Controlled Human Inhalation-Exposure Studies at EPA (2017) / Chapter Skim
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Appendix C: Assessment of Eight Controlled Human Exposure Studies
Appendix C: Assessment of Eight Controlled Human Exposure Studies
Pages 112-142
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From page 112... ...
Effects of Wood Smoke Particles on Influenza-Induced Nasal Inflammation in Normal Volun teers (WOODSIE) Physiologic Changes in Adults with Metabolic Syndrome Exposed to Concentrated Ultrafine Chapel Hill Air Particles (XCON)
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From page 113... ...
Research goal regarding the Relationship between physiologic function and pollutant exposure, Biologic plausibility and/or mechanisms of air pollution health effects, Interpretation of effects observed in toxicologic or epidemiologic studies, and Other: Statistical analysis plan in detail at proposal stage.
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From page 114... ...
190.3 ug/m3) GSTM1 Null and Sufficient Individuals to Concentrated Ambient Air Particles (11-1807)
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From page 115... ...
. In addition to samples of FVC and FEV1, the protocol called for monitoring of heart rate variability and blood pressure, and collection of samples of blood, saliva, and urine, and included information on cardiovascular function.
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From page 116... ...
he data obtained from this study will contribute to the overall assessment of air pollution effects in the U.S. and thereby may influence future health policy." Critical toxicologic pathways and evidence of perturbations For DE exposures, evidence is presented of adverse cardiopulmonary effects including premature mortality, cardiopulmonary problems including infections, exacerbation of asthma symptoms, and heart attacks.
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From page 117... ...
Biologic plausibility and or mechanisms of air pollution health effects One research goal was to elucidate the effect of the GSTM1 null genotype on the effects of O3 exposure on lung function. Interpretation of effects observed in toxicologic or epidemiologic studies It had been observed in a mouse model that both DE and O3 were needed to increase lung resistance, which was not observed with individual pollutant exposures (Madden et al.
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From page 118... ...
Quantification of the relationship between physiologic function and pollutant exposure. The study provided quantitative information on the physiologic response to exposure to O3, DE, and O3+DE, and response to O3 following earlier exposures O3, DE, and O3+DE, in a few healthy volunteers, under specific exposure conditions.
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From page 119... ...
Increased ability to interpret effects observed in toxicologic or epidemiologic studies. The results from this study could possibly provide reinforcement to interpretations of effects observed other studies.
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Is the health status of the study subjects reflective of the sensitive subgroups that the relevant air pollution standard is intended to protect? No, but the population to be studied is the correct one for this exploratory study of sequential exposures.
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From page 121... ...
The study design was appropriate for this limited goal. Is the health status of the study subjects reflective of the sensitive subgroups that the relevant air pollution standard is intended to protect?
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From page 122... ...
The subjects will all be exposed to clear air then will be randomized to ozone or clean air, then after 13 days there will be a crossover. Responses of interest include lung inflammation, lung function, and epigenetic changes evaluated by bronchopulmonary lavage.
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From page 123... ...
There are few long-term or broad hypotheses for future work offered in the submission. Is the health status of the study subjects reflective of the sensitive subgroups that the relevant air pollution standard is intended to protect?
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From page 124... ...
It is known that omega-3 polyunsaturated fatty acids have several potential cardioprotective effects including antiarrhythmic, antithrombotic, anti-inflammatory, and lowering lipid levels. Range and variation of pollutant exposures in the United States and perhaps elsewhere.
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From page 125... ...
Current air quality standard and relevance for future review of standard N/A Critical toxicologic pathways and evidence of perturbations For PM exposures, evidence is presented of adverse cardiopulmonary effects including premature mortality, cardiopulmonary problems including infections, exacerbation of asthma symptoms, and heart attacks. For PM exposures, evidence is presented for decrements of lung function and an influx of neutrophils and other markers of inflammation.
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From page 126... ...
Is the health status of the study subjects reflective of the sensitive subgroups that the relevant air pollution standard is intended to protect? The subjects in this study were selected from among healthy adults (men and women between the ages of 50 and 75 years)
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From page 127... ...
The results of this study reinforced the biologic plausibility of effects upon particulate matter mean 253±16 µg/m3 and the cardiovascular, thrombolytic systems observed in toxicologic or epidemiologic studies. Increased ability to interpret effects observed in toxicologic or epidemiologic studies.
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From page 128... ...
2015. Dietary Supplementation with Olive Oil or Fish Oil and Vascular Effects of Concentrated Ambient Particulate Matter Exposure in Human Volunteers.
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From page 129... ...
Interestingly, there was no mention of the 2012 paper in the discussion. In that report the same authors found that OO supplementation had the negative impact by elevating the heart rate variability and prolonged QT interval caused by acute pollution exposure, i.e., omega-3 was protective.
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From page 130... ...
It should have been within strata. Is the health status of the study subjects reflective of the sensitive subgroups that the relevant air pollution standard is intended to protect?
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From page 131... ...
There is a clear and testable hypothesis: exposure to wood smoke particles enhances influenza virus– induced granulocyte and NK cell activation via hyaluronic acid–mediated effects on IFNg production. Range and variation of pollutant exposures in the United States and perhaps elsewhere.
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From page 132... ...
Wood smoke exposure studies might help identify sensitive subgroups. Does the design of the study adequately reflect the information uncertainty being addressed?
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From page 133... ...
PHYSIOLOGICAL CHANGES IN ADULTS WITH METABOLIC SYNDROME EXPOSED TO CONCENTRATED ULTRAFINE CHAPEL HILL AIR PARTICLES (XCON) Is the research question well focused?
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From page 134... ...
The hypothesis is that UF particular matter (PM) exposure in this population will result in changes in endothelial response as assessed by flow-mediated dilation of the brachial artery and various electrophysiologic outcomes (e.g., heart rate variability)
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Air quality standards related to UF PM exposure and lung function are not discussed in the proposal. Also, there is no description of how the results of this study could affect air quality standards.
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From page 136... ...
This study is part of the charter of the EPA to study susceptible populations and determine health risks with ambient levels UF PM. If the investigators find associations of UF PM with the subclinical outcomes they are measuring, this may lend biologic plausibility to observational studies linking UF with clinical health outcomes, and may inform regulation if it is feasible for the EPA to regulate UF, which fall off rapidly as distance from traffic increases.
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From page 137... ...
Is the health status of the study subjects reflective of the sensitive subgroups that the relevant air pollution standard is intended to protect? Metabolic syndrome and its components are risk factors for CVD and type-2 DM.
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From page 138... ...
and heart rate variability, peripheral venous blood samples, specific and nonspecific immune responses (cytokines and C-reactive protein) , coagulation factors (von Willibrand factor, factor IX, fibrinogen and thrombin)
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From page 139... ...
Exposure to UF causes changes in cardiac repolarization and heart rate variability. Exposure to UF causes changes in vascular markers of inflammation and fibrinolysis.
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From page 140... ...
2014. Con trolled exposure of humans with metabolic syndrome to concentrated ultrafine ambient particulate matter causes cardiovascular effects.
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From page 141... ...
2005. Omega-3 fatty acid prevents heart rate variability reductions associated with particulate matter.
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