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In recent years, air pollution has increasingly become recognised as a major contributor to adverse health effects. Numerous studies have shown that poor air quality can adversely affect those with respiratory conditions such as asthma and chronic obstructive pulmonary disease and, more recently, cardiovascular conditions such as myocardial infarctions and stroke.1 Wherever the location, air pollution has been shown to be associated with deterioration in patients with these conditions, as well as with increased mortality.
In patients with asthma, air pollution increases symptoms, medication use, bronchoconstriction, emergency room admissions and hospitalisations. These effects are linked to pollutants such as ozone, nitrogen dioxide and particulate matter (PM) and, increasingly, the role of traffic-related air pollution has been highlighted. Traffic pollution consists of a complex mixture of particles and gases from gasoline and diesel engines, together with dust from wear of road surfaces, tyres and brakes. The coarse particles from road dust have been clearly associated with worsening of asthma and respiratory symptoms.2 Motor engine particles from diesel engines have been linked with worsening of asthma and increased bronchial hyper-responsiveness, a hallmark of asthma.3 There is also literature suggesting that diesel particles enhance allergen sensitisation in animals and humans and that they differentially affect the airway mucosa in healthy individuals and those with asthma.4 5 While it is generally accepted that air pollutants may trigger the sensitive airways of subjects with asthma via a number of established pathophysiological processes, it has been more controversial to suggest that air pollution directly contributes to the occurrence of asthma.
In a recent issue of Thorax, Salam and coworkers6 concluded that certain genetic variants in glutathione S-transferase (GST) and microsomal epoxide hydrolase (EPHX) contribute strongly to the susceptibility and occurrence of asthma in children living near busy roads. Their findings arose from the Californian Children’s Health Study in which the same authors earlier showed that PM air pollution in residential areas was associated with impaired lung growth during adolescence.7 Furthermore, the same team recently reported that living in close proximity to major roads impaired lung development even more than that seen in those living in residential areas with poor air quality. After taking into account a wide range of socioeconomic factors, they concluded that specific pollutant components in the air in the immediate proximity to traffic are of importance, with diesel exhaust the main focus.8 Diesel exhaust consists primarily of extremely high numbers of nanoparticles in nucleation mode around 10–20 nm together with gaseous components which agglomerate to produce particles around 100 nm. The carbon core particles carry polyaromatic organic hydrocarbon (PAH) components on their surface, some of which can cause oxidative stress.9 Oxidative stress with increased consumption of antioxidants has been highlighted as a key component in asthma,10 and polymorphisms in GST have been indicated to play a role in this condition.11 Further, there is evidence that, in patients with asthma, the epithelium is deficient in its ability to neutralise oxidant attack through a decrease in antioxidant enzymes such as superoxide dismutase and glutathione peroxidase.12
Given this background, it is interesting that Salam and coworkers have addressed the role of GST M1, P1 and T1, which not only represent defensive components for limiting oxidative stress but also, together with EPHX, play an important role in the metabolism of PAHs. GSTs detoxify PAHs through the formation of glutathione conjugates. Through the trans-dehydrodiol pathways, reactive semi-quinones are generated which may result in the generation of reactive oxygen species. EPHX1 is of importance in the metabolism of reactive epoxides from activated PAHs.
Salam and coworkers showed that high EPHX1 activity increased the risk of lifetime asthma, but that this was dependent on the GSTP1 variant with the Ile105VAL genotype and, furthermore, residential proximity to major roads. Interestingly, children with GSTP1 105Val/Val genotype and high EPHX1 phenotype had a several fold increase in lifetime asthma compared with those with a low to intermediate phenotype. These findings are important since they suggest plausible mechanisms whereby constituents of incomplete combustion of fossil fuels in motor engines in general—and diesel engines in particular—may adversely affect the delicate cells lining the respiratory tract. It also draws attention to the fact that reactive PAH-derived components such as quinones are of importance, as recently indicated by Nel.13
The study by Salam et al highlights the importance of attaining a better understanding of the traffic-related air pollution components responsible for specific health effects. An increased understanding of the chemistry, metabolism and biological consequences of PAHs is warranted, as are the roles for engine types, fuels, exhaust gases and particles, as well as exhaust filters. The knowledge of how primary emissions influence the air at and near busy roads and how they change further away from major traffic is important to evaluate.
The toxicity of tobacco smoke components is also dependent on GSTs, and Salam and coworkers appreciated that exposure to environmental tobacco smoke (ETS) could have influenced their study outcome. To address this important issue, the authors explored ETS and a range of socioeconomic factors to determine if they could have modified the outcome. Adjustments for socioeconomic and demographic factors, community of residence, maternal smoking during pregnancy and smoking at home were examined, as well as restrictions to analysis in children with health insurance with similar results. The authors recognised that complementary studies are needed to fully dissect the interaction between ETS in relation to pollutants in ambient air.
In conclusion, the study by Salam et al indicates a role for genetic variants in GST and microsomal EPHX1 in detoxifying PAHs from traffic and together to ascertain the susceptibility and occurrence of childhood asthma. It also highlights a lack of detailed knowledge of how air pollutant components differ near heavy trafficked roads and how these vary at increasing distances from roads. It also reminds us that we understand little about the contributions of diesel and gasoline exhaust components to the toxicity of traffic pollution. The fusion of a well-designed epidemiological asthma study with the mechanistic approach to genetic variation in enzymes of PAH detoxification and oxidative stress places this paper in the forefront of asthma and air pollution research.
Competing interests: None.