Modification by influenza on air pollution effects on hospitalization. The difficulty in assess‑ ing the interaction between influenza and air pollutants at the population level may occur partly because their seasonal peaks do not overlap. For example, in Hong Kong NO2 and PM10 are highest in December and January, SO2 is highest around August, and O3 peaks from September through December (data not shown), and influenza tends to reach peaks in January–February and May– July (Wong et al. 2004). Taking advantage of long‑ standing surveillance for air pollutants and influenza virus activity, we estimated the extent to which influenza modifies the effects of air pollutants in this study. Interestingly, our results suggest that positive effect modification of influenza on the effects of O3 might be more pronounced compared with its modification of the impact of the other three pollutants. O3 is a strong oxidative agent and also a potent pulmonary irritant. For effects of air pollution on mortal‑ ity, we found significant increases in influenza intensity only in the effect of O3 on RD and COPD; this result did not change the effects of the other air pollutants. For effects of air pollution on hospitalization, effect modifica‑ tion of influenza on the effects of O3 could be detected for ARD, RD, and COPD. However, for the other three pollutants, we detected such modification only for one of the three RD categories (i.e., NO2 for COPD, SO2 for ARD, and PM10 for RD). Several laboratory‑based studies have demonstrated the positive interaction between effects of O3 and influenza. In a study using mice, con‑ tinuous exposure of 0.5 ppm (1.0 mg/m3) O3 attenuated acute lung damage during early influenza infection but, conversely, exacer‑ bated long‑term lung injury (Jakab and Bassett 1990). Studies on respiratory viruses other than influenza also suggested a possible synergistic effect of O3 on respiratory infec‑ tion. For example, exposure to 0.2 ppm (0.4 mg/m3) O3 has been reported to increase the efficiency of rhinovirus infection of respiratory epithelial cells from 41% to 67%, and this effect could be attenuated by the use of anti‑ oxidants (Spannhake et al. 2002). Exposure to 0.2 ppm O3 markedly increased adhesion of polymorphonuclear leukocytes (PMNs) to human tracheal epithelial cells (Tosi et al. 1994). However, another study in young male volunteers showed that intermittent exposure to 0.3 ppm O3 after infection by rhinovirus did not change adhesion of PMNs to the nasal epithelium, or levels of interferon (Henderson et al. 1988). Interaction between influenza and O3 needs more support from laboratory studies. Table 4. Modifying effects of influenza for PM10 and O3 effects on hospitalization. Age group (years) Modifying effecta 95% CI p-Value ER –0.16 –0.15 0.13 –0.11 –0.14 0.09 –0.02 –0.12 0.24 0.40 0.46 –0.19 0.17 0.40 0.20 0.21 0.05 0.38 0.22 0.48 0.01 –0.27 0.05 –0.19 0.02 0.25 0.63 0.88 0.21 0.30 0.14 0.17 –0.34 to 0.01 –0.36 to 0.06 –0.14 to 0.40 –0.40 to 0.19 –0.40 to 0.12 –0.19 to 0.37 –0.20 to 0.16 –0.33 to 0.09 0.04 to 0.43 0.16 to 0.64 0.15 to 0.76 –0.51 to 0.13 –0.14 to 0.48 0.07 to 0.73 –0.02 to 0.41 –0.03 to 0.46 –0.18 to 0.27 0.08 to 0.69 –0.03 to 0.48 0.15 to 0.82 –0.31 to 0.33 –0.67 to 0.14 –0.30 to 0.41 –0.65 to 0.28 –0.32 to 0.36 –0.15 to 0.65 0.19 to 1.07 0.36 to 1.40 –0.06 to 0.49 –0.03 to 0.62 –0.13 to 