NCT06943989

Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air at Rest

Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air for 6.6 Hours at Rest in Healthy Young Adults.

• Status: Enrolling By Invitation
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Environmental Protection Agency (EPA) · Federal
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

The primary purpose of this study is to measure pulmonary function, symptoms, and pulmonary inflammatory responses in healthy young adults during and immediately after exposure to a low concentration of ozone (0.070 ppm) or clean air for 6.6 hours while at rest. This concentration is the current EPA NAAQS standard for ozone.

Detailed description

Potential health effects of ozone have been extensively studied over decades at various levels of exposure concentration for varying time periods while at varying levels of exertion. The effects of ground level ozone exposure have been well documented, particularly for decrements in lung function and for markers of pulmonary inflammation, such as neutrophils in sputum. (1) The majority of previous studies were done at ozone concentrations between 0.12 and 0.40 ppm, for one to four hours of exposure, with moderate to intermittent exercise to simulate daily activities. These concentrations are considerably higher than the level of the current EPA National Ambient Air Quality Standards (NAAQS) ozone standard of 0.07 ppm (8-hour average). Only a small number of studies have assessed changes in lung function and inflammatory markers following longer exposure to ozone (2-10). These latter studies have shown that exposure to low concentrations of ozone for 6.6 hours at concentrations between 0.06 and 0.08 ppm while performing moderate exercise causes mild reversible decrements in lung function (\<5%) as measured by forced vital capacity (FVC) and forced expired volume at 1 s (FEV1) assessed immediately after exposure in healthy young adults. There are also many studies of ozone exposures which included healthy adults at rest that report a mix of respiratory effects, but these studies were carried out at very high concentrations ranging from 0.1 to 1.0 ppm for one-to-two-hour durations ppm is the lowest concentration eliciting lung function decrements in controlled human exposure studies of one-to-two-hour exposure with participants at rest (not exercising). Taken together, the controlled human exposure evidence suggests that ozone-induced respiratory effects are determined by the ozone concentration as well as the exposure duration and activity level of exposed participants. In the 2015 and 2020 O3 NAAQS reviews, the strongest evidence of respiratory effects causally related to short-term O3 exposures came from controlled human exposure studies reporting an array of respiratory effects in study participants while exercising moderately. The 2015 decision to revise the level of the standard to 70 ppb (and the 2020 decision to retain this standard), relied on 70 ppb being below the O3 exposure concentration (80 ppb) shown in 6.6 hour controlled human exposure studies with moderate exercise to result in the widest range of respiratory effects and below the lowest O 3 exposure concentration (73 ppb) shown to result in the adverse combination of lung function decrements and respiratory symptoms. In 2021, the EPA Administrator decided to reconsider the 2020 decision to retain the current O3 NAAQS. As part of that process EPA released a draft Policy Assessment (PA) for the Reconsideration of the Ozone National Ambient Air Quality Standards v.2 (draft PA) that concluded that the available evidence was largely unchanged since the 2015 and 2020 reviews provided support for retaining the current primary standard. As part of the reconsideration process, EPA had provisionally considered a recent controlled human exposure study by Hernandez et al., (2021) which reported a small but significant change in lung function (FEV1 decrement) in 14 participants exposed largely at rest to an average O3 concentration of 70 ppb for 6.6 hours (Duffney Memo 2021). EPA noted that this study was designed to test the responsiveness of air quality sensors under rapidly changing air quality conditions and utilized an unusual exposure protocol that differed from protocols used in other controlled human exposure studies, including those with or without exercise. Specifically, the O 3 concentrations were changed from 60 ppb to 80 ppb then back to 60 ppb during each hour of the study. This pattern and magnitude of varying concentrations are unlike patterns observed in ambient air, and it is unclear how this may have affected the observed responses. The Clean Air Scientific Advisory Committee (CASAC) was established under the Clean Air Act Amendments of 1977 to provide independent advice to the EPA Administrator. The CASAC reviewed the 2021 draft PA on ozone and provided their advice in a June 2023 report. Relying in part on the Hernandez et al study (10), the CASAC recommended that the level of the current 0.07 ppb standard was not adequate to protect public health and that the NAAQS be revised. In particular, the CASAC noted that the small but significant decrement in FEV1 in participants exposed to an average 0.07 ppm O3 concentration for 6.6 hours while at rest (without exercise) called into question the assumption that moderate to heavy exercise is necessary for adverse health effects to occur at low levels of O3 exposure. The EPA is considering whether a level of 0.07 ppm provides adequate protection for public health. EPA researchers have been asked to conduct a study similar to those previously done at ozone exposure concentrations of 0.06, 0.07, and 0.08 ppm with healthy volunteers, but with volunteers at rest, rather than exercising. EPA believes such a study would provide clinical evidence for whether moderate to heavy exercise is necessary for adverse health effects to occur at the current level of the ozone standard.

Conditions

• Lung Inflammation
• Experimental Lung Inflammation

Interventions

Type	Name	Description
OTHER	Ozone Exposure	6.6 hour exposure to 0.07 ppm ozone while at rest
OTHER	Clean air (0.0 ppm ozone)	6.6 hour exposure to clean air (0.00 ppm ozone) while at rest

Timeline

• Start date: 2024-11-05
• Primary completion: 2025-12-01
• Completion: 2026-12-01
• First posted: 2025-04-25
• Last updated: 2025-04-27

Locations

1 site across 1 country: United States