Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza

Darwish, Ilyse; Miller, Chris; Kain, Kevin C.; Liles, W. Conrad

Influenza A viruses infect approximately 5-15% of the population, resulting in 250-500 thousands deaths each year (1) . The most widely used class of drugs for treatment of clinical influenza is the neuraminidase inhibitors, including oseltamivir and zanamivir. The clinical impact of these drugs is limited by the development of antiviral drug resistance. Specifically, decreased efficacy of neuraminidase inhibitors has been reported against seasonal H1N1 influenza and 2009 novel swine-origin H1N1 influenza, as well as avian influenza H5N1 virus (2) (3) (4) (5) (6) (7) (8) (9) . In addition, initiation of antiviral therapy in influenza A virus-infected individuals beyond the first 48-72 hours after the onset of influenza symptoms is asso-ciated with greater mortality and decreased antiviral efficacy compared with treatment initiated within 48-72 hours of symptom onset (10) (11) (12) (13) (14) (15) . These caveats underscore the need to develop novel and effective influenza therapeutic strategies. Further investigation of other intervention strategies which have shown promising results against influenza A viruses in vitro but have not been investigated in vivo are warranted.