Grant: Team Grant: Lung Health - Inflammation and Lung Health

This summer saw the largest number of asthma patients with exacerbations that required medical attention. We think the tiny particles generated by forest fires carry microbes (some from soil and other sources) that we normally do not encounter. This leads to stimulation of the innate inflammatory response which includes recruitment of different immune cells than would normally be encountered in asthmatic lungs (neutrophils rather than eosinophils) and the commonly used drugs no longer work. We will start by examining what microbes are found on the smoke particles and fully characterize their composition by collaborating with a chemist who specializes in pollution. Once he and a microbiologist have fully characterized the contents we will deliver them to mice. We think a number of bad things happen. First the microbe laden particles activate sensory neurons which activate macrophages to make inflammatory molecules that call neutrophils into the lungs. In addition, the particles are eaten by macrophages and this paralyzes them so they can no longer clear bacteria leading to more inflammation. This causes more neutrophils to come in in a vicious circle. This also leads to a reprogramming of the immune system such that each bout of forest fires begets a worse and worse response. The drugs and even standard antibiotics will not work due to the nature of the microbes. We will determine whether similar issues happen in humans and particularly in humans that live close to the fires such as indigenous communities. We have three potential novel treatment approaches that we will try in mice first and then in a small cohort of humans.