Researchers at Imperial College London, working with colleagues from King’s College London and University of British Columbia, have demonstrated a mechanism by which diesel exhaust particles directly affect the lungs to initiate symptoms such as a tightening of the airways and cough. These triggered respiratory reflexes can potentially worsen underlying conditions, such as asthma.
Previous research has shown a strong association between urban air pollution and respiratory symptoms such as coughing, wheezing and shortness of breath, but the underlying mechanism has been unclear. In the study, published as an open-access paper in the Journal of Allergy and Clinical Immunology, the team showed that polycyclic aromatic hydrocarbons (PAHs) in the exhaust particles directly stimulate nerves in the lungs, causing a reflex response in the airways.
The findings may provide a key link between exposure to air pollution on city streets and respiratory symptoms which can lead to hospitalisation for people at higher risk, such as the very young, the elderly, and those with respiratory diseases.
Previously, scientists showed that the effects of air pollution on the lungs of asthmatics correlated with the concentration of small, ultrafine particles inhaled, although the exact mechanism was unclear. These tiny particles (less than 100nm in diameter), can get deep into lungs and are so small that cells recognize them as biological molecules which can be absorbed and processed, possibly accounting for their adverse health effects. However, the new findings suggest a more complicated mechanism.
When the particles in diesel exhaust were processed to separate the insoluble carbon core from the soluble, outer organic fraction, the researchers found that it was chemicals on their surface (the PAHs) which directly stimulated nerves, while the central carbon particles did not. The researchers say that the small size of the particles helps the chemicals to reach deep into the lungs, and cross membranes, where they can activate the nerves.
The team tested the effects of exposure in a guinea pig model and animal nerve tissue. The effects were also tested on human tissue, using sections of vagus nerve from donor lung tissue that was surplus to transplant requirement.
The researchers found that when the tissue had been exposed to PAHs, sensory nerves responsible for the reflex events and initiating common respiratory symptoms, such as coughing and wheezing, were stimulated. The evidence suggests that when these organic compounds are inhaled, they interact with receptors in the airways to cause oxidative stress. This stress then cascades and opens ion channels, tipping the electrochemical balance and causing the nerves to ‘fire’.
These findings were further supported using nerve tissue from mice lacking the functioning ion channel (called TRPA1), in which this change to the electrochemical balance in the nerves, and subsequent symptoms, was not seen.
Our work shows that particles from diesel exhaust can activate these ion channels, stimulating the nerves in the lungs. This may be responsible for the respiratory symptoms we see following exposure to urban air pollution.—Professor Maria Belvisi, head of the Respiratory Pharmacology group at Imperial’s National Heart and Lung Institute (NHLI), who led the research.
In a previous study in 2013, a group including researchers at Imperial showed that high levels of air pollution on London’s busy Oxford Street had a measurable effect on the lungs of people with asthma, compared with exposure in less polluted areas of the city. The results showed a link between the levels of ultrafine particles (including diesel exhaust particles) at street level and reductions in lung function.
Professor Belvisi explained the latest work adds to a growing body of evidence demonstrating the direct effects of air pollution on public health. Combined with previous clinical exposure studies, in which people were exposed to real world levels of diesel exhaust particles in the lab, the mechanism illustrates the effects of typical exposure for people living and working in an urban environment.
Ryan K. Robinson, Mark A. Birrell, John J. Adcock, Michael A. Wortley, Eric D. Dubuis, Shu Chen, Catriona M. McGilvery, Sheng Hu, Milo SP. Shaffer, Sara J. Bonvini, Sarah A. Maher, Ian S. Mudway, Alexandra E. Porter, Chris Carlsten, Teresa D. Tetley, Maria G. Belvisi (2017) “Mechanistic Link between Diesel Exhaust Particles and Respiratory Reflexes,” Journal of Allergy and Clinical Immunology doi: 10.1016/j.jaci.2017.04.038.