First-Ever Objective Marker of Chronic Bronchitis Discovered
CHAPEL HILL, NC --- September 6, 2017 -- In a study published in the New England Journal of Medicine, researchers describe how the concentration of mucins is abnormally high in chronic bronchitis and that high mucin concentrations are associated with disease severity in people with chronic bronchitis.
The finding could become the first-ever objective marker of chronic bronchitis and lead to the creation of diagnostic and prognostic tools.
The research, led by Mehmet Kesimer, PhD, University of North Carolina School of Medicine, Chapel Hill, North Carolina, 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.
“Until now, we have had little knowledge of what causes the airway mucus accumulation that plagues chronic bronchitis patients, and the only way we have to diagnose chronic bronchitis is based on what the patient tells us,” said Richard Boucher, MD, University of North Carolina at Chapel Hill. “Frankly, it’s a little embarrassing. Chronic bronchitis is a very common reason why people see their doctor, and we have had no real understanding how it develops or how to diagnose it. This study is a breakthrough in our understanding of this serious condition that affects millions of people in the United States.”
Although chronic bronchitis has a variety of causes, by far the most common is smoking. Smokers with chronic bronchitis are prone to bacterial infections and face a high risk of developing chronic obstructive pulmonary disease (COPD).
A key mystery has been what causes the accumulation of mucus in the lungs of patients with chronic bronchitis. The current 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
“Chronic bronchitis symptoms are often the first tip that a patient will go on to develop COPD,” said Dr. Boucher. “We always tell patients to stop smoking, but to really convince somebody to stop smoking, it helps to have a clear understanding of what causes their symptoms and have an objective measurement to say, ‘look, this is abnormal. This is why you are sick.’”
Such a test could also reveal where a patient’s health might be headed in the next 5 to 10 years.
The researchers suspected mucus might hold the key to differentiating true chronic bronchitis from benign conditions. To test their hypothesis, they analysed phlegm samples from about 1,000 smokers and non-smokers participating in a study of COPD called SPIROMICS.
Mucus in in itself 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. Therefore, Dr. Kesimer developed an innovative testing protocol to measure total mucin concentration and the concentrations of the 2 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% water and 2% 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% mucins versus 4% mucins can mean the difference between breathing normally and having gobs of bacteria-trapping phlegm clogging your airways.
“The optimum quantity of mucins appears to be very important in the clearance of mucus,” said Dr. Kesimer. “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.”
The research is significant not only because it suggests mucins can be used as a biomarker for diagnosing and predicting the risk for chronic bronchitis, but also because it offers new scientific tools to measure mucin concentrations.
“As a next step, we plan to look for ways to translate our findings into a practical test that could find its way into your doctor’s office, not just for chronic bronchitis but also for other muco-obstructive diseases of the lung, such as bronchiectasis and asthma,” said Dr. Kesimer.
In addition to helping doctors diagnose chronic bronchitis objectively, the researchers said their work could open doors to new therapies that seek to restore a normal mucus balance by reducing the quantity of mucins manufactured inside airways or rehydrating airway surfaces. Such therapies could potentially help to relieve the burden of chronic bronchitis and other muco-obstructive lung diseases.
SOURCE: University of North Carolina Health Care System
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