Cardiopulmonary Responses to Exposure to Ozone and Diesel Exhaust

NCT01874834 | Completed

• 1 other identifier: EPA 09-1344
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The US EPA Clean Air Multiyear research program is moving toward a multi-pollutant approach to the assessment of air pollution in response to recommendations by the NRC 2004 and the BOSC in 2005. Such an approach better reflects the complexity of real-world air pollution problems and parallels evolving scientific and regulatory considerations. Ozone (O3) and diesel exhaust (DE) generally are major and important components of ambient air pollution. This proposed study will address the agency's goals by investigating the cardiopulmonary health effects in healthy human subjects co-exposed to O3 and DE. The findings derived from these exposures will provide NCEA findings for risk assessments of O3 and DE, as well as the Office of Air and Radiation (includes OTAQ and OAQPS) with information relevant to possible modulation of PM-induced health effects and responses by a gaseous co-pollutant for potential standard setting. Additionally the findings will address the fundamental driving principle of the Clean Air Research strategy related to reduction of health due to air pollutant exposures.

Conditions

Respiratory Depression; Blood Pressure

Keywords

ozone; diesel; lung function; cardiac electrophysiology; mediators of inflammation and clotting

Outcome Measures

Primary Outcomes (1)

• Lung Function Decrement

  Lung function decrements are typically expressed as changes in FEV1 and FVC. Measurements are made pre-exposure (defined as baseline, immediately post exposure, 1-4 hr post exposure, and 24 hr post exposure (follow up).

  Immediately post to 24 hr post exposure

Secondary Outcomes (1)

• Heart rate variability

  immediately post to 24 hr post exposure

Other Outcomes (1)

• plasma cytokine levels

  immediately post to 24 hr post exposur

Study Arms (4)

Filtered air exposure

PLACEBO COMPARATOR

2 hr exposure to clean, filtered air with intermittent exercise

Other: ozone

Ozone

EXPERIMENTAL

2 hr exposure to 300 ppb ozone with intermittent exercise

Other: ozone

Diesel Exhaust, No ozone

EXPERIMENTAL

2 hr exposure to whole diesel exhaust (300 ug/m3; gases + particles) with intermittent exercise; no ozone

Other: ozone

Ozone + Diesel Exhaust

EXPERIMENTAL

2 hr exposure to a combination of 300 ppb ozone an 300 ug/m3 whole diesel exhaust with intermittent exercise

Other: ozone

Interventions

ozone OTHER

Exposure to 300 ppb ozone with intermittent exercise about 20 hr after exposure to each arm (ie, either air, ozone, diesel exhaust, or ozone combined with diesel exhaust)

Also known as: cas # 10028-15-6, trioxygen

Diesel Exhaust, No ozone; Filtered air exposure; Ozone; Ozone + Diesel Exhaust

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men and women between 18 and 55 years of age
• Physical conditioning allowing intermittent, moderate exercise for 2 hours
• Normal lung function:
• FVC \> 75 % of that predicted for gender, ethnicity, age and height.
• FEV1 \> 75 % of that predicted for gender, ethnicity, age and height.
• FEV1/FVC ratio \> 75 % of predicted values.
• Oxygen saturation \> 96 %.

You may not qualify if:

• A history of acute and chronic cardiovascular disease, chronic respiratory disease, diabetes, rheumatologic diseases, immunodeficiency state, and acute respiratory illness within 4 weeks.
• Subjects who are asthmatic or have a history of asthma.
• Allergic to chemical vapors or gases.
• Any allergic symptoms during the time of participation in the study
• Female subjects who are currently pregnant, attempting to become pregnant, or breastfeeding
• Current and past smokers within 1 year.
• Uncontrolled hypertension (\> 150 systolic, \> 90 diastolic).
• Subjects who do not understand or speak English
• Subjects unable to perform the moderately active exercise required for the study.
• Subjects with a history of skin allergies to adhesives used in securing heart rate monitor electrodes.
• Subjects unwilling to stop taking over-the-counter pain medications such as aspirin, Advil, Aleve or other non-steroidal anti-inflammatory medications ("NSAIDS") for 48 hr prior to the exposures and post-exposure visits.
• Subjects with a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds (ms))

Sponsors & Collaborators

• Environmental Protection Agency (EPA): lead

Study Sites (1)

US EPA Human Studies Facility

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (1)

• Madden MC, Stevens T, Case M, Schmitt M, Diaz-Sanchez D, Bassett M, Montilla TS, Berntsen J, Devlin RB. Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers. Part Fibre Toxicol. 2014 Sep 2;11:37. doi: 10.1186/s12989-014-0037-5.

  PMID: 25178924 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency; Thrombosis

Interventions

Ozone

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Oxygen; Gases; Inorganic Chemicals

Study Officials

• Michael Madden, PhD

  Environmental Protection Agency (EPA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Biologist

Study Record Dates

• First Submitted: June 7, 2013
• First Posted: June 11, 2013
• Study Start: August 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: January 1, 2013
• Last Updated: June 11, 2013

Record last verified: 2013-06

Locations

US (1)