Research Discovers How Persistent Pulmonary Diseases Develop

Washington [US], August 26 (ANI): A new study found that short-lived lung infections can lead to long-term lung damage.

The results of this study were published in the Journal of Clinical Investigation.

The most deadly period of viral respiratory illness is actually after the virus has been cleared from the body.

The destructive process that begins at the pinnacle of infection weeks after the virus is defeated leads to damage to organs that can cause chronic illness and even death.

For example, after the first attack of COVID-19, some people suffer from persistent coughing, dyspnea, and shortness of breath. This is a sign of ongoing lung disease.

Researchers at the University of Washington School of Medicine in St. Louis have found clues about how lung damage occurs in the aftermath of a respiratory infection.

Studies of mice have shown that infection causes the expression of a protein called IL-33, which causes lung stem cells to proliferate in the airspace, increasing lung mucus production and inflammation.

The findings reveal potential points of intervention to prevent chronic lung damage caused by viral infections.

“Vaccines, antivirals, and antibody therapies are all useful, but not a solution for those who are already on the road to progressive disease,” said Michael J., senior author of Selma and Herman Seldin, a medical professor. Dr. Holtzmann said. Professor of Cell Biology and Physiology.

“While COVID-19 has been successful in treating acute illness, what happens after the initial injury stage is a major obstacle to better outcomes,” Holtzmann continued.

“At this point, we are facing tens of millions of people who are already infected, many of whom have long-term illnesses, especially with respiratory symptoms. We have a problem.” Holtzmann added.

It has long been recognized that acute respiratory infections can lead to chronic lung disease.

For example, children hospitalized for respiratory syncytial virus are two to four times more likely to develop asthma, and asthma can last for a long time, or even for life.

However, how acute respiratory infections cause chronic illness is not fully understood and it is difficult to develop treatments to prevent or treat it.

As part of this study, Holtzman and colleagues, including the first authors, medical instructors Kangyun Wu and PhD, studied mice infected with Sendai virus.

Sendai does not cause serious illness in humans, but it naturally infects other animals, including mice, and causes respiratory infections that develop in the same way as human respiratory infections.

Researchers examined the lung tissue of mice 12 and 21 days after infection with Sendai virus and compared the sample to the lung tissue of uninfected mice.

They found that two populations of stem cells helped maintain the barrier between the lungs and the outside world of uninfected mice. However, after being infected with the Sendai virus, these two populations begin to grow separately and spread into the airspace.

Basal cells take over the small airways and air sacs, while AT2 cells remain confined to the air sacs. Some of the new basal cells become mucus-producing cells, while others release molecules that mobilize immune cells into the lungs.

Overall, this process reduces lung space, increases mucus, develops inflammation, and interferes with breathing.

What is the function of the nucleus : Further experiments have shown that this process depends on the protein IL-33. Under normal conditions, IL-33 builds up in the nucleus of lung stem cells in response to stress and damage, helping the lungs repair the damaged barrier. However, IL-33 can play a more detrimental role during and after infection.

To assess the role of IL-33 in lung damage after viral infection, researchers genetically modified mice to abstain IL-33 from the basic set of lung stem cells.

Scientists then infected those mice (and another group of unmodified mice) with the Sendai virus. Two groups of mice were equally effective in combating the initial Sendai virus infection.

However, three weeks after infection, the lungs of mice lacking IL-33 show less cell overgrowth, mucus, inflammation, and less signs of harmful lung changes.

Even in mice that lack IL-33 in their basal cells 7 weeks after infection, blood oxygen levels are high and airway hyperresponsiveness is low, both of which are signs of improvement in chronic lung disease.

“These results were very good, as things could get worse with the removal of IL-33 and then the loss of basal stem cells,” Holtzmann said.

“The manipulated mice may have died because they were unable to perform the usual repairs of viral damage to the lung barrier, but they are not,” Holtzmann explained.

“Instead, mice lacking this population of basal cells gave much better results. That’s what makes us excited. These findings are a cure for the bad behavior of basal stem cells. We have laid a solid foundation for finding, “Holtzmann added.

The step of targeting the pathway between IL-33 and basal cell activation is to prevent or treat lung disease caused by various viruses and possibly other forms of damage in the lungs and elsewhere where the body meets. It has the potential to form the basis of a wide range of effective treatments. The outside world, Holtzmann said.

“The lungs have a fairly stereotyped response to damage, including viral damage,” Holtzmann said.

“A particular type of virus, host genetics, severity of early illness-all of which affect outcomes, but they are a matter of degree. Still, the same important factors are seen across conditions. That’s why we believe there is a common strategy for treatment, “Holtzmann explained.

“We have a drug discovery program to find such a general strategy, and this study fits it well,” Holtzmann concludes. (ANI)