Proteomic Profiling to Identify Blood Biomarkers Predictive of Response to Azithromycin in Children and Adolescents With Cystic Fibrosis.

Autor: Dong, Kang, Singh, Amrit, Ng, Raymond T., Sin, Don D., Tebbutt, Scott J., Ratjen, Felix, Quon, Bradley S.
Předmět:
Zdroj: CHEST; Oct2019, Vol. 156 Issue 4, p667-673, 7p
Abstrakt: Background: Azithromycin 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 children and adolescents with CF.Methods: Novel proteomic technologies were applied to examine 188 serum and plasma protein samples from 40 patients with CF who were randomized to receive azithromycin in the AZ0004 trial. Early changes in blood protein levels from day 0 to day 28 of treatment were examined in relation to changes in FEV1 percent predicted and weight by days 28 and 168, and to predict PEx risk by day 168.Results: Early changes in the levels of 15 plasma proteins following 28 days of azithromycin significantly correlated with changes in FEV1 percent predicted from day 0 to day 28 (Q value < 0.10), but this finding was not sustained to day 168. Early changes in serum calprotectin levels following 28 days of azithromycin were predictive of PEx risk by day 168 of treatment (area under the curve = 0.76; 95% CI, 0.57-0.95). Based on a calprotectin cutoff to maximize test sensitivity (88%) and specificity (68%), 40% of subjects who had a calprotectin reduction less than the cutoff experienced at least one PEx compared with only 8% of subjects with calprotectin reduction greater than the cutoff.Conclusions: Early changes in blood protein biomarkers following azithromycin treatment were associated with short-term changes, but not longer term changes, in lung function. Early change in serum calprotectin level was predictive of response to azithromycin in terms of modifying PEx risk. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index