Club cell protein 16 and disease progression in chronic obstructive pulmonary disease.

TitleClub cell protein 16 and disease progression in chronic obstructive pulmonary disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsPark, HYun, Churg, A, Wright, JL, Li, Y, Tam, S, Man, SFPaul, Tashkin, D, Wise, RA, Connett, JE, Sin, DD
JournalAm J Respir Crit Care Med
Volume188
Issue12
Pagination1413-9
Date Published2013 Dec 15
ISSN1535-4970
KeywordsAdult, 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
Abstract

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.

DOI10.1164/rccm.201305-0892OC
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID24245748
PubMed Central IDPMC3917377
Grant List / / Canadian Institutes of Health Research / Canada