External validation of a biomarker and clinical prediction model for hospital mortality in acute respiratory distress syndrome

Abstract

PURPOSE Mortality prediction in ARDS is important for prognostication and risk stratification. However, no prediction models have been independently validated. A combination of two biomarkers with age and APACHE III was superior in predicting mortality in the NHLBI ARDSNet ALVEOLI trial. We validated this prediction tool in two clinical trials and an observational cohort. METHODS The validation cohorts included 849 patients from the NHLBI ARDSNet Fluid and Catheter Treatment Trial (FACTT), 144 patients from a clinical trial of sivelestat for ARDS (STRIVE), and 545 ARDS patients from the VALID observational cohort study. To evaluate the performance of the prediction model, the area under the receiver-operator-characteristic-curve (AUC), model discrimination and calibration were assessed and recalibration methods were applied. RESULTS The biomarker/clinical prediction model performed well in all cohorts. Performance was better in the clinical trials with an AUC of 0.74 (95% CI: 0.70–0.79) in FACTT, compared to 0.72 (95% CI: 0.67–0.77) in VALID, a more heterogeneous observational cohort. The AUC was 0.73 (95% CI: 0.70–0.76) when FACTT and VALID were combined. CONCLUSION We validated a mortality prediction model for ARDS that includes age, APACHE III, SP-D and IL-8 in a variety of clinical settings. Although the model performance as measured by AUC was lower than in the original model derivation cohort, the biomarker/clinical-model still performed well and may be useful for risk assessment for clinical trial enrollment, an issue of increasing importance as ARDS mortality declines and better methods are needed for selection of the most severely ill patients for inclusion.

Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine

“…IL-18 has been noted to be increased in patients with ARDS, and been associated with mortality [37]. An external validation of biomarkers and a clinical prediction model for hospital mortality in ARDS included SP-D and IL8 in various clinical settings, and suggested that these biomarkers may be useful in risk assessment for clinical trial enrolment [38].…”

Bioinformatics analysis of the potential biomarkers for acute respiratory distress syndrome

“…Prognosis evaluation and early intervention in ARDS patients at high risk would benefit the clinic outcome. Previous studies suggested that multiple plasma biomarkers, such as IL-6, IL-8, angiopoietin-2 (ANG-2), Kerbs von Lungren 6 antigen (KL-6), receptor for advanced glycation endproducts (RAGEs), and surfactant protein D (SP-D), had a predictive value for ARDS prognosis [1][2][3][4]. Nevertheless, bronchoalveolar lavage fluid (BALF) is likely to provide more timely and detailed biomarkers for evaluating the degree of lung injury.…”

Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial

“…Acute respiratory distress syndrome (ARDS) remains a life-threatening illness characterized by dysregulated inflammation and alveolar-capillary barrier disruption (1). Given the limited number of effective treatments for established ARDS, identification of early molecular and cellular events associated with development of ARDS can complement clinical and immunological markers of established ARDS (2,3) and may lead to therapeutic strategies aimed at ARDS prevention (4).…”