Abstract
Asthma patient response to inhaled corticosteroids (ICS) is variable and difficult to quantify. We aimed to define a measure of steroid response suitable for pharmacogenetic research in longitudinal and cross-sectional cohorts. Using longitudinal data from the Childhood Asthma Management Program (CAMP) asthma cohort, we defined the Cross-sectional Asthma STEroid Response (CASTER) measure in cross-sectional data. We then applied this to cross-sectional slices of four independent asthma cohorts: The Improving Asthma Control Trial (IMPACT), the Salmeterol or Corticosteroids Study (SOCS), the Pediatric Asthma Controller Trial (PACT), and the Genetics of Asthma in Costa Rica Study (GACRS). CASTER achieved high accuracy on the childhood asthma cohorts: GACRS, PACT, and also on cross-sectional data from CAMP (AUCs 82%, 71%, 63%, respectively). This demonstrates that select cross-sectional clinical information is sufficient to identify good and poor responders to ICS treatment in childhood asthma. Thus, CASTER represents a major improvement in the usability and applicability of steroid response measures in asthma research.
Highlights
Inhaled corticosteroids (ICS) are the most commonly prescribed controller medications for asthma
Bursts was more variable with Childhood Asthma Management Program (CAMP) (1.4 +/− 1.8) and Genetics of Asthma in Costa Rica Study (GACRS) (1.9 +/− 0.66) having more than Pediatric Asthma Controller Trial (PACT) (0.88 +/− 1.0), and Improving Asthma Control Trial (IMPACT) (.17 +/− 0.43) and Salmeterol or Corticosteroids Study (SOCS) (0.17 +/− 0.42) having much fewer
bronchodilator response (BDR): Bronchodilator response to Albuterol, percentage change in FEV1. * In GACRS all subjects were on ICS, and we report here the number with at least one asthma-related emergency department (ED) visit/hospitalization, which was used as the proxy for ICS response. p-values computed with ANOVA
Summary
Inhaled corticosteroids (ICS) are the most commonly prescribed controller medications for asthma. ICS are among the most effective medications for preventing future asthma exacerbations, an estimated 25–30% of patients do not respond to ICS therapy [1,2]. Steroid-resistant asthma is generally more severe, and, by virtue of being resistant to ICS, harder to treat, and results in a greater proportion of the costs incurred nationally by asthma morbidity [3]. Steroid-resistant asthma is etiologically different from allergic asthma in that it is usually not a result of type-2 cytokine inflammation. This can occur through a number of mechanisms, including malfunction of the glucocorticoid receptor [4] and viral or bacterial respiratory infections [5]. The mechanisms of steroid resistance have been recently reviewed by Wadwha et al [5]
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