Phenotype, subphenotype, and endotype in sepsis and ARDS: a new layer of heterogeneity?
By
Liyuan Zhao
Cuixia Zhao
Minmin Wang
Wei Huang
April 10, 2026
Clinical Scorecard: Exploring Phenotypes, Subphenotypes, and Endotypes in Sepsis and ARDS: Uncovering a New Dimension of Heterogeneity?
At a Glance
Category Detail
Condition Sepsis and Acute Respiratory Distress Syndrome (ARDS) Key Mechanisms Biological heterogeneity and diverse phenotypes, subphenotypes, and endotypes. Target Population Patients diagnosed with sepsis and ARDS. Care Setting Clinical settings involving critical care and emergency medicine.
Key Highlights
Current subtyping efforts risk adding layers of heterogeneity. Existing classifications show incomplete concordance across subtypes. Subtyping has primarily revealed hidden treatment effects in negative trials. The assumption of distinct subgroups may not reflect true disease biology. The field faces methodological and taxonomic complexity. Guideline-Based Recommendations
Diagnosis
Utilize syndromic clinical criteria while acknowledging biological heterogeneity. Management
Focus on precision medicine to optimize individual patient management. Monitoring & Follow-up
Assess treatment responses in identified subgroups. Risks
Potential for subtyping to exacerbate existing heterogeneity. Patient & Prescribing Data
Patients with sepsis and ARDS requiring individualized treatment approaches.
Retrospective analyses have yet to translate into standard care practices.
Clinical Best Practices
Embrace causal investigation over descriptive proliferation. Be cautious of statistical artifacts in subtype classifications. References
