Study explores reduction in airway inflammation in lung diseases

UNMC researchers received a $1.9 million grant to explore a discovery that challenges current knowledge related to mucous and how it’s cleared in the lungs.

The National Institutes of Health National Heart, Lung and Blood Institute study, led by UNMC’s John Dickinson, MD, PhD, will explore the UNMC team’s recent discovery — published in the journal Scientific Reports — that challenges existing dogma that secretory cells only secrete mucous.

Their findings suggest that the cell’s internal digestive system contributes to recovery of airway attacks by degrading or breaking down excess mucous in the airway. Answers could help better explain recovery rates among patients with asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD).

Mucous plays a critical role in such airway diseases because it builds up in the lungs, blocks airways and results in attacks of coughing, wheezing, shortness of breath and loss of lung function. In severe cases, it can lead to death.

Using cell culture models from airway epithelial cells and mouse models of airway disease and asthma attacks, the team found that the digestion occurs primarily during the resolution of airway inflammation. Instead of being released into the lung, some mucous is degraded (digested) inside the cell by the lysosome.

Dr. Dickinson, an assistant professor in the UNMC Department of Internal Medicine Division of Pulmonary, Critical Care, Sleep Medicine and associate director of the adult cystic fibrosis program at UNMC, explained the research.

"We propose that instead of being released into the airway, some of the mucous can be digested internally by the cell’s "trash can," an organelle called the lysosome," he said. "By identifying that mucous can be eliminated inside the cell as a way to rid the body of excess mucous, we hope to exploit this knowledge to identify new drugs that will accelerate the process of resolution and reduce blockages in the airway.

"This research is relevant to how fast patients with asthma or COPD improve or fail to improve after an attack. It may even be important in how fast patients recover from a common cold causing a persistent cough," Dr. Dickinson said, assistant professor.

The team’s next step is to identify the cellular pathways that control how this mucous digestion occurs in the airway, he said.