A normally bad agent that causes inflammation contains what might be a potential therapy that could help treat severe lung disease like pneumonia, a Georgia Regents University researcher said.
A drug that mimics the crucial sequence was tested in Vienna, Austria, and helped pneumonia patients with severe lung injury get off ventilators sooner and recover quicker. There is no good therapy for pneumonia other than ventilators and each year about 400,000 people are hospitalized with it. About 5-7 percent of people die but the death rate could be as high as 50 percent among elderly patients, the Centers for Disease Control and Prevention said.
One key way pneumonia causes damage is through pulmonary edema, when fluid builds up in the tiny sacs in the lungs called alveoli that facilitate the exchange of oxygen with tiny blood vessels.
One of the agents that causes this fluid buildup is called tumor necrosis factor-alpha or TNF-alpha, which causes the tiny blood vessels to leak and to close sodium channels in certain alveoli. That allows sodium, and fluid with it, to drain out of cells, said researcher Rudolf Lucas, an associate professor in the GRU’s Vascular Biology Center. Bacterial toxins can also close those sodium channels, he said.
“Once you get edema formation, accumulation of liquid in the alveoli, it will just stay there,” Lucas said. “These patients then will have huge problems breathing and they need ventilator support.”
The ventilator itself can also cause lung injury in those patients, he said, and at that point the fluid-filled lungs are difficult to treat. But Lucas and his colleagues discovered a certain domain of the inflammatory agent that appears to have the opposite effect and binds to the sodium channels to keep them open, even in the presence of bacterial toxins. They created a peptide that mimics that domain that appears to have the same effect.
Their work was published online in the American Journal of Respiratory and Critical Care Medicine. The peptide was tested in mice and in pigs and now in a small clinical trial in Vienna. The patients who got the peptide had less fluid and had fewer days on the ventilator, Lucas said.
“So that looked pretty promising,” he said. “Of course, care has to be taken. This was a small group of patients only 20 per group so now it has to be investigated in larger groups of patients.”
Because of the cost, however, that will probably only happen if a large drug company gets involved, Lucas said. Still, the results were encouraging.
“It was very rewarding for us to see there could be a similar effect in patients as what we see in animals,” he said. “I think it is honestly promising. If there is one day that even one patient could be positively treated with this I would be very happy.”