In children and adolescents with cystic fibrosis (CF), early changes in blood protein levels after 28 days of treatment with azithromycin is associated with short-term, but not long-term, changes in lung function, as measured by forced expiratory volume in 1 second percent (FEV1 %) predicted. Results of the study were published in the journal CHEST.1

Investigators sought to determine protein biomarkers that are predictive of clinical response to azithromycin therapy in children and adolescents with CF. They used novel proteomic technologies to study 188 serum and plasma protein samples collected from 40 individuals who had received azithromycin in the AZ0004 clinical trial (ClinicalTrial.gov Identifier: NCT00431964).2 Changes in blood protein levels from day 0 to day 28 of treatment were evaluated relative to changes in FEV1 % predicted and weight by day 28 and day 168, and as a predictor of risk for pulmonary exacerbation.

Results of the study showed that early change in levels of 15 plasma proteins after treatment with 28 days of azithromycin correlated significantly with changes in FEV1 % predicted from day 0 to day 28 (q-value <.10). This change, however, was not sustained until day 168. Moreover, early change in serum calprotectin levels after 28 days of azithromycin treatment predicted risk for pulmonary exacerbation by day 168 of therapy (area under the receiver operating characteristics curve, 0.76; 95% CI, 0.57-0.95).

Use of receiver operating characteristic analysis was associated with a 28-day calprotectin change cutoff of -0.26 (sensitivity=0.88; specificity=0.68). Overall, 40% (6 of 15) of participants with a calprotectin change above the cutoff from day 0 to day 28 experienced ≥1 pulmonary exacerbation. In contrast, only 8% of participants with a calprotectin change below the cutoff experienced pulmonary exacerbation.

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The investigators concluded that early change in serum calprotectin predicts response to azithromycin with respect to modifying risk for pulmonary exacerbation. Serum calprotectin level thus represents a promising biomarker for identifying children and adolescents with CF who might derive a longer-term benefit from treatment with azithromycin. In addition, early changes in blood protein levels after 28 days of azithromycin are linked to short-term but not long-term changes in FEV1 % predicted.

References

  1. Dong K, Singh A, Ng RT, et al. Proteomic profiling to identify blood biomarkers predictive of response to azithromycin in children and adolescents with cystic fibrosis [published online June 12, 2019]. CHEST. doi:10.1016/j.chest.2019.05.017
  2. Saiman L, Anstead M, Mayer-Hamblett N, et al; for the AZ0004 Azithromycin Study Group. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010;303(17):1707-1715.