CC16 as an Inflammatory Biomarker in Induced Sputum Reflects Chronic Obstructive Pulmonary Disease (COPD) Severity

Abstract

The progression of an abnormal inflammatory response plays a crucial role in the lung function decline of chronic obstructive pulmonary disease (COPD) patients. Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of inflammatory processes in the airways. Patients and Methods: A total of 102 COPD participants were divided into a mild-to-moderate group (FEV1%pred≥ 50%, n=57) and a severe-to-very-severe group (FEV1%pred<50%, n=45). We measured a series of inflammatory biomarkers in induced sputum and analyzed their association with lung function and SGRQ in COPD patients. To evaluate the relationship between inflammatory biomarkers and the inflammatory phenotype, we also analyzed the correlation between biomarkers and airway eosinophilic phenotype. Results: We found increased mRNA levels of MMP9, LTB4R, and A1AR and decreased levels of CC16 mRNA in induced sputum in the severe-to-very-severe group. After adjustment for age, sex and other biomarkers, CC16 mRNA expression was positively associated with FEV1%pred (r=0.516, p=0.004) and negatively correlated with SGRQ scores (r=−0.3538, p=0.043). As previously known, decreased CC16 was related to the migration and aggregation of eosinophils in airway. It was also found that CC16 had a moderate negative correlation with the eosinophilic inflammation in airway (r=−0.363, p=0.045) in our COPD patients. Conclusion: Low CC16 mRNA expression levels in induced sputum were associated with low FEV1%pred and a high SGRQ score in COPD patients. Sputum CC16 as a potential biomarker for predicting COPD severity in clinical practice might attribute to the involvement of CC16 in airway eosinophilic inflammation.

The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells

“…The work presented here supports these findings and further suggests that CC16 regulates pulmonary epithelial-driven responses during Mp infection. Based on this, as well as our previous work, the clinical implications for individuals with low CC16 levels, such as asthma, COPD, and cystic fibrosis patients [23,[25][26][27]29,30,39,42], is that they may have chronic or persistent pathogen burden resulting in increased airway remodeling, which is in part due to pulmonary epithelialdriven responses.…”

“…Based on these supporting data, and since Mp targets the pulmonary epithelium during infection, we seek to define how CC16 −/− MTECs respond when challenged with Mp. Clinically, for patients with known low CC16 levels, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis patients [5,[22][23][24][25][26][27][28][29][30], an impairment in host responses would likely result in increased respiratory infections, inflammation, and remodeling.…”

CC16 drives VLA-2-dependent SPLUNC1 expression

“…Clinically, these results suggest that individuals with low CC16 may have decreased SPLUNC1 and higher susceptibility to Mp infection and that administration of CC16 as a therapeutic may be important to activate the expression of SPLUNC1 to aid in the induction of antimicrobial responses and decrease pathogen burden. Since several chronic respiratory diseases have been associated with low CC16 levels, including asthma ( 42 , 43 , 59 – 61 ), COPD ( 1 , 6 , 10 , 46 , 62 – 65 ), and cystic fibrosis ( 14 ), those individuals may be at an increased risk for respiratory infections due to loss of SPLUNC1 as well as low CC16. Taken together, our findings reinforce the potential of CC16 augmentation as a novel therapeutic approach to enhance resilience to respiratory infections among a variety of airway diseases.…”