| Peer-Reviewed

Effect of Inhaled Nitrogen Oxide on the Plasma Concentration of Cytokines and Endogenous Nitrogen Oxide

Received: 22 March 2021     Accepted: 7 April 2021     Published: 20 April 2021
Views:       Downloads:
Abstract

Rationale. The nitrogen oxide molecule (NO) is a fundamental factor of the anti-infectious resistance of an organism. Research objective. To evaluate the effectiveness and safety of the prevention of sepsis by the inhalation of nitrogen oxide (iNO) in newborns with respiratory pathology on artificial pulmonary ventilation. Methods. Controlled, randomized, blind clinical trial included 97 newborns with respiratory pathology for artificial pulmonary ventilation. Patients received standard intensive therapy. The main group (n=44) received inhaled nitrogen oxide. The control group (n=53) did not receive inhaled nitrogen oxide. On Days 1, 3, and 20, the plasma concentrations of IL-1ß, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, and nitrogen oxide were measured by capture ELISA. Results. Inhaled nitrogen oxide as a part of intensive care decreased the rate of sepsis development, the duration of mechanical ventilation, and the period of hospitalization. It provided a tendency towards a decrease in the rate of lethal outcomes and reduced cytokine aggression. Conclusions. Inhaled nitrogen oxide in standard intensive care effectively and safely prevented the development of sepsis in newborns with respiratory pathology on artificial lung ventilation. A decrease in the concentration of pro-inflammatory cytokines, including IL-6, against the background of nitrogen oxide inhalation, confirmed the possibility of using inhaled nitrogen oxide as a therapy for COVID-19.

Published in American Journal of Pediatrics (Volume 7, Issue 2)
DOI 10.11648/j.ajp.20210702.15
Page(s) 62-67
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Sepsis, Newborn, Nitrogen Oxide Inhalation

