On the Road Again
words by susan preston / photograph by pete byron
howard kipen, MD, mph, professor of environmental and occupational medicine, UMDNJ-Robert Wood Johnson Medical School (RWJMS) and chief , Division of Clinical Research and Occupational Medicine, Environmental and Occupational Health Sciences Institute (EOHSI).
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ew Jersey is a traveling state. With so many people sharing the road for so many hours each day with diesel-powered trucks and buses, it seems logical that a team of NJ environmental health specialists are exploring the effects of air pollution on the human body.
“That air pollution causes cardiorespiratory problems has been well documented by epidemiologists,” says Howard Kipen, MD, “but the biological mechanisms are less well understood.
Epidemiologists, including Kipen, David Rich, ScD, from UMDNJ’s School of Public Health (SPH) and John Kostis, MD, from UMDNJ-Robert Wood Johnson Medical School (RWJMS), have documented that when air pollution levels increase, so do the number of people experiencing heart attacks. They also have evidence that suggests exposure to air pollution during commuting may trigger a heart attack and that particulate air pollution contributes to arrhythmias, stroke, hypertension, and heart failure.
In fact, Kipen and Rich published a pilot study seeking to explain the association between an increase in hospital admissions for congestive heart failure in NJ and ambient concentrations of fine particles. They examined right heart pressures in 11 patients with moderate to severe heart failure, who had an experimental device implanted for many years. They also looked at air pollution concentrations for the same time frame. Their conclusion: Heart failure patients are at greater risk for an increase in pulmonary and right ventricular pressure from ambient fine particle pollution. But why?
Several UMDNJ studies are now underway with the goal of providing answers to that question. “We want to understand the specific biological mechanisms that explain how particulate air pollution leads to certain adverse cardiovascular or respiratory outcomes,” Kipen states. “With this information, we may be able to suggest specific prevention strategies, perhaps medications or dietary supplements, which can be targeted to interfere with the pathophysiological mechanisms.” In addition to Kipen and Rich, RWJMS faculty members Sabiha Hussein, MD, and Robert Laumbach, MD, MPH, and Junfeng (Jim) Zhang, PhD, from SPH are conducting the studies.
The researchers are using two approaches to test hypotheses about the links between particulate pollution and cardiorespiratory problems. In one, participants are exposed to diluted diesel admissions in a specially designed chamber located in the Environmental and Occupational Health Sciences Institute (EOHSI). In the other, participants are literally “on-the-road,” traveling the NJ Turnpike during morning and evening rush hours in order to maximize their exposure to diesel exhaust and other ambient air pollution. “Our diesel engine exposure chamber is useful, but we found that real-world model exposure elicits stronger effects. We’re not sure why—timing, other pollutants co-present with particles, or maybe just chance,” Kipen explains.
The team is currently focusing on several studies
Ambient air pollution accounts for 10 percent of lung cancers in western populations. Recent studies report that increases in ambient air pollution may be associated with decreased plasma antioxidant levels and increased oxidative stress markers. The team is comparing changes in oxidative stress markers between 25 automobile commuters with a week of heavy exposure to traffic and 25 individuals with light exposure. They think the first group will have greater oxidative stress at the beginning of the study and more changes over the work week.
Evidence suggests that acute ischemic events are related to fine and ultrafine particles present in the air. After particle inhalation, the development of pulmonary — followed by systemic — inflammation has long been thought to explain the increase in cardiovascular morbidity, but researchers have focused on mechanisms that occur more rapidly. They think that the particles move rapidly from the lungs into the blood, leading to platelet activation and endothelial dysfunction. These effects can occur hours before evidence of an inflammatory response is detectible. Moreover, healthy individuals bearing a specific single nucleotide polymorphism (SNP) in endothelial nitric oxide synthase are more susceptible to heart attacks and may be more vulnerable to these biochemical effects as well. In this study, which takes place in the diesel exhaust chamber, 25 participants with the SNP and 25 without are exposed to diesel exhaust, a secondary organic aerosol, or clean air in three separate sessions one week apart.
