TY - JOUR
T1 - Club cell protein 16 and disease progression in chronic obstructive pulmonary disease
AU - Park, Hye Yun
AU - Churg, Andrew
AU - Wright, Joanne L.
AU - Li, Yuexin
AU - Tam, Sheena
AU - Man, S. F.Paul
AU - Tashkin, Donald
AU - Wise, Robert A.
AU - Connett, John E.
AU - Sin, Don D.
PY - 2013/12/15
Y1 - 2013/12/15
N2 - 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 (2/2) 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-162/2 mice did not demonstrateanenhancedrisk ofemphysemaor 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 cigaretterelated COPD in mice.
AB - 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 (2/2) 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-162/2 mice did not demonstrateanenhancedrisk ofemphysemaor 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 cigaretterelated COPD in mice.
KW - Biomarker
KW - Chronic obstructive pulmonary disease
KW - Disease progression
KW - Smoking
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U2 - 10.1164/rccm.201305-0892OC
DO - 10.1164/rccm.201305-0892OC
M3 - Article
C2 - 24245748
AN - SCOPUS:84890541399
SN - 1073-449X
VL - 188
SP - 1413
EP - 1419
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 12
ER -