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Serum CC-Chemokine Ligand 18 Concentration Predicts Outcome in Idiopathic Pulmonary Fibrosis

¹ Department of Pneumology, ³ Department of Medical Biometry and Statistics, University Freiburg, Freiburg, Germany; ² Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan; ⁴ Policlinico Le Scotte, Dipartimento di Medicina Clinica e Scienze Immunologiche, Sezione di Malattie dell Apparato Respiratorio, University of Siena, Siena, Italy

Correspondence and requests for reprints should be addressed to Antje Prasse, M.D., Department of Pneumology, University Medical Center, Killianstr. 5, 79106 Freiburg, Germany. E-mail: antje.prasse{at}uniklinik-freiburg.de

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a poor prognosis. There is great effort to find predictors of outcome. Conclusive data for any serum biomarker are lacking. We have recently documented that serum CCL18 concentrations correlate with the course of pulmonary function data in patients with pulmonary fibrosis of various causes.

Objectives: To test the value of serum CCL18 concentrations in IPF, we included 72 patients in a prospective study.

Methods: IPF was defined according to the ATS/ERS criteria. Serum CCL18 concentrations were measured by a commercially available ELISA. Patients were followed for 24 months. Pulmonary function tests were performed at least every 6 months.

Measurements and Main Results: Baseline serum CCL18 concentrations predicted the change in TLC and FVC at the 6-month follow-up. Receiver operating characteristics (ROC) revealed a significant relation between survival and baseline CCL18 concentrations. By ROC analysis, the cutoff value with the highest diagnostic accuracy was defined as 150 ng/ml (sensitivity, 0.83; specificity, 0.77). There was a significantly higher mortality in patients with serum CCL18 concentrations above 150 ng/ml (P < 0.0001). The hazard proportional ratio adjusted for age, sex, and baseline pulmonary function data was 8.0. There was a higher incidence of disease progression in the group with high serum CCL18 concentrations.

Conclusions: Our data demonstrate that serum CCL18 concentrations have a predictive value in IPF and may be a useful tool in the clinical management of patients with IPF and in clinical trials.

Key Words: pulmonary fibrosis • IPF • CCL18 • biomarker • serum

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject At present, there is no established serum marker which adequately probes pulmonary fibrotic activity. Pulmonary function data are used to guage therapeutic effects, but these are only predictive if their course is considered. What This Study Adds to the Field Serum CCL18 concentration is the first serum biomarker described which clearly predicts mortality in idiopathic pulmonary fibrosis.