|Title||Club cell protein 16 and disease progression in chronic obstructive pulmonary disease.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Park, HYun, Churg, A, Wright, JL, Li, Y, Tam, S, Man, SFPaul, Tashkin, D, Wise, RA, Connett, JE, Sin, DD|
|Journal||Am J Respir Crit Care Med|
|Date Published||2013 Dec 15|
|Keywords||Adult, Animals, Biological Markers, Disease Progression, Female, Follow-Up Studies, Humans, Linear Models, Logistic Models, Male, Mice, Mice, Knockout, Middle Aged, Pulmonary Disease, Chronic Obstructive, Risk Factors, ROC Curve, Smoking, Spirometry, Tobacco Smoke Pollution, Uteroglobin|
RATIONALE: 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.
OBJECTIVES: To evaluate the possibility of using serum CC-16 as a biomarker for disease progression in chronic obstructive pulmonary disease (COPD).
METHODS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: 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.
|Alternate Journal||Am. J. Respir. Crit. Care Med.|
|PubMed Central ID||PMC3917377|
|Grant List||/ / Canadian Institutes of Health Research / Canada|