CORRESPONDENCE driven by the decline of renal function accompanying ageing and obesity (6). n Author disclosures are available with the text of this letter at www.atsjournals.org. Alfred Bernard, Ph.D. Catholic University of Louvain Brussels, Belgium

References 1. Park HY, Churg A, Wright JL, Li Y, Tam S, Man SP, Tashkin D, Wise RA, Connett JE, Sin DD. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med 2013;188:1413–1439. 2. Bernard A, Marchandise FX, Depelchin S, Lauwerys R, Sibille Y. Clara cell protein in serum and bronchoalveolar lavage. Eur Respir J 1992;5:1231–1238. 3. Hermans C, Bernard A. Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med 1999;159:646–678. 4. Hermans C, Aly O, Nyberg B-I, Peterson C, Bernard A. Determinants of Clara cell protein (CC16) concentration in serum: a reassessment with two different immunoassays. Clin Chim Acta 1998;272: 101–110. 5. Helleday R, Segerstedt B, Forsberg B, Mudway I, Nordberg G, Bernard A, Blomberg A. Exploring the time dependence of serum Clara cell protein as a biomarker of pulmonary injury in humans. Chest 2006;130:672–675. 6. de Boer IH, Katz R, Fried LF, Ix JH, Luchsinger J, Sarnak MJ, Shlipak MG, Siscovick DS, Kestenbaum B. Obesity and change in estimated GFR among older adults. Am J Kidney Dis 2009;54:1043–1051.

Copyright © 2014 by the American Thoracic Society

Reply From the Authors: We thank Professor Bernard for his interest in our article and his insightful comments. Because our study did not take into account

Correspondence

renal function of the subjects or the timing of the blood draw, we may have underestimated the biomarker potential of club (Clara) cell protein 16 (CC-16) to predict disease progression in chronic obstructive pulmonary disease (COPD) (1). As suggested by Bernard, we measured surfactant protein D (SFTPD) as a potential surrogate of airway permeability in the Lung Health Study (2). In this cohort, serum SFTPD was not significantly associated with serum CC-16 (P = 0.240, adjusted for age and sex), which suggests that airway permeability was not a major confounder to our analysis. Finally, we agree with Bernard’s suggestion that CC-16 is unlikely to be a major molecular driver of COPD. In our study, we exposed CC-16–deficient mice to 6 months of cigarette smoke and found that these were not protected from emphysema or small airway remodeling (1). In sum, we share Bernard’s enthusiasm for CC-16 as a very promising biomarker but not as a therapeutic target in COPD. n Author disclosures are available with the text of this letter at www.atsjournals.org. Hye Yun Park, M.D. Samsung Medical Center Seoul, Korea Don D. Sin, M.D. St. Paul’s Hospital Vancouver, Canada

References 1. Park HY, Churg A, Wright JL, Li Y, Tam S, Man SF, Tashkin D, Wise RA, Connett JE, Sin DD. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013;188:1413–1419. 2. Hill J, Heslop C, Man SF, Frohlich J, Connett JE, Anthonisen NR, Wise RA, Tashkin DP, Sin DD. Circulating surfactant protein-D and the risk of cardiovascular morbidity and mortality. Eur Heart J 2011;32: 1918–1925.

Copyright © 2014 by the American Thoracic Society

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Reply: Club cell protein and chronic obstructive pulmonary disease progression: the unrealized potential of a peripheral lung biomarker.

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