Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index

Abstract

Background: A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials.

Objective: This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy.

Methods: The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab.

Results: A higher saEPI was associated with an exacerbation in both the GBT alone (P < .001; area under the curve, 0.76) and the GBT + omalizumab group (P < .01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups.

Conclusions: An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.

Keywords: Fall asthma exacerbation; Seasonal Asthma Exacerbation Predictive Index (saEPI); asthma exacerbation predictors; guidelines-based therapy; omalizumab.

Figure 1

Association between saEPI and the probability of an asthma exacerbation. Risk score on the x-axis is composite saEPI score, y-axis represents the probability of having an exacerbation in the 90 day PROSE treatment period. The shaded areas represent the 95% confidence interval. The saEPI successfully predicts exacerbations in the fall treatment period.

Figure 2

Relative importance of index variables for predicting exacerbations during the intervention period. Bar length represents the independent % contribution of the variable in explaining exacerbations. The numbers at the end of each bar represent the independent effect of each variable.