In a study published in The New England Journal of Medicine, UNC researchers describe how the concentration of mucins – the proteins that make mucus thick – is abnormally high in chronic bronchitis and that high mucin concentrations are associated with disease severity in people with chronic bronchitis. This finding could become the first-ever objective marker of chronic bronchitis and lead to the creation of diagnostic and prognostic tools.

This research, led by Mehmet Kesimer, PhD, associate professor of pathology and laboratory medicine at the UNC School of Medicine, also raises the possibility that developing new drugs to reduce mucin concentrations could help relieve bronchitis symptoms and prevent disease progression in chronic bronchitis subjects.

A key mystery has been what causes the accumulation of mucus in the lungs of chronic bronchitis patients – an accumulation that produces symptoms and disease progression. This UNC-led study suggests that the inability to normally hydrate airway surfaces leads to increased mucin concentrations and the accumulation of mucus in the lung. This process then leads to phlegm production and chronic airway infections typical of chronic bronchitis patients.

Kesimer, who is a member of the UNC Marsico Lung Institute, said, “We really wanted to see if we could use this measure to predict risk, in the same way that we use cholesterol measurements to predict cardiovascular disease.”

One of the main purposes of mucus is to trap pathogens and clear them from the lungs. But if mucus gets too thick and sticky, it accumulates in the lungs and starts working against you, obstructing the airways and allowing bacterial infections to take hold.

Knowing this, the researchers suspected mucus might hold the key to differentiating true chronic bronchitis from benign conditions. To test their hypothesis, Kesimer and colleagues analyzed phlegm samples from about 1,000 smokers and non-smokers participating in a NHLBI-funded national study of COPD called SPIROMICS.

But mucus, it turns out, is pretty hard to study. Mucins are large, sticky, and fragile polymers; their propensity to clump together and break into pieces makes them challenging to measure.

Based on his previous work analyzing the mucins involved in cystic fibrosis, Kesimer developed an innovative testing protocol to measure total mucin concentration and the concentrations of the two predominant mucins found in phlegm – MUC5AC and MUC5B.

Running the phlegm samples through their tests, the researchers found a strong association between mucin concentrations and chronic bronchitis disease severity and symptoms in SPIROMICS participants.

In healthy people, mucus is about 98 percent water and 2 percent solids (mostly mucin proteins). People with chronic bronchitis fail to normally hydrate their mucus, producing nearly double the overall concentration of mucins as do their healthy counterparts. Mucus hydration is so important that the difference between having mucus with 2 percent mucins versus 4 percent mucins can mean the difference between breathing normally and having gobs of bacteria-trapping phlegm clogging your airways. Mucins in the lung have very narrow tolerances, Kesimer said.

“The optimum quantity of mucins appears to be very important in the clearance of mucus,” Kesimer said. “Because these molecules are so large, a doubling of mucin concentrations is important in the dynamics of mucus transport, making mucin concentrations a key determinant of whether mucus is able to flow or not.”