Research

DAI's unique approach to epidemiologic research emphasizes the inclusion of physiologic (and other) mechanisms in the epidemiologic research project planning phase. The selected health outcome measures will be more meaningful (because of knowing the physiologic mechanism) and generalizable (beyond a single testing condition).

With a better understanding of associations between ambient and indoor air pollution (and ecological hazards) and adverse health outcomes, this new information can be applied to the design, implementation, and assessment of successful organization-wide epidemiologic interventions.

Air Pollution

DAI's expertise is in using data linkage methodologies, epidemiologic data analysis designs, and categorical data analysis statistical procedures to compute statistical measures of risk between elevated ambient PM_2.5 concentration levels (with or without ecological hazards) and increases in respiratory-cardiovascular-cerebrovascular emergency department visits and inpatient hospitalizations.

Oxidative stress and inflammation are two physiologic mechanisms that have been proposed to explain the adverse effects of elevated fine PM concentration levels (with or without ecological hazards) on increased respiratory-cardiovascular-cerebrovascular hospital events.

The type and severity of adverse health outcomes resulting from exposure to elevated PM concentration levels depend on particle size. PM size is measured in micrometers (μm):

• Coarse PM, PM₁₀, includes particles less than or equal to 10 μm. PM₁₀ exposure produces inflammation in the upper part of the lungs.

• Fine PM, PM_2.5, can travel deeper into the lungs and produce inflammation of lung tissue.

• Ultrafine PM, PM_0.1, can traverse lung tissue, enter the circulatory system, distribute throughout the body, and accumulate in end-organs such as the lungs, heart, and brain.

These three PM particle size categories are not mutually exclusive because a larger PM category can also include a smaller PM category. For example, PM₁₀ can also include PM_2.5 and PM_0.1. PM_2.5 excludes PM₁₀ but contains PM_0.1.

Combustion engines produce all three PM types. But diesel exhaust and vehicle brake friction produce more PM_0.1 than the other two PM particle size categories – coarse PM and fine PM.

PM_2.5 and PM_0.1 from diesel exhaust have been shown to produce structural changes to the human brain.

Other PM-related anatomic changes include bioaccumulation of heavy metals such as lead (Pb) and mercury (Hg) in brain tissue. These and other metals can bond with fine and ultrafine PM. Because both Pb and Hg are neurotoxic, a parsimonious explanation of the fine and ultrafine PM-induced brain damage could be attributed to the bioaccumulation of Pb and Hg in neurons.

Some previously completed epidemiologic analyses on the association between elevated PM_2.5 concentration levels and increases in respiratory-cardiovascular-cerebrovascular hospital events have excluded the contribution of PM-produced metabolic disorders such as Type 2 diabetes while other investigations have focused on evaluating Type 2 diabetes. DAI epidemiologic studies will include, when appropriate, metabolic co-morbidities such as Type 2 diabetes, as effect modifiers. This way, it will be possible to evaluate the contribution of Type 2 diabetes, when it is present or absent in the statistical analysis, to the strength of the association between environmental hazard exposure and health outcome.

In addition, exposure to higher ambient PM_2.5 concentration levels adversely affects the pancreas by changing the amount of insulin this organ can produce. Physiologic explanations of PM’s effects on the pancreas have included oxidative stress and inflammation.

Obesity

Increased ingestion of refined carbohydrates, such as commercially processed foods containing large amounts of sugar, and a sedentary lifestyle are two obesity risk factors.

Obesity is also a comorbid chronic disease associated with Type 2 diabetes. Both obesity and Type 2 diabetes are metabolic disorders.

Metabolic Syndrome

For some obese persons, obesity eventually results in the development of the metabolic syndrome. The metabolic syndrome include a constellation of adverse health outcomes in addition to obesity; for example, higher blood pressure and hypertension.

Obesity and Metabolic Syndrome

Elevated PM_2.5 exposure is also a risk factor for obesity and the metabolic syndrome.

Oxidative Stress and Inflammation

Oxidative stress and inflammation are two mechanisms that have been proposed to explain how air pollution adversely impacts and eventually results in the subsequent occurrence of respiratory-cardiovascular-cerebrovascular chronic diseases, as well as the metabolic disorders of obesity, Type 2 diabetes, and the metabolic syndrome.

Oxidative stress results from the presence of individual oxygen atoms (O) in cells of different organs. Their presence in cells leads to cellular, tissue, and organ inflammation.

Oxidative stress and inflammation have been proposed as mechanisms that result in the occurrence of asthma, heart failure, myocardial infarction, and stroke following exposure to higher ambient concentration levels of fine and ultrafine PM.

Mitochondria

Mitochondria are tiny organelles that are found in many organ-specific cells. Mitochondria contribute to normal cell functioning. Four examples of how mitochondria maintain normal cell functioning include:

• The energy demands of specialized lung, heart, and brain cells are met by mitochondria's production of adenosine triphosphate (ATP), a source of energy.

• Through mitochondria's lysosome activity, free oxygen radicals are engulfed and removed from the cell.

