Club Cell Secretory Protein-Derived Acute Respiratory Distress Syndrome Phenotypes Predict 90-Day Mortality: A Reanalysis of the Fluids and Catheter Treatment Trial

Design: A secondary biomarker analysis of a prospective randomized-controlled trial. The primary outcome was area under the receiver operating characteristic (AUROC) of CC16 for prediction of 90-day mortality. Secondary outcomes included differences in mortality, length of stay, and ventilator-free days (VFDs) between patients with high and low CC16. Statistical analyses were performed with IBM SPSS Statistics.

Setting: Single-center laboratory analysis.

Subjects: Plasma samples from 68 FACTT subjects and 20 healthy controls.

Interventions: CC16 was measured in patient plasma samples by enzyme-linked immunosorbent assay.

Measurements And Main Results: Subjects were an average of 48 years old (sd, 16.7 yr old) and 51.5% male. AUROC analysis of CC16 on day 1 showed an area under the ROC curve of 0.78 for prediction of mortality (odds ratio, 1.011; 95% CI, 1.003-1.021) with an optimal cutoff value of 45 ng/mL. Patients in the low CC16 group (<45 ng/mL) had lower mortality (7.5 vs 50.0%; < 0.001) and similar VFD (11.9 vs 13.2; = 0.638). When stratified by CC16 concentration, there was no difference between mortality in the fluid liberal (36.4 vs 58.8%; = 0.256) or conservative (4.3 vs 11.8%; = 0.366) groups.

Conclusions: CC16 demonstrated an acceptable AUROC for prediction of patient mortality with a cut point of 45 ng/mL. Patients with high CC16 on day 1 had worse outcomes compared with those with low CC16, suggesting a prognostic role for this lung-specific biomarker.