James F Chmiel1, Michael W Konstan2, Frank J Accurso3, James Lymp4, Nicole Mayer-Hamblett5, Donald R VanDevanter6, Lynn M Rose5, Bonnie W Ramsey5. 1. Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA. Electronic address: james.chmiel@uhhospitals.org. 2. Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA. 3. Children's Hospital Colorado and University of Colorado, 13123 East 16th Avenue, Aurora, CO 80045, USA. 4. Seattle Children's Hospital Research Institute and Cystic Fibrosis Therapeutics Development Network Coordinating Center, 2001 Eighth Avenue, Seattle, WA 98121, USA. 5. Seattle Children's Hospital and University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA. 6. Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA.
Abstract
BACKGROUND: High-dose ibuprofen (HDI) is a clinically beneficial anti-inflammatory regimen that may be a useful reagent to study induced sputum inflammatory marker changes over short study periods appropriate for early-phase CF clinical trials. METHODS: We conducted a 28-day, open-label, randomized, controlled trial among 72 clinically stable CF subjects (FEV1≥40% predicted) randomized to HDI or routine care that assessedIL-6, IL-8, TNF-α, IL-1-β, free neutrophil elastase, and white cell counts with differentials change from baseline in induced sputum. RESULTS:IL-6 was the only biomarker with significant within-group change: 0.13 log10 pg/mL mean reduction among ibuprofen-treated subjects (p=0.04); and no change in the control group. IL-6 change between groups was statistically significant (p=0.024). No other inflammatory biomarker differences were observed between groups after 28 days. CONCLUSION: Although we studied only one agent, HDI, these results suggest that one month may be inadequate to assess anti-inflammatory candidates using markers from induced sputum.
RCT Entities:
BACKGROUND: High-dose ibuprofen (HDI) is a clinically beneficial anti-inflammatory regimen that may be a useful reagent to study induced sputum inflammatory marker changes over short study periods appropriate for early-phase CF clinical trials. METHODS: We conducted a 28-day, open-label, randomized, controlled trial among 72 clinically stable CF subjects (FEV1≥40% predicted) randomized to HDI or routine care that assessed IL-6, IL-8, TNF-α, IL-1-β, free neutrophil elastase, and white cell counts with differentials change from baseline in induced sputum. RESULTS:IL-6 was the only biomarker with significant within-group change: 0.13 log10 pg/mL mean reduction among ibuprofen-treated subjects (p=0.04); and no change in the control group. IL-6 change between groups was statistically significant (p=0.024). No other inflammatory biomarker differences were observed between groups after 28 days. CONCLUSION: Although we studied only one agent, HDI, these results suggest that one month may be inadequate to assess anti-inflammatory candidates using markers from induced sputum.
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Authors: J Stuart Elborn; Michael W Konstan; Jennifer L Taylor-Cousar; Isabelle Fajac; Alexander Horsley; Sivagurunathan Sutharsan; Shawn D Aaron; Cori L Daines; Ahmet Uluer; Damian G Downey; Vincenzina V Lucidi; Sanjeev Ahuja; Eric Springman; John Mershon; Ralph Grosswald; Steven M Rowe Journal: J Cyst Fibros Date: 2021-09-17 Impact factor: 5.482