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


OBJECTIVE
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.


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.
1 University of British Columbia James Hogg Research Center and the Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Hye Yun
HY
Park
Andrew
A
Churg
Joanne L
JL
Wright
Yuexin
Y
Li
Sheena
S
Tam
S F Paul
SF
Man
Donald
D
Tashkin
Robert A
RA
Wise
John E
JE
Connett
Don D
DD
Sin
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D012372:ROC Curve; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014598:Uteroglobin / Q000097:blood* / Q000172:deficiency
D015415:Biomarkers; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D014028:Tobacco Smoke Pollution; D014598:Uteroglobin