Ambient Ozone Concentrations and the Risk of Perforated and Nonperforated Appendicitis: A Multicity Case-Crossover Study

Background: Environmental determinants of appendicitis are poorly understood. Past work suggests that air pollution may increase the risk of appendicitis. Objectives: We investigated whether ambient ground-level ozone (O(3)) concentrations were associated with appendicitis and whether these associations varied between perforated and nonperforated appendicitis. Methods: We based this time-stratified case-crossover study on 35,811 patients hospitalized with appendicitis from 2004 to 2008 in 12 Canadian cities. Data from a national network of fixed-site monitors were used to calculate daily maximum O(3) concentrations for each city. Conditional logistic regression was used to estimate city-specific odds ratios (ORs) relative to an interquartile range (IQR) increase in O(3) adjusted for temperature and relative humidity. A random-effects meta-analysis was used to derive a pooled risk estimate. Stratified analyses were used to estimate associations separately for perforated and nonperforated appendicitis. Results: Overall, a 16-ppb increase in the 7-day cumulative average daily maximum O(3) concentration was associated with all appendicitis cases across the 12 cities (pooled OR = 1.07; 95% CI: 1.02, 1.13). The association was stronger among patients presenting with perforated appendicitis for the 7-day average (pooled OR = 1.22; 95% CI: 1.09, 1.36) when compared with the corresponding estimate for nonperforated appendicitis [7-day average (pooled OR = 1.02, 95% CI: 0.95, 1.09)]. Heterogeneity was not statistically significant across cities for either perforated or nonperforated appendicitis (p > 0.20). Conclusions: Higher levels of ambient O(3) exposure may increase the risk of perforated appendicitis.