“Air That Once Was Breath” Part 1: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation – “Climate Change, Allergy and Immunology” Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023

Abstract

<b><i>Background:</i></b> Wildfires are a global concern due to their wide-ranging environmental, economic, and public health impacts. Climate change contributes to an increase in the frequency and intensity of wildfires making smoke exposure a more significant and recurring health concern for individuals with airway diseases. Some of the most prominent effects of wildfire smoke exposure are asthma exacerbations and allergic airway sensitization. Likely due to the delayed recognition of its health impacts in comparison with cigarette smoke and industrial or traffic-related air pollution, research on the composition, the mechanisms of toxicity, and the cellular/molecular pathways involved is poor or non-existent. <b><i>Summary:</i></b> This review discusses potential underlying pathological mechanisms of wildfire-smoke-related allergic airway disease and asthma. We focused on major gaps in understanding the role of wildfire smoke composition in the development of airway disease and the known and potential mechanisms involving cellular and molecular players of oxidative injury at the epithelial barrier in airway inflammation. We examine how PM2.5, VOCs, O<sub>3</sub>, endotoxin, microbes, and toxic gases may affect oxidative stress and inflammation in the respiratory mucosal barrier. We discuss the role of AhR in mediating smoke’s effects in alarmin release and IL-17A production and how glucocorticoid responsiveness may be impaired by IL-17A-induced signaling and epigenetic changes leading to steroid-resistant severe airway inflammation. <b><i>Key Message:</i></b> Effective mitigation of wildfire-smoke-related respiratory health effects would require comprehensive research efforts aimed at a better understanding of the immune regulatory effects of wildfire smoke in respiratory health and disease.

Impact of Wildfires on Cardiovascular Health

“…Noting that WFS exposure promotes oxidative stress leading to activation of resident immune and inflammatory cells within lung tissues, 86,87 several controlled human exposure studies measured levels of inflammatory markers (CRP, SAA, MCP-1, ILs, TNF-α [tumor necrosis factor alpha], IFN-γ [interferon gamma], and MPO [myeloperoxidase]), soluble adhesion molecules (ICAM-1, VCAM-1, and selectins), and soluble hemostasis and thrombosis factors (fibrinogen, FVIII [factor VIII], and VWF [von Willebrand factor]) within the peripheral blood, along with the concentration of lipid (8-isoprostane-prostaglandin F2α) and protein (3-nitrotyrosine) peroxidation products in plasma or urine. Exposure of healthy volunteers to the smoke generated by combusting a hardwood/softwood mixture for 4 hours (279 mg/m 3 median PM 2.5 ) augmented both SAA levels and the FVIII:VWF plasma concentration ratio, immediately after and for up to 20 hours post-treatment, compared with filtered air.…”