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

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

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1413-1419
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Issue number12
StatePublished - Dec 15 2013


  • Biomarker
  • Chronic obstructive pulmonary disease
  • Disease progression
  • Smoking

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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