MOSES Trial Protocol
Overview of the MOSES Trial
The MOSES (Multicenter Ozone Study in Older Subjects) trial was a randomized crossover, controlled exposure study designed to assess acute cardiovascular and respiratory effects of low-level ozone exposure in older healthy adults. 1
Study Design and Population
- The trial enrolled 87 healthy adults with a mean age of 59.9 ± 4.5 years, of whom 60% were female 1
- Participants were exposed to three different ozone concentrations (0,70, and 120 ppb) in a randomized crossover design 1
- Each exposure session lasted 3 hours with intermittent exercise to simulate real-world conditions 1
- The trial was registered at www.clinicaltrials.gov under identifier NCT01487005 1
Primary Focus and Outcome Measures
- While the primary focus was on acute cardiovascular effects, the trial also evaluated respiratory responses to ozone exposure 1
- Respiratory outcome measures included spirometry (FEV1 and FVC), sputum markers of airway inflammation, and plasma club cell protein-16 (CC16) as a marker of airway epithelial injury 1
- Statistical significance was defined a priori as P < 0.01, with mixed-effect linear models used to evaluate ozone effects 1
Key Findings
Lung Function Effects
- After filtered air exposure (0 ppb), mean FEV1 and FVC increased by 2.7% (95% CI: 2.0-3.4) and 2.1% (95% CI: 1.3-2.9), respectively, at 15 minutes post-exposure 1
- Ozone exposure reduced these increases in a concentration-dependent manner, with 120 ppb exposure causing FEV1 to decrease by 1.7% (95% CI: 1.1-2.3) and FVC by 0.8% (95% CI: 0.3-1.3) 1
- The concentration-dependent pattern remained discernible 22 hours after exposure 1
Airway Injury and Inflammation
- Plasma CC16 increased from preexposure levels in an ozone concentration-dependent manner at 4 hours post-exposure 1
- Sputum neutrophils obtained 22 hours after exposure showed a marginally significant increase in a concentration-dependent manner (P = 0.012) 1
- Proinflammatory cytokines (IL-6, IL-8, and tumor necrosis factor-α) were not significantly affected 1
Clinical Significance
The MOSES trial demonstrated that exposure to ozone at near ambient levels (70-120 ppb) induced measurable lung function decrements, airway injury, and airway inflammation in older healthy adults, establishing that even low-level environmental ozone exposure has clinically relevant respiratory effects in this population. 1