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Impact of azithromycin on serum inflammatory markers in children with cystic fibrosis and new Pseudomonas

Published:March 05, 2022DOI:https://doi.org/10.1016/j.jcf.2022.02.015

      Highlights

      • Decrease in high sensitivity C-reactive protein (hsCRP) from baseline to week 39 in the OPTIMIZE clinical trial was significantly larger in the azithromycin treated group than placebo.
      • No difference between the groups was seen in hsCRP at 78 weeks compared to baseline.
      • Calprotectin, myeloperoxidase, absolute neutrophil count and total white blood cell count showed no differences between groups at any time point.
      • The findings are consistent with a transient systemic immunomodulatory effect of azithromycin in children with new pseudomonas.

      Abstract

      Chronic azithromycin improves outcomes in cystic fibrosis (CF), but its mechanism of action is unclear. The OPTIMIZE trial demonstrated improvement in time to first pulmonary exacerbation in children with new Pseudomonas treated with azithromycin. Azithromycin effect on systemic markers of inflammation over 18 months was assessed by change from baseline for high-sensitivity C-reactive protein, myeloperoxidase, calprotectin and absolute neutrophil count in the OPTIMIZE population. Subjects treated with chronic azithromycin or placebo had samples collected at baseline, 39 and 78 weeks of treatment. In 129 subjects, a significant decrease in high-sensitivity C-reactive protein was present at 39 weeks in the azithromycin group compared to placebo, but no significant difference between the groups at 78 weeks. No differences in change from baseline in myeloperoxidase, calprotectin or absolute neutrophil count were present at either time point. This supports the concept of a transient immunomodulatory effect for chronic azithromycin therapy in children with CF.

      Keywords

      Abbreviations:

      ANC (absolute neutrophil count), DSMB (data safety monitoring board), hsCRP (high-sensitivity c-reactive protein), MPO (myeloperoxidase), Pa (Pseudomonas aeruginosa), PEx (pulmonary exacerbation), SAA (serum amyloid)
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