Study uncovers how exposure to PM2.5 air pollutants causes airway dysfunction

Air pollution is the second leading risk factor for death globally, with most of the world population subject to harmful air pollutant levels. However, the mechanisms behind air pollution affecting human health and mortality remain poorly understood, leaving treatment strategies unknown.

In a recent study published in The Journal of Clinical Investigation, a multi-institutional research team led by The University of Osaka have discovered the mechanism by which exposure to ≤2.5 µm air pollutants (PM_2.5) causes airway dysfunction.

A large portion of natural and human-made air pollutants fall under the PM_2.5 category: dust, vehicle exhaust and wildfire smoke, for example. When inhaled, it causes severe airway damage and respiratory diseases. To understand how exactly air pollution particles affect the respiratory system, the researchers ran a series of experiments on mice. They exposed the mice to environmental pollutants and then examined their respiratory tracts for changes in structure and function.

Our results were quite informative. We found that PM_2.5 air pollutants negatively affect mucociliary clearance, a major protective mechanism in the respiratory tract. Mucociliary clearance basically involves trapping pollutants in a sticky mucus and then sweeping the pollutants out the airway with hair-like projections called cilia."

Noriko Shinjyo, lead author

The researchers found that the pollutants caused oxidative injury in the airways, which facilitates the formation of lipid peroxide-derived aldehydes. This substance is a reactive aldehyde that damages the protective cells in the airway, including airway cilia. As damaged airway cells and cilia can no longer move debris and pollutants out of the airways, the risk of infection is increased.

The team continued their investigation to find out how to restore normal cellular function and reverse damage. For this, the researchers investigated how one gene from the ALDH family, known to protect the body against harmful aldehydes, may counter the effect of airway pollutants.

"Aldehyde dehydrogenase (ALDH1A1) is an enzyme that plays an important role in protection against aldehydes. We used experimental mice that lacked ALDH1A1 to investigate the impact of air pollutants without the gene," explains Yasutaka Okabe, senior author. "As expected, the mice had impaired cilia formation and function and high levels of aldehydes."

The research team also found that the absence of ALDH1A1 left the cells at a higher risk of serious respiratory infection when exposed to air pollutants. The importance of ALDH1A1 was further emphasized when it was also found that drug-enhanced ALDH1A1 levels improved the mice's mucociliary function in response to pollutants.

Owing to the researchers' work, we now know how PM_2.5 pollutants disrupt the lungs' self-cleaning system. What's more, their work offers a potential therapeutic target: the enzyme ALDH1A1. As air pollution continues to be a major health concern worldwide, these findings could be key for new treatments that strengthen our respiratory defenses.