Progression of Airway Obstruction in Childhood Asthma

儿童哮喘气道阻塞的进展

• 批准号: 7529073
• 负责人: Stanley J Szefler
• 金额: $ 23.4万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7529073
• 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; Endopeptidases; 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; Obstruction; Oral; Outcome; Pancreatic Elastase; Participant; Pattern; Peptide Hydrolases; Phenotype; Physiological; Physiology; Plasma; Population Programs; Populations at Risk; Proteins; Proteolysis; Public Health; 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; falls; follow-up; improved; insight; prevent; programs; 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（由适用提供）：儿童时期持续性哮喘的过程是高度可变且未完全理解的。 NHLBI儿童期哮喘管理计划（CAMP）和CAMP延续研究（CAMPCS）为评估1000多名参与者的持续哮喘发展提供了独特的机会，从童年到成年早期，经历了观察。正在进行的CAMCC将为每个参与者提供18年的观察。在随访的前10年之后，大约1/3的营地人口具有显着的气道目标。我们确定了两组具有肺功能模式的组，导致气道的明显目标和高哮喘发病率，紧急护理就诊和住院的频率增加：（1）在儿童早期，目的异常和（持续性阻塞）和（2）最初肺部功能持续正常（持续性障碍），而肺部功能会随着时间的推移而出现明显的反应（晚期阻塞）。将这两组与其他两组具有正常肺功能和有利的长期结局的组进行了比较：（1）最初随着时间的推移（正常晚期）和（2）在整个随访过程中（持续正常）的正常和（2）正常。导致明显反对的持续性和晚期阻塞的模式是气道异议的中间表型，并继续发展。两种模式都与气道蛋白酶/抗蛋白酶失衡，结构性肺特征和对口服类固醇治疗的反应不佳有关。然而，该组滞后的组以增加的气道壁厚度，过度充气，尿液嗜酸性蛋白X和血浆TGF的增加而区别，并具有改进的弹性酶配合物，这表明正在进行的注射和气道保护剂机制。为了探索与这些发展模式有关的重要气道异议的机制，包括该营地队列中肺功能的持续下降，我们将研究诱导的痰液，尿液，血液和暴露的空气，类固醇敏感性，肺部生理学和成像的指标。在继续随访期间，持续表征这四种不同的肺功能模式，将为当前和持续的哮喘进展提供信息，并提供一组有助于识别有哮喘进展风险的年轻人群的特征。此外，这些研究将产生以假设为驱动的研究，这将导致发现新的策略来管理营地队列中的进步。他们还将提供有关进行研究的方法来定义机制并制定策略以监测旨在预防幼儿哮喘进展的研究的策略的方法。 公共卫生相关性：在NHLBI儿童期哮喘管理计划期间，在轻度至中度哮喘的儿童中发现了肺功能损失的不同模式。肺功能的这种损失可能与持续的炎症对当前疗法无反应有关。这项研究将测量与肺部结构和生理变化有关的气道炎症指标，并洞悉青少年和成年早期哮喘进展的机制。