Mechanistic impact of outdoor air pollution on asthma and allergic diseases

Abstract

Over the past decades, asthma and allergic diseases, such as allergic rhinitis and eczema, have become increasingly common, but the reason for this increased prevalence is still unclear. It has become apparent that genetic variation alone is not sufficient to account for the observed changes; rather, the changing environment, together with alterations in lifestyle and eating habits, are likely to have driven the increase in prevalence, and in some cases, severity of disease. This is particularly highlighted by recent awareness of, and concern about, the exposure to ubiquitous environmental pollutants, including chemicals with oxidant-generating capacities, and their impact on the human respiratory and immune systems. Indeed, several epidemiological studies have identified a variety of risk factors, including ambient pollutant gases and airborne particles, for the prevalence and the exacerbation of allergic diseases. However, the responsible pollutants remain unclear and the causal relationship has not been established. Recent studies of cellular and animal models have suggested several plausible mechanisms, with the most consistent observation being the direct effects of particle components on the generation of reactive oxygen species (ROS) and the resultant oxidative stress and inflammatory responses. This review attempts to highlight the experimental findings, with particular emphasis on several major mechanistic events initiated by exposure to particulate matters (PMs) in the exposure-disease relationship.

Keywords: Air pollution; allergic disease; aryl hydrocarbon receptor (AhR); asthma; particulate matter (PM); polycyclic aromatic hydrocarbon (PAH); transition metal.

Figure 1

A mechanistic model of the exposure-disease relationship illustrating a sequential event originating from the exposure to the development of asthma. This model encompasses the major events known to be involved in asthma, including activation of pulmonary resident cells, including epithelium, fibroblasts and airway smooth muscle cells, as well as of those immune regulatory cell types, including dendritic cells (DCs), Th2, Th17, mast cells, granulocytes (eosinophils and neutrophils) and innate-type lymphoid cells (iLCs). They all could potentially be the target cell types and, collectively, contribute to the generation of oxidative stress and inflammatory responses. In this model, [1] the impact of air pollutants, including VOCs, metals and PAHs, either working alone or serving as immune adjuvant in conjunction with relevant allergens, is expected to be variable with pollutant-specific responses, but it appears to invariably converge on the induction of oxidative stress response either through their intrinsic oxidant-generating capacity, their ability to inhibit anti-oxidant activity or the combination thereof. [2] In this regard, the aryl-hydrocarbon receptor (AhR)-ligand (primarily PAHs) axis may provide a receptor-mediated mechanistic link between the exposure and the redox imbalance, as a part of a series of detoxification or bio-transformation of air pollutants, such as PAHs. [3] As the consequence of elevated ROS and RNS, concomitant with ER stress and mitochondrial dysfunction, changes in signaling events and a shift in cellular metabolism occur, resulting in the generation of metabolites, for example eicosanoids, and lipid peroxidation as well as modification of proteins by oxidation and/or nitration, some of which are able to induce, or amplify the existing, inflammatory response, either alone or play a role in conditioning the cells to become more sensitive to subsequent stimulation by pollutants and/or allergens. But, [4] any disturbance in the redox balance and/or homeodynamic state will result in the generation of pro-inflammatory mediators, including those involved in oxidative, metabolic and inflammatory responses, generated in each step of this sequential process, and [5] collectively, contribute to the development and exacerbation of the disease in genetically susceptible individuals and/or those with epigenetic modifications as the result of exposure to air pollutants.