• Reuse of recycled cellular material to form new mitochondria.

• The elimination of damaged cells through apoptosis.

As stated previously, normal mitochondrial functioning is disrupted through exposure to diesel exhaust-produced fine and ultrafine PM particles. Air pollution compromised mitochondria no longer provide lung, heart, and brain cells with ATP, do not remove free oxygen radicals, and are no longer able to mitigate the occurrence of oxidative stress and inflammation.

By including what we currently know about mitochondrial mechanisms in the initial design of epidemiologic studies, this type of physiologic mechanistic information can help in the selection of outcome measures that are informative and make study results robust.

Climate Change Associated Ambient Temperature Increases

Current scientific evidence suggests that the excessive use of carbon-based fuels such as gasoline and diesel have contributed to the increase in carbon dioxide in the atmosphere, the subsequent elevation in ambient temperature, and the occurrence of more temperature extreme days – both are recognized physiologic stressors.

Higher ambient temperatures also contribute to increases in air pollution, especially particulate matter, and ozone.

One way to conceptualize the effects of climate change induced elevations in ambient temperature and the subsequent increases in ambient air pollution is to consider differences between warm and cold seasons. Some studies have reported higher fine PM and more respiratory-cardiovascular hospital events during the warm season in comparison to the cold season (e.g., Braggio, Hall, Weber, Huff, 2020, 2022). These warm vs. cold season outcome differences could also occur because persons respond to not just the absolute increase in ambient temperature, but also to the relative increase in ambient temperature. Because of climate change, absolute and relative increases in ambient temperature are now increasing, compared to earlier decades. Through statistical modeling, similar climate change produced increases in ambient temperature are predicted to continue in future decades.

Obesity and Temperature

For the same ambient air pollution concentration level, the synergism between higher body weight and higher ambient temperature should result in more adverse health effects from the exposure to higher ambient air pollution and to the occurrence of respiratory, cardiovascular, and cerebrovascular chronic diseases in obese persons on warmer days compared to persons who are not obese on warmer days. Similar synergistic effects between obesity and ambient temperature change should be greater among heavier persons than normal weight persons on days when the temperature change is more remarkable compared to days when the higher temperature increase is less. The same absolute and relative temperature changes should result in more hospital events (emergency department visits and inpatient hospitalizations) and increased mortality in obese persons than in other individuals of average weight.

The explanation for this anticipated greater adverse effect of air pollution in obese persons could be that on warmer days persons who are obese have to exert more effort than they would otherwise show on days that are not as warm. One consequence of this ambient temperature physiologic stressor is the body's need to inhale more oxygen. Thus, the greater exertion on warmer days that is accompanied by breathing more polluted air could be the reason why increased ambient temperature could result in pejorative health outcomes among persons who are obese compared to other persons who are of normal weight.

The same physiologic mechanisms that involve air pollution disrupted mitochondrial functioning followed by oxidative stress and inflammation have been proposed as explanations for the adverse effects of air pollution on respiratory-cardiovascular-cerebrovascular and metabolic chronic diseases.

Asthma and Obesity or Asthma and Metabolic Syndrome, and Temperature

An asthma chronic disease diagnosis can occur independently of another comorbid chronic disease condition, or when either obesity or the metabolic syndrome are also present.

Asthma management becomes a greater challenge among persons who also have a secondary metabolic chronic disease diagnosis – obesity or the metabolic syndrome.

The asthma with obesity or asthma with the metabolic syndrome management issue becomes even more challenging on days when ambient temperature is higher.

Outdoor vs. Indoor

Absolute and relative increases in ambient temperature can be mitigated through limiting how much time persons spend outdoors. Other ways to minimize the adverse effects of ambient temperature increases are through the access to air conditioning, clothing choices, and limiting outdoor exercise intensity and duration.

These climate change adaptive behavioral strategies are less effective, however, when it comes to decreasing the adverse effects of increased air pollution concentration levels, for both particles such as fine and ultrafine PM and gasses such as ozone, in producing adverse health outcomes.

It is more challenging to minimize the detrimental effects of ambient air pollution than ambient temperature by going indoors. The indoor workspace temperature can be controlled by the use of air conditioners. Ambient and indoor air pollution can be mitigated by using air conditioning and air filtration systems to a point, but they cannot be eliminated completely because building construction materials are also sources of air pollution contaminants and ecological hazards.

Organizational members also commute from home to work before the start of the workday and from work to home at the end of the workday. For these reasons, organizational workforce members are exposed to outdoor ambient air pollution during their commute between home and work. In a similar manner, organizational customers are also adversely impacted by ambient air pollution during their daily commute from home to the service site, and from the service location back home at the end of the day.

The adverse effects of higher air pollution concentration levels on workers’ and customers’ health status represents the combined exposure that occurs only at home, but also while commuting to or from the work (or instructional site), and the ecologic hazards that could be present in the workplace or place of instruction. Each of these locations – at home, at work or in the instruction location, and in transit between the two, can also include different ecological hazard types and concentration levels.