Nitric Oxide Metabolites as Biomarkers for Influenza-Like Acute Respiratory Infections Presenting to the Emergency Room

Asad I Mian*, 1, Federico R Laham2, #, Andrea T Cruz1, 2, Harsha Garg3, Charles G Macias1, A. Chantal Caviness1, Pedro A Piedra2, 4
1 Dept of Pediatrics, Section of Emergency Medicine, Texas Children’s Hospital, Baylor College of Medicine, Houston TX 77030, USA
2 Dept. of Pediatrics, Section of Infectious Diseases, Texas Children’s Hospital, Baylor College of Medicine, Houston TX 77030, USA
3 Brown Foundation Institute of Molecular Medicine, University of Texas - Houston Health Science Center, Houston TX 77030, USA
4 Molecular Virology & Microbiology, Baylor College of Medicine, Houston TX 77030, USA

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© Mian et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Dept. of Pediatrics, Section of Emergency Medicine, Texas Children’s Hospital, Baylor College of Medicine, 1102 Bates Street, FC 1850.00, Houston, TX. 77030, USA; Tel: 832-824-5497; Fax: 832-825-1181; E-mail:
# Current affiliation: Pediatric Infectious Diseases Practice, Arnold Palmer Hospital for Children, Orlando FL 32806, USA



Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic.


Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR.


Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002).


Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner.

Keywords: Acute respiratory infections, emergency department, nitrate, Novel H1N1, pediatrics, RSV..