Pulmonary MRI of Ex-preterm Children With and Without BPD To Understand Risk of Emphysematous Changes

NCT02921308 | Completed

• 1 other identifier: REB #16/31E
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Bronchopulmonary Dysplasia

Keywords

Prematurity; Bronchopulmonary dysplasia; MRI; PFT; Emphysema

Outcome Measures

Primary Outcomes (1)

• Primary Outcome: MRI-derived Pulmonary Microstructure measurements

  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

  Assessed at one time point at Baseline

Secondary Outcomes (16)

• Height

  Assessed at one time point at Baseline

• Weight

  Assessed at one time point at Baseline

• Airflow limitations

  Assessed at one time point at Baseline

• Airflow limitations

  Assessed at one time point at Baseline

• Airflow limitations

  Assessed at one time point at Baseline

Study Arms (2)

With BPD

No intervention will be administered. After informed consent is obtained, children will undergo ultra-short echo time pulmonary MRI, followed by PFT and completion of questionnaires.

Without BPD

No intervention will be administered. After informed consent is obtained, children will undergo ultra-short echo time pulmonary MRI, followed by PFT and completion of questionnaires.

Eligibility Criteria

• Age: 7 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Children born pre-term at less than 28 weeks' gestation, currently aged 7-9 years, with and without BPD will be included. BPD will be defined as need for oxygen at 36 weeks' postmenstrual age,2 which includes those with moderate-severe disease.47 Children 7-9 years of age were selected in order to include the youngest age at which pulmonary function, including lung volumes and single breath pulmonary diffusing capacity for carbon monoxide, can routinely be reliably measured using methods that require subject cooperation.

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead

Study Sites (4)

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

The Children"s Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

CHU-Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Katz SL, Parraga G, Luu TM, Santyr G, Abdeen N, Deschenes S, Tse SM, Couch MJ, Barrowman N, Hayawi L, Momoli F, Blinder H, Thebaud B, Nuyt AM, Ben Fadel N, Moraes TJ. Pulmonary Magnetic Resonance Imaging of Ex-Preterm Children with and without Bronchopulmonary Dysplasia. Ann Am Thorac Soc. 2022 Jul;19(7):1149-1157. doi: 10.1513/AnnalsATS.202106-691OC.

  PMID: 35030070 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth; Emphysema

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sherri Katz

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Respirologist

Study Record Dates

• First Submitted: August 18, 2016
• First Posted: October 3, 2016
• Study Start: January 5, 2018
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)