In a fight against respiratory infections, the body typically produces a little fluid to help the lungs generate a productive cough.
But new research suggests that the influenza virus can tip the balance toward too much fluid in the lungs, interfering with the supply of oxygen to the rest of the body.
An immune response ultimately is needed to eliminate the virus, but this research suggests that it's not the presence of the virus alone that does all the harm to a sick person. Instead, the fluid buildup deep inside the lungs might help kill a person infected with the flu, according to the research, which was conducted in mice.
"My take is that when people die of these illnesses, they're dying because they can't breathe," said Ian Davis, assistant professor of veterinary biosciences at Ohio State University and senior author of the study. "If the lungs aren't working well, then it doesn't matter whether a week from now you can make an immune response and clear the virus if you can't survive that long because you just can't get oxygen."
Detailing exactly how flu interferes with fluid clearance in the lungs lays the groundwork for a second phase of related studies to test a new therapy - a drug that is already known to regulate the amount of fluid that builds up in infected lungs.
In the event of a flu pandemic, such a drug, which scientists hope could be inhaled by mouth, might be an important supplement to antiviral medications and ventilators, Davis said.
The research is published in a recent issue of the American Journal of Respiratory and Critical Care Medicine .
Davis and colleagues infected mice with high doses of an influenza A virus to compare oxygen levels and fluid clearance in infected mice to those of healthy mice.
Mice that were infected with the highest doses of flu experienced a steady decline in oxygen in their blood and higher levels of fluid in the lungs. Two days after infection, fluid clearance in these mice was only half as effective as fluid clearance from the lungs of uninfected mice.
Lung infections have been known to cause problems with what is called alveolar fluid clearance, but the effects of the flu on the lungs had not been tested before, Davis said. The alveoli are air spaces deep inside the lungs where oxygen enters the blood in exchange for carbon dioxide to be exhaled.
The scientists used an unusual method to observe the fluid clearance. After being infected, the mice were anesthetized and put on ventilators. The researchers then placed fluid containing protein into one lung of each mouse and tested the fluid 30 minutes later. The amount of protein left in the remaining fluid allowed the investigators to determine whether the infected lung was clearing fluid adequately.
Davis said the study showed that when the flu virus infects cells in the lung, those cells release small molecules, or nucleotides, that are part of the energy-producing and replication machinery of the cell. Those nucleotides then bind to receptors of other cells in a series of events that ultimately shut down the transport of sodium from airways to the blood. All of these interactions take place in the epithelium, the lining of the airways in the lungs.