TY - JOUR
T1 - Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa
AU - Ratjen, Felix
AU - Saiman, Lisa
AU - Mayer-Hamblett, Nicole
AU - Lands, Larry C.
AU - Kloster, Margaret
AU - Thompson, Valeria
AU - Emmett, Peggy
AU - Marshall, Bruce
AU - Accurso, Frank
AU - Sagel, Scott
AU - Anstead, Michael
N1 - 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
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
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U2 - 10.1378/chest.12-0628
DO - 10.1378/chest.12-0628
M3 - Article
C2 - 22595153
AN - SCOPUS:84866076450
SN - 0012-3692
VL - 142
SP - 1259
EP - 1266
JO - CHEST
JF - CHEST
IS - 5
ER -