References
[1] Fleischmann C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. The Lancet Respiratory medicine; 2018; 6 (3): 223-30.
[2] Charles E, Hunt KA, Harris C, Hickey A, Greenough A. Small for gestational age and extremely low birth weight infant outcomes. J Perinat Med; 2019; 47: 247–51. https://doi.org/10.1515/jpm-2018-0295. Search in Google Scholar
[3] Solov'eva AG, Kuznetsova VL, Peretyagin SP, Didenko N., Dudar AI. The Role of Nitric Oxide in Free-radical Oxidation Processes. Bulletin of the Russian Military Medical Academy; 2016; 53 (1): 228-233.
[4] Greenough A, Decobert F, Field D, et al. Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial. J Perinat Med. 2020; Sep 7:/j/jpme.ahead-ofprint/jpm-2020-0164/jpm-2020-0164.xml.
[5] Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2017b; Jan 3; 1: CD000509.
[6] Barrington KJ, Finer N, Pennaforte T, et al. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev. 2017a Jan 5; 1: CD000399.
[7] Wang X, Li B, Ma Y, et al. Effect of NO inhalation on ECMO use rate and mortality in infants born at or near term with respiratory failure. Medicine (Baltimore). 2019; 98 (41): 7139.
[8] Siefkes HM, Lakshminrusimha S. Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: an illustrated review. Arch Dis Childhood Fetal Neonatal Ed. 2021. doi: 10.1136/archdischild-2020-319705. [Epub ahead of print].
[9] Indo H. P. et al. A mitochondrial superoxide for oxidative stress diseases and aging. J. Clin. Biochem. Nutr. 2015; 1 (56): 1-7.
[10] Yu B, Ichinose F, Bloch DB, Zapol WM. Inhaled nitric oxide. Br. J. Pharmacol. 2019; 176 (2): 246–255. Published online 2018 Nov 16. doi: 10.1111/bph.14512.
[11] Novikov VE, Levchenkova OS, Pozhilova EV. Mitochondrial synthase of nitric oxide and its role in the mechanisms of cell adaptation to hypoxia. Reviews of clinical pharmacology and drug therapy; 2016; 14 (2): 38-46.
[12] Ahmed MS, Giesinger RE, Ibrahim M, Baczynski M, Louis D, McNamara KP, et al. Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxic pre-term neonates. J Paediatr Child Health. 2019; 55: 753–61. doi: 10.1111/jpc.14286.
[13] Pukhtinskaya M, Estrin V. Clinical and diagnostic value of plasma concentration of nitrogen oxide in newborn with respiratory disease. Critical Care; 2018; 22 (1): 018.
[14] Christmas P. Role of cytochrome P450s in inflammation. Adv Pharmacol. 2015; 74: 163–92. doi: 10.1016/bs.apha.2015.03.005.
[15] Cavalcante GC, Schaan AP, Cabral GF, Santana-da-Silva MN, Pinto P, Vidal AF, Ribeiro-Dos-Santos Â. A Cell's Fate: An Overview of the Molecular Biology and Genetics of Apoptosis. Int J Mol Sci. 2017; 4133 (2019).
[16] Savchenko AA, Borisov AG, Zdzitovetsky DE, Gvozdev II. Cytokine regulation of respiratory burst in blood neutrophils for prediction of abdominal sepsis in patients with extended purulent peritonitis. Medical Immunology; 2016; 18 (5): 475-482.
[17] Deppisch C, Herrmann G, Graepler-Mainka U et al. Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. Infection. 2016; 44: 513-520.
[18] Jamaati H, Mortaz E, Pajouhi Z et al. Nitric Oxide in the Pathogenesis and Treatment of Tuberculosis. Front. Microbiol. 2017; 8: 2008.
[19] Sekar K, Szyld E, McCoy M, Wlodaver A, Dannaway D, Helmbrecht A, et al. Inhaled nitric oxide as an adjunct to neonatal resuscitation in premature infants: a pilot, double blind, randomized controlled trial. Pediatr Res. 2020; 87: 523–8. doi: 10.1038/s41390-019-0643-x.
[20] Vieira F., Makoni M, Szyld E, Sekar K. The Controversy Persists: Is There a Qualification Criterion to Utilize Inhaled Nitric Oxide in Pre-term Newborns? Front. Pediatr., 31 March 2021 / https://doi.org/10.3389/fped.2021.631765.
[21] Burov AA, Grebennikov VA, Krychko DS. Draft clinical protocol for diagnosis and therapy of persistent pulmonary hypertension in newborns. Neonatology: news, opinions, training; 2014; 1 (3): 145-161.
[22] Hayes, Inc. Hayes Directory Review of Reviews. Inhaled nitric oxide for the treatment of respiratory failure in preterm newborns. Lansdale, Pa: Hayes, Inc.; 2018.
[23] Manja V, Guyatt G, Lakshminrusimha S, Jack S, Kirpalani H, Zupancic JAF, et al. Factors influencing decision making in neonatology: inhaled nitric oxide in pre-term infants. J Perinatol. 2019; 39: 86–94. doi: 10.1038/s41372-018-0258-9.
[24] Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst. Rev; 2006; 18 (4) CD000399.
[25] Ballard RA, Truog WE, Cnaan А. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N. Engl. J. Med.; 2006; 355: 343-353.
[26] De Nadai C, Sestili Р, Cantoni О, Lièvremont JP, Sciorati С, Barsacchi R. Nitric oxide inhibits tumor necrosis factor-alpha-induced apoptosis by reducing the generation of ceramide. Proc. Natl. Acad. Sci USA; 2000; 97 (10): 5480-5485.
[27] Alexandrovitch US, Vizisnov KV. Acute respiratory distress syndrome in pediatric practice. Messenger of intensive therapy; 2014; 3: 23-29.
[28] Boytsov EV, Bialashova MA, Ovsyannikov DU. Modern insights into interstitial lung diseases in children. Journal of the Russian Academy of Medical Sciences; 2015; 70 (2): 227-236.
Cite This Article
  • APA Style

    Vladimir Vladimirovich Estrin, Marina Gaevna Pukhtinskaya. (2021). Effect of Inhaled Nitrogen Oxide on the Plasma Concentration of Cytokines and Endogenous Nitrogen Oxide. American Journal of Pediatrics, 7(2), 62-67. https://doi.org/10.11648/j.ajp.20210702.15

    Copy | Download

    ACS Style

    Vladimir Vladimirovich Estrin; Marina Gaevna Pukhtinskaya. Effect of Inhaled Nitrogen Oxide on the Plasma Concentration of Cytokines and Endogenous Nitrogen Oxide. Am. J. Pediatr. 2021, 7(2), 62-67. doi: 10.11648/j.ajp.20210702.15

    Copy | Download

    AMA Style

    Vladimir Vladimirovich Estrin, Marina Gaevna Pukhtinskaya. Effect of Inhaled Nitrogen Oxide on the Plasma Concentration of Cytokines and Endogenous Nitrogen Oxide. Am J Pediatr. 2021;7(2):62-67. doi: 10.11648/j.ajp.20210702.15

