From: Lung fluid biomarkers for acute respiratory distress syndrome: a systematic review and meta-analysis
Reference | Biomarkers | Diagnostic criteria for ARDS | Study size | Male (%) | Age | Mortality (%) | Sample retrieved time | Sample retrieved location | Sample type (vol. of irrigation solution) |
---|---|---|---|---|---|---|---|---|---|
Studies related to diagnosis | |||||||||
 Armstrong [14] | Procollagen peptide I | AECC | 66 | 66.7 | 64.65 | 48.5 (nsp.) | Within 48 h of ICU admission | Right middle lobe | BALF (20 mL*6) |
 Bersten [15] | Total phospholipids | Clinical criteria | 21 | np. | np. | np. | Within 7 h of study entry | np. | LAF |
 Calfee [16] | Soluble intercellular adhesion molecule-1 | Clinical criteria | 67 | 59.84 | 50.63 | 44.79 (hosp mort) | Within 4 h of intubation | np. | PEF |
 Chollet-Martin [18] | Interleukin-8 | LIS | 29 | np. | 62.12 | np. | Within 72 h of ARDS diagosis | np. | ELF |
Tumor necrosis factor-α |  |  |  |  |  |  |  |  | |
Interleukin-6 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Conner [20] | Soluble intercellular adhesion molecule-1 | Clinical criteria+EF/plasma protein | 27 | np. | np. | np. | Within 1 h of intubation | np. | PEF |
 Delclaux [21] | Albumin | Clinical criteria | 29 | 71.43 | 54 | 64.29 (nsp.) | np. | np. | BALF (3*50mL) |
 El Solh [22] | Plasminogen activator inhibitor-1 | AECC | 51 | 43.14 | 36.57 | 5.88 (hosp mort) | Within 8 h of intubation | Blind BAL | PEF |
 Prabhakaran [52] | Plasminogen activator inhibitor-1 | AECC | 51 | 58 | 50 | 47 (hosp mort) | Within 12h of intubation | np. | PEF |
 Song [56] | Plasminogen activator inhibitor-1 | Clinical criteria | 33 | 39 | 70 | 15 (28-day mort) | When patients were suspected to have VAP | np. | BALF (20mL*3) |
 Farjanel [23] | Procollagen peptide III | LIS | 61 | 60.7 | 49.23 | 47.5 (hosp mort) | 3 days after intubation | A subsegmental of middle lobe | BALF (3*50mL) |
Procollagen peptide I | Â | Â | Â | Â | Â | Â | Â | Â | |
Albumin | Â | Â | Â | Â | Â | Â | Â | Â | |
 Geerts [25] | Club cell protein | AECC | 26 | 73.1 | 51 | np. | Within 12 h of ARDS diagnosis | Right middle lobe | BALF (50mL*3) |
Total protein | Â | Â | Â | Â | Â | Â | Â | Â | |
 González-López [26] | Interleukin-8 | AECC | 22 | np. | 50.1 | 31.8 (ICU mort) | np. | np. | BALF (20mL*3) |
Matrix metalloproteinases-9 | Â | Â | Â | Â | Â | Â | Â | Â | |
Procollagen peptide III | Â | Â | Â | Â | Â | Â | Â | Â | |
Interleukin-6 | Â | Â | Â | Â | Â | Â | Â | Â | |
Vascular endothelial growth factor | Â | Â | Â | Â | Â | Â | Â | Â | |
 Hallgren [27] | Albumin | Clinical criteria | 40 | 66.67 | 46.87 | 25 (nsp.) | np. | Right middle lobe | BALF (3*20mL) |
 Hamacher [28] | Tumor necrosis factor-α | AECC | 56 | 75 | 45.41 | 25.07 (hosp mort) | np. | np. | BALF (nsp.) |
Soluble TNF-α receptors II |  |  |  |  |  |  |  |  | |
Transforming growth factor-β1 |  |  |  |  |  |  |  |  | |
 Idell [29] | Total protein | Clinical criteria | 16 | np. | np. | np. | Within 96 h of ARDS diagnosis | Right middle lobe/right lower lobe/lingula | BALF (30mL*5) |
 Jabaudon [60] | Soluble receptor for advanced glycation end products | AECC | 60 | 55 | 61 | 66.67 | Within 24 h of disease onset. | np. | LAF |
 Karagiorga [32] | Total protein | Clinical criteria | 31 | 64.52 | 41.43 | 22.58 (nsp.) | Within 72 h of ARDS diagnosis | np. | BALF (20mL*6) |
