Research News

In a new study published in the American Journal of Physiology, researchers led by physician-scientist Fariba Rezaee, MD, analyzed the impact of co-exposure to respiratory syncytial virus (RSV) and particulate matter to gain better insight into the impact of air pollution on disease course. Titanium dioxide, they found, intensified the effect of RSV on airway epithelial cell integrity and airway inflammation.

RSV is a leading cause of lower respiratory tract infections in children worldwide. In 2015 alone, an estimated 33 million occurrences of RSV-related acute lower respiratory infection led to 3 million hospitalizations.

While some patients with RSV may be asymptomatic or have only mild disease, other children develop severe symptoms that may require hospitalization, oxygen treatment and sometimes treatment in pediatric intensive care units. Data indicate that risk factors, such as prematurity and asthma, have been associated with more severe RSV-related illnesses. These conditions, however, do not account for all of the variations.

Air pollution may intensify RSV symptoms

One possible explanation for the variation in disease course may be environmental, as supported by Dr. Rezaee’s latest study. “Epidemiological data are indicating that for children living in a polluted area or close to the highway, RSV infection can be more severe,” said Dr. Rezaee, a joint staff member in the Department of Inflammation and Immunity and the Center for Pediatric Pulmonary Medicine.

“In this study, we sought to investigate the effect of air pollution and RSV infection on airway epithelial cell integrity,” explained Dr. Rezaee. “We exposed epithelial cells to RSV, titanium dioxide nanoparticles or both. We found that the effect of the RSV on airway epithelial cell integrity and airway inflammation was intensified by titanium dioxide.”

Why titanium dioxide?

Titanium dioxide is used as an additive in many commonly used household and personal care products. Household uses include paints and coatings, adhesives, paper, plastics, ceramics and floor coverings. In terms of personal products, titanium dioxide is added to sunscreens as a UV filter, used in pressed and loose powders, lotions and creams and as a whitening agent in things like toothpaste.

When in a lotion, there is a lower risk of exposure to titanium dioxide nanoparticles. However, adverse effects of titanium dioxide have been uncovered. When titanium dioxide is inhalable, as it may be in powder form, it is considered a possible carcinogen and may irritate the airway. The particles come in different sizes: they are coarse, fine or extra fine, and the smaller, nanoparticles can move from the airway into the body, according to Dr. Rezaee. These particles have been found in patients’ lungs, heart, liver and even brain.

Adding nanoparticles exacerbates airway inflammation

Here, the researchers incubated bronchial epithelial cells with titanium dioxide nanoparticles or a combination of the nanoparticles and RSV. They analyzed the structure and function of the epithelial cell barrier and evaluated the viral titer (a measure of how much virus there is in a given volume of fluid) and the role of reactive oxygen species generation.

Moving into preclinical models, Dr. Rezaee and her team intranasally administered the nanoparticles, RSV or a combination. “We found that the addition of titanium dioxide nanoparticles to RSV exacerbated airway inflammation. The titers of the viral infection were higher in these models, with more inflammatory cytokines, and we noted barrier disruptions,” said Dr. Rezaee. “While RSV and titanium dioxide can cause disruption to airway epithelial cells on their own, when you have both together, the disruption is intensified.”

Dr. Rezaee hopes this study can be used as groundwork for future studies that look into how these co-exposures affect barrier disruption or inflammation, contributing to disease severity.

“Future studies might include a deep-dive into different kinds of treatment for models with co-exposure to RSV and titanium dioxide nanoparticles. We would also like to identify biomarkers that show inflammation or the various disruptions, and measure those in humans. We would like to cohort the data so that when a patient presents with RSV, we are able to analyze the air properties in their neighborhoods, which might give clinicians insight into the disease course.”

Article adapted from Consult QD.