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Published on: October 31, 2012
Evaluation of a Rapid Immunoassay for Molecular Subphenotype Classification in Pediatric Acute Cardiorespiratory
Colin J Sallee1, Clove S Taylor1, Matt S Zinter2
1University of California Los Angeles.
Insights
Rapid biomarker assays accurately identify molecular subphenotypes in critically ill children, enabling precision medicine. This approach facilitates targeted therapies for conditions like hyperglycemia and cardiorespiratory failure, improving patient outcomes.
Area of Science:
- Critical care medicine
- Biomarker discovery
- Pediatric health
Background:
- Molecular subphenotyping aids targeted therapeutics in critical care.
- Intensive insulin management shows subphenotype-specific benefits in pediatric hyperglycemia and cardiorespiratory failure.
- Real-time subphenotype-based strategies are challenging due to operational assay limitations.
Purpose of the Study:
- To compare a rapid immunoassay with a conventional multiplex assay for biomarker measurement.
- To assess the rapid assay's ability to classify molecular subphenotypes using a parsimonious classifier.
- To compare clinical outcomes between subphenotypes identified by the rapid immunoassay.
Main Methods:
- Retrospective multicenter study of 269 children with acute cardiorespiratory failure and hyperglycemia.
- Re-assaying plasma samples using both rapid immunoassay and conventional laboratory assays.
- Latent class analysis (LCA) previously defined hyper-inflammatory and hypo-inflammatory classes; a parsimonious classifier (IL-6, IL-8, sTNFR-1) was developed.
Main Results:
- Biomarkers showed strong correlation between platforms (Pearson r = 0.87-0.93), despite rapid assay overestimation.
- Subphenotype classification agreement between platforms was high (95%).
- Rapid immunoassay-based subphenotypes achieved high accuracy (AUC = 0.90) and identified a hyper-inflammatory class linked to higher mortality and varied treatment response.
Conclusions:
- Subphenotyping using a rapid immunoassay is feasible and accurate in pediatric critical care.
- This approach supports the development of precision medicine strategies.
- Rapid assays can enable real-time clinical decision-making for targeted therapies.
Abstract:
Molecular subphenotypes, identified through biomarker profiling independent of clinical diagnosis, have the potential to guide targeted therapeutics in critical care. We have previously published that intensive insulin management has subphenotype-specific beneficial effects among children with hyperglycemia accompanying cardiorespiratory failure. However, due to the operational aspects of biomarker assays, prospective real-time application of subphenotype-based strategies remains daunting. This study compared biomarker values measured via a rapid immunoassay requiring minimal handling to a conventional laboratory-based multiplex assay, assessed its ability to classify subphenotypes with a parsimonious classifier, and compared clinical outcomes between rapid immunoassay-based subphenotypes. This retrospective multicenter study included re-assaying plasma samples from 269 children with acute cardiorespiratory failure and hyperglycemia. Latent class analysis (LCA) was previously used to derive hyper-inflammatory and hypo-inflammatory classes. A parsimonious classifier was fit to LCA-derived subphenotypes and produced a model consisting of IL-6, IL-8, and sTNFR-1. We found that, despite the rapid immunoassay systematically overestimating biomarker values relative to the conventional assay, biomarkers were strongly correlated between platforms (Pearson r = 0.87-0.93). Using the parsimonious classifier, subphenotype classifications matched between platforms in 95% of patients (n = 256/269). When compared to previously derived LCA-derived subphenotypes, rapid immunoassay-based subphenotypes demonstrated an AUC of 0.90 (95% CI 0.85-0.95). The rapid immunoassay-based hyper-inflammatory class was associated with higher mortality (26% vs. 11%; P = 0.01) and heterogeneity of treatment effect to intensive insulin management (interaction P = 0.01). Our findings suggest that subphenotyping using a rapid immunoassay is feasible and accurate, laying the foundation for future precision medicine strategies in pediatric critical care.
