Fricker M, et al. - In a subpopulation of the AMAZES trial that demonstrated significantly reduced asthma exacerbations with azithromycin (AZM) add-on treatment for uncontrolled moderate-to-severe asthma, researchers assessed a sputum gene expression signature of six biomarkers (6GS) as a predictor of future exacerbation and inflammatory phenotypes. They also investigated the influence of AZM therapy on 6GS expression and prognostic capacity. Participants included 142 patients (73 placebo-treated, 69 AZM-treated) who were examined at baseline and after 48 weeks of treatment. All future exacerbation phenotypes tested were significantly predicted by the 6GS. Compared with AUCs for peripheral blood eosinophil counts, sputum neutrophil counts and combined sputum eosinophils and neutrophil counts, significantly higher AUCs were reported for 6GS. Albeit non-significant, 6GS AUCs were also numerically higher than FeNO and sputum eosinophil counts. On the 6GS expression, as well as the predictive capacity of the 6GS for future exacerbation phenotypes, no impact of AZM treatment was found. The 6GS significantly predicted airway inflammatory phenotype in this population.