Pulmonary Magnetic Resonance Imaging of Ex-preterm Children With and Without Bronchopulmonary Dysplasia To Understand Risk of Emphysematous Changes (PICTURE)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- Primary Outcome: MRI-derived Pulmonary Microstructure measurements
研究概览
简要总结
Health Issue: Bronchopulmonary dysplasia (BPD), a chronic lung disease, is the most common complication of being born premature. Damage to the still developing lung stops the normal formation of the alveoli. Young adults with a history of BPD have lower lung function, early heart disease, and increased risk of death, compared to those without BPD. Recently, it has been reported that they may also develop a type of lung disease typically seen in older adults with a longstanding history of smoking. The severity of lung disease is usually measured using pulmonary function tests (PFT), but these tests may be normal, even in the presence of important changes in the fine structure of the lung. Such structural changes may be early markers of future lung disease and can be detected using lung magnetic resonance imaging (MRI). Unlike other ways of imaging the lungs, MRI does not expose people to harmful X-rays. To date, no studies have been done to examine the fine structure of the lung of school-aged children who had a history of BPD, to determine whether there are signs of lung disease that might not otherwise be obvious. This is important because once armed with this information, preventive measures can be taken to avoid worsening of lung disease.
Objective: 1) In 7-9 year-old children born extremely premature, lung MRI will be compared between those with and without BPD. The Investigators expect to observe more severe structural lung abnormalities in children with BPD, compared to those without BPD; 2) The Investigators will test to see if children with more severe MRI abnormalities also have worse lung function, and/or more symptoms of breathing problems. The Investigators expect to observe more PFT abnormalities in children with BPD than in those without and that these will match up with lung fine structure abnormalities identified on MRI.
How will work be undertaken? Children 7-9 years old who were born extremely prematurely will be recruited to participate in this study. Participants will be identified from Neonatal Follow-up clinics they attended. The Investigators will enroll 20 children with BPD and 20 without BPD. Participants will have lung MR images taken, during which they need to lie still for a few minutes. PFT will also be performed, during which they will blow into a machine. Parents will be asked to complete questionnaires about breathing problems, their living conditions (environment) and any doctor visits or hospital stays. Medical charts will be reviewed for information about their birth.
Unique/Innovative Aspects: This will be the first study using MRI as an innovative way to visualize and measure fine structure of the lung in children born prematurely with and without BPD. These findings may be early markers of lung disease, which would identify children who have, or are at risk of developing lung disease later in life, for whom the Investigators may be able to offer treatments now and/or prevent worsening of lung disease.
详细描述
Knowledge to Date: Bronchopulmonary dysplasia (BPD), the most common pulmonary complication of prematurity, occurs in 41% of infants born before 28 weeks' gestation.
Defined as a need for oxygen at 36 weeks' postmenstrual age,2 BPD results in longterm morbidity in children and adults, including reduced lung function, early cardiovascular disease and premature death The reported severity of such impairments varies, as studies have been conducted on small numbers of children with differing degrees of prematurity. Furthermore, it is unclear what markers are most sensitive to predict long-term respiratory compromise. While functional measures have been studied, micro-structural differences, that may be quantified using pulmonary magnetic resonance imaging (MRI), have not been evaluated in this population, and may provide earlier quantitative markers of future respiratory disease, including chronic obstructive pulmonary disease (COPD). Recent advances in the clinical care of preterm infants have permitted survival of ever more premature infants, in whom alveolar development is incomplete, representing a new, relatively unstudied and growing cohort with a new form of BPD.
This BPD is associated with arrested alveolar growth and development, with reduction in alveolar surface area and pulmonary capillary blood volume. Yet, little is known about the trajectory of associated lung changes through childhood. Traditional measures of pulmonary function are lower in school aged children with history of BPD than in those preterm-born without BPD, but they may still be within normal reference ranges. There is, however, evidence that pulmonary function declines more steeply between age 8-18 years in those with BPD and that lower infant lung function predicts lower adult lung function.
