CHEST Guidelines-Precision-Medicine-and-Heterogeneity-of-Treatment-

Precision-Medicine-and-Heterogeneity-of-Treatment-

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The document is a review on Acute Respiratory Distress Syndrome (ARDS) that highlights its clinical heterogeneity as a significant challenge in developing effective treatments. ARDS is characterized by acute hypoxemia and is caused by various factors, contributing to its heterogeneous nature which affects treatment efficacy in clinical trials. Traditionally, many therapies have not shown a mortality benefit, suggesting possible heterogeneity of treatment effect (HTE) where treatment impacts differ among ARDS subphenotypes. <br /><br />The review identifies several ARDS subphenotypes including physiological, clinical, and biological variations such as PaO2/FIO2 ratios, systemic compliance, inflammatory biomarkers, and causes of ARDS (direct vs indirect lung damage). Understanding these subphenotypes and associated HTE can help tailor treatments more effectively. This approach is part of precision medicine aimed at improving ARDS management.<br /><br />Studies have shown that interventions like lung-protective ventilation and different ventilation strategies might benefit particular subgroups. For instance, open lung ventilation shows benefit in patients with a PaO2/FIO2 ratio ≤ 200 mmHg and those with hyperinflammatory phenotypes. Meanwhile, treatments like high-frequency oscillatory ventilation and neuromuscular blocking agents manifest beneficial outcomes related to specific disease severity or subphenotypes. The differences in outcomes across trials highlight the need for recognizing HTE in ARDS treatment approach and clinical trial designs.<br /><br />Identifying these subphenotypes effectively needs further research but can potentially shift therapeutic strategies in ARDS from generalized to more personalized approaches. Future research should focus on validating subphenotype-specific interventions through targeted clinical trials and developing practical tools for real-time subphenotype identification in clinical settings. The findings advocate moving towards a paradigm of precision medicine in ARDS to exploit potential benefits initially obscured in broader clinical trials.

Keywords

ARDS

clinical heterogeneity

hypoxemia

subphenotypes

precision medicine

lung-protective ventilation

PaO2/FIO2 ratio

heterogeneity of treatment effect

personalized treatment

biomarkers