A Common Pathophysiologic Mechanism?
Several mechanisms have been hypothesized to explain the adverse effects of ambient air pollution on health, particularly on the cardiopulmonary system. Although each pollutant can exert different toxic effects, "there are some unifying themes in terms of the pathophysiology," Dr Balmes proposes. "It is somewhat speculative, but research supports that all the pollutants that have been associated with health outcomes in epidemiologic studies are drivers of oxidative stress,[32,33,34] so they generate reactive oxygen species in the airways when inhaled. That can cause local airway injury and inflammation, which seem to be associated with a systemic inflammatory response, and there is some consensus—although not 100%—that the systemic inflammatory response elicited by exposure to air pollution contributes to the pathologic processes that are involved with several of the health outcomes that have been associated with air pollution, including atherosclerosis, cognitive decline, obesity, and diabetes," Dr Balmes explains. "So my thinking about the unifying mechanism is that the oxidative stress leading to systemic inflammation ties many of these health outcomes, which seem to be disparate, together with ambient air pollution exposure," he summarizes. The general consensus suggests that the mechanism of ambient air pollution-induced health effects involves an inflammation-related cascade and oxidation stress in lung, vascular, and heart tissue.
Effects of Early Life Exposure
"There is increasing appreciation of the chronic impact of air pollution on children," Dr Balmes stresses. "Exposure to air pollution early in life, even in utero, may have health consequences later in life," he notes. Lung function studies by Dr Balmes' group and by investigators at the University of Southern California suggest that early life exposures reduce the lung function of adults, which may result in a lower reserve for dealing with subsequent exposures later in life, including smoking and occupational exposures.[23,25,35,36] Evidence is also emerging about the contribution of air pollution to obesity and diabetes risk,[4,5,6,7,8,9] although fewer studies have been carried out in children.[8,37] Dr Balmes is leading a project to examine the contribution of ambient air pollution to the development of metabolic syndrome during childhood. "The research that we are currently doing in Fresno is based on my hypothesis that early life exposures to air pollution, particularly the PAHs, may increase the risk for diabetes and obesity later in life," Dr Balmes explains. His group is investigating whether chronic exposure to PAHs is associated with increased glycated hemoglobin (A1c) and body mass index (BMI). "We are still collecting the data, so we don't have a definite answer at this point, but research already published from Columbia University in New York has suggested an association between early life exposure to PAHs with several outcomes, including obesity, later in childhood," he notes. The researchers are also looking at the utility of selected biomarkers to identify children at risk for metabolic syndrome. The biomarkers include 8-isoprostane, a biomarker of oxidative stress; C-reactive protein, a biomarker of systemic inflammation; and leptin, adiponectin, and high-density lipoprotein cholesterol, all biomarkers of abnormal fat and glucose metabolism. The study will also examine whether dysfunction of regulatory T cells (Treg) and T-effector cells induced by ambient air pollution are associated with increased A1c and BMI; and, if so, whether epigenetic modifications of the gene encoding the Forkhead box transcription factor 3 (Foxp3), a key transcription factor in Treg-cell activity, are involved in the association between Treg dysfunction and A1c or BMI. Dr Balmes' group previously showed that ambient air pollution suppressed Treg through hypermethylation of Foxp3 in peripheral blood of children with asthma.
"We don't think that air pollution is a primary cause of diabetes," Dr Balmes admits, "but it may be particularly problematic in kids who have a tendency to get the greatest exposure because of where they live. Poor kids, who may also have poor diets (drinking giant sodas and eating junk food), often live near freeways and power plants and are getting more exposure," he observes.
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Cite this: Linda Brookes. Why Should You Care About the Air? - Medscape - Sep 10, 2015.