Defining Treatment Response in Pediatric Asthma Pharmacogenomics: Comments on “Gene Polymorphisms Associated with Treatment Response of Asthma in Chinese Children” [Letter]

Abstract

I read with great interest the study by Zhu et al investigating genetic polymorphisms associated with asthma susceptibility and response to budesonide/formoterol in Chinese children. 1 Identifying reproducible pharmacogenomic markers of treatment response is an important step toward precision therapy in pediatric asthma. The reported associations between eight single-nucleotide polymorphisms (SNPs) and outcomes during 12 weeks of budesonide/formoterol treatment are therefore intriguing. Before these variants are interpreted as markers that could guide treatment selection, however, two aspects of the treatment-response phenotype deserve clarification. The first concerns the direction of ΔFEV1%. In the Methods, ΔFEV1% is defined as “FEV1% before inhaler therapy − FEV1% after 12 weeks of inhaler therapy”, while a ΔFEV1% ≥10% is simultaneously defined as clinically significant improvement. 1 These definitions point in opposite directions. If FEV1% increased from 70% to 85%, for example, the stated formula would yield −15 rather than +15. The Results, however, appear to use the opposite convention: a value of +16.97 in TBXT-rs2305089 C-allele carriers is described as improvement, whereas −9.10 in TT carriers is described as deterioration. A similar direction is used for LTA4H-rs2540487. 1 This may simply reflect a reversed equation in the Methods rather than an error in the underlying analysis. Nevertheless, the distinction is consequential because the reported efficacy rates for LTC4S-rs730012 and CYSLTR1-rs320995 are defined by the ΔFEV1% ≥10% threshold. 1