Controlled Human Inhalation-Exposure Studies at EPA (2017) / Chapter Skim
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4 Assessment of Controlled Human Inhalation Exposure Studies at EPA and Associated Adverse Events
4 Assessment of Controlled Human Inhalation Exposure Studies at EPA and Associated Adverse Events
Pages 52-67
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From page 52... ...
. Nearly all of the EPA CHIE studies were conducted either in healthy young adults or in carefully selected subjects over a wider age range with predispositions to measurable transient and reversible physiologic or biomarker responses, while attempting to minimize the likelihood of adverse events.1,2 Therefore, the objective of EPA CHIE studies has been to produce transient and reversible biomarker or physiologic responses that inform about biologic mechanisms of pollutant effects but do not cause clinical effects.
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From page 53... ...
However, the CHIE study findings could add relevant new knowledge to future NAAQS reviews. For example, the findings of CHIE studies of PM2.5 extracted from Chapel Hill ambient air could add new insights concerning human responses to PM2.5 in Chapel Hill ambient air as well as possible insights to observed responses to ambient air exposures in other U.S.
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From page 54... ...
[Particulate matter (PM) Completed 1 PM and 1 clean air Avg: 236 < 2.5 µm]
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From page 55... ...
The comparative exposures to DE in ambient air described in EPA's application for IRB approval either were not documented or were from a simulation study, in which the exposures were much briefer than exposures of the DEPOZ study subjects. Like all studies of limited and prescribed exposures to subjects, many questions remain.
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From page 56... ...
Study Design and Outcome Measures: Healthy study subjects are involved in four exposure regimens: Regimen 1: Exposure to clean air followed by O3. Regimen 2: Exposure to NO2 followed by O3.
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From page 57... ...
Study Design and Outcome Measures: Healthy MZ twins and healthy nontwin subjects are exposed during two sessions separated by an interval of about 14 days, to clean air on one day and O3 on the other day, and involving intermittent exercise. Primary outcome measures include pulmonary function, lung inflammation, and epigenetic changes as indicated by bronchoalveoalar lavage.
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From page 58... ...
After that treatment, each subject is involved in a 2-day exposure sequence: clean air on the first day, and PM2.5 and UFPs on the second day. Primary outcome measures are heart rate variability measurement and peripheral venous blood markers for specific and nonspecific immune responses.
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From page 59... ...
Study Design and Outcome Measures: A randomized double-blind crossover study design is used to compare the cardiopulmonary responses of two groups of healthy adults with different levels of perceived chronic stress to O3 and clean air. Subjects who score less than 2 on the 4-point Perceived Stress Scale (PSS4)
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From page 60... ...
Study Design and Outcome Measures: A randomized, placebo-controlled study compares nasal lavage fluid granulocyte responses to LAIV administered after either WSP or clean air, in normal healthy volunteers. Subjects receive either WSP or placebo (clean air)
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From page 61... ...
Another key consideration is whether any future UFP NAAQS should rely on particle number concentration as an index of exposure, instead of a mass concentration. EVALUATION OF EVIDENCE FOR ADVERSE EVENTS RESULTING FROM PARTICIPATION IN A CHIE STUDY As mentioned previously, EPA's CHIE studies are not intended to induce adverse effects that would require medical intervention in study subjects.
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From page 62... ...
TABLE 4-2 Potential Health Outcomes Described in EPA CHIE Study Protocols Exposure Agent CHIE Study Potential Health Outcome from Exposure Particulate Matter KINGCON, OMEGACON, Chest pain, mild dyspnea, headache, cough, wheeze, and decrements in (Ambient Air and Diesel XCON pulmonary function. All of these effects are expected to resolve a few Engine Exhaust)
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From page 63... ...
Another subject, exposed to O3, was found to have a cardiac arrhythmia on the follow-up day. The reported unexpected serious adverse event of paroxysmal atrial fibrillation experienced by a study subject a very short time after being exposed to concentrated ambient particles during the XCON CHIE study was appropriately noted on monitoring and, as reported in the published case report, the subject's response reverted to normal sinus rhythm spontaneously without clinical sequelae approximately 2 hours after cessation of the controlled exposure (Ghio et al., 2012)
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From page 64... ...
CAPTAIN Subject showed a 12-beat run of ectopic atrial tachycardia about No None needed 2 hours following exposure to PM. CAPTAIN Subject was disqualified following clean air exposure based on No None needed overnight Holter findings.
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From page 65... ...
clean air exposure. OMEGACON A female study subject with a history of migraine headaches had Yes Protocol was modified to exclude people with history of migraine after exposure to concentrated airborne particulate migraine headaches.c matter.
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From page 66... ...
. RELATIONSHIP OF SHORT-TERM CHIE STUDY EXPOSURE TO CHRONIC DISEASE RISKS Ambient air fine particulate matter (PM2.5)
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From page 67... ...
For the study participants in the eight EPA CHIE studies reviewed by the committee, it is the committee's judgment that any risks of a serious adverse event with long-term sequelae were unlikely large enough to be of concern, realizing it is not possible to ever conclude that there was no risk. Specific concerns have been expressed about CHIE-study risks of chronic diseases, such as lung cancer and ischemic heart disease, which are correlated with long-term cumulative exposure to PM2.5 (particles with an aerodynamic diameter less than or equal to 2.5 μm)
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