Enhanced AHR in asthmatic mice with A(H1N1)pdm09 infection
The central airway resistance revealed by the Rrs value was significantly increased in the A(H1N1)pdm09 mouse group compared to that in the seasonal H1N1 mouse or control group (Fig. 2 ); this was particularly prominent after treatment with 48 mg/mL methacholine at 3 and 7 days after infection [3 days post-infection A(H1N1)pdm09vs. seasonal; 4.40 vs. 3.29 cmH2O.s/mL, p < 0.001, vs. control; vs. 3.11 cmH2O.s/mL, p < 0.001; 7 days post-infection A(H1N1)pdm09 vs. seasonal; 8.60 vs. 3.24 cmH2O.s/mL, p < 0.001, vs. control;vs. 3.00 cmH2O.s/mL, p < 0.001]. However, there was no significant difference among the three groups at 10 days post-infection. In contrast, there were no significant differences in the Rrs between the seasonal H1N1 and mock groups at 3, 7, or 10 days post-infection.
Next, peripheral airway resistance as reflected by G was compared among the three groups (Fig. 3 ). The peripheral airway resistance was also significantly increased in the A(H1N1)pdm09 group compared to that in the seasonal H1N1 and control groups; this difference was particularly prominent after treatment with 48 mg/mL methacholine at 3 and 7 days post-infection [3 days post-infection A(H1N1)pdm09 vs. seasonal; 25.2 vs. 16.5 cmH2O/mL, p < 0.001, vs. control; vs. 15.5 cmH2O/mL, p < 0.001; 7 days post-infection A(H1N1)pdm09 vs. seasonal; 50.0vs. 16.7 cmH2O/mL, p < 0.001,vs. control; vs. 15.6 cmH2O/mL, p < 0.001]. However, these differences in airway resistance were not significantly different among the three groups at 10 days post-infection.
We investigated the changes in AHR of non-asthmatic mice with A(H1N1)pdm09 infection (Figs. 2, 3 ). Although AHR was enhanced with A(H1N1)pdm09 infection in non-asthmatic mice, the changes in AHR were slight compared to the changes observed in asthmatic mice, suggesting that A(H1N1)pdm09 infection more robustly enhances AHR in asthmatic animals.
We further evaluated the alternations of AHR in asthmatic mice during the post-infection period of A(H1N1)pdm09 infection (Fig. 4 ). Airway resistance was significantly enhanced at 7 days post-infection compared to at 3- or 10-days post-infection (p < 0.001), whereas there were no differences in airway resistance between 3 and 10 days post-infection. When the body weight of mice was compared among the three groups to evaluate the systemic damage caused by A(H1N1)pdm09 infection at 3, 7, or 10 days post-infection, no significant differences between days were detected (data not shown).