title: Challenges, priorities and novel therapies for hypoxemic respiratory failure and pulmonary hypertension in the neonate.
abstract: Future priorities for the management of hypoxemic respiratory failure (HRF) and pulmonary hypertension include primary prevention of neonatal lung diseases, 'precision medicine' and translating promising clinical and preclinical research into novel therapies. Promising areas of investigation include noninvasive ventilation strategies, emerging pulmonary vasodilators (for example, cinaciguat, intravenous bosentan, rho-kinase inhibitors, peroxisome proliferator-activated receptor-γ agonists) and hemodynamic support (arginine vasopressin). Research challenges include the optimal timing for primary prevention interventions and development of validated biomarkers that predict later disease or serve as surrogates for long-term respiratory outcomes. Differentiating respiratory disease endotypes using biomarkers and experimental therapies tailored to the underlying pathobiology are central to the concept of 'precision medicine' (that is, prevention and treatment strategies that take individual variability into account). The ideal biomarker should be expressed early in the neonatal course to offer an opportunity for effective and targeted interventions to modify outcomes. The feasibility of this approach will depend on the identification and validation of accurate, rapid and affordable point-of-care biomarker tests. Trials targeting patient-specific pathobiology may involve less risk than traditional randomized controlled trials that enroll all at-risk neonates. Such approaches would reduce trial costs, potentially with fewer negative trials and improved health outcomes. Initiatives such as the Prematurity and Respiratory Outcomes Program, supported by the National Heart, Lung, and Blood Institute, provide a framework to develop refined outcome measures and early biomarkers that will enhance our understanding of novel, mechanistic therapeutic targets that can be tested in clinical trials in neonates with HRF.
authors.affiliation: Department of Pediatrics, and Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Aschner
authors.affiliation: Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gien
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Kinsella
authors.affiliation: Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Konduri
authors.affiliation: Department of Pediatrics, University of Buffalo, Buffalo, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lakshminrusimha
authors.affiliation: Department of Pediatric Research, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: O D
authors.initials: OD
authors.lastname: Saugstad
authors.affiliation: Department of Pediatrics, Children's National Medical Center, Washington DC, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Steinhorn
mesh_terms: D015415:Biomarkers / Q000032:analysis; D006801:Humans; D000860:Hypoxia / Q000628:therapy*; D007231:Infant, Newborn; D010547:Persistent Fetal Circulation Syndrome / Q000628:therapy*; D010641:Phenotype; D057285:Precision Medicine / Q000639:trends; D011322:Primary Prevention; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000628:therapy*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D014665:Vasodilator Agents