    Copy | Download

  • @article{10.11648/j.ajp.20210702.15,
      author = {Vladimir Vladimirovich Estrin and Marina Gaevna Pukhtinskaya},
      title = {Effect of Inhaled Nitrogen Oxide on the Plasma Concentration of Cytokines and Endogenous Nitrogen Oxide},
      journal = {American Journal of Pediatrics},
      volume = {7},
      number = {2},
      pages = {62-67},
      doi = {10.11648/j.ajp.20210702.15},
      url = {https://doi.org/10.11648/j.ajp.20210702.15},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20210702.15},
      abstract = {Rationale. The nitrogen oxide molecule (NO) is a fundamental factor of the anti-infectious resistance of an organism. Research objective. To evaluate the effectiveness and safety of the prevention of sepsis by the inhalation of nitrogen oxide (iNO) in newborns with respiratory pathology on artificial pulmonary ventilation. Methods. Controlled, randomized, blind clinical trial included 97 newborns with respiratory pathology for artificial pulmonary ventilation. Patients received standard intensive therapy. The main group (n=44) received inhaled nitrogen oxide. The control group (n=53) did not receive inhaled nitrogen oxide. On Days 1, 3, and 20, the plasma concentrations of IL-1ß, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, and nitrogen oxide were measured by capture ELISA. Results. Inhaled nitrogen oxide as a part of intensive care decreased the rate of sepsis development, the duration of mechanical ventilation, and the period of hospitalization. It provided a tendency towards a decrease in the rate of lethal outcomes and reduced cytokine aggression. Conclusions. Inhaled nitrogen oxide in standard intensive care effectively and safely prevented the development of sepsis in newborns with respiratory pathology on artificial lung ventilation. A decrease in the concentration of pro-inflammatory cytokines, including IL-6, against the background of nitrogen oxide inhalation, confirmed the possibility of using inhaled nitrogen oxide as a therapy for COVID-19.},
     year = {2021}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Effect of Inhaled Nitrogen Oxide on the Plasma Concentration of Cytokines and Endogenous Nitrogen Oxide
    AU  - Vladimir Vladimirovich Estrin
    AU  - Marina Gaevna Pukhtinskaya
    Y1  - 2021/04/20
    PY  - 2021
    N1  - https://doi.org/10.11648/j.ajp.20210702.15
    DO  - 10.11648/j.ajp.20210702.15
    T2  - American Journal of Pediatrics
    JF  - American Journal of Pediatrics
    JO  - American Journal of Pediatrics
    SP  - 62
    EP  - 67
    PB  - Science Publishing Group
    SN  - 2472-0909
    UR  - https://doi.org/10.11648/j.ajp.20210702.15
    AB  - Rationale. The nitrogen oxide molecule (NO) is a fundamental factor of the anti-infectious resistance of an organism. Research objective. To evaluate the effectiveness and safety of the prevention of sepsis by the inhalation of nitrogen oxide (iNO) in newborns with respiratory pathology on artificial pulmonary ventilation. Methods. Controlled, randomized, blind clinical trial included 97 newborns with respiratory pathology for artificial pulmonary ventilation. Patients received standard intensive therapy. The main group (n=44) received inhaled nitrogen oxide. The control group (n=53) did not receive inhaled nitrogen oxide. On Days 1, 3, and 20, the plasma concentrations of IL-1ß, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, and nitrogen oxide were measured by capture ELISA. Results. Inhaled nitrogen oxide as a part of intensive care decreased the rate of sepsis development, the duration of mechanical ventilation, and the period of hospitalization. It provided a tendency towards a decrease in the rate of lethal outcomes and reduced cytokine aggression. Conclusions. Inhaled nitrogen oxide in standard intensive care effectively and safely prevented the development of sepsis in newborns with respiratory pathology on artificial lung ventilation. A decrease in the concentration of pro-inflammatory cytokines, including IL-6, against the background of nitrogen oxide inhalation, confirmed the possibility of using inhaled nitrogen oxide as a therapy for COVID-19.
    VL  - 7
    IS  - 2
    ER  - 

    Copy | Download

Author Information
  • Department of Anesthesiology and Resuscitation, State Medical University, Rostov-on-Don, Russia

  • Department of Anesthesiology and Resuscitation, State Medical University, Rostov-on-Don, Russia

  • Sections