Nemr S Eid, Adrian O’Hagan, Scott Bickel, Ronald Morton, Sarah Jacobson, John A Myers

Low-dose theophylline has been recognized for its ability to restore histone deacetylase-2 activity which leads to improved steroid responsiveness and thus improved clinical outcome. We retrospectively evaluated the effect of low-dose theophylline therapy in pediatric patients hospitalized for an acute asthma exacerbation as a proof of concept study. We compared patients who received low-dose theophylline (5-7 mg/kg/day) in addition to current standard of care to patients who were treated with current standard of care alone. The primary outcome of the study was hospital length of stay (LOS). Generalized linear mixed-effects modeling (GLMM) was used to test whether receiving theophylline independently predicted outcomes. A Cox (proportional hazards) regression model was also developed to examine whether theophylline impacted LOS. After adjustment for illness severity measures, theophylline significantly reduces LOS (β=-21.17, P<0.001), time to discontinue oxygen (β=-15.88, P=0.044), time to spirometric improvement (β=-16.60, P=0.014), and time to space albuterol (β=-23.2, P<0.001) as well as reduced costs (β=-US$2,746, P<0.001). Furthermore, theophylline significantly increased the hazards of being discharged from the hospital (hazards ratio =1.75, 95% confidence interval 1.20-2.54, P=0.004). There was no difference in side effects between patients who receive low-dose theophylline and those who did not. The results of this retrospective study suggest low-dose theophylline may have a positive effect in acute status asthmaticus. This study suggests that further research with a prospective, randomized, double-blinded, placebo controlled trial may be warranted to confirm and extend our findings.