Platelet activating factor-acetyl choline | Â | Â | Â | Â | Â | Â | Â | Â | |
Total phospholipids | Â | Â | Â | Â | Â | Â | Â | Â | |
Total phospholipases A2 activity | Â | Â | Â | Â | Â | Â | Â | Â | |
 Keane [33] | Interleukin-8 | AECC | 9 | np. | np. | np. | np. | np. | BALF (nsp.) |
Procollagen peptide III | Â | Â | Â | Â | Â | Â | Â | Â | |
Procollagen peptide I | Â | Â | Â | Â | Â | Â | Â | Â | |
 Kurdowska [36] | Interleukin-8 | LIS | 26 | np. | np. | 41.2 (nsp.) | Upon ICU admission | Right middle lobe | BALF (60mL*3) |
 Lanchou [37] | Matrix metalloproteinases-9 | AECC | 21 | 47.6 | 54 | 33.3 (nsp.) | Within 24 h of ARDS diagnosis | Right middle lobe | BALF (20mL*3) |
Matrix metalloproteinases-2 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Martin [44] | Total protein | AECC | 69 | 68 | 45 | 56 (nsp.) | Within 72 h of ARDS diagnosis | Right middle lobe/lingula | BALF (30mL*5) |
 Martin [43] | Soluble receptor for advanced glycation end products | AECC | 69 | 59 | 53.9 | 46 (nsp.) | np. | np. | BALF (nsp.) |
 Medford [45] | Vascular endothelial growth factor | AECC | 70 | 40 | 59.37 | 38.57 (28-day mort) | With 72 h of intubation | np. | ELF |
 Miller [46] | Interleukin-8 | AECC | 35 | np. | 48.54 | np. | Within 30 min of intubation | np. | PEF |
 Nakos [49] | Total protein | AECC | 21 | 76.2 | 61 | np. | Within 24 h of intubation | Right middle lobe/lingula. | BALF (20mL*6) |
Albumin | Â | Â | Â | Â | Â | Â | Â | Â | |
Platelet activating factor-acetyl choline | Â | Â | Â | Â | Â | Â | Â | Â | |
Total phospholipids | Â | Â | Â | Â | Â | Â | Â | Â | |
 Nakos [48] | Total protein | AECC | 19 | 66.67 | 45 | 33.33 (nsp.) | Within 12 h of intubation | np. | BALF (20mL*6) |
Albumin | Â | Â | Â | Â | Â | Â | Â | Â | |
Platelet activating factor-acetyl choline | Â | Â | Â | Â | Â | Â | Â | Â | |
Total phospholipids | Â | Â | Â | Â | Â | Â | Â | Â | |
 Nakos [47] | Platelet activating factor-acetyl choline | AECC | 31 | 29 | 55.54 | 32.2 (ICU mort) | Upon ARDS diagnosis | np. | BALF (20mL*6) |
Total phospholipases A2 activity | Â | Â | Â | Â | Â | Â | Â | Â | |
 Park [51] | Tumor necrosis factor-α | AECC | 54 | 59.1 | 44.67 | 20.1 (nsp.) | Within 24 h of ARDS diagnosis | Right middle lobe/lingula | BALF (30mL*5) |
Soluble TNF-α receptors II |  |  |  |  |  |  |  |  | |
Interleukin-1β |  |  |  |  |  |  |  |  | |
Interleukin-6 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Pugin [53] | Interleukin-8 | AECC | 31 | 54.84 | 48.87 | 57.65 (nsp.) | np. | blind BAL | PEF |
Matrix metalloproteinases-2 | Â | Â | Â | Â | Â | Â | Â | Â | |
Procollagen peptide III | Â | Â | Â | Â | Â | Â | Â | Â | |
 Ricou [55] | Interleukin-6 | Clinical criteria+LIS | 24 | 79.2 | 50.5 | 33.3 (nsp.) | Within 24 h of ARDS diagnosis | np. | BALF (nsp.) |
 Stern [57] | Procollagen peptide III | AECC | 25 | 64 | 67.08 | 60 (30-day mort) | Within 72 h of ARDS diagnosis | The abnormal area on the chest radiography | BALF (20mL*6) |
Albumin | Â | Â | Â | Â | Â | Â | Â | Â | |
Hepatic growth factor | Â | Â | Â | Â | Â | Â | Â | Â | |
 Uchida [58] | Soluble receptor for advanced glycation end products | AECC | 33 | 57.67 | 43 | 51.33 (hosp mort) | np. | np. | PEF |
Studies related to mortality | |||||||||
