Study: Treatment May Aid Asthma Sufferers

ST. LOUIS -- A two-drug treatment may one day help restore healthy breathing in those with asthma and chronic bronchitis, according to a study at Washington University in St. Louis.

Dr. Michael Holtzman and other researchers found that some cells lining the air passages of the lungs transform into another cell type in mice and humans with those disorders, leading to the overproduction of mucus in the airways.

Though researchers expect it would take at least a few years for further testing of the treatments, they think that combining two drugs ultimately could prevent the harmful transformation of the lining cells, allowing for healthy airway function.

Holtzman said the findings are "pushing the rock a little further up the hill" when it comes to understanding airway diseases.

The study appeared Wednesday in the Journal of Clinical Investigation.

Holtzman explained that doctors currently prescribe treatments to ease breathing difficulties, but said those treatments don't address mucus production.

Researchers studied mice with a lung condition resembling asthma and chronic obstructive pulmonary disease, a disease classification that includes chronic bronchitis.

They saw that the airway lining maintained an overabundance of mucus-producing cells, called goblet cells because they have a cup-like shape.

Those goblet cells built up because of two cellular mechanisms. One mechanism allowed for the prolonged survival of cells with cilia, tiny hairs that help sweep debris out of the lungs. The other encouraged those cells to transform into goblet cells.

Holtzman said in some people viral infections or other factors seemed to cause an excess of goblet cells, leading to certain breathing disorders. He said the researchers showed that the excess cells could be blocked, using a combination of two types of inhibitors.

One impedes the activity of a protein called the epidermal growth factor receptor. The protein is overactive on the ciliated airway cells in mice with the asthma-like condition. If the protein was blocked, the inhibitor prevented the buildup of those cells.

The researchers also tested a second inhibitor that interferes with signaling pathways activated by an immune-system protein known as interleukin-13. They found that IL-13 brought out the change from ciliated to goblet cells in mouse airways and human airway cells in culture. If IL-13 was interfered with, the transformation from one cell type to the other was prevented.

Holtzman said if the inhibitors are combined, they can "restore the normal architecture of the airway lining."

Dr. Kenneth Adler, a cell biology professor at North Carolina State University in Raleigh, said the researchers' work to inhibit cells that increase mucus was significant, because currently there aren't any therapies to effectively treat that problem.

"Mice aren't people, and cells in culture aren't airways in people," he noted. But, he said, if the findings held true in additional studies, they could be highly significant in treating humans.