Tantalizing Therapeutics in Bronchopulmonary Dysplasia

Description

Tantalizing Therapeutics in Bronchopulmonary Dysplasia is a concise reference that provides an overview of emerging concepts in the understanding of lung development and injury from a molecular and cellular point-of-view, including exciting pathways that are paving the way for new options to prevent or treat Bronchopulmonary Dysplasia (BPD). The book's chapters are written by experts who are at the forefront of BPD research. Coverage includes chapters on exosomes, stem cells and miRs, as well as a section on new discoveries in BPD research with translational potential. This is a must-have reference for researchers, physicians and trainees working on BPD, lung developmental biology, and more. Cover Tantalizing Therapeutics in Bronchopulmonary Dysplasia Copyright Dedication Contributors Preface Section 1: Current therapeutics: State of the art 1 - Systemic and topical glucocorticoids to prevent BPD Introduction Dexamethasone Dexamethasone and hydrocortisone in the brain: different actions, different outcomes? Hydrocortisone Other systemic steroids Topical steroids (inhaled and instilled) Conclusion References 2 - Use of caffeine for prevention of bronchopulmonary dysplasia Brief history of caffeine use in premature neonates Epidemiology of caffeine use Pharmacology of caffeine in premature neonates Cellular mechanism of action of caffeine Mechanism of action of caffeine for prevention of BPD Dosing and route of caffeine administration Drug interactions with caffeine Serum drug monitoring for caffeine Timing of caffeine use – early vs. late Evidence for the use of late caffeine for prevention of BPD Evidence for the use of early caffeine for prevention of BPD Adverse effects of caffeine Caffeine and neurodevelopmental outcomes Caffeine controversies What is the optimal duration of caffeine? Is it safe to discharge babies home on caffeine? Conclusions Recommendations References 3 - Next generation ventilation strategies to prevent and manage bronchopulmonary dysplasia Introduction Pathophysiology of ventilator-associated lung injury General strategies to prevent PBD Respiratory support at birth and lung injury Positive end-expiratory pressure in the delivery room Sustained inflation (SI) Non-invasive respiratory support Less invasive surfactant administration Lung-protective strategies of mechanical ventilation Volume-controlled and volume-targeted ventilation Volume-controlled versus volume-targeted ventilation How does VTV work? Documented benefits of volume-controlled and volume-targeted ventilation General guidelines for clinical application of VTV in preterm infants Importance of the open lung strategy High-frequency ventilation Neurally adjusted ventilatory assist (NAVA) Airway pressure release ventilation (APRV) Respiratory support of infants with established BPD Conclusion References Section 2: Ongoing therapeutic studies with translational potential 4 - End points for therapeutic trials for BPD: lessons learned from clinical trials Introduction Limitations of common BPD definitions as clinical trials endpoints Does a BPD diagnosis predict important long-term outcomes with high sensitivity and specificity? Is 36 weeks PMA the optimal timing for a BPD endpoint? Is 40 weeks PMA a better endpoint than 36 weeks? Should a diagnosis of BPD be based on respiratory status on a single day of a protracted hospital stay? Should BPD be based on use of oxygen, positive pressure or both? Are there advantages to a graded severity score over a dichotomous BPD endpoint? Incorporating pulmonary function tests (PFTs) as endpoints in clinical trials of BPD Respiratory death as an outcome Considerations when defining clinical trials endpoints after NICU discharge Long-term clinical trials endpoints; how long is too long? Conclusions References 5 - What can exogenous surfactant provide in the fight against BPD? Introduction Conventional surfactant therapy and BPD Late surfactant therapy and BPD New modes of exogenous surfactant administration Anti-inflammatory and immunomodulatory effects of surfactant Exogenous surfactant preparations in clinical use Newer synthetic surfactant preparations Surfactant proteins A and D Surfactant as a vehicle for anti-inflammatory therapy Exogenous surfactant therapy as a vehicle – right place, right time, right patient The biophysical advantage of surfactant as a delivery vehicle Known effects of relevant additives on the biophysical profile of surfactant Known effects of surfactant on the potency/bioactivity of therapies targeting BPD Specific therapies partnered with surfactant Conclusion References 6 - Stem cells in the treatment of bronchopulmonary dysplasia Introduction Prospects and challenges for successful clinical translation The right cells Sources Allogenic versus autologous MSCs Standardization of MSCs Paracrine potency assay Preconditioning of MSCs Genetic engineering of MSCs The right patients The right route The right timing The right dose Long-term outcomes and safety of MSCs transplantation Conclusions References Section 3: Future therapeutic directions 7 - Extracellular vesicles in the therapy of BPD Bronchopulmonary dysplasia (BPD) and the rationale for stem cell-based therapies EVs: Intro and nomenclature EV isolation methods EV characterization methods EVs as therapeutic vectors EVs in BPD Acknowledgment References 8 - Growth factors in the therapy of bronchopulmonary dyplasia Introduction IGF-1 VEGF HIF PDGF PEDF EMAP II TGFα TGFβ Connective tissue growth factor (CTGF) Epidermal growth factor (EGF) Hepatocyte growth factor (HGF) KGF MIF Summary and conclusions References 9 - Antenatal approaches in the therapy of BPD Introduction Antenatal treatment to prevent BPD Antenatal treatment targets to decrease BPD Maternal factors influencing lung fetal lung development Pre-existing maternal conditions Pre-existing maternal condition: risk of preterm birth Pre-existing maternal condition: hypertension Pre-existing maternal condition: maternal body mass index (BMI) Maternal toxin exposure Maternal toxin exposure: smoking Maternal toxin exposure: alcohol consumption Maternal toxin exposure: air pollution Maternal nutrition Maternal nutrition: Vitamin A Maternal nutrition: Vitamin D Maternal nutrition: Vitamin E Placental factors influencing fetal lung development Placental factors: inflammatory Placental factors: inflammatory-anti-microbial agents Placental factors: anti-inflammatory micronutrients Placental factors inflammatory: interleukin 1 (IL-1) antagonists Placental factors: abnormal placentation Placental factors: abnormal placentation-VEGF Fetal growth restriction (FGR) Fetal growth restriction: phosphodiesterase-5 inhibitor The fetal environment Intra-amniotic therapy Intra-amniotic therapy: vascular endothelial growth factor (VEGF) Intra-amniotic therapy: epidermal growth factor Intra-amniotic therapy: thyroxine Intra-amniotic therapy: stem cells Intra-amniotic therapy: surfactant Antenatal therapy to advance lung maturation Antenatal steroid therapy Ambroxol-trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanol hydrochloride Antenatal leptin to advance fetal lung maturity The fetal environment-intra-uterine surgical procedures Fetal tracheal occlusion Fetal intra-tracheal drug delivery Placental replacement Conclusions References 10 - miRs – Mere hype or master regulators in the therapy of BPD? Introduction MicroRNA and early lung development MicroRNA and late lung development MicroRNAs for BPD risk prediction and therapeutic targets miRs and BPD sex predilection miRs and the lung microbiome Conclusions Funding References 11 - Immune modulators for the therapy of BPD Introduction Antenatal corticosteroids Macrophage migration inhibitory factor (MIF) MIF and BPD Complexity of MIF signaling pathways Development of MIF modulating agents Future possibilities for MIF research in BPD IL-1β Impact of IL-1β and the NLRP3 inflammasome on lung development Use of the recombinant IL-1RA anakinra in BPD NLRP3 inflammasome as a potential therapeutic target in BPD Surfactant protein D in the treatment of neonatal lung disease Conclusion References Index A B C D E F G H I K L M N O P R S T U V W Z Back Cover