Respiratory nitric oxide levels in experimental human influenza

Exhaled oral nitric oxide (NO), a reported marker of inflammation in the respiratory tract, can be elevated by "upper respiratory tract infections." However, the responsible viruses and the time course of this rise in NO are not clear.

To determine the expired nasal and oral NO levels during experimentally induced influenza A infection in 14 healthy volunteers without a history of asthma, rhinitis, or sinusitis.

After being housed in individual rooms, susceptible volunteers were inoculated with 10(6) 50% tissue culture infective dose of influenza A/Texas/36/91/(H1N1) virus on a single occasion by intranasal drops. Volunteers remained in the isolation unit for 8 days and returned for follow-up 21 days after inoculation. Symptom scores and nasal washing for viral culture were obtained daily. NO samples from the mouth and nose were obtained on days 0 through 4, 8, and 21 by having the patient perform a slow vital capacity maneuver through a plastic tube into a Mylar balloon.

All patients had influenza 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 levels showed a slight decrease on days 2 to 4 but returned to baseline by day 8.

Experimental influenza virus infection can increase oral but not nasal exhaled NO levels. The timing of exhaled NO changes suggests that NO does not contribute to illness manifestations directly.