Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa

Abstract

Background: While the mechanism of action by which azithromycin exerts positive effects inpatients with cystic fibrosis remains unclear, evidence suggests that azithromycin may act as an immunomodulatory agent. We examined changes in systemic inflammatory markers in a doubleblind, randomized, controlled trial of oral azithromycin in patients 6-18 years of age with cystic fibrosis who were uninfected with Pseudomonas aeruginosa.

Methods: WBC counts and differential, serum myeloperoxidase (MPO), high-sensitivity C reactive protein (hsCRP), intracellular adhesion molecule 1, IL-6, calprotectin, serum amyloid A (SAA),and granulocyte colony-stimulating factor (G-CSF) were measured at baseline and after 28 and 168 days of treatment in patients receiving either oral azithromycin or placebo.

Results: Inflammatory markers were similar in both groups at baseline. HsCRP, MPO, SAA, calprotectin,and the absolute neutrophil count (ANC) significantly decreased from baseline today 28 in the azithromycin group compared with the placebo group ( P < .05). This treatment effect was sustained at day 168 for ANC, calprotectin, and SAA ( P < .05). Changes in hsCRP, calprotectin,and SAA at day 28 were negatively correlated with changes in FEV 1 (L) and FEV 1(% predicted), as well as both absolute and relative changes in weight ( P < .05). Except for weight (%),the associations remained significant for calprotectin; FEV 1 (L) and weight (%) remained significantly correlated with the 168-day change in hsCRP. The 168-day change in ANC was significantly correlated with changes in lung function, but not in weight; the change in G-CSF was significantly correlated with the change in weight (%) only.

Conclusions: In patients not infected with P aeruginosa , oral azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment.

Trial registry: ClinicalTrials.gov; No.: NCT00431964; URL: www.clinicaltrials.gov

Figures

Figure 1.

Changes in absolute neutrophil counts, serum amyloid A, and calprotectin during the 168-d study period. A, Absolute neutrophil counts. B, Calprotectin. C, Serum amyloid A. Absolute neutrophil counts, serum amyloid A, and calprotectin decreased significantly from baseline in the azithromycin group after 28 d, while no significant changes were observed in the placebo group. The asterisk shows significant differences between the azithromycin and the placebo group. Similar trends were observed at day 168, but the differences were less pronounced and reached the level of statistical significance only for calprotectin and serum amyloid A.

Figure 2.

Forest plot of correlations between baseline measures of inflammation and baseline FEV1 in L and % predicted, as well as absolute and relative weight change. A, after 28 d of treatment. B, After 168 d of treatment. The mean and 95% CI are shown for the correlations; correlations are significant if the CI does not cross zero. ANC = absolute neutrophil count; G-CSF = granulocyte colony-stimulating factor; hsCRP = high-sensitivity C reactive protein; MPO = myeloperoxidase; SAA = serum amyloid.

Figure 3.

Forest plot of correlations changes in markers of inflammation and FEV1 in L and % predicted, as well as absolute and relative weight change. A, At day 28. B, At day 168. The mean and 95% CI of the correlations are shown; correlations are significant if the CI does not cross zero. See Figure 2 legend for expansion of abbreviations.