Budesonide Improved Epithelial Barrier Function in Asthma

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Neither formoterol nor montelukast showed any protective effect in the barrier model.
Neither formoterol nor montelukast showed any protective effect in the barrier model.

This article is part of Pulmonology Advisor's coverage of the American Thoracic Society's International Conference, taking place in San Diego, California. Our staff will report on medical research related to asthma and other respiratory conditions, conducted by experts in the field. Check back regularly for more news from ATS 2018.


SAN DIEGO— Budesonide may help restore epithelial function after acute mucosal inflammation from exposure to viral RNA, according to scientists at the American Thoracic Society 2018 International Conference.

Virally induced epithelial barrier dysfunction has been identified as an important aspect of asthma pathophysiology. However, “We currently have limited information about whether or how epithelial barrier dysfunction can be restored therapeutically,” explained lead author Clara Rimmer, MD, from the Pulmonary and Critical Care department at the University of Rochester Medical Center, Rochester, New York.

Dr Rimmer and colleagues developed a model of transient barrier dysfunction caused by low-dose polyl:C, a synthetic analog of viral double-stranded RNA. The team measured transepithelial electrical resistance (TEER) before and then at 6 and 24 hours after polyl:C exposure. Following this, monolayers were washed and incubated with different doses of budesonide (0.01-1 uM), montelukast (0.01-1 uM), formoterol (0.01-1 uM), budesonide plus formoterol, or fresh media.

TEER was measured at hours 6, 24, and 48 post-treatment, and epithelial permeability to 4 kDa fluorescein isothiocyanate dextran was determined at 48 hours using a fluorescent plate reader.

The data showed that barrier function was restored to ~80% of baseline during the 48-hour period in the presence of fresh medium alone. No significant improvement was seen in the rate or extent of recovery with any of the compounds tested.

Cells exposed to budesonide, however, had a slight reduction in permeability vs cells exposed to polyl:C in culture alone (~20% improvement for all doses; P <.005). Neither formoterol (with or without budesonide) nor montelukast exerted any protective effect in the barrier recovery model. 

The restored epithelial barrier function seen with budesonide after acute mucosal inflammation from viral RNA exposure may be “one of the ways budesonide works therapeutically in patients with asthma,” Dr Rimmer concluded. More studies evaluating these compounds in other types of epithelial barrier dysfunction are warranted.

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Reference

Rimmer C, Hetelekides S, Veazey J, Smyth T, Georas SN, Chapman T. Effects of commonly used asthma medications on virally-induced epithelial barrier dysfunction: budesonide restores barrier integrity. Presented at: American Thoracic Society 2018 International Conference; May 18-23, 2018; San Diego, CA. Abstract 7176.