Limitations of short-term studies in predicting long-term adverse effects of inhaled corticosteroids

This paper examines the value of short-term studies in predicting long-term , clinically relevant adverse effects of inhaled corticosteroids (ICS) in c hildren with asthma, increasing use of ICS in younger and less severely aff ected children with asthma justifies concern about long-term adverse effect s. For each system potentially affected by ICS, short-term and sensitive st udies have limited value in predicting clinically relevant effects, even wh en correlations are highly statistically significant. This is due to inhere nt limitations of the short-term tests utilized and normal physiologic Vari ations in systems being studied. Specific limitations include: 1) poor distinction between systemic presence of ICS and adverse systemic e ffects (e.g., integrated plasma cortisol) 2) lack of data validating the connection between test results and the end point in question (bone markers to predict growth and fracture risk) 3) sensitivity confounded by normal physiologic variation (knemometry to pr edict long-term growth). Consequently, predicting clinically relevant long-term effects from short-t erm studies detecting physiologic perturbations remains a challenge. Positi ve predictive value is improved by well-designed intermediate-term (>12 mon ths) studies utilizing dynamic hypothalamic-pituitary-adrenal (HPA) axis te sting, dual x-ray absorptiometry (DXA) scanning, or precise stadiometry. Ul timately, however, long-term studies are required to assess long-term risks , and the reliability of short-term assessments in predicting them.