The Lung Clearance Index as a Marker of Early Lung Disease in Preschool Children

肺清除指数作为学龄前儿童早期肺部疾病的标志

• 批准号: 8549960
• 负责人: Felix Ratjen
• 金额: $ 45.57万
• 依托单位: HOSPITAL FOR SICK CHLDRN (TORONTO)
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549960
• 关键词: 18 year old; 6 year old; Address; Age; Agreement; Asthma; Birth; Breathing; Child; Chronic; Clinical; Clinical Research; Clinical Trials; Cross-Sectional Studies; Cystic Fibrosis; Data; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early Intervention; Future; Gases; Gold; Health; Infant; Intervention; Intervention Studies; Knowledge; Longevity; Longitudinal Studies; Lung; Lung diseases; Mass Spectrum Analysis; Measurement; Measures; Methods; Monitor; Neonatal Screening; Nitrogen; Normal Range; North America; Nursery Schools; Outcome; Outcome Measure; Patients; Peripheral; Preschool Child; Primary Ciliary Dyskinesias; Protocols documentation; Pulmonary Cystic Fibrosis; Pulmonary Function Test/Forced Expiratory Volume 1; Reaction Time; Reproducibility; Respiratory physiology; Saline; Severity of illness; Signs and Symptoms; Spirometry; Sulfur Hexafluoride; System; Technology; Testing; Therapeutic Agents; Therapeutic Intervention; Therapy Clinical Trials; Time; Tracer; Treatment Efficacy; Validation; Variant; abstracting; age group; aged; base; children with cystic fibrosis; clinical care; clinically relevant; cystic fibrosis patients; design; improved; indexing; pulmonary function; recombinant human DNase; time interval; tool; validation studies

DESCRIPTION (provided by applicant): Cystic Fibrosis, (CF) is associated with chronic respiratory disease, which is responsible for the shortened life span in most patients. There is increasing evidence that CF lung disease begins shortly after birth and progresses even in the absence of clinical signs and symptoms. Traditional measures of lung function, such as spirometry, are difficult to measure in young children and are not able to detect abnormalities in this age group. Therefore, more sensitive and easier measures of lung function are needed for clinical studies in CF patients younger than 6 years. Multiple breath washout testing (MBW) measures the efficiency with which gas mixes in the lungs, and has been shown to detect abnormalities in lung function before traditional measures of lung function. In addition the test requires minimal cooperation as it is performed during normal breathing and is therefore ideally suited for younger children. There is currently no validated multiple breath washout system available for centers in North America. Recently, a commercial system has been developed, but the data in younger children (aged 3-6 years), a critical window for disease progression, is currently lacking. However, there is minimal data to define what constitutes a significant change in LCI over time. The overall aim of this proposal is to develop the lung clearance index into a tool for interventional studies and for clinical care in CF patients younger than 6 years of age. This will be accomplished through three specific aims: Aim 1: Validation of the LCI measured by nitrogen washout against the gold standard in preschool children. Aim 2: Define repeatability of LCI measurements at time intervals relevant for clinical trials. Aim 3: Determine the utility of LC as a monitoring tool in a clinical setting. The validation study in Aim 1 is essential to verify agreement with the gold standard, and to refine the protocol for this age group. Following validation, we will utilize the nitrogen washout system to characterize the reproducibility of LCI n health and CF, in order to define the limits of normal measurement variation that are both statistically valid, and clinically relevant. This will be done in a one-year longitudinal study tht mimics the design of interventional trials. This information will be directly applicable to the design and interpretation of clinical studies for children with CF in this age group. Finally, we wll test the clinical utility of the LCI to monitor pulmonary exacerbations in preschool children, and to assess whether the LCI can be used to track changes in clinical disease severity over time. These studies will form the basis for subsequent interventional trials in preschool children with CF and for future studies on the utility of LCI in CF infants. Furthermore, the information gained in this study will be a critical step for subsequent studies in other airway diseases such as asthma and primary ciliary dyskinesia. (End of Abstract)

描述(申请人提供)：囊性纤维化(CF)与慢性呼吸道疾病有关，这是导致大多数患者寿命缩短的原因。越来越多的证据表明，慢性肺病在出生后不久就开始发病，即使在没有临床体征和症状的情况下也会进展。传统的肺功能测量方法，如肺活量测定法，在幼儿中很难测量，也无法检测到这个年龄段的异常。因此，在对6岁以下的CF患者进行临床研究时，需要更敏感和更容易的肺功能测量。多次呼吸冲洗测试(MBW)测量气体在肺部混合的效率，已被证明在传统的肺功能测量之前检测到肺功能的异常。此外，这项测试需要最少的合作，因为它是在正常呼吸期间进行的，因此非常适合年幼的儿童。目前还没有经过验证的多次呼气冲洗系统可供北美的中心使用。最近，已经开发了一个商业系统，但目前缺乏较小年龄儿童(3-6岁)的数据，这是疾病进展的关键窗口。然而，有很少的数据来定义什么构成了LCI随时间的显著变化。这项建议的总体目标是将肺清除指数发展成为介入研究和6岁以下CF患者临床护理的工具。这将通过三个具体目标来实现：目标1：根据学龄前儿童的黄金标准，验证通过氮气冲洗测量的LCI。目的2：确定与临床试验相关的时间间隔LCI测量的可重复性。目的3：确定LC在临床环境中作为监测工具的实用性。AIM 1中的验证研究对于验证与黄金标准的一致性以及完善这一年龄段的方案至关重要。在验证之后，我们将利用氮气冲洗系统来表征LCI n Health和CF的重复性，以便定义统计上有效的和临床相关的正常测量变异的限度。这将在一项为期一年的纵向研究中完成，该研究模仿干预试验的设计。这些信息将直接适用于这个年龄段的CF儿童的临床研究的设计和解释。最后，我们将测试LCI在监测学龄前儿童肺部恶化方面的临床效用，并评估LCI是否可以用于跟踪临床疾病严重程度随时间的变化。这些研究将为随后对患有慢性纤维性心脏病的学龄前儿童进行干预试验，并为未来关于LCI在慢性阻塞性肺疾病婴儿中的效用的研究奠定基础。此外，这项研究中获得的信息将是后续其他呼吸道疾病研究的关键一步，如哮喘和原发纤毛运动障碍。(摘要结束)