 Adamzik [12] | Tumor necrosis actor-α | AECC | 47 | 68.09 | 44.53 | 36.17 (30-day mort) | Within 24 h of ICU admission | np. | BALF (40mL*4) |
Total protein | Â | Â | Â | Â | Â | Â | Â | Â | |
Interleukin-6 | Â | Â | Â | Â | Â | Â | Â | Â | |
Interleukin-2 | Â | Â | Â | Â | Â | Â | Â | Â | |
Interleukin-1β |  |  |  |  |  |  |  |  | |
Interleukin-10 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Clark [19] | Procollagen peptide III | AECC | 117 | 64.1 | 42.78 | 41 (hosp mort) | Within 72h of ARDS diagosis | Right middle lobe/lingula | BALF (30mL*5) |
 Frenzel [24] | Interleukin-6 | AECC | 46 | 60.9 | 62 | 45.7 (28-day mort) | Within 96h of intubation | Right middle lobe/lingula | BALF (20mL*5) |
Interleukin-8 | Â | Â | Â | Â | Â | Â | Â | Â | |
Tumor necrosis factor-α |  |  |  |  |  |  |  |  | |
Interleukin-1β |  |  |  |  |  |  |  |  | |
Interleukin-10 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Kondo [34] | Kerbs von Lungren-6 | AECC | 32 | 84.38 | 70.1 | 31.3 (hosp mort) | Within 24 h of ARDS diagnosis | Right middle lobe | ELF |
 Lee [38] | Interleukin-8 | AECC | 31 | 51.6 | 54.5 | 51.6 (28-day mortality) | Within 48 h of ARDS diagnosis | Right middle lobe/lingular | BALF (30mL*5) |
 Lin [41] | Interleukin-6 | AECC | 39 | 69.2 | 68 | 43.6 (hosp mort) | Within 24h of ARDS diagnosis | Right middle lobe/lingula | BALF (20mL*6) |
Interleukin-8 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Nathani [50] | Kerbs von Lungren-6 | AECC | 42 | 57.1 | 60.13 | np. | Upon study entry | Middle lobe | BALF (50mL*3) |
 Ishizaka [30] | Kerbs von Lungren-6 | AECC | 38 | 77% | 68 | 32 (hosp mort) | Upon onset of ARDS | Right middle lobe | ELF |
Studies related to diagnosis and mortality | |||||||||
 Agouridakis [13] | Interleukin-2 | AECC | 34 | 74.42 | 47.79 | 27.9 (nsp.) | Within 2h of ICU admission | np. | BALF (nsp.) |
 Chesnutt [17] | Procollagen peptide III | AECC+EF/plasma protein | 44 | 47.73 | 56.25 | 63.64 (hosp mort) | Within 1h of intubation | np. | PEF |
 Jorens [31] | Club cell protein | Fowler+LIS | 35 | 88.6 | 55 | 42.9 (nsp.) | Within 12 h of ARDS diagnosis | Right middle lobe | BALF (50mL*3) |
 Kropski [35] | Club cell protein | AECC+EF/plasma protein | 32 | 46.9 | 48 | 56.5 (nsp.) | Within 24 h of intubation | np. | PEF |
 Lee [39] | IL-8 | Clinical criteria | 112 | 78.6 | 66.5 | 77.3 (nsp) | With 24h of ICU admission | The most abnormal area on the chest radiography/right middle lobe/lingula | BALF (20mL*6) |
Tumor necrosis factor-α |  |  |  |  |  |  |  |  | |
Interleukin-1β |  |  |  |  |  |  |  |  | |
Interleukin-6 | Â | Â | Â | Â | Â | Â | Â | Â | |
Interleukin-10 | Â | Â | Â | Â | Â | Â | Â | Â | |
 Lesur [40] | Interleukin-2 | AECC | 33 | 36.4 | 51.52 | 24.2 (hosp mort) | Within 72h of intubation | Right middle lobe/lingula | BALF (20mL*5) |
 Marshall [42] | Procollagen peptide III | AECC | 60 | 53.33 | 51.35 | 31.67 (nsp.) | Within 24h of ARDS diagnosis | np. | BALF (nsp.) |
 Quesnel [54] | Interleukin-8 | AECC | 122 | 64.8 | 67 | 33.6 (28-day mort) | np. | np. | BALF (20mL*6) |
Procollagen peptide I | Â | Â | Â | Â | Â | Â | Â | Â | |
Transforming growth factor-β1 |  |  |  |  |  |  |  |  | |
Hepatic growth factor | Â | Â | Â | Â | Â | Â | Â | Â | |
 Ware [59] | Vascular endothelial growth factor | AECC | 102 | 62.8 | 49 | 60 (nsp.) | np. | np. | PEF |