Susceptibility to virus infection with exposure to nitrogen dioxide

The interaction between nitrogen dioxide (NO2) exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, blinded trial that was conducted in an environmentally controlled research chamber over a three-year period. Healthy, non-smoking volunteers, 18 to 35 years old, who were seronegative to influenza A/Korea/82 (H3N2) virus, were randomly assigned either to breathe filtered clean air (clean air group) or nitrogen dioxide (exposure group) for two hours a day for three consecutive days. The nitrogen dioxide concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects after the second day of exposure. Only one of the 152 volunteers had any symptoms, and that subject had only a low-grade fever. No adverse changes in pulmonary function or nonspecific airway reactivity to methacholine were observed after 2 or 3 ppm nitrogen dioxide exposure, virus infection, or both. Infection was defined by virus recovery, a four-fold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups exposed to nitrogen dioxide and those breathing clean air were: 12/21 (2 ppm nitrogen dioxide) versus 15/23 (clean air) in Year 1; 17/22 (3 ppm nitrogen dioxide) versus 15/21 (clean air) in Year 2; and 20/22 (2 ppm nitrogen dioxide) and 20/22 (1 ppm nitrogen dioxide) versus 15/21 (clean air) in Year 3. Although the differences were not statistically significant, the groups exposed to 1 or 2 ppm nitrogen dioxide in the last year became infected more often (91 percent) than those breathing clean air (71 percent). The frequencies of infection in two of the four groups exposed to nitrogen dioxide were higher than the 56 to 73 percent infection rate observed in previous studies in healthy human volunteers with the same dose of ca-influenza A (H3N2) virus. Our findings suggest, but do not prove, that nitrogen dioxide alone may play a role in increasing the susceptibility of adults to respiratory virus infections.