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: 8411636
• 负责人: Felix Ratjen
• 金额: $ 26.8万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411636
• 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 treatment; 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（由申请人提供）：囊性纤维化（CF）与慢性呼吸道疾病相关，这是大多数患者寿命缩短的原因。越来越多的证据表明，CF肺病在出生后不久就开始了，即使没有临床体征和症状也会进展。肺功能的传统测量方法，如肺活量测定法，很难在幼儿中测量，并且不能检测到这个年龄组的异常。因此，在6岁以下CF患者的临床研究中，需要更敏感和更容易的肺功能测量。多次呼吸冲洗试验（MBW）测量气体在肺中混合的效率，并已被证明可以在传统的肺功能测量之前检测肺功能异常。此外，测试需要最小的合作，因为它是在正常呼吸过程中进行，因此非常适合年幼的儿童。目前北美的中心还没有经过验证的多次呼吸冲洗系统。最近，已经开发了一个商业系统，但目前缺乏幼儿（3-6岁）的数据，这是疾病进展的关键窗口。然而，几乎没有数据可以界定什么构成LCI随时间的重大变化。本提案的总体目标是将肺清除指数开发为6岁以下CF患者的干预性研究和临床护理工具。这将通过三个具体目标来实现：目标1：验证学龄前儿童的氮洗脱金标准测量的LCI。目的2：定义与临床试验相关的时间间隔内LCI测量的重复性。目的3：确定LC作为临床监测工具的实用性。目标1中的验证研究对于验证与金标准的一致性以及完善该年龄组的方案至关重要。确认后，我们将利用氮气冲洗系统来表征健康和CF下LCI的重现性，以定义统计学有效和临床相关的正常测量变异限度。这将在一项为期一年的纵向研究中完成，该研究模拟了干预性试验的设计。该信息将直接适用于该年龄组CF儿童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急性加重中的临床效用，并评估LCI是否可用于跟踪临床疾病严重程度随时间的变化。这些研究将为随后的学龄前CF儿童干预试验和未来的CF婴儿LCI效用研究奠定基础。此外，在这项研究中获得的信息将是其他气道疾病，如哮喘和原发性纤毛运动障碍的后续研究的关键一步。 (End摘要）