Respiratory failure & ventilation
Effects of inflammatory phenotypes in acute respiratory distress syndrome on mortality and partitioning of lung and chest wall mechanics in patients in the USA and Canada: a retrospective cohort study
Authors' conclusion
Our findings suggested that in ARDS, the association between lung-protective mechanical ventilation and 60-day mortality is greater in patients with the hypoinflammatory phenotype than the hyperinflammatory phenotype
Study context
- Population
- Adults (≥18 years) with moderate-to-severe acute respiratory distress syndrome (ARDS) monitored with oesophageal manometry, EPVent-2 trial (14 hospitals, USA and Canada) and Beth Israel Deaconess Medical Center cohort, 2008–20245,778 assessed
- Participants
- 890 adults
- Exposure
- Hyperinflammatory vs Hypoinflammatory
- Hyperinflammatoryn = 424
- Hypoinflammatoryn = 466reference
- Outcome
- 60-day mortality after ARDS onset
- Follow-up
- 60 days
Methodological detailsharmonised data from two cohorts (EPVent-2 trial and single-centre retrospective cohort), multivariable Cox models
- Harmonised data from two cohorts (EPVent-2 trial and single-centre retrospective cohort)
- Multivariable Cox models
Main finding
As reported in the abstract
60-day mortality and association with lung-protective ventilation measures by phenotype
Adjusted hazard ratio (95% CI)P value
Hypoinflammatoryhigh driving pressure (≥15 cm H2O)
2.01(1.39–2.91)
Hyperinflammatory vs Hypoinflammatoryhigh driving pressure (≥15 cm H2O)
1.46(1.11–1.94)
P = 0.033for interactionHypoinflammatoryhigh transpulmonary driving pressure (≥12 cm H2O)
2.36(1.64–3.39)
Hyperinflammatory vs Hypoinflammatoryhigh transpulmonary driving pressure (≥12 cm H2O)
1.18(0.84–1.60)
P = 0.0010for interactionHypoinflammatoryend-expiratory transpulmonary pressure within ±2 cm H2O; protective
0.66(0.46–0.93)
Hyperinflammatory vs Hypoinflammatoryend-expiratory transpulmonary pressure within ±2 cm H2O; not protective
0.97(0.73–1.27)
Observational data: associations, not effects.
Further findings
Mediation of excess mortality in hyperinflammatory phenotype
- Proportion mediated by extrapulmonary organ failure
- 46% [+17 to +79]
- Proportion mediated by respiratory failure
- 0% [−3 to +4]
Original publication
Effects of inflammatory phenotypes in acute respiratory distress syndrome on mortality and partitioning of lung and chest wall mechanics in patients in the USA and Canada: a retrospective cohort study. Lancet Respir Med. Published 19 May 2026. doi:10.
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