This is particularly concerning since there is increasing recognition that preterm born adults have a significant burden of early lung disease. Emphysema has been reported in young adults with a history of prematurity less extreme than the prematurity seen today. X-ray computed tomography (CT) imaging detects pulmonary abnormalities in 98%, with emphysema in 47% of this less premature cohort as young adults. Not all of those with CT abnormalities, however, have impaired pulmonary function tests (PFTs), thus highlighting the limitations of conventional PFTs to detect disease. In childhood, PFTs, while very powerful indicators of global lung health, may be relatively insensitive to detect early pulmonary structural changes and regional lung abnormalities. Pulmonary dysfunction may not cause symptoms at rest or correlate with PFTs in childhood, but may become apparent with exercise, infection, or aging. Structural changes in the lung parenchyma may already be present in childhood and may be earlier markers of current and future respiratory disease than conventional PFT. Such changes may be detected with pulmonary MRI of the lung, as has been shown in COPD and in pilot work in BPD MRI has significant advantages over CT, including lack of exposure to ionizing radiation and high resolution of fine tissue structure. Recent advances in pulmonary MRI, including ultra-short echo time pulse sequences, generate pulmonary images with enhanced parenchymal signal intensity which rival CT images for visualization of lung parenchyma and vasculature. MRI is emerging as a research tool and may ultimately replace CT for pediatric thoracic imaging tasks and serial evaluations.
To the Investigators knowledge, conventional and ultra-short echo time 1H MRI studies of children with histories of prematurity and BPD have not been performed to quantify microstructural pulmonary abnormalities. The Investigators therefore propose a study to compare pulmonary micro-structural (MRI) and functional (PFT) abnormalities in premature children with and without history of BPD. The investigators hypothesize that pulmonary tissue destruction and/or emphysematous changes will be evident on MRI and will be worse in ex-premature infants with a history of BPD than in those without history of BPD. Further, the investigators hypothesize that MRI will be more sensitive to detect lung changes than PFT, but that MRI changes will correlate with PFT abnormalities. Ultimately, this information will form the basis of future longitudinal studies to evaluate progression of pulmonary disease and assess effects of new treatment strategies in this population.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 7 Years 至 9 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria: Children born pre-term at less than 28 weeks' gestation, currently aged 7-9 years, with and without BPD will be included.
排除标准
- •Children with known interstitial lung disease, congenital lung anomalies, cystic fibrosis, ciliary dysfunction, immunodeficiency, neuromuscular disease or structural heart disease, which may have associated PFT and/or MRI findings;
- •Genetic syndromes which may have other associated structural lung anomalies;
- •Any contraindications for MRI;
- •Severe neurosensory deficits which would prevent test completion;
- •Viral or bacterial respiratory infection within 6 weeks.50
结局指标
主要结局
Primary Outcome: MRI-derived Pulmonary Microstructure measurements
时间窗: Assessed at one time point at Baseline
Images will be acquired in 10-15 seconds in all subjects using a 2D radial ultra-short echo time pulse sequence, to quantify signal intensity as a surrogate of parenchymal tissue density. Subjects will be asked to breath normally and then inhale a fixed volume of air from functional residual capacity (the volume of which is calibrated to 50% of inspiratory capacity) and hold their breath while images are acquired, as previously described. The pulse sequence for imaging will be developed as previously described and validated for the different MR scanner platforms at the three participating sites, through the Imaging platform of the Canadian Respiratory Research Network. All image volumes will be scaled to functional residual capacity plus 50% of inspiratory capacity and will be acquired in breath-hold at that inspiratory volume. The CRRN Imaging platform will also provide test objects for calibration of 1H MRI signal intensity to ensure
次要结局
- Spirometry pre and post bronchodilators(Assessed at one time point at Baseline)
- DLCO(Assessed at one time point at Baseline)
- Weight(Assessed at one time point at Baseline)
- Airflow limitations(Assessed at one time point at Baseline)
- Lung Volumes - Total Lung Capacity(Assessed at one time point at Baseline)
- Lung Volumes - RV/TLC ratio(Assessed at one time point at Baseline)
- ATS-DLD-78-c(Assessed at one time point at Baseline)
- Height(Assessed at one time point at Baseline)
- Pediatric Sleep Questionnaire (Chervin);(Assessed at one time point at Baseline)
- Lung Volumes - Residual Volume(Assessed at one time point at Baseline)
- Diffusion capacity(Assessed at one time point at Baseline)
- MODIFIED EPWORT SLEEPINESS SCALE(Assessed at one time point at Baseline)
- Medical History(Assessed once from the Canadian Neonatal Network database)
- The Habitual Activity Estimation Scale (HAES)(Assessed at one time point at Baseline)
研究者
Sherri Katz
Pediatric Respirologist
Children's Hospital of Eastern Ontario