Douglas Bush1, Steven H Abman2, Csaba Galambos3. 1. The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO; Department of Pediatrics, The Section of Pulmonary Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO. Electronic address: doug.bush@childrenscolorado.org. 2. The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO; Department of Pediatrics, The Section of Pulmonary Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO. 3. The Pediatric Heart Lung Center, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO; Department of Pathology, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
Abstract
OBJECTIVES: To determine the frequency of histologic features of impaired lung vascular and alveolar development and to identify the presence of intrapulmonary bronchopulmonary anastomoses (IBA) in infants and children who died with Down syndrome. STUDY DESIGN: A retrospective review of autopsy reports and lung histology from 13 children with Down syndrome (ages: 0-8 years) was performed. Histologic features of abnormal lung development were identified and semiquantified, including the presence of IBA. Three-dimensional reconstructions of IBA were also performed. Comparisons were made with 4 age-matched patients without Down syndrome with congenital heart defects who underwent autopsies during this time period. RESULTS: Of the 13 subjects with Down syndrome, 69% died from cardiac events, 77% had a congenital heart defect, and 46% had a clinical diagnosis of pulmonary hypertension. Lung histology from all subjects with Down syndrome demonstrated alveolar simplification, and 92% had signs of persistence of a double capillary network in the distal lung. The lungs from the subjects with Down syndrome frequently had features of pulmonary arterial hypertensive remodeling (85%), and prominent bronchial vessels and IBA were observed in all subjects with Down syndrome. These features were more frequent in subjects with Down syndrome compared with control subjects. CONCLUSIONS: Children with Down syndrome who died of cardiopulmonary diseases often have histologic evidence of impaired lung alveolar and vascular development, including the presence of prominent IBA and pulmonary hypertension. We speculate that children with Down syndrome are at risk for reduced lung surface area and recruitment of IBA, which may worsen gas exchange in subjects with Down syndrome.
OBJECTIVES: To determine the frequency of histologic features of impaired lung vascular and alveolar development and to identify the presence of intrapulmonary bronchopulmonary anastomoses (IBA) in infants and children who died with Down syndrome. STUDY DESIGN: A retrospective review of autopsy reports and lung histology from 13 children with Down syndrome (ages: 0-8 years) was performed. Histologic features of abnormal lung development were identified and semiquantified, including the presence of IBA. Three-dimensional reconstructions of IBA were also performed. Comparisons were made with 4 age-matched patients without Down syndrome with congenital heart defects who underwent autopsies during this time period. RESULTS: Of the 13 subjects with Down syndrome, 69% died from cardiac events, 77% had a congenital heart defect, and 46% had a clinical diagnosis of pulmonary hypertension. Lung histology from all subjects with Down syndrome demonstrated alveolar simplification, and 92% had signs of persistence of a double capillary network in the distal lung. The lungs from the subjects with Down syndrome frequently had features of pulmonary arterial hypertensive remodeling (85%), and prominent bronchial vessels and IBA were observed in all subjects with Down syndrome. These features were more frequent in subjects with Down syndrome compared with control subjects. CONCLUSIONS:Children with Down syndrome who died of cardiopulmonary diseases often have histologic evidence of impaired lung alveolar and vascular development, including the presence of prominent IBA and pulmonary hypertension. We speculate that children with Down syndrome are at risk for reduced lung surface area and recruitment of IBA, which may worsen gas exchange in subjects with Down syndrome.
Authors: Laura A Adang; David B Frank; Ahmed Gilani; Asako Takanohashi; Nicole Ulrick; Abigail Collins; Zachary Cross; Csaba Galambos; Guy Helman; Usama Kanaan; Stephanie Keller; Dawn Simon; Omar Sherbini; Brian D Hanna; Adeline L Vanderver Journal: Mol Genet Metab Date: 2018-09-07 Impact factor: 4.797
Authors: Yong Zhou; Jeffrey C Horowitz; Alexandra Naba; Namasivayam Ambalavanan; Kamran Atabai; Jenna Balestrini; Peter B Bitterman; Richard A Corley; Bi-Sen Ding; Adam J Engler; Kirk C Hansen; James S Hagood; Farrah Kheradmand; Qing S Lin; Enid Neptune; Laura Niklason; Luis A Ortiz; William C Parks; Daniel J Tschumperlin; Eric S White; Harold A Chapman; Victor J Thannickal Journal: Matrix Biol Date: 2018-03-08 Impact factor: 11.583