A completed study involved participants with diabetes traveling the dedicated truck lanes on the NJ Turnpike. Endothelial function and heart rate variability were measured. The hypothesis was that an increased risk of cardiac morbidity/mortality associated with exposure to fine particulates is due in part to autonomic and endothelial changes. Changes in heart rate variability were demonstrated. The study is in press.
In another study, 20 patients with mild and moderate asthma are being exposed to diesel exhaust in the environmental chamber to determine the impact of diesel emissions on their lung function and airway hyperactivity. Levels of oxidative stress and inflammatory response are also being evaluated. In addition, researchers are looking at whether asthmatic individuals with common functional variants of GST (glutathione-s-transferase) genes have increased oxidative stress or inflammatory response.
In a real-world traffic study, chronic obstructive pulmonary disease (COPD) patients, both smokers and non-smokers, will be riding for two hours on the NJ Turnpike. Their oxidative stress levels, heart rate variability, and vascular production of nitrite and nitrate will be measured prior to the ride and two and 24 hours after exposure. Researchers are also trying to determine if the subset of non-smokers with COPD are more susceptible to the effects of pollution.
The team is looking at the biological mechanisms of how exposure to diesel exhaust combined with an increase in psychological stress can lead to increased markers of physical stress and cardiovascular changes. Participants are exposed to diesel exhaust for one hour in the controlled exposure facility. Half of them are then asked to do a public speaking exercise with the purpose of eliciting an acute stress response. In the middle of the exercise, they are told they will be videotaped giving a five-minute speech on a controversial subject to a panel of experts. The winner will receive $10. The data are being analyzed.
Junfeng Zhang, PhD, associate dean for Global Public Health, and professor and acting chair, Department of Environmental and Occupational Health at umdnj-school of public health
In a study based in Beijing, the team is determining molecular and physiological responses to drastic changes in the composition and concentration of particulate air pollution. During the Olympics last summer, the ambient air pollution rates were reduced 30 to 50 percent. The researchers are evaluating changes in seven cardiorespiratory biomarkers when the pollution levels were high, dropped and then increased again. The study involves 250 individuals, including children, the elderly and medical students. The group is also looking at whether and how genetic factors are significant in susceptibility to the changes in response and the ability of some participants to recover from lung inflammation and increases in oxidative stress.
In addition to these research projects, Rich has a paper in press about the impact of ambient air particles on pregnant women in early and late pregnancy to determine if exposure affects fetal growth or causes other developmental changes. Zhang is studying whether a new design for wood and coal-burning stoves used by thousands of people in rural villages in China reduces the level of indoor air pollution and therefore the number of cases of cardiovascular and lung diseases.
Sabiha Hussein, MD, assistant professor of medicine at
umdnj-robert wood johnson medical school
How will the conclusions of these studies impact global health?
“It’s only been in the last five years that we’ve realized that relatively low levels of air pollution can have an impact on people with cardiovascular as well as respiratory disease,” Laumbach explains. “We’re finding that while poor air quality doesn’t automatically trigger a heart attack in the general population, chronic conditions such as COPD increase a person’s risk. These studies are helping us identify populations beyond the elderly, infants and those with lung disease who may be more susceptible to particulate air pollution.”
“For example, if we can determine the biological mechanisms triggered by prolonged exposure to air pollution that place people with cardiovascular problems at a greater risk of forming blood clots,” Zhang says, “we might suggest a therapeutic intervention such as increasing the amount of antioxidants that person is taking in order to ameliorate the effects of the bad air quality.”
“Having a better understanding of what exacerbates a patient’s respiratory condition is changing the way I practice medicine,” Hussein says. “This research may tell us if we can reverse lung inflammation in patients or how aggressive we can be with treatment. If we know that oxidative stress is a major factor, perhaps a longer course of steroid treatment will make a real difference. If the problem is caused by repeated exposure to a biomass source, the best course may be to recommend the patient go on oxygen because the condition will be unresponsive to treatment.”
Kipen concludes: “We’re just beginning to understand the link between exposure to high levels of particulate air pollution and the biological mechanisms that are triggered. Such knowledge will strengthen scientific arguments for continually evaluating acceptable air quality standards as the primary approach for preventing these health effects.”