14 DAY TRIAL // A team of researchers from Duke University Medical Center, made a step forward on the road to new therapies for people with airway disease risks, by discovering how nanoparticles from diesel exhaust damage lung airway cells.
Another big discovery they made, is that the severity of the injury depends on the affected individual's genetics, and as Wolfgang Liedtke, MD, PhD, assistant professor in the Duke Department of Medicine, an attending physician in the Duke Clinics for Pain and Palliative Care and lead author of the study says, this is what explains “why some people can remain relatively healthy in polluted areas and why others don't.”
People living in metropolis are used to seeing urban smog every day, but living in a city covered in smog can be very dangerous.
Diesel exhaust particles are a major part of urban smog, and they are made up of a carbon core coated with organic chemicals and metals.
Duke researchers showed that the particle core delivers these organic chemicals onto brush-like surfaces that clear mucus from the airway lining, called cilia.
Upon contact, the body cells respond to these chemicals by triggering a 'signaling cascade', but in some patients, with a single 'letter' difference in their DNA, the circuit called the TRPV4 ion channel reacts more strongly to the pollutants.
According to prior research, it looks like this gene variant is the culprit for people's predisposition to developing chronic-obstructive pulmonary disease – COPD, and this new research confirms it.
The authors say that nearly 75% of people have the MMP-1 gene version which leads to a higher production of the molecule MMP-1 mediator, responsible for lung tissue destruction.
According to Liedtke, this genetic structure favors a turbo-charged production of MMP-1 that damages airways and lungs at several levels.
Of course, there are the remaining 25% of people who are far more lucky and escape this level of MMP-1 production.
These are the ones that can manage the effects of air pollution better, with no serious airway damage.
MMP-1 is a very harmful molecule, since it stimulates the development of certain devastating lung diseases, like COPD – a top-ten ailment in world-wide morbidity and mortality, according to WHO.
The molecule can also lead to lung emphysema (a chronic reduction of the lung surface dedicated to gaseous exchange) and to the spread of lung cancer cells, which migrate from infected lung tissue.
Liedtke added that this study will help future therapeutics for people who are genetically more susceptible to air pollution and airway damage.
“If we can find a way to stop the hyperactivation of MMP-1 in response to diesel-engine exhaust particles and reduce it to levels that the airways can manage, then we will be helping a large number of people worldwide.
“It is attractive to envision inhaled TRPV4 inhibitor drugs, rather than swallowing a pill or taking an injection.
“I envision this as rather similar to inhaled drugs for allergic airway disease that are currently available.”
This research is published on-line today (January 18) in the journal Environmental Health Perspectives.