1,000 participants undergoing observation from early childhood into early adulthood. The ongoing CAMPCS will provide a total 18 years observation for each participant. After the first 10 years of follow-up, approximately 1/3 of the CAMP population had significant airway obstruction. We identified two groups with lung function patterns resulting in significant airway obstruction and high asthma morbidity with increased frequency of urgent care visits and hospitalizations: (1) abnormal obstruction in early childhood and remaining abnormal (Persistent Obstruction) and (2) initially normal pulmonary function progressing to significant obstruction over time (Late Obstruction). These two groups were compared to two other groups with normal pulmonary function and favorable long-term outcomes: (1) initially abnormal and improving over time (Late Normal) and (2) normal throughout follow-up (Persistent Normal). The patterns of Persistent and Late Obstruction leading to significant obstruction are an intermediate phenotype of airway obstruction and continue to evolve. Both patterns are associated with airway proteinase/anti-proteinase imbalance, structural lung characteristics and poor response to oral steroid therapy. However, the group with Late Obstruction is distinguished by increased airway wall thickness, hyperinflation, urinary eosinophilic protein X, and plasma TGF¿ with decreased elastase complex, suggesting ongoing inflammation and compromised airway protective mechanisms. To explore the mechanisms of significant airway obstruction related to these developing patterns including ongoing decline in pulmonary function in this CAMP cohort, we will study biomarkers in induced sputum, urine, blood and exhaled air, indicators of steroid sensitivity, pulmonary physiology and imaging. Ongoing characterization of these four distinct patterns of pulmonary function during continued follow-up of this unique CAMP cohort will inform current and continued asthma progression as well as provide a set of characteristics useful in identifying a younger population at risk for asthma progression. Furthermore, these studies will generate hypothesis-driven research that will lead to the discovery of new strategies to manage progression in the CAMP cohort. They will also provide insight into methods to conduct studies to define mechanisms and formulate strategies to monitor efficacy in studies designed to prevent asthma progression in early childhood. PUBLIC HEALTH RELEVANCE: Distinct patterns of loss in pulmonary function were identified in children with mild to moderate asthma participating in a 10-year observation period during the NHLBI Childhood Asthma Management Program. This loss in pulmonary function is likely related to ongoing inflammation unresponsive to current therapy. This study will measure indicators of airway inflammation which are associated with structural and physiologic changes in the lung and provide insight into mechanisms of asthma progression in adolescence and early adulthood.

描述（由申请人提供）：儿童期持续性哮喘的病程变化很大且尚未完全了解。NHLBI 儿童期哮喘管理计划 (CAMP) 和 CAMP 继续研究 (CAMPCS) 提供了一个独特的机会来评估 1,000 多名参与者的持续性哮喘进展情况。正在进行的 CAMPCS 将为每个参与者提供总共 18 年的观察期，在前 10 年的随访中，大约有 1/3 的观察期。 CAMP 人群有明显的气道阻塞，我们确定了两组肺功能模式导致显着的气道阻塞和高哮喘发病率，且紧急护理就诊和住院的频率增加：(1) 儿童早期的异常阻塞和持续异常（持续性阻塞）和(2) 最初正常的肺功能随着时间的推移进展为严重阻塞（晚期阻塞） 将这两组与肺功能正常且长期结果良好的其他两组进行比较：(1) 最初异常并随着时间的推移而改善（晚期正常）。 ） 和(2)正常随访（持续正常）导致显着阻塞的持续性和晚期阻塞的模式是气道阻塞的中间表型并且继续发展，这两种模式都与气道蛋白酶/抗蛋白酶失衡、结构性肺有关。然而，晚期梗阻组的特点是气道壁厚度增加、过度充气、尿嗜酸性蛋白 X 和血浆 TGF¿随着弹性蛋白酶复合物的减少，表明持续的炎症和气道保护机制受损。为了探索与这些发展模式相关的显着气道阻塞的机制，包括该 CAMP 队列中肺功能的持续下降，我们将研究诱导痰、尿液、血液和气道中的生物标志物。在这个独特的 CAMP 队列的持续随访过程中，呼出气、类固醇敏感性指标、肺部生理学和影像学的持续表征将告知当前和持续的哮喘进展，并提供一组有用的特征。识别一个此外，这些研究将产生假设驱动的研究，从而发现控制 CAMP 队列进展的新策略，他们还将深入了解进行研究的方法，以定义机制和制定方案。旨在预防儿童早期哮喘进展的研究中监测疗效的策略。 公共健康相关性：在 NHLBI 儿童哮喘管理计划的 10 年观察期中，发现患有轻度至中度哮喘的儿童存在明显的肺功能丧失模式，这种肺功能丧失可能与对当前治疗无反应的持续炎症有关。这项研究将测量与肺部结构和生理变化相关的气道炎症指标，并深入了解青春期和成年早期哮喘进展的机制。