A Retrospective, Nested Case-Control Study to Develop a Biomarker-Based Model for ARDS Diagnostics.

BACKGROUND: Several biomarkers could be intercalated with traditional measures to improve ARDS diagnostics. METHODS: There were 211 ICU patients enrolled in this retrospective, nested case-control study. Participants were divided into an ARDS (n = 79) and non-ARDS (n = 132) groups, according to the Berlin criteria. Patient characteristics, vital signs, and laboratory tests were collected within three hours of admission. CC16, Ang-2, sRAGE, HMGB1, and SPD were measured within three hours and again at 24 hours, after admission to ICU. Receiver Operating Characteristic curves and multivariate logistic regression analyses were applied for predictive purposes. RESULTS: C-reactive protein (CRP), NT-proBNP, and pH values were intercalated with five established ARDS indicators, and the PaO2/FiO2 ratio. Only four potential indicators were analyzed, with CRP having high diagnostic value. Areas under curve (AUC) were as follows: CC16 (AUC: 0.752; 95% CI 0.680 - 0.824), Ang-2 (AUC: 0.695; 95% CI 0.620 - 0.770), HMGB1 (AUC: 0.668; 95% CI 0.592 - 0.744), sRAGE (AUC: 0.665; 95% CI 0.588 - 0.743), CRP (AUC: 0.701; 95% CI 0.627 - 0.776). No single indicator improved upon the PaO2/FiO2 ratio which had an AUC: 0.844 (95% CI 0.789 - 0.898). However, when the binary logistic model was transformed and the model was constructed, the AUC increased from 0.647 (95% CI 0.568 - 0.726) to 0.911 (95% CI 0.864 - 0.946). Among the combinations tested, PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1 resulted in the highest AUC of 0.910 (95% CI 0.863 - 0.945), although there are other factors which must be considered. CONCLUSIONS: A combination of biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we tentatively recommend PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1. This is because of the cost implications in contrast with benefit involved in utilizing the more elaborate model. Further health economics research is required to consider the opportunity cost for emergency care policy.

Renal dysfunction reduces the diagnostic and prognostic value of serum CC16 for acute respiratory distress syndrome in intensive care patients.

BACKGROUND: Contradictory results regarding changes in serum club cell protein 16 (CC16) levels in patients with acute respiratory distress syndrome (ARDS) have been reported, challenging the value of CC16 as a diagnostic and prognostic marker for ARDS. We have also observed increased serum CC16 levels in patients with renal dysfunction (RD). Therefore, the present study aimed to determine whether RD affects the diagnostic performance of CC16 for ARDS in intensive care unit (ICU) patients. METHODS: We measured serum CC16 concentrations in 479 ICU patients, who were categorized into six groups according to their diagnoses: control, acute kidney injury (AKI), chronic kidney disease (CKD), ARDS, ARDS+AKI, and ARDS+CKD. The sensitivity, specificity, and cutoff values for serum CC16 were assessed by receiver operating characteristic curve analysis. RESULTS: Serum CC16 concentrations were higher in the ARDS group than in the control group, and in ARDS patients with normal renal function, serum CC16 could identify ARDS and predict survival outcomes at 7 and 28 days. However, serum CC16 levels were similar among the ARDS+AKI, ARDS+CKD, AIK, and CKD groups. Consequently, in patients with AKI and/or CKD, the specificity of CC16 for diagnosing ARDS or ARDS+RD decreased from 86.62 to 2.82% or 81.70 to 2.12%, respectively. Consistently, the CC16 cutoff value of 11.57 ng/ml in patients with RD differed from the established values of 32.77-33.72 ng/ml with normal renal function. Moreover, the predictive value of CC16 for mortality in ARDS+RD patients was lost before 7 days but regained by 28 days. CONCLUSION: RD reduces the diagnostic specificity, diagnostic cutoff value, and predictive value for 7-day mortality of serum CC16 for ARDS among ICU patients.