There's something in the air: disentangling the role of airborne microbes and pollutants in the inflammatory response of asthma along a latitudinal gradient in Canada

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Asthma is an inflammatory respiratory disease that affects over 3.8 million Canadians, approximately a quarter of which are children. Few studies have investigated the morbidity of asthma in Northern Canada, but Inuit children have been found to have lower prevalence of asthma compared to other Indigenous and non-Indigenous children. This is interesting because asthma is not only influenced by genetics but also by environmental factors. Therefore, where an individual lives has a significant impact on the risk of developing asthma and its severity. This can be due to exposure to allergens but also to other protective or inflammatory processes. For example, recent studies have found that growing up in areas with diverse microbial communities such as farmland can decrease the likelihood of developing asthma, by helping human-associated microbes (the microbiome) train the immune system. More directly, certain airborne microorganisms have been found to have a protective role against the development of asthma by preventing serious inflammation of the airways. Microorganisms are not the only aspect of air quality that can contribute to asthma. Pollutants associated with resource extraction, transportation, as well as consumer and commercial products can have the opposite effect and induce inflammation and oxidative damage to the airways thus contributing to severity of symptoms. Airborne environmental microbes and pollutants therefore have opposite effects in asthma, and these factors are highly specific to where a person lives. However, it is unclear how these two variables intersect, and how together they may promote or impede the presentation of asthma. Our goal is to investigate how air quality may contribute to inflammation and asthma in an in vitro co-culture cell model of the human respiratory tract. We will sample 4 regions along a gradient varying in population size, but also in vegetation and land use: Scarborough (Ontario, population ~632k), Saguenay (Quebec, ~69k), Kuujjuarapik (Nunavik, ~686) and Resolute Bay (Nunavut, ~198). At all sites, we will measure air pollutants (volatile organic compounds, trace elements, particulate matter), pollen, and microbial communities for characterization through metagenomic sequencing. Airborne microbes will also be collected and concentrated from each site. In the lab, we will expose a co-culture cellular model of the human respiratory airway to these field microbes. The co-culture will also be exposed to varying concentrations of pollutants, representative of our field data. We will then measure indicators of oxidative stress and inflammation, to quantify the role of both microbes and pollutants in asthma and identify organisms that protect from inflammation. We hypothesize that the diversity of airborne microbes in an environment will have a protective effect in our northern sites, which decreases closer to the treeline. We also expect airborne pollutant levels representative of our Northern sites to induce less inflammation. This study proposes to use a novel approach to understand how the environment shapes the etiology of asthma. Our mechanistic approach will allow us to disentangle the role of the major environmental variables in inflammation of respiratory airways, and to identify the drivers of asthma along a latitudinal gradient in Canada.