Club Cell Protein 16 and Disease Progression in Chronic Obstructive Pulmonary Disease

• Published in: American journal of respiratory and critical care medicine Vol. 188; no. 12; pp. 1413 - 1419
• Main Authors: HYE YUN PARK, CHURG, Andrew, WRIGHT, Joanne L, YUEXIN LI, SHEENA TAM, MAN, S. F. Paul, TASHKIN, Donald, WISE, Robert A, CONNETT, John E, SIN, Don D
• Format: Journal Article
• Language: English
• Published: New York, NY American Thoracic Society 15.12.2013
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Biomarkers; Biomarkers - blood; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Cigarettes; Disease Progression; Female; Follow-Up Studies; Humans; Intensive care medicine; Linear Models; Logistic Models; Lungs; Male; Medical sciences; Mice; Mice, Knockout; Middle Aged; Pathogenesis; Pneumology; Proteins; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - physiopathology; Regression analysis; Risk Factors; ROC Curve; Smoking; Smoking - adverse effects; Spirometry; Tobacco Smoke Pollution - adverse effects; Tobacco, tobacco smoking; Toxicology; Uteroglobin - blood; Uteroglobin - deficiency; Lung disease; Intensive care; Prognosis; Disease; Respiratory disease; Tobacco smoking; Biological marker; disease progression; biomarker; Protein; Tobacco; smoking; Bronchus disease; Evolution; Chronic obstructive pulmonary disease; Cell; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201305-0892oc

Club (Clara) cell protein 16 (CC-16) is a protein that is synthesized predominantly in the lungs and is detectable in serum. Its expression decreases with lung injury and smoking, and is thus a marker of bronchial cell dysfunction. To evaluate the possibility of using serum CC-16 as a biomarker for disease progression in chronic obstructive pulmonary disease (COPD). We measured serum CC-16 levels from 4,724 subjects with mild-to-moderate airflow limitation in the Lung Health Study. Using a linear regression model, we determined the relationship of serum CC-16 concentrations to decline in lung function over 9 years. In addition, to determine whether CC-16 plays a major role in the pathogenesis of mild COPD, we exposed CC-16-deficient (-/-) mice to 6 months of cigarette smoke. Reduced serum concentrations of CC-16 were associated with accelerated decline in FEV1 over 9 years (P < 0.0001), and this association persisted after adjustments for age, sex, race, smoking status, airway reactivity, body mass index, and baseline FEV1 (P = 0.0002). However, CC-16(-/-) mice did not demonstrate an enhanced risk of emphysema or small airway remodeling in response to cigarette smoke. Serum CC-16 is associated with disease progression, and may assist in the identification of "rapid progressors." However, the absence of CC-16 does not appear to modify the risk of cigarette-related COPD in mice.