0.41 –0.14 to 0.47 All ≥ 65 All 0–14 All ≥ 65 All ≥ 65 All ≥ 65 All 0–14 All ≥ 65 All ≥ 65 All ≥ 65 All ≥ 65 All 0–14 All 0–14 All ≥ 65 All ≥ 65 All ≥ 65 All ≥ 65 NS NS NS NS NS NS NS NS * # ** NS NS * NS NS NS * NS ** NS NS NS NS NS NS ** # NS NS NS NS Pollutant PM10 O3 RD ARD COPD CVD Disease RD ARD COPD CVD RD ARD COPD CVD Male Female Male Female Male Female Male Female Abbreviations: CI, confidence interval; NS, not significant. aChange in ER per 10-µg/m3 increase in concentration of air pollutant averaged over the lag 0 and lag 1 days when influenza intensity changed from the baseline (0%) to the mean level (10%). bER per 10-µg/m3 increase in concentration of air pollutant averaged over the lag 0 and lag 1 days when influenza intensity is assumed equal to 0. cER per 10-µg/m3 increase in concentration of air pollutant averaged over the lag 0 and lag 1 days when intensity is assumed equal to 10% (mean level of influenza intensity). *0.01 < p ≤ 0.05; **0.001 < p ≤ 0.01; #p ≤ 0.001. Disease Table 5. The baseline and modifying effects of influenza for effects of O3 on hospitalization by sex. Age group Modifying effecta Baseline effectb Sex (years) ER 95% CI p-Value ER 95% CI Abbreviations: CI, confidence interval; NS, not significant. aChange in ER per 10-µg/m3 increase in concentration of air pollutant averaged over the lag 0 and lag 1 days when influenza intensity changed from the baseline (0%) to the mean level (10%). bER per 10-µg/m3 increase in concentration of air pollutant averaged over the lag 0 and lag 1 days when influenza intensity is assumed equal to 0. cER per 10-µg/m3 increase in concentration of air pollutant averaged over the lag 0 and lag 1 days when intensity is assumed equal to 10% (mean level of influenza intensity). *0.01 < p ≤ 0.05; **0.001 < p ≤ 0.01; #p ≤ 0.001. Environmental Health Perspectives • volume 117 | number 2 | February 2009 251 ER 0.78 0.98 0.70 0.55 1.49 1.02 0.64 0.90 0.60 0.53 0.84 0.94 1.39 0.70 0.00 –0.03 0.79 0.66 0.65 0.72 1.03 0.95 0.58 1.23 0.91 0.71 1.55 1.09 –0.10 –0.05 0.11 0.22 Baseline effectb 95% CI 0.51 to 1.06 0.64 to 1.32 0.24 to 1.16 0.06 to 1.03 1.06 to 1.92 0.55 to 1.49 0.35 to 0.93 0.57 to 1.23 0.32 to 0.88 0.17 to 0.89 0.37 to 1.31 0.43 to 1.45 0.93 to 1.85 0.19 to 1.20 –0.29 to 0.30 –0.37 to 0.31 0.46 to 1.13 0.20 to 1.11 0.26 to 1.04 0.20 to 1.25 0.52 to 1.54 0.31 to 1.59 0.01 to 1.15 0.49 to 1.98 0.40 to 1.43 0.10 to 1.32 0.87 to 2.23 0.27 to 1.91 –0.49 to 0.30 –0.53 to 0.42 –0.28 to 0.50 –0.23 to 0.66 p-Value # # ** * # # # # # ** # # # ** NS NS p-Value # ** ** ** # ** * ** # * # ** NS NS NS NS Effect at mean level of influenza intensityc ER 95% CI p-Value 0.62 0.41 to 0.82 # 0.82 0.57 to 1.08 # 0.83 0.48 to 1.18 # 0.44 0.08 to 0.81 * 1.34 1.02 to 1.67 # 1.11 0.75 to 1.47 # 0.62 0.40 to 0.84 # 0.78 0.53 to 1.03 # 0.84 0.61 to 1.06 # 0.93 0.64 to 1.22 # 1.30 0.91 to 1.68 # 0.75 0.34 to 1.16 # 1.56 1.18 to 1.93 # 1.10 0.69 to 1.52 # 0.20 –0.05 to 0.45 NS 0.18 –0.11 to 0.47 NS Effect at mean level of influenza intensityc ER 95% CI p-Value 0.84 0.57 to 1.11 # 1.04 0.68 to 1.41 # 0.87 0.56 to 1.19 # 1.21 0.79 to 1.63 # 1.03 0.63 to 1.44 # 0.68 0.17 to 1.19 ** 0.63 0.18 to 1.09 ** 1.04 0.45 to 1.64 # 0.93 0.51 to 1.35 # 0.96 0.47 to 1.46 # 2.19 1.63 to 2.75 # 1.97 1.31 to 2.65 # 0.11 –0.21 to 0.44 NS 0.24 –0.15 to 0.64 NS 0.25 –0.07 to 0.58 NS 0.38 0.02 to 0.75 *