Mucus-based test shows promise for measuring health of lungs in COPD
Study: Higher scores associated with worse function, higher exacerbation risk
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A novel test based on the levels and composition of certain proteins in mucus, called mucins, may help assess lung health in people with chronic obstructive pulmonary disease (COPD), according to a new study.
Findings show that higher Mucin Quantitative Score (MUCQ) values were significantly associated with worse lung function and a higher risk of exacerbations, or periods of sudden symptom worsening. COPD patients with higher MUCQ scores also tended to spend more time in the hospital, according to the data.
“The association between elevated MUCQ scores and increased exacerbation rates, as well as higher healthcare use, in particular highlight the potential clinical relevance of MUCQ as a predictive marker for disease severity and progression,” researchers wrote.
Elevated MUCQ values were also observed in smokers with respiratory symptoms but normal lung function tests, suggesting that the new score may accurately detect lung disease earlier than standard lung function tests.
“MUCQ allows us to detect underlying mucus abnormalities before significant lung damage appears on standard lung function tests,” Mehmet Kesimer, PhD, the study’s first author at the University of North Carolina, said in a university news story. “With an objective, biology-based measurement, we can now issue far more compelling evidence that will help physicians provide diagnoses and treatments sooner, rather than later.”
The study, “A Quantitative Lung Mucin Score to Identify Chronic Bronchitis,” was published in NEJM Evidence. The National Institutes of Health funded the work.
Specific mucin proteins are affected in different ways in COPD
Mucus is a slimy, slippery substance that’s secreted in the lungs and other organs to help maintain tissue health and guard against infections. Healthy mucus is mostly water, but it also contains proteins called mucins, which give mucus its slimy texture.
COPD and other muco-obstructive lung diseases are generally marked by an increase in mucin production, but recent studies have shown that specific mucin proteins are affected in different ways.
Specifically, data suggest that levels of MUC5B, the dominant mucin in mucus coughed up from the lungs in healthy people, increase in muco-obstructive lung diseases, but levels of a minor mucin, called MUC5AC, increase much more dramatically.
Building on this finding, scientists developed the MUCQ score, which combines mucin concentration and mucin composition by multiplying the total mucin level and the MUC5AC-to-MUC5B ratio. The idea was that this score would yield a single number that better reflects lung health than simply measuring total levels of mucin proteins.
“By combining three key mucin measurements, total mucins, MUC5AC, and MUC5B, we derived a … score that reflects independent yet complementary properties of [disease-related] airway mucus,” the researchers wrote.
MUCQ identified people with CB more accurately than a similar score
To test MUCQ, the scientists used data from hundreds of participants in an observational study called SPIROMICS (NCT01969344), which collected long-term data on people with COPD and those without the disease.
The researchers found that higher MUCQ scores correlated with various clinical disease manifestations, including lung function measures, small airway dysfunction, and exacerbation rate.
In addition to testing the MUCQ’s relationship with clinical variables in people with manifest COPD, the researchers also assessed how well the score could identify people with chronic bronchitis (CB), a key, often initial component of COPD.
CB is marked by long-term airway inflammation, leading to a persistent cough with mucus for at least three months per year. It is a significant risk factor for developing the progressive, irreversible airflow limitation that defines COPD.
Currently, CB is diagnosed only through questionnaires that ask about a person’s cough and mucus history. The researchers found that the new MUCQ could identify people with CB significantly more accurately than a similar score based solely on total mucin levels.
In the clinic, doctors always tell patients to stop smoking, but behavior change is hard. Being able to show a patient an objective numeric value —like their MUCQ score— especially when their lung function still appears normal, can be far more convincing.
MUCQ scores were found to be higher in a group of participants at risk of COPD with a smoking history and some respiratory symptoms, but no signs of airflow obstruction, a hallmark of COPD. Notably, among these, two who had not smoked for at least one year had a threefold lower score.
Overall, these data support the MUCQ score as a potential tool for monitoring lung health in COPD and detecting early signs of the disease, the researchers noted. The scientists called for further studies to explore how this score may help guide clinical care.
“Objective classification of patients with CB, and the linking of MUCQ to many measures of lung function, sets the stage for its use to be tested … in clinical and research settings,” the scientists wrote.
Kesimer said he hopes the new score will allow clinicians to “identify and monitor at-risk populations, pushing them [toward] behavioral adaptations that would allow them to enjoy a higher quality of life and reduce the economic burden on the healthcare system.”
“In the clinic, doctors always tell patients to stop smoking, but behavior change is hard,” he added. “Being able to show a patient an objective numeric value —like their MUCQ score — especially when their lung function still appears normal, can be far more convincing.”
