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oai:figshare.com:article/33476596 2026-09-30T14:33:57Z portal_1172 item_type_8 month_year_09_2026

Critical care subphenotypes: prospective identification and extension beyond syndromic definitions Kiran Reddy (22203154) PUREID: 695179966 acute respiratory distress syndrome acute respiratory failure critical care intensive care precision medicine subphenotype <p dir="ltr">Acute hypoxaemic respiratory failure (AHRF) and the acute respiratory distress syndrome (ARDS) are clinically and biologically heterogeneous, and this heterogeneity has hindered the development of effective pharmacotherapies. Reproducible inflammatory subphenotypes (the hypoinflammatory and hyperinflammatory subphenotypes) carry prognostic and predictive significance, but they have typically been identified retrospectively using latent class analysis (LCA) and studied only within ARDS, limiting their translation into clinical practice and prospective trials.<br><br>This thesis examines whether inflammatory subphenotypes can be identified in clinically relevant, real-time settings, extended beyond ARDS, characterised across disease severity and over time, and operationalised to inform precision-medicine trial design. Following a review of the field, its terminology, and the barriers to clinical translation, inflammatory subphenotypes are examined in patients with severe respiratory failure requiring veno-venous extracorporeal membrane oxygenation. The prospective, multicentre PHIND study then evaluates bedside identification of subphenotypes in 30 intensive care units across the United Kingdom and Ireland, using a near-patient immunoanalyser and a parsimonious model (interleukin-6, soluble tumour necrosis factor receptor-1, and bicarbonate) to assign subphenotypes in real time and to test their association with 60-day mortality. Subsequent analyses compare prospectively assigned subphenotypes with those derived retrospectively by LCA, characterise their temporal stability over the first days of illness, and evaluate how the recent global definition of ARDS affects patient characteristics, prognostication, and trial eligibility. These observations are then translated into the design of an international, adaptive, phenotype-stratified platform trial for ARDS and AHRF.<br>Overall, the work demonstrates that inflammatory subphenotypes can be identified prospectively at the bedside, are present beyond ARDS, carry differential outcomes, and can be operationalised, thereby providing a foundation for precision-medicine trials in critical care.<br></p> 2026-09-30T14:33:57Z Text Thesis 10.17034/33476596.v1 https://figshare.com/articles/thesis/Critical_care_subphenotypes_prospective_identification_and_extension_beyond_syndromic_definitions/33476596 All Rights Reserved Open Access after 2028-12-31