We collected and calculated study means, medians, standard errors, standard deviations, 95% confidence interval, and inter-quartile ranges using the statistical algorithms in Microsoft Excel 2002. We then conducted fixed effect meta-analyses to obtain mean point estimates, 95% confidence intervals, and two standard deviations for each exacerbation level [40] . Exacerbation Severity Levels I and II, II and III, and I and III were each compared using a twotailed Z-test. The alpha level of p < 0.05 was adjusted for multiple testing according to the Bonferroni correction procedure [41] . In the event that a specific exacerbation severity level had a large number of studies in which only median data were available, the data were considered to be normally distributed and medians were treated as means. Since many studies did not publish data for individual patients, we were limited in addressing non-normality in the data by using a log 10 -transformation.