Epigenetic Effects of Diesel Exhaust and Ozone Exposure

Completed · Not applicable

Conditions studied: Exposure to Pollution, Inhalation of Ozone

In brief

Purpose: The purpose of this protocol is to compare the genetic and epigenetic effects between diesel exhaust and ozone exposure in healthy individuals and in mild/moderate asthmatics. Participants: The investigators will recruit up to 30 mild to moderate asthmatics and up to 50 healthy adults to participate in this study. Procedures (methods): Subjects will be exposed to clean air, to 300 µg/m3 of diesel exhaust for 2 hours and to 0.3 ppm of ozone for 2 hours with intermittent exercise in a controlled environment chamber. Primary endpoints will include spirometry and lung cell changes post-exposure. Secondary endpoints will include analysis of blood clotting/coagulation factors, Holter monitoring of cardiac parameters, analysis of soluble factors present in plasma and bronchial lavage and analysis of intracellular factors present in lung tissue obtained from a brush biopsy.

Key facts

Study ID

NCT01492517

Run by

Environmental Protection Agency (EPA)

People needed

42

Starts

2010-05-01

Expected to finish

2015-05-01

Last updated by the study team

2016-01-18

Who can join

Age: 18 and older, up to 55. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Healthy Individuals Specific Inclusion Criteria
• Physical exams will be performed by study physicians during the screening visit (IRB approved EPA protocol 95-EPA-66).
• Normal lung function (pre or post albuterol), defined by Knudson 1976/1984 as:
• FVC of > 75 % of that predicted for gender, ethnicity, age and height.
• FEV1 of > 75 % of that predicted for gender, ethnicity, age and height.
• FEV1/FVC ratio of > 75 % of predicted values.
• Oxygen saturation of > 96 %.
• Ability to tolerate intervals of moderate exercise
• Mild to Moderate Asthmatics
• Inclusion Criteria:
• Physical exams will be performed by study physicians during the screening visit (IRB approved EPA protocol 95-EPA-66) where diagnosis will be judged by EPA physicians.
• Mild/Moderate asthmatics as defined by NHLBI guidelines.
• Positive history of asthma (wheezing, chest tightness, and reversible airway obstruction);
• Baseline FEV1/FVC ≥ 60%;
• Oxygen saturation of ≥ 94%
• Ability to tolerate moderate exercise

You may not qualify if…

• Healthy Individuals
• A history of chronic illnesses such as diabetes, rheumatological diseases, immunodeficiency state, known clinically significant cardiac disease (including myocardial infarction, congestive heart failure and angina), chronic respiratory diseases such as chronic obstructive pulmonary disease, and lung cancer.
• If the subject is pregnant, attempting to become pregnant or breastfeeding.
• Allergy to any medications which may be used or prescribed in the course of this study.
• Subjects currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the PM and/or ozone challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). Subjects must refrain from all over the counter anti-inflammatory agents including those for allergies, and naproxen, and anti-oxidants for a period of one week prior to exposure. Medications not specifically mentioned here may be reviewed by the investigators prior to a subject's inclusion in the study.
• Smoking history within 2 years of the study.
• Use of inhaled steroids, cromolyn, or leukotriene inhibitors (Montelukast, Zafirkulast, etc) initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy.
• Untreated hypertension (> 150 systolic, > 90 diastolic)
• Dementia.
• Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with PM inhalation challenge or exercise, will be a basis for exclusion.
• History of skin allergy to tape or electrodes.
• Subjects who do not understand or speak English
• Subjects who are unable to perform moderate exercise
• Exclusion criteria for bronchoscopy:
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• Any food or fluids after midnight prior to bronchoscopy
• FEV1/FVC ratio less than 60% predicted on AM of bronchoscopy.
• Regular use of aspirin or other nonsteroidal anti-inflammatory drugs (which inhibit platelet function).
• Mild to Moderate Asthmatics
• Use of oral steroid therapy within the past month
• Physician directed emergency treatment for asthma exacerbation within the preceding 6 months.
• Abnormal EKG that precludes evaluating heart rate variability. 4. Aside from mild/moderate asthma, a history of chronic illnesses such as diabetes, rheumatological diseases, immunodeficiency state, known clinically significant cardiac disease (including myocardial infarction, congestive heart failure and angina), chronic respiratory diseases such as chronic obstructive pulmonary disease or severe asthma, and cancer (possible exception for history of nonmelanoma skin cancer).
• If the subject is pregnant, attempting to become pregnant or breastfeeding. 6. Allergy to any medications which may be used or prescribed in the course of this study 7. Subjects currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the PM challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). Subjects must refrain from all over the counter anti-inflammatory agents including those for allergies, and naproxen, and anti-oxidants for a period of one week prior to exposure. Medications not specifically mentioned here may be reviewed by the investigators prior to a subject's inclusion in the study.
• Dosing level of an inhaled steroid must be consistent with mild asthma as outlined by the NHLBI NAEPP guidelines. Regular use of oral corticosteroids, or use of inhaled steroid at doses typically used for severe asthma, will result in exclusion of that individual from the protocol.
• Severe asthmatics as defined by: nighttime symptoms of cough or wheeze greater than 1 time per week at baseline, daily exacerbation of asthma or requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness, but not to include prophylactic use of albuterol prior to exercise), more than mild interference with normal activity, any episode of physician directed emergency treatment for asthma requiring oral corticosteroid therapy within the past twelve months.

Where it is running

• U.S. EPA Human Studies Facility — Chapel Hill, North Carolina, United States

Full record on ClinicalTrials.gov

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