HeadWay Winter 2018

Although human population studies have linked air pollution to chronic inflammation of nasal and sinus tissues, direct biological and molecular evidence for cause and effect has been scant. Now, research in mice, led by Johns Hopkins otolaryngologist-head and neck surgeon Murugappan Ramanathan, suggests that continual exposure to dirty air can lead to a bevy of consequences that mimic human chronic sinusitis—a condition that affects more than 29 million individuals in the U.S.

The new findings, Ramanathan says, have broad implications for the health and well-being of people who live in large cities and industrial areas with polluted air, particularly in the developing world.

“In the U.S., regulations have kept a lot of air pollution in check, but in places like New Delhi, Cairo or Beijing, where people heat their houses with wood-burning stoves, and factories release pollutants into the air, our study suggests people are at higher risk of developing chronic sinus problems,” he explains.

To see how pollution may directly affect the biology of the upper airways, the researchers exposed 38 eight-week-old male mice to either filtered air or concentrated Baltimore air with particles measuring 2.5 micrometers or less, which excludes most allergens, like dust and pollen. The aerosolized particles, although concentrated, were 30 to 60 percent lower than the average concentrations of particles of a similar size in cities like New Delhi, Cairo and Beijing.

Nineteen mice breathed in filtered air, and 19 breathed polluted air for 6 hours per day, 5 days a week for 16 weeks.

After flushing the noses and sinuses of the mice with water and examining the resulting fluid under a microscope, the researchers saw significantly more white blood cells that signal inflammation, including macrophages, neutrophils and eosinophils, in the mice that breathed in the polluted air compared with those that breathed in filtered air. The elevated neutrophils and eosinophils seen in the sinonasal mucosa of mice exposed to polluted air is very similar to the profile that chronic rhinosinusitis patients exhibit in Asian countries suffering from air pollution.

Further investigation found elevated levels of direct biomarkers for inflammation such as interleukin 1b, interleukin 13, oncostatin M and eotaxin-1. Other signs of inflammation included a thicker epithelium and lower levels of proteins that hold epithelial cells together. Ramanathan says his team will continue to study the upper respiratory changes that occur after exposure to pollution, as well as potential ways to reverse them. For example, he says, it’s not yet known whether removing the pollutant—or the individual from a polluted environment—can reverse any pollutant-related damage. The findings also suggest some molecular pathways that could serve as targets for prophylactic or therapeutic interventions that could prevent or treat chronic sinusitis caused by fine particulates.

“Someday,” he says, “we may have a drug that could completely reverse this condition in our patients.”

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