DE 1 STUDY: Diesel exhaust inhalation in asthmatics: Oxidative stress as a mediator of airway reactivity and immune response
The use of diesel engines is increasing because they are more fuel-efficient than gasoline engines, however, diesel engines produce different emissions than gasoline engines. Diesel exhaust is emitted from the tailpipe of both “on- road” diesel engine vehicles (diesel cars, buses and trucks) and “non-road” diesel engines (locomotives, marine vessels and some construction equipment). Diesel exhaust consists of both gaseous and particulate air pollutants. Since people with asthma and allergic diseases appear to be sensitive to air pollution, we wanted to know how diesel exhaust (DE) affected their respiratory and immune systems. Below we present our research findings in this study.
Jiang R, Jones MJ, Sava F, Kobor MS, Carlsten C. Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics. Part Fibre Toxicol. 2014;11(1):1-12. doi:10.1186/s12989-014-0071-3
Carlsten C, MacNutt MJ, Zhang Z, Sava F, Pui M. Anti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity. Toxicol Sci. 2014;139(2):479-487. doi:10.1093/toxsci/kfu040
Yamamoto, M., Singh, A., Sava, F., Pui, M., Tebbutt, S. J., & Carlsten, C. (2013). MicroRNA expression in response to controlled exposure to diesel exhaust: attenuation by the antioxidant N-acetylcysteine in a randomized crossover study. Environmental health perspectives. 2013; 121(6), 670. doi:10.1289/ehp.1205963
Air pollution collectively describes the presence of a complex mixture of particulate matter (PM), organic compounds (e.g. polycyclic aromatic hydrocarbons and endotoxins), gases (e.g. carbon monoxide, sulfur oxides, ground-level ozone, nitrogen oxides) and metals present in indoor and outdoor air, which can cause harm or discomfort to humans or other living organisms. Although the effects of prolonged exposure to traffic-related air pollution (TrAP), specifically, are well characterized with respect to respiratory and cardiovascular outcomes, comparatively little is known about the impact of particulate matter on affective and cognitive processes, neurodegenerative effects and microcirculation. Research using animal models, along with epidemiology, has greatly enhanced our understanding of DE-related cognitive and learning outcomes, and has implicated several important potential mechanisms. However, such models are inherently limited given interspecies differences (animal models), some degree of unavoidable residual confounding (epidemiology), and a bias towards subacute or chronic effects (epidemiology). By largely overcoming these limitations, our in vivo human model, using freshly-generated exhaust that is diluted and aged to reflect real-world conditions, allows us to augment existing knowledge in a manner applicable both to current research on environmental effects on cognition, as well as current public health concerns of great relevance to Canadians. This study has finished subject enrolment and data analysis is now underway.
Cliff R, Curran J, Hirota JA, Brauer M, Feldman H, Carlsten C. Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: A controlled, blinded crossover study. Inhal Toxicol. 2016;28(3):145-153. doi:10.3109/08958378.2016.1145770
Curran J, Cliff R, Sinnen N, Koehle M, Carlsten C. Acute diesel exhaust exposure and postural stability: A controlled crossover experiment. J Occup Med Toxicol. 2018;13(1):2. doi:10.1186/s12995-017-0182-5
IDEA STUDY – THE EFFECTS OF AIR POLLUTION AND INHALED SALBUTAMOL ON LUNG FUNCTION AND ATHLETIC PERFORMANCE IN ASTHMATIC INDIVIDUALS (Collaboration project with Dr. Koehle’s lab)
The detrimental effects of air pollution on cardiovascular and respiratory health are described in a large body of scientific literature. Olympic Games in cities known for high levels of air pollution such as Beijing 2008 and Athens 2000 raised concerns regarding athlete’s health and athletic performance. Ironically, especially athletes, who tend to follow a health-conscious lifestyle, are at risk of cardiorespiratory symptoms and illnesses triggered by air pollution. Physical activity leads to the release of epinephrine. Epinephrine induces a widening of the airways to facilitate the increased minute ventilations required to sustain the physical demands placed by the training loads. The inhalation of increased volumes of polluted air through widened airways, ultimately leads to an impairment in healthy lung function and athletic performance. function and athletic performance.The acute treatment of choice for these asthma-like symptoms is the inhalation of beta-2-agonists (IBA), which mimic epinephrine. While IBAs induce a further widening of the airways and relieve respiratory distress in the short-term, IBA use may increase the chance of pollutants reaching deeper areas in the bronchial tree, where they can cause structural (airway remodeling) and functional (decreased abilities to generate air flow) damage in the long term. The purpose of this proposed study is to investigate short- and long-term effects of IBA-use in the treatment of respiratory symptoms triggered by air pollution exposure in elite athletes.
DE 2 & 3 STUDY – EFFECTS OF EXPOSURE TO ALLERGENS AND AIR POLLUTION ON LUNG FUNCTION AND IMMUNITY
Asthma is a disease associated with considerable health consequences whose prevalence has increased sharply over the past 40 years on a global level. Asthma is characterized by chronic inflammation and airway hyper-responsiveness to both irritant and allergenic exposures. While viral and allergenic exposures have been the primary focus of research of asthma exacerbation, the evidence linking combustion-derived particulate matter (PM) to asthma symptoms and exacerbations is considerable. Diesel exhaust (DE) is a key source of ambient PM less than 2.5 microns in diameter (PM2.5), which penetrates deeply into the lung and has been strongly associated with acute worsening of asthmatic lung function. Air pollution is a multi-inhalant mixture, but related research typically focuses on single exposures in each experiment. While binary “stimulus-response” types of questions are important initial steps to elucidating the mechanisms of asthma, our goal is to mimic the real-world milieu of inhaled toxicants by combining an allergen challenge with DE exposure. Therefore, our goal is to document, in humans and in-vivo, DE’s ability to augment allergen-induced immune responses (eg: oxidative stress, eosinophilia, IgE and Th2 cytokines in the lung).