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, doubledummy,
double-blind, placebo-controlled 3-period crossover design
alternating single orally inhaled doses of fluticasone propionate
(inhaled corticosteroids, 2mg), oral prednisolone (oral
corticosteroids, 50mg), ormatched 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.