Wildfire Smoke: Assessing Possible Treatments for Exposure

In a year when wildfires have burned 8 million acres across America, and Colorado and California both suffered through the  largest fires  in their respective histories this year, we need a critical re-evaluation of what we can do to prevent fire smoke and air pollution-induced cardiovascular disease and respiratory damage to the population of the Western United States.   

Demographics for those considered "sensitive" to air pollution make up about 30 percent of the U.S. population: children under 18, adults over 65, women who are pregnant and those with medical conditions including heart or lung disease, COPD, asthma, diabetes or compromised immune systems.  

 As an example, on Sept. 9th, 2020 the I-5 corridor in Oregon had air quality index (AQI) readings that hit 599 on the  EPA’s map  for the state, and approximately 700 in some locations on the crowd-sourced  PurpleAir  monitoring site. Again, the EPA AQI scale only reaches 500, so the effects of these high levels of exposure have are unknown. 

An NPR analysis of  U.S. Environmental Protection Agency air quality data  found that nearly 50 million people in California, Oregon and Washington live in counties that experienced at least one day of "unhealthy" or worse air quality during wildfire season so far in 2020. That's 1 in 7 Americans, an increase of more than 9 million people compared with 2018, the worst previous year. 

More than 17 million people — the most ever recorded during fire season — live in counties where air quality reached levels deemed "very unhealthy" or "hazardous."  

Lung Function Declines for Years After Exposure

A recent study assessed lung function in older adult residents of Seeley Lake, MT after a bad 7-week fire smoke exposure season (a daily average of 220.9 μg/m3). The results clearly showed rapidly declining lung function for the following 2 years after the wildfire event. (see Wildfires Smoke Blankets the West – Air Quality Worst in History for a detailed summary of that study) And that 2 year period was only the end of the study, follow-up may show the effect is continuous.  

Given the same and more serious exposure for those in Oregon and Northern California for the entire wildfire season, we may see something similar if not more serious.  

A 2012 study of Washington state residents looking at the association between wildfire smoke PM2.5 and hospital admissions for asthma and COPD found a 10 μg/m3  increase in wildfire smoke PM2.5 associated with an 8% increased risk in asthma‐related hospital admissions.    

And after severe fire seasons, a study revealed that influenza was three to five times worse during the traditional flu season of fall and winter. The study identified that after four bad fire years, including 2017, the number of annual flu cases in Montana jumped from the typical 3,000 to around 12,000. 

What does particulate matter do to the lungs and the vascular system and is it reversible? These are the questions worth exploring to see if there are strategies for treatment. 

We do know a little about particulate air pollution and its effect on the lungs, blood vessels and immune system.  

PM2.5 (or smaller) in fire smoke and air pollution have been linked with endothelial dysfunction, systemic inflammatory and oxidative stress responses and the progression of atherosclerosis. And chronic exposure to PM2.5 leads to chronic pulmonary inflammation and sets the stage for chronic obstructive pulmonary disease, which affects 12–16 million people in the United States and is the third-leading cause of death. 

Alveolar macrophages, think of them as the waste removal service of the body, process inhaled particulate matter—everything from “soot” (PM 10) to fine (PM 2.5 μm or less) and ultrafine (0.1 μm or less) particles.  

Alveolar macrophages function normally to surround these particles—which include metal (lead, iron, etc.) nanoparticles and PAH (polycyclic aromatic hydrocarbons) and to evacuate them from the lungs via the lymphatic circulation. As a result of contact between these particles (PM 2.5 in particular)  and the lung lining, phospholipids in the lung tissue are oxidized and  stimulate the activation of the alveolar macrophages generating reactive oxygen species (ROS).  

In response to big particles of wildfire smoke (PM10) the lungs produce tumor necrosis-factor (TNF), interleukin 6 (IL-6),  and cyclo-oxygenase 2 (COX-2) all mediators of inflammation that also upregulate oxidant stress. This innate immune response results in other mediators of inflammation, including the production of nuclear factor (NF)-κB and interleukin (IL)-1β. 

Even though the mechanism responsible for this damage starts with local macrophage activation, it initiates a systemic cellular inflammatory response, specifically in the sensitive endothelial lining of the circulatory system. 

This response is like an alarm that rings throughout the body and effects the entire vascular system, causing inflammation and potential formation of both microthrombi and emboli. This is one of the mechanisms for particulate matter exposure in air pollution that leads to cardiovascular disease. In animal models, exposure to PM2.5 leads to decreased prothrombin and partial thromboplastin times (decreased plasma clotting times), increased levels of fibrinogen, and increased activity of factor II, VIII, and X. The animals that could not produce IL-6 were protected from the prothrombotic effect of particulate matter exposure, indicating that IL-6 is an important mediator in the inflammatory response.  

This systemic response includes not just an upregulation of IL-6, but more oxidative stress, activation of Toll-Like Receptor4 and activation of NADPH oxidase (NOX)-dependent pathways. In addition to causing vascular injury, this series of inflammatory events has also been shown to cause acute lung injury and is the same mechanism in H5N1, SARS, and some features of COVID-19.  

Research looking at plant extracts and nutrients may be strategies for addressing these inflammatory pathways and could aid in reducing potential ongoing damage from fire smoke and air pollution exposure. 

Resveratrol

Constituents of resveratrol have been shown to reduce inflammation by downregulation of IL-6 and TNFα and promotion of anti-inflammatory sirtuins. Sirtuins (like SIRT1) are a family of enzymes that occur in all living organisms and regulate cellular aging, apoptosis, and resistance to stress and oxidative damage.  

Studies have evaluated the activity of a resveratrol derivative in effectively reducing NF-kB-related inflammation in an animal model of acute lung injury. Resveratrol has also been shown to protect lung epithelia against the effects of cigarette smoke by upregulating Nrf2 to promote glutathione production intracellularly. In animal models of inflammation resveratrol has been shown to be effective in upregulating SIRT1, and inhibiting NF-κB as a result.  

Asthma is characterized by airway inflammation, remodeling, and airway hyper responsiveness. Resveratrol, in animal models, has been shown to significantly alleviate asthma, inhibit mucus overproduction and down- regulate the inflammatory mediator TGF-β1.  

There are no extensive clinical studies using resveratrol in asthma, but it has been shown to have significant anti-inflammatory effects in cardiac disease. In a clinical study of 60 cardiac failure patients (half of them were given 100 mg. resveratrol daily for 3 months) the results were significant. Exercise capacity, ventilation parameters and quality of life improved dramatically in the resveratrol group. As importantly, markers of oxidative stress: IL-6 and IL-1 were significantly lowered in the patients on resveratrol.                                      

Cardiac failure occurs in an environment of oxidative stress and resveratrol has been shown to have other positive antioxidant effects in cardiac and vascular pathologies by increasing endothelial nitric oxide synthase (eNOS) activity as well as lowering levels of  TNF-α, IL-1β or IL-6 in other studies.  

Meta-analyses of clinical trials with resveratrol assessing cardiometabolic risk and treatment for respiratory disease indicate that long-term dosing of moderate doses (450 mg. day) may be more beneficial than lower doses of 100 mg. day or infrequent dosing at higher doses of 1000 mg.  

In addition to other nutrients specified in earlier blogs (see Wildfires Smoke Blankets the West – Air Quality Worst in History) resveratrol and other anti-inflammatory plant extracts like curcumin may be helpful in preventing chronic damage to lungs exposed to high levels of wildfire smoke. See Part II of this Blog coming up in December for more information on plant extracts and the role of the microbiome in smoke-exposure.