Chest | 2019
Proteomic Profiling to Identify Blood Biomarkers Predictive of Response to Azithromycin in Children and Adolescents with Cystic Fibrosis.
Abstract
BACKGROUND\nAzithromycin reduces pulmonary exacerbation (PEx) risk in cystic fibrosis (CF) but not all individuals benefit. The goal of this study was to discover blood protein biomarkers predictive of clinical response to azithromycin treatment in CF children and adolescents.\n\n\nMETHODS\nNovel proteomic technologies were applied to examine 188 serum and plasma proteins from 40 CF subjects randomized to azithromycin in the AZ0004 trial. Early change in blood protein levels from day 0 to day 28 of treatment were examined in relation to changes in FEV1 % predicted (ppFEV1) and weight by day 28 and 168, and to predict PEx risk by day 168.\n\n\nRESULTS\nEarly change in the levels of 15 plasma proteins following 28 days of azithromycin significantly correlated with changes in ppFEV1 from day 0 to day 28 (q-value < 0.10) but this was not sustained to day 168. Early change in serum calprotectin levels following 28 days of azithromycin was predictive of PEx risk by day 168 of treatment (AUC = 0.76, 95% CI: 0.57-0.95). Based on a calprotectin cut-off to maximize test sensitivity (88%) and specificity (68%), 40% of subjects who had a calprotectin reduction less than the cut-off experienced at least one PEx compared to only 8% of subjects with calprotectin reduction greater than the cut-off.\n\n\nCONCLUSIONS\nEarly change in blood protein biomarkers following azithromycin treatment are associated with short but not longer-term changes in lung function. Early change in serum calprotectin is predictive of response to azithromycin in terms of modifying PEx risk.