Challenges, priorities and novel therapies for hypoxemic respiratory failure and pulmonary hypertension in the neonate. J Perinatol 2016 Jun;36 Suppl 2:S32-6
Date
05/27/2016Pubmed ID
27225964DOI
10.1038/jp.2016.47Scopus ID
2-s2.0-84971426679 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
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.
Author List
Aschner JL, Gien J, Ambalavanan N, Kinsella JP, Konduri GG, Lakshminrusimha S, Saugstad OD, Steinhorn RHAuthor
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BiomarkersHumans
Hypoxia
Infant, Newborn
Persistent Fetal Circulation Syndrome
Phenotype
Precision Medicine
Primary Prevention
Randomized Controlled Trials as Topic
Respiration, Artificial
Respiratory Insufficiency
Vasodilator Agents