Felix Ratjen1, Lisa Saiman2, Nicole Mayer-Hamblett3, Larry C Lands4, Margaret Kloster3, Valeria Thompson3, Peggy Emmett5, Bruce Marshall6, Frank Accurso5, Scott Sagel5, Michael Anstead7. 1. Division of Respiratory Medicine, Department of Pediatrics, and Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, and University of Toronto, Toronto, ON, Canada. Electronic address: felix.ratjen@sickkids.ca. 2. Department of Pediatrics, Columbia University, New York, NY. 3. University of Washington, Seattle, WA. 4. Department of Pediatrics, McGill University, Montreal, QC, Canada. 5. University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO. 6. Cystic Fibrosis Foundation, Bethesda, MD. 7. Children's Hospital, Lexington, KY.
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
RCT Entities:
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
Authors: Hara Levy; Leslie A Kalish; Ian Huntington; Nathaniel Weller; Craig Gerard; Edwin K Silverman; Juan C Celedón; Gerald B Pier; Scott T Weiss Journal: Pediatr Pulmonol Date: 2007-03
Authors: P Zarogoulidis; N Papanas; I Kioumis; E Chatzaki; E Maltezos; K Zarogoulidis Journal: Eur J Clin Pharmacol Date: 2011-11-22 Impact factor: 2.953
Authors: Geert M Verleden; Bart M Vanaudenaerde; Lieven J Dupont; Dirk E Van Raemdonck Journal: Am J Respir Crit Care Med Date: 2006-06-01 Impact factor: 21.405
Authors: Brian D Corbin; Erin H Seeley; Andrea Raab; Joerg Feldmann; Michael R Miller; Victor J Torres; Kelsi L Anderson; Brian M Dattilo; Paul M Dunman; Russell Gerads; Richard M Caprioli; Wolfgang Nacken; Walter J Chazin; Eric P Skaar Journal: Science Date: 2008-02-15 Impact factor: 47.728
Authors: Scott D Sagel; Brandie D Wagner; Assem Ziady; Tom Kelley; John P Clancy; Monica Narvaez-Rivas; Joseph Pilewski; Elizabeth Joseloff; Wei Sha; Leila Zelnick; Kenneth D R Setchell; Sonya L Heltshe; Marianne S Muhlebach Journal: J Cyst Fibros Date: 2019-12-20 Impact factor: 5.482
Authors: Philip A Reid; David A McAllister; A Christopher Boyd; J Alastair Innes; David Porteous; Andrew P Greening; Robert D Gray Journal: Am J Respir Crit Care Med Date: 2015-01-15 Impact factor: 21.405
Authors: Charles R Esther; Marianne S Muhlebach; Camille Ehre; David B Hill; Matthew C Wolfgang; Mehmet Kesimer; Kathryn A Ramsey; Matthew R Markovetz; Ian C Garbarine; M Gregory Forest; Ian Seim; Bryan Zorn; Cameron B Morrison; Martial F Delion; William R Thelin; Diane Villalon; Juan R Sabater; Lidija Turkovic; Sarath Ranganathan; Stephen M Stick; Richard C Boucher Journal: Sci Transl Med Date: 2019-04-03 Impact factor: 17.956
Authors: Marianne S Muhlebach; J P Clancy; Sonya L Heltshe; Assem Ziady; Tom Kelley; Frank Accurso; Joseph Pilewski; Nicole Mayer-Hamblett; Elizabeth Joseloff; Scott D Sagel Journal: J Cyst Fibros Date: 2016-10-27 Impact factor: 5.482
Authors: Steven M Rowe; Drucy S Borowitz; Jane L Burns; John P Clancy; Scott H Donaldson; George Retsch-Bogart; Scott D Sagel; Bonnie W Ramsey Journal: Thorax Date: 2012-10 Impact factor: 9.139
Authors: James F Chmiel; Timothy R Aksamit; Sanjay H Chotirmall; Elliott C Dasenbrook; J Stuart Elborn; John J LiPuma; Sarath C Ranganathan; Valerie J Waters; Felix A Ratjen Journal: Ann Am Thorac Soc Date: 2014-10