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Challenges, priorities and novel therapies for hypoxemic respiratory failure and pulmonary hypertension in the neonate

Journal of Perinatology volume 36, pages S32–S36 (2016)Cite this article

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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.

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Acknowledgements

This article is based on discussions at a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. Presentations and discussions were developed solely by the participants, without grantor input. The meeting chair (RHS) determined the agenda and attendees. JLA, JG, NA, JPK, GGK, SL, ODS and RHS developed the presentations and led the discussions upon which this article is based. Participants provided critical review and revisions to the outline and manuscript drafts, provided final approval of the version to be published, and are accountable for the integrity of the content and for addressing questions. Writing and editorial assistance was provided by John Kross, and Sharon Suntag and Julie Gerke of Quintiles.

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Authors and Affiliations

  1. Department of Pediatrics, and Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, The Children’s Hospital at Montefiore, Bronx, NY, USA

    J L Aschner

  2. Department of Pediatrics, Section of Neonatology, University of Colorado School of Medicine, Children’s Hospital Colorado, Aurora, CO, USA

    J Gien & J P Kinsella

  3. Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    N Ambalavanan

  4. Department of Pediatrics and Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA

    G G Konduri

  5. Department of Pediatrics, University of Buffalo, Buffalo, NY, USA

    S Lakshminrusimha

  6. Department of Pediatric Research, Oslo University Hospital, University of Oslo, Oslo, Norway

    O D Saugstad

  7. Department of Pediatrics, Children's National Medical Center, Washington DC, USA

    R H Steinhorn

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  1. J L Aschner
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  6. S Lakshminrusimha
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  8. R H Steinhorn
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Correspondence to J L Aschner.

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Competing interests

JLA, JG, NA, JPK, GGK, SL, ODS and RHS received honoraria for their participation in a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. JLA is named on an intellectual property rights patent for the use of intravenous citrulline for neonatal lung diseases. NA has received research support from Pfizer and has received research support as a mentor from Ikaria. GGK has received consulting fees from Boston Health Economics and Actelion Clinical Research. SL was a member of the speaker’s bureau for Ikaria from June 2010 to October 2014 and has received grant support from the American Academy of Pediatrics and Canadian Pediatric Society. RHS has received research grant support from Pfizer. NIH Grants: 1U01HL101456 (JLA); U01 HL122626 and R01 HD067126 (NA); 5R01HD072929-03 (SL); 5R01HL057268-11 (GGK); 5R01HL054705-13 (RHS).

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Aschner, J., Gien, J., Ambalavanan, N. et al. Challenges, priorities and novel therapies for hypoxemic respiratory failure and pulmonary hypertension in the neonate. J Perinatol 36 (Suppl 2), S32–S36 (2016). https://doi.org/10.1038/jp.2016.47

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