Browsing by Subject "Bronchopulmonary Dysplasia"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Initial Suppression of Transforming Growth Factor-β Signaling and Loss of TGFBI Causes Early Alveolar Structural Defects Resulting in Bronchopulmonary Dysplasia
    (Elsevier, 2016-04) Ahlfeld, Shawn K.; Wang, Wang; Gao, Yong; Snider, Paige; Conway, Simon J.; Pediatrics, School of Medicine
    Septation of the gas-exchange saccules of the morphologically immature mouse lung requires regulated timing, spatial direction, and dosage of transforming growth factor (TGF)-β signaling. We found that neonatal hyperoxia acutely initially diminished saccular TGF-β signaling coincident with alveolar simplification. However, sustained hyperoxia resulted in a biphasic response and subsequent up-regulation of TGF-β signaling, ultimately resulting in bronchopulmonary dysplasia. Significantly, we found that the TGF-β–induced matricellular protein (TGFBI) was similarly biphasically altered in response to hyperoxia. Moreover, genetic ablation revealed that TGFBI was required for normal alveolar structure and function. Although the phenotype was not neonatal lethal, Tgfbi-deficient lungs were morphologically abnormal. Mutant septal tips were stunted, lacked elastin-positive tips, exhibited reduced proliferation, and contained abnormally persistent alveolar α-smooth muscle actin myofibroblasts. In addition, Tgfbi-deficient lungs misexpressed TGF-β–responsive follistatin and serpine 1, and transiently suppressed myofibroblast platelet-derived growth factor α differentiation marker. Finally, despite normal lung volume, Tgfbi-null lungs displayed diminished elastic recoil and gas exchange efficiency. Combined, these data demonstrate that initial suppression of the TGF-β signaling apparatus, as well as loss of key TGF-β effectors (like TGFBI), underlies early alveolar structural defects, as well as long-lasting functional deficits routinely observed in chronic lung disease of infancy patients. These studies underline the complex (and often contradictory) role of TGF-β and indicate a need to design studies to associate alterations with initial appearance of phenotypical changes suggestive of bronchopulmonary dysplasia.
  • Thumbnail Image
    Item
    Membrane and Capillary Components of Lung Diffusion in Infants with Bronchopulmonary Dysplasia
    (American Thoracic Society, 2016-04-01) Chang, Daniel V.; Assaf, Santiago J.; Tiller, Christina J.; Kisling, Jeffrey A.; Tepper, Robert S.; Pediatrics, School of Medicine
    RATIONALE: Autopsied lungs of infants with bronchopulmonary dysplasia (BPD) demonstrate impaired alveolar development with larger and fewer alveoli, which is consistent with our previous physiologic findings of lower pulmonary diffusing capacity of the lung for carbon monoxide (DL(CO)) in infants and toddlers with BPD compared with healthy controls born at full term (FT). However, it is not known whether the decreased DL(CO) in infants with BPD results from a reduction in both components of DL(CO): pulmonary membrane diffusing capacity (D(M)) and Vc. OBJECTIVES: We hypothesized that impairment of alveolar development in BPD results in a decrease in both D(M) and Vc components of DlCO but that the D(M)/Vc ratio would not differ between the BPD and FT groups. METHODS: DL(CO) was measured under conditions of room air and high inspired oxygen (90%), which enabled D(M) and Vc to be calculated. MEASUREMENTS AND MAIN RESULTS: D(M) and Vc increased with increasing body length; however, infants with BPD had significantly lower D(M) and Vc than FT subjects after adjustment for race, sex, body length, and corrected age. In contrast to D(M) and Vc, the D(M)/Vc ratio remained constant with increasing body length and did not differ for infants with BPD and FT subjects. CONCLUSIONS: Our findings are consistent with infants with BPD having impaired alveolar development with fewer but larger alveoli, as well as a reduced Vc.
  • Thumbnail Image
    Item
    Quantitative assessment of chronic lung disease of infancy using computed tomography
    (European Respiratory Society, 2012-04) Sarria, E. E.; Mattiello, R.; Rao, L.; Tiller, C. J.; Poindexter, B.; Applegate, K. E.; Granroth-Cook, J.; Denski, C.; Nguyen, J.; Yu, Z.; Hoffman, E.; Tepper, R. S.; Department of Pediatrics, IU School of Medicine
    The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls. Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers;38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe;lung volumes and tissue density were also measured. The relationship between airway size and airway generation differed between the CLDI and full-term groups;the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects. Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI.
  • Thumbnail Image
    Item
    Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes
    (Nature Publishing Group, 2020-02-04) Harmon, Heidi M.; Jensen, Erik A.; Tan, Sylvia; Chaudhary, Aasma S.; Slaughter, Jonathan L.; Bell, Edward F.; Wyckoff, Myra H.; Hensman, Angelita M.; Sokol, Gregory M.; DeMauro, Sara B.; Pediatrics, School of Medicine
    Objective: To determine the associations between age at first postnatal corticosteroids (PNS) exposure and risk for severe bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Study Design: Cohort study of 951 infants born <27 weeks gestational age at NICHD Neonatal Research Network sites who received PNS between 8 days of life (DOL) and 36 weeks’ postmenstrual age was used to produce adjusted odds ratios (aOR). Results: Compared to infants in the reference group (22–28 DOL-lowest rate), aOR for severe BPD was similar for children given PNS between DOL 8–49 but higher among infants treated at DOL 50–63 (aOR 1.77, 95% CI 1.03–3.06), and at DOL ≥64 (aOR 3.06, 95% CI 1.44–6.48). The aOR for NDI did not vary significantly by age of PNS exposure. Conclusion: For infants at high risk of BPD, initial PNS should be considered prior to 50 DOL for the lowest associated odds of severe BPD.