Research Snapshot: easing the symptoms of chronic inflammatory lung disease

April 6, 2016

Researchers at the University of Minnesota College of Veterinary Medicine are looking to help people with chronic inflammatory lung diseases like COPD and asthma.

Mathur Kannan, Ph.D., and a research team will conduct a two-year NIH-funded study that aims to ease the harsh effects of these diseases by decreasing adenosine in the body. Adenosine acts as part of a signaling system and is naturally produced in the body at a higher rate in inflammatory environments.

Researchers believe that controlling levels of adenosine that enter the lungs can ease the negative symptoms brought on by chronic lung diseases. The more adenosine in the lungs, the more likely the lungs will be inflamed and produce negative symptoms.

To the average person, adenosine has little effects, but for those with COPD and chronic lung diseases, symptoms worsen.

The researchers discovered that an enzyme found in the lung called CD38 could affect adenosine levels; CD38 converts Nicotinamine adenine dinucleotide (NAD), a naturally-occurring coenzyme involved in metabolism, to adenosine.

CD38 levels are significantly higher in an inflammatory site, like the lung. This means that an inflammatory environment, like the lungs of those with chronic lung disease, is perfect for generating more adenosine, creating harsh symptoms in those with chronic lung diseases.

“Asthmatics have the capacity to produce more adenosine from NAD, “ Kannan explained.

With this idea in mind, the researchers are going to look at cells from the lungs of healthy people and those who died from chronic asthma. They will also use mouse models. After exposing mice lungs to an allergen that produces chronic inflammation, researchers will attempt to reduce the amount of CD38, which they hypothesize could reduce the amount of NAD-derived adenosine in the lungs, easing symptoms.

Most pharmaceutical companies have developed drugs that reduce the effects of adenosine, which can include a scratchy throat and itchy eyes. Rather than treat the symptoms, Kannan and his colleagues want to directly fix the problem by reducing the amount of symptom-causing adenosine levels in the lungs.

But there’s a fine balance that needs to be met. Adenosine is naturally produced in everyone’s bodies, so it’s important to only reduce the levels that would cause negative side effects, not completely get rid of it.

“If we block all adenosine levels, we lose positive effects,” Kannan said. “If we reduce them directly in the lungs, we wont have the bad effects, but will still get the good effects.”