Summary of studies that report ARDS subphenotypes
| Parameter | Bos et al9 | Calfee C et al13 | Famous et al12 |
| Sample size | 700 | 1022 | 1000 |
| Recruitment period | 2011–2013 | 1996–2002 | 2000–2005 |
| Study design | Observational cohort | RCT analysed as cohort | RCT analysed as cohort |
| ARDS P/F criteria | ≤300 | <300 | <300 |
| Blood sampling | Around ARDS diagnosis | At baseline | At baseline |
| Biomarkers used for deriving sub-phenotypes | Lung epithelial: none Endothelial: E-selectin; P-selectin; ANG1/2 Coagulation: antithrombin; D-Dimer; tPA; PAI-1; Inflammation: fractalkine; GM-CSF; ICAM-1; IFN-γ; IL-1β; IL-6; IL-8; IL-10; IL-13; TNF-α; MMP-8; TIMP-1; | Lung epithelial: SP-D Endothelial: ICAM-1; vWF Coagulation: protein C; PAI-1 Inflammation: sTNFR-1; IL-6; IL-8 | Lung epithelial: SP-D Endothelial: ICAM-1; vWF; ANG-2 and RAGE Coagulation: protein C; PAI-1 Inflammation: sTNFR-1; IL-6; IL-8 |
| Clinical variables used for deriving subphenotypes | None | Age, gender, ethnicity, BMI, respiratory*; cardiovascular†; creatinine; urine output; bilirubin; temperature; haematocrit; WBC count; sodium; glucose; albumin; platelets; bicarbonate; aetiology of ARDS‡ | Age, gender, ethnicity, BMI, respiratory#; cardiovascular†; creatinine; urine output; bilirubin; temperature; haematocrit; WBC count; sodium; glucose; albumin; platelets; bicarbonate; aetiology of ARDS‡ |
| Analytical approach to derive ARDS subsets | Cluster analyses based only on biomarker data | Latent class analyses based grouping based on clinical and biomarker data | Latent class analyses based grouping based on clinical and biomarker data |
| ARDS subset (prevalence %) | Reactive phenotype (58.0%) versus Uninflamed (42.0%) | Hyperinflammatory (29.4%) versus Phenotype 1 (70.6%) | Hyperinflammatory (27.3%) versus Phenotype 1 (72.7%) |
| Mortality (%) by ARDS subset | Reactive phenotype=36.8% versus Uninflamed=14.9% | Hyperinflammatory=47.3% versus Phenotype 1=19.4% | Hyperinflammatory=45.0% versus Phenotype 1=22.0% |
| Discriminant markers between phenotypes | IL-6; IFN-γ; ANG1/2; PAI-1 | IL-6; sTNFR1; vasopressor use; IL-8; HCO3 | IL-8; sTNFR1; vasopressor use; HCO3; minute ventilation |
The table shows the summary of three recent studies that report ARDS subphenotypes. The Respiratory system variables* included minute ventilation, mean airway pressure, plateau pressure, respiratory rate, tidal volume, positive end-expiratory pressure; partial pressure PaO2 of carbon dioxide (PaCO2) and PaO2/FiO2 ratio.
The Cardiovascular† system variables include highest heart rate, lowest systolic blood pressure and vasopressor use.
The aetiology of ARDS‡ was coded as trauma, sepsis, aspiration, pneumonia or other.
ANG1/2, angiopoietin 1 and 2; ARDS, acute respiratory distress syndrome; BMI, body mass index; GM-CSF, granulocyte-monocyte colony stimulating factor; HCO3, bicarbonate; ICAM-1, intracellular adhesion molecule-1; IFN-γ, interferon gamma; IL, interleukins 6, 8, 10, 13; IL-1β, interleukin-1 beta; MMP-8, matrix metalloproteinase-8; P/F, PaO2/FiO2 ratio; PAI-1, plasminogen activator inhibitor-1; RAGE, receptor for advanced glycation end products; RCT, randomised controlled trial; SP-D, surfactant protein-D; sTNFR-1, soluble tumour necrosis factor receptor-1; TIMP-1, tissue inhibitor of metalloproteinase-1; TNF-α, tumour necrosis factor-alpha; tPA, tissue plasminogen activator; vWF, von-Williebrand’s factor; WBC, white blood cell count.