Molecular phenotypes of critical illness confer prognostic and biological enrichment in sub-Saharan Africa: a prospective cohort study from Uganda

The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiologic...

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Vydané v:	Thorax Ročník 80; číslo 3; s. 175 - 179
Hlavní autori:	Cummings, Matthew J, Lutwama, Julius J, Tomoiaga, Alin S, Owor, Nicholas, Lu, Xuan, Ross, Jesse E, Muwanga, Moses, Nsereko, Christopher, Nayiga, Irene, Nie, Kai, Kayiwa, John, Che, Xiaoyu, Wayengera, Misaki, Kim-Schulze, Seunghee, Lipkin, W Ian, O’Donnell, Max R, Bakamutumaho, Barnabas
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England BMJ Publishing Group Ltd and British Thoracic Society 17.02.2025 BMJ Publishing Group LTD
Predmet:	Adult Biomarkers Blood pressure Cohort analysis Critical care Critical Illness Cytokine Biology Female Genotype & phenotype Heart rate HIV Human immunodeficiency virus Humans Hypotension Illnesses Infections Influenza Malaria Male Mann-Whitney U test Medical prognosis Middle Aged Mortality Oxygen saturation Pathogens Patients Phenotype Probability Prognosis Prospective Studies Protein expression Regression analysis Sepsis Sepsis - mortality Severity of Illness Index Tuberculosis Uganda - epidemiology Urine Variables Uganda Africa Critical Care Cytokine Biology
ISSN:	0040-6376, 1468-3296, 1468-3296
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Abstract	The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings.
AbstractList	The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings. The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings.The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings.
Author	Lipkin, W Ian Tomoiaga, Alin S Owor, Nicholas Che, Xiaoyu O’Donnell, Max R Nie, Kai Nsereko, Christopher Cummings, Matthew J Ross, Jesse E Kim-Schulze, Seunghee Muwanga, Moses Kayiwa, John Lu, Xuan Nayiga, Irene Wayengera, Misaki Lutwama, Julius J Bakamutumaho, Barnabas
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SubjectTerms	Adult Biomarkers Blood pressure Cohort analysis Critical care Critical Illness Cytokine Biology Female Genotype & phenotype Heart rate HIV Human immunodeficiency virus Humans Hypotension Illnesses Infections Influenza Malaria Male Mann-Whitney U test Medical prognosis Middle Aged Mortality Oxygen saturation Pathogens Patients Phenotype Probability Prognosis Prospective Studies Protein expression Regression analysis Sepsis Sepsis - mortality Severity of Illness Index Tuberculosis Uganda - epidemiology Urine Variables
Title	Molecular phenotypes of critical illness confer prognostic and biological enrichment in sub-Saharan Africa: a prospective cohort study from Uganda
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