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(Chest. 2003;124:2119-2125.)
© 2003 American College of Chest Physicians

Study of Clara Cell 16, KL-6, and Surfactant Protein-D in Serum as Disease Markers in Pulmonary Sarcoidosis*

Rob Janssen, MD; Hiroe Sato, MD, PhD; Jan C. Grutters, MD; Alfred Bernard, PhD; Heleen van Velzen-Blad, MS; Roland M. du Bois, MD, PhD and Jules M. M. van den Bosch, MD, PhD

* From the Heart Lung Center Utrecht (Drs. Janssen, Grutters, and van den Bosch), Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands; Interstitial Lung Disease Unit (Drs. Sato and du Bois), Imperial College, National Heart and Lung Institute and Royal Brompton Hospital, London, UK; Industrial Toxicology and Occupational Medicine Unit (Dr. Bernard), Medical School, Catholic University Louvain, Brussels, Belgium; and Department of Medical Microbiology and Immunology (Ms. van Velzen-Blad), St. Antonius Hospital, Nieuwegein, the Netherlands.

Correspondence to: Jules M. M. van den Bosch, MD, PhD, Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands; e-mail: j.vandenbosch{at}antonius.net

Study objectives: To determine the discriminative value of serum Clara cell 16 (CC16), KL-6, and surfactant protein (SP)-D as markers of interstitial lung diseases, and their ability to reflect pulmonary disease severity and prognosis in sarcoidosis.

Subjects: Seventy-nine patients with sarcoidosis and 38 control subjects.

Measurements: Serum CC16, KL-6, and SP-D concentrations at disease presentation were measured. Pulmonary function tests and chest radiographs were analyzed at presentation and 2-year follow-up.

Results: All markers co-correlated, and a significant difference was found between CC16, KL-6 (Krebs von den Lungen-6), and SP-D levels in patients with sarcoidosis and control subjects (p < 0.0001). Receiver operating characteristic curve analysis revealed largest area under the curve for KL-6. Significantly higher levels of CC16 and KL-6 were found in patients with parenchymal infiltration (stage II, III) compared to patients without parenchymal infiltration (stage I). In concordance, CC16 and KL-6 levels inversely correlated with diffusion capacity and total lung capacity, and KL-6 also with inspiratory vital capacity. Moreover, higher KL-6 levels were weakly but significantly associated with persistence or progression of parenchymal infiltrates at 2-year follow-up.

Conclusion: In this study, KL-6 appears to be the best discriminative marker in differentiating patients with sarcoidosis from healthy control subjects; however, as it is not a specific marker for this condition, this quality is unlikely to be useful as a diagnostic tool. Both CC16 and KL-6 may be of value in reflecting disease severity, and KL-6 tends to associate with pulmonary disease outcome.

Key Words: Clara cell 16 • KL-6 • sarcoidosis • serum markers • surfactant protein-D




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