Browsing by Subject "Bronchopulmonary Dysplasia"

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    In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia.
    (Journal of perinatology : official journal of the California Perinatal Association, 2017-07) Jackson, W; Hornik, CP; Messina, JA; Guglielmo, K; Watwe, A; Delancy, G; Valdez, A; MacArthur, T; Peter-Wohl, S; Smith, PB; Tolia, VN; Laughon, MM
    OBJECTIVE:To characterize in-hospital outcomes of premature infants diagnosed with severe bronchopulmonary dysplasia (BPD). STUDY DESIGN:Retrospective cohort study including premature infants with severe BPD discharged from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2015. RESULTS:There were 10 752 infants with severe BPD, and 549/10 752 (5%) died before discharge. Infants who died were more likely to be male, small for gestational age, have received more medical interventions and more frequently diagnosed with surgical necrotizing enterocolitis, culture-proven sepsis and pulmonary hypertension following 36 weeks of postmenstrual age compared with survivors. Approximately 70% of infants with severe BPD were discharged by 44 weeks of postmenstrual age, and 86% were discharged by 48 weeks of postmenstrual age. CONCLUSIONS:A majority of infants diagnosed with severe BPD were discharged home by 44 weeks of postmenstrual age. These results may inform discussions with families regarding the expected hospital course of infants diagnosed with severe BPD.
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    Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension.
    (Stem cells translational medicine, 2022-08) Sharma, Mayank; Bellio, Michael A; Benny, Merline; Kulandavelu, Shathiyah; Chen, Pingping; Janjindamai, Chawisa; Han, Chenxu; Chang, Liming; Sterling, Shanique; Williams, Kevin; Damianos, Andreas; Batlahally, Sunil; Kelly, Kaitlyn; Aguilar-Caballero, Daniela; Zambrano, Ronald; Chen, Shaoyi; Huang, Jian; Wu, Shu; Hare, Joshua M; Schmidt, Augusto; Khan, Aisha; Young, Karen
    Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have beneficial effects in preclinical bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) models. The optimal source, dosing, route, and duration of effects are however unknown. The objectives of this study were to (a) compare the efficacy of GMP-grade EVs obtained from Wharton's Jelly MSCs (WJ-MSCs) and bone marrow (BM-MSCs), (b) determine the optimal dosing and route of administration, (c) evaluate its long-term effects, and (d) determine how MSC EVs alter the lung transcriptome. Newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P)1-P14 were given (a) intra-tracheal (IT) BM or WJ-MSC EVs or placebo, (b) varying doses of IT WJ-MSC EVs, or (c) IT or intravenous (IV) WJ-MSC EVs on P3. Rats were evaluated at P14 or 3 months. Early administration of IT BM-MSC or WJ-MSC EVs had similar beneficial effects on lung structure and PH in hyperoxia-exposed rats. WJ-MSC EVs however had superior effects on cardiac remodeling. Low, medium, and high dose WJ-MSC EVs had similar cardiopulmonary regenerative effects. IT and IV WJ-MSC EVs similarly improved vascular density and reduced PH in hyperoxic rats. Gene-set enrichment analysis of transcripts differentially expressed in WJ-MSC EV-treated rats showed that induced transcripts were associated with angiogenesis. Long-term studies demonstrated that a single early MSC EV dose has pulmonary vascular protective effects 3 months after administration. Together, our findings have significant translational implications as it provides critical insight into the optimal source, dosing, route, mechanisms of action, and duration of effects of MSC-EVs for BPD-PH.
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    Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.
    (BMC pediatrics, 2020-12) Schneider, Simone; Bailey, Mary; Spears, Tracy; Esther, Charles R; Laughon, Matthew M; Hornik, Christoph P; Jackson, Wesley

    Background

    Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia, the most common pulmonary morbidity of prematurity. Despite these catastrophic consequences, no evidence-based therapies are available for the prevention of pulmonary hypertension in this population. Sildenafil is a potent pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of pulmonary hypertension in adults. Preclinical models suggest a beneficial effect of sildenafil on premature lungs through improved alveolarization and preserved vascular development. Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary vascular remodeling and lowering pulmonary vascular resistance; however, clinical trial evidence is needed. The present study, supported by the National Institutes of Health's National Heart Lung and Blood Institute, will generate safety, pharmacokinetics, and preliminary effectiveness data on sildenafil in a population of premature infants with severe bronchopulmonary dysplasia at risk for pulmonary hypertension.

    Methods

    We have designed a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety trial of sildenafil in premature infants with severe bronchopulmonary dysplasia. We will randomize 120 premature infants < 29 weeks gestational age with severe bronchopulmonary dysplasia at 32-40 weeks postmenstrual age in a dose-escalating approach 3:1 (sildenafil: placebo) sequentially into each of 3 cohorts at ~ 30 clinical sites. Participants will receive up to 34 days of study drug, followed by 28 days of safety monitoring. The primary outcome will be safety as determined by incidence of hypotension. Secondary outcomes will include pharmacokinetics and preliminary effectiveness of sildenafil based on presence or absence of pulmonary hypertension diagnosed by echocardiography at the end of treatment period.

    Discussion

    Sildenafil is a promising intervention to prevent the development of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Clinical trials of sildenafil specifically designed for premature infants are urgently needed. The current study will make substantial contributions to scientific knowledge of the safety of sildenafil in premature infants at risk for pulmonary hypertension. Results from the study will be used by investigators to inform the design of a pivotal efficacy trial.

    Trial registration

    ClinicalTrials.gov NCT04447989 . Registered 25 June 2020.