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

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.

• Authors: Hye Yun Park, Andrew Churg, Joanne L Wright, Yuexin Li, Sheena Tam, S F Paul Man, Donald Tashkin, Robert A Wise, John E Connett, Don D Sin
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 188 Issue 12 Pg. 1413-9 (Dec 15 2013) ISSN: 1535-4970 [Electronic] United States
• PMID: 24245748 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• SCGB1A1 protein, human
• Scgb1a1 protein, mouse
• Tobacco Smoke Pollution
• Uteroglobin

Topics

• Adult
• Animals
• Biomarkers (blood)
• Disease Progression
• Female
• Follow-Up Studies
• Humans
• Linear Models
• Logistic Models
• Male
• Mice
• Mice, Knockout
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (blood, etiology, physiopathology)
• ROC Curve
• Risk Factors
• Smoking (adverse effects)
• Spirometry
• Tobacco Smoke Pollution (adverse effects)
• Uteroglobin (blood, deficiency)