Low CC16 Protein Levels Linked to COPD Progression, Worse Lung Function in Study

Low levels of the protein CC16 in blood are associated with worse lung function and more severe disease among people with chronic obstructive pulmonary disease (COPD), a new study suggests.

The study, “Reduced Serum Concentration of CC16 Is Associated with Severity of Chronic Obstructive Pulmonary Disease and Contributes to the Diagnosis and Assessment of the Disease,” was published in the International Journal of Chronic Obstructive Pulmonary Disease.

The Clara cell secretory protein, known as CC16, plays an important role in protecting cells in the lungs from inflammation and stress. As such, it has been thought to play a role in several lung conditions, including idiopathic pulmonary fibrosis, sarcoidosis, and asthma. However, its association with COPD is still unclear.

Now, researchers in China sought to explore the possible role of CC16 in COPD. To do so, they measured the protein’s levels in the blood of 98 people — 56 men and 42 women, average age 63.8 years — with stable COPD. Those levels were then compared with those of 48 people without COPD, specifically 19 men and 29 women, with an average age of 62.5 years.

The average level of CC16 was significantly lower in the COPD group (94.2 versus 111.3 ng/mL). Statistical modeling suggested that, at a cutoff value of 99.32 ng/mL, CC16 levels could be used to differentiate between people with or without COPD with a sensitivity, or true-positive rate of 65.3% and a specificity, or true-negative rate of 75%.

“We found that CC16 concentration was significantly reduced in serum from patients with stable COPD compared with healthy controls,” the researchers said.

This data suggests that “CC16 may play a protective role in the development of COPD,” and that determining a person’s protein levels may be useful in diagnosing the disease.

The investigators then looked for possible associations between CC16 and clinically relevant disease features in the COPD group.

Among those with COPD, smokers had significantly lower levels of the protein compared with non-smokers (88.0 versus 102.5 ng/mL). In addition, those with a longer medical history — of more than 20 years — had lower levels of CC16 compared with those with shorter histories (85.2 ng/mL versus 98.4 ng/mL for a 10-20-year history; 101.9 ng/mL for a history of less than 10 years).

Lower levels also were seen among those with higher “disease grades” on the  Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD), a measure of COPD severity. Individuals with a disease grade of three or four, indicating severe disease, had lower CC16 levels than those with grade one or two, which indicates milder disease (89.4 versus 109.2 ng/mL).

Those with greater shortness of breath, as assessed by the modified British medical research council (mMRC) scale, had lower average CC16 levels as well (98.3 ng/mL for mMRC score of 3 and 85.2 ng/mL for a mMRC score of 4 versus 110.9 ng/ML for a mMRC score of 2).

Additionally, CC16 levels were found to be significantly correlated with lung function, as assessed by forced expiratory volume. This meant that as CC16 levels decreased, so did patients’ lung function.

Further statistical analyses found significant associations between the levels of CC16 — also called Clara cells — and smoking status, mMRC score, GOLD disease grade, and lung function. The theoretical basis for these findings is that, as the lungs become increasingly damaged over the course of COPD, the cells that produce CC16 die.

“Clara cells may be one of the major targets attacked by toxic substances in cigarette smoke,” the researchers noted, which could explain the association between low CC16 levels and smoking status.

Based on these observations, the team proposed that “a decrease in serum CC16 concentration can be used as a biomarker for predicting lung function decline and disease progression in COPD patients.”

They acknowledged the study “was only conducted for patients with COPD in Chinese medical institutions,” which could limit the extent to which these findings apply to other populations, especially those comprised of people of different races. As such, more research is needed to validate these findings, the researchers said.