Mirjam Stahl1,2,3,4,5, Eva Steinke1,6,3,4, Simon Y Graeber1,2,6,3,4, Cornelia Joachim3,4, Christoph Seitz7,8, Hans-Ulrich Kauczor6,9,4, Monika Eichinger9,4,10, Susanne Hämmerling3, Olaf Sommerburg6,3,4, Mark O Wielpütz9,4,11, Marcus A Mall1,2,6,3,4,5. 1. Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. 2. German Center for Lung Research (DZL), Berlin, Germany. 3. Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center and. 4. Translational Lung Research Center Heidelberg (TLRC), DZL, Heidelberg, Germany. 5. Berlin Institute of Health, Charité-Universitätsmedizin, Berlin, Germany. 6. Department of Translational Pulmonology. 7. Division of Neonatology, Department of Pediatrics, and. 8. Pediatric Practice, Bad Saulgau, Germany. 9. Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany. 10. Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany; and. 11. Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract
Rationale: Previous cross-sectional studies have demonstrated that chest magnetic resonance imaging (MRI) is sensitive to detect early lung disease in infants and preschool children with cystic fibrosis (CF) without radiation exposure. However, the ability of MRI to detect the progression of lung disease and the impact of early diagnosis in preschool children with CF remains unknown. Objectives: To investigate the potential of MRI to detect progression of early lung disease and impact of early diagnosis by CF newborn screening (NBS) in preschool children with CF. Methods: An annual MRI was performed from diagnosis over 4 years in a cohort of 96 preschool children with CF (age, 0-4 yr) who received concurrent diagnoses on the basis of NBS (n = 28) or clinical symptoms (n = 68). MRI scans were evaluated using a dedicated morphofunctional score, and the relationship between longitudinal MRI score and respiratory symptoms, pulmonary exacerbations, upper airway microbiology, and mode of diagnosis was determined. Measurements and Main Results: The MRI global score increased in the total cohort of children with CF during preschool years (P < 0.001) and was associated with cough, pulmonary exacerbations (P < 0.0001), and the detection of Staphylococcus aureus and Haemophilus influenzae (P < 0.05). MRI-defined abnormalities in lung morphology-especially airway wall thickening/bronchiectasis-were lower in children with CF diagnosed by NBS than in children with clinically diagnosed CF throughout the observation period (P < 0.01). Conclusions: MRI detected progression of early lung disease and benefits of early diagnosis by NBS in preschool children with CF. These findings support MRI as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).
Rationale: Previous cross-sectional studies have demonstrated that chest magnetic resonance imaging (MRI) is sensitive to detect early lung disease in infants and preschool children with cystic fibrosis (CF) without radiation exposure. However, the ability of MRI to detect the progression of lung disease and the impact of early diagnosis in preschool children with CF remains unknown. Objectives: To investigate the potential of MRI to detect progression of early lung disease and impact of early diagnosis by CF newborn screening (NBS) in preschool children with CF. Methods: An annual MRI was performed from diagnosis over 4 years in a cohort of 96 preschool children with CF (age, 0-4 yr) who received concurrent diagnoses on the basis of NBS (n = 28) or clinical symptoms (n = 68). MRI scans were evaluated using a dedicated morphofunctional score, and the relationship between longitudinal MRI score and respiratory symptoms, pulmonary exacerbations, upper airway microbiology, and mode of diagnosis was determined. Measurements and Main Results: The MRI global score increased in the total cohort of children with CF during preschool years (P < 0.001) and was associated with cough, pulmonary exacerbations (P < 0.0001), and the detection of Staphylococcus aureus and Haemophilus influenzae (P < 0.05). MRI-defined abnormalities in lung morphology-especially airway wall thickening/bronchiectasis-were lower in children with CF diagnosed by NBS than in children with clinically diagnosed CF throughout the observation period (P < 0.01). Conclusions: MRI detected progression of early lung disease and benefits of early diagnosis by NBS in preschool children with CF. These findings support MRI as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).
Entities:
Keywords:
cystic fibrosis; early lung disease; magnetic resonance imaging; newborn screening; noninvasive monitoring