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

Felix Ratjen, Lisa Saiman, Nicole Mayer-Hamblett, Larry C. Lands, Margaret Kloster, Valeria Thompson, Peggy Emmett, Bruce Marshall, Frank Accurso, Scott Sagel, Michael Anstead

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Background: While the mechanism of action by which azithromycin exerts positive effects in patients with cystic fibrosis remains unclear, evidence suggests that azithromycin may act as an immunomodulatory agent. We examined changes in systemic inflammatory markers in a double-blind, 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 to day 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 FEV1 (L) and FEV1 (% predicted), as well as both absolute and relative changes in weight (P < .05). Except for weight (%), the associations remained significant for calprotectin; FEV1(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.

Original languageEnglish
Pages (from-to)1259-1266
Number of pages8
JournalChest
Volume142
Issue number5
DOIs
StatePublished - Nov 2012

Bibliographical note

Funding Information:
Funding/Support: This research was funded by the Cystic Fibrosis Foundation, and grants from the National Institutes of Health/National Heart, Lung and Blood Institute [Grant 1 U01 HL081335-01] and National Center for Research Resources [Grant 1 UL1 RR025780].

Funding Information:
Financial/nonfinancial disclosures: The authors have reported the following conflicts of interest: Dr Ratjen has received funding from the Canadian Institutes of Health Research, National Institutes of Health, Cystic Fibrosis Foundation, and Cystic Fibrosis Canada. He also acts as a consultant for Bayer AG; Genentech, Inc; Novartis AG; Talecris; and Vertex Pharmaceuticals Inc. The remaining authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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