Validation of the human ozone challenge model as a tool for assessing anti-inflammatory drugs in early development.
This study aimed to test the utility of the ozone challenge model for profiling novel compounds designed to reduce airway inflammation. The authors used a randomized, double-dummy, double-blind, placebo-controlled 3-period crossover design alternating single orally inhaled doses of fluticasone propionate (inhaled corticosteroids, 2 mg), oral prednisolone (oral corticosteroids, 50 mg), or matched placebo. At a 2-week interval, 18 healthy ozone responders (>10% increase in sputum neutrophils) underwent a 3-hour ozone (250 ppb)/intermittent exercise challenge starting 1 hour after drug treatment. Airway inflammation was assessed at 2 hours (breath condensate) and 3 hours (induced sputum) after ozone challenge. Compared to placebo, pretreatment with inhaled corticosteroids or oral corticosteroids resulted in a significant reduction (mean [95% confidence interval]) of sputum neutrophils by 62% (35%, 77%) and 64% (39%, 79%) and of sputum supernatant myeloperoxidase by 55% (41%, 66%) and 42% (25%, 56%), respectively. The authors conclude that an optimized ozone challenge model (including ozone responders and ensuring adequate drug levels during exposure) may be useful for testing novel anti-inflammatory compounds in early development.
Holz
Olaf
O
Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Wöhrendamm 80, D-22927 Grosshansdorf, Germany.
Tal-Singer
Ruth
R
Kanniess
Frank
F
Simpson
Kathy J
KJ
Gibson
Anthony
A
Vessey
Rupert S J
RS
Janicki
Stanislawa
S
Magnussen
Helgo
H
Jörres
Rudolf A
RA
Richter
Kai
K
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001985:Bronchial Provocation Tests / Q000379:methods*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004341:Drug Evaluation / Q000379:methods*; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008954:Models, Biological; D010126:Ozone; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000378:metabolism
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D010126:Ozone; D011239:Prednisolone; D000068298:Fluticasone