Background
Methods
Data source and study selection
Data extraction and quality assessment
Data synthesis and data analysis
Results
Literature search
Study characteristics and quality assessment
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 | |||||||||
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 | |||||||||
Albumin | |||||||||
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 | |||||||||
González-López [26] | Interleukin-8 | AECC | 22 | np. | 50.1 | 31.8 (ICU mort) | np. | np. | BALF (20mL*3) |
Matrix metalloproteinases-9 | |||||||||
Procollagen peptide III | |||||||||
Interleukin-6 | |||||||||
Vascular endothelial growth factor | |||||||||
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 | |||||||||
Total phospholipids | |||||||||
Total phospholipases A2 activity | |||||||||
Keane [33] | Interleukin-8 | AECC | 9 | np. | np. | np. | np. | np. | BALF (nsp.) |
Procollagen peptide III | |||||||||
Procollagen peptide I | |||||||||
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 | |||||||||
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 | |||||||||
Platelet activating factor-acetyl choline | |||||||||
Total phospholipids | |||||||||
Nakos [48] | Total protein | AECC | 19 | 66.67 | 45 | 33.33 (nsp.) | Within 12 h of intubation | np. | BALF (20mL*6) |
Albumin | |||||||||
Platelet activating factor-acetyl choline | |||||||||
Total phospholipids | |||||||||
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 | |||||||||
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 | |||||||||
Pugin [53] | Interleukin-8 | AECC | 31 | 54.84 | 48.87 | 57.65 (nsp.) | np. | blind BAL | PEF |
Matrix metalloproteinases-2 | |||||||||
Procollagen peptide III | |||||||||
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 | |||||||||
Hepatic growth factor | |||||||||
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 | |||||||||
Interleukin-6 | |||||||||
Interleukin-2 | |||||||||
Interleukin-1β | |||||||||
Interleukin-10 | |||||||||
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 | |||||||||
Tumor necrosis factor-α | |||||||||
Interleukin-1β | |||||||||
Interleukin-10 | |||||||||
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 | |||||||||
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 | |||||||||
Interleukin-10 | |||||||||
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 | |||||||||
Transforming growth factor-β1 | |||||||||
Hepatic growth factor | |||||||||
Ware [59] | Vascular endothelial growth factor | AECC | 102 | 62.8 | 49 | 60 (nsp.) | np. | np. | PEF |
Biomarkers associated with ARDS diagnosis
Biomarker | No. of study | No. of patients | RoM (95% CI) |
p
| Heterogeneity | |
---|---|---|---|---|---|---|
Q (p value) | I2 (%) | |||||
Total phospholipases A2 activity | 62 | 17.995 (11.381, 28.454) | < 0.05 | 10.54 (0.001) | 90.50 | |
Total protein | 179 | 9.299 (7.575, 11.414) | < 0.05 | 40.48 (< 0.1) | 90.10 | |
Albumin | 191 | 6.544 (4.908, 8.725) | < 0.05 | 27.35 (< 0.1) | 85.40 | |
Plasminogen activator inhibitor-1 | 135 | 5.525 (3.876, 7.877) | < 0.05 | 3.69 (0.158) | 45.8 | |
Soluble receptor for advanced glycation end products | 162 | 4.901 (3.603, 7.673) | < 0.05 | 31.19 (0.000) | 93.6 | |
Platelet activating factor-acetyl choline | 120 | 4.783 (3.495, 6.545) | < 0.05 | 71.83 (< 0.1) | 95.80 | |
Soluble TNF-α receptors II | 110 | 3.253 (1.765, 5.993) | < 0.05 | 4.95 (0.026) | 79.80 | |
Hepatic growth factor | 144 | 3.199 (1.668, 6.135) | < 0.05 | 0.02 (0.892) | 0 | |
Interleukin-8 | 377 | 3.008 (2.322, 3.896) | < 0.05 | 62.08 (< 0.1) | 90.30 | |
Soluble intercellular adhesion molecule-1 | 96 | 2.952 (1.902, 4.581) | < 0.05 | 0.28 (0.6) | 0 | |
Procollagen peptide I | 133 | 2.949 (1.867, 4.659) | < 0.05 | 0.11 (0.743) | 0.00 | |
Interleukin-2 | 67 | 2.761 (1.508, 5.057) | 0.001 | 17.34 (< 0.1) | 94.20 | |
Procollagen peptide III | 195 | 2.328 (1.456, 3.723) | < 0.05 | 2.81 (0.729) | 0 | |
Interleukin-6 | 250 | 1.826 (1.170, 2.852) | 0.008 | 9.1 (0.0059) | 56 | |
Club cell protein | 93 | 0.553 (0.369, 0.827) | 0.004 | 3.6 (0.166) | 44.40 | |
Matrix metalloproteinases-9 | 43 | 0.548 (0.336, 0.893) | 0.016 | 15.45 (< 0.1) | 93.50 | |
Transforming growth factor-β1 | 116 | 1.32 (0.575, 3.034) | 0.513 | 0.93 (0.334) | 0 | |
Tumor necrosis factor-α | 247 | 1.3 (0.917, 1.843) | 0.14 | 2.97 (0.397) | 0 | |
Matrix metalloproteinases −2 | 52 | 1.066 (0.889, 1.278) | 0.493 | 0.06 (0.814) | 0 | |
Total phospholipids | 110 | 1.003 (0.862, 1.166) | 0.973 | 34.25 (< 0.1) | 91.20 | |
Interleukin-1β | 166 | 0.952 (0.628, 1.444) | 0.817 | 4.23 (0.04) | 76.30 | |
Vascular endothelial growth factor | 194 | 0.812 (0.544, 1.212) | 0.309 | 3.4 (0.183) | 41.20 |
Biomarkers associated with ARDS mortality
Biomarker | No. of study | No. of patients | RoM (95% CI) |
p
| Heterogeneity | |
---|---|---|---|---|---|---|
Q (p value) | I2 (%) | |||||
Interleukin-1β | 137 | 4.617 (4.331, 4.921) | < 0.05 | 11.24 (0.004) | 82.20 | |
Interleukin-6 | 176 | 3.882 (3.270, 4.608) | < 0.05 | 41.09 (< 0.1) | 92.70 | |
Interleukin-8 | 160 | 3.679 (3.414, 3.964) | < 0.05 | 20.59 (< 0.1) | 85.40 | |
Kerbs von Lungren-6 | 65 | 3.178 (2.931, 3.446) | < 0.05 | 0.83 (0.363) | 0.00 | |
Plasminogen activator inhibitor-1 | 32 | 2.085 (2.039, 2.133) | < 0.05 | 1.31 (0.252) | 23.70 | |
Tumor necrosis factor-α | 137 | 1.923 (1.656, 2.233) | < 0.05 | 11.47 (0.003) | 82.60 | |
Procollagen peptide III | 194 | 1.714 (1.613, 1.822) | < 0.05 | 34.08 (< 0.1) | 94.10 | |
Total protein | 208 | 1.667 (1.595, 1.742) | < 0.05 | 82.47 (< 0.1) | 97.60 | |
Interleukin-2 | 27 | 0.828 (0.715, 0.959) | 0.012 | 1.49 (0.223) | 32.70 | |
Club cell protein | 37 | 0.406 (0.362, 0.405) | < 0.05 | 21.08 (< 0.1) | 95.30 | |
Interleukin-10 | 137 | 1.019 (0.922, 1.127) | 0.709 | 54.54 (< 0.1) | 96.30 |