RESPIRATORY NITRIC-OXIDE LEVELS IN EXPERIMENTAL HUMAN INFLUENZA

Background: Exhaled oral nitric oxide (NO), a reported marker of infla mmation in the respiratory tract, can be elevated by ''upper respirato ry trace infections,'' However, the responsible viruses and the time c ourse of this rise in NO are not clear. Objective: To determine the ex pired nasal and oral NO levels during experimentally induced influenza A infection in 14 healthy volunteers without a history of asthma, rhi nitis, or sinusitis, Methods: After being housed in individual rooms, susceptible volunteers were inoculated with 10(6) 50% tissue culture i nfective dose of influenza A/Texas/36/91/(H1N1) virus on a single occa sion by intranasal drops. Volunteers remained in the isolation unit fo r 8 days and returned for follow-up 21 days after inoculation, Symptom scores and nasal washing for viral culture were obtained daily. NO sa mples from the mouth and nose were obtained on days 0 through 4, 8, an d 21 by having the patient perform a slow vital capacity maneuver thro ugh a plastic tube into a Mylar balloon, Results: All patients had inf luenza virus cultured from nasal washings (12 of 14 on day 1, 14 of 14 by day 5). Patient symptom scores peaked on day 3 (mean+/-SE; 15.4+/- 3.2) and returned to baseline by day 8. Preinfection exhaled nasal NO (right, 28.4+/-3.7 parts per billion [ppb]; left, 27.7+/-4.6 ppb) was significantly higher than oral NO (5.8 ppb; p<0.001). Exhaled oral NO was significantly elevated on day 8 postinoculation (12.9+/-0.8 ppb; p <0.01 Bonferroni) and returned to baseline at follow-up, Nasal NO leve ls showed a slight decrease on days 2 to 4 but returned to baseline by day 8, Conclusion: Experimental influenza virus infection can increas e oral but not nasal exhaled NO levels. The timing of exhaled NO chang es suggests that NO does not contribute to illness manifestations dire ctly.