Background
Methods
Search strategy
Data selection and extraction
Statistical analysis
Results
Literature search
Study characteristics
Authors | Country | Year | Study design | Sample size | Mean or median age (years) | Gender (m/f) | Underlying disease | Patient status | Judgment method of ARDS/ALI | Specimen source | Test time | Follow-up | NOS score |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hoeboer [12] | Netherlands | 2015 | Prospective | 101 | 64.0 | 69/32 | Fever | ARDS | Berlin definition/LIS | Blood | 7 days | 7 days | 8 |
Roubinian [13] | U.S | 2015 | Prospective | 317 | 58.0 | 153/164 | Pulmonary transfusion reactions hypoxemia | ALI | Defined | Blood | 1 day | NA | 6 |
Jones [14] | U.S | 2013 | Prospective | 43 | 45.6 | 40/9 | Inhalation and burns | ALI | PaO2/FiO2 | BALF | 3 days | 3 days | 7 |
Agrawal [15] | U.S | 2013 | Prospective | 230 | 65.0 | 79/88 | Critically ill | ALI | Berlin definition | Blood | 1 day | 60 days | 7 |
Schultz [16] | Netherlands | 2012 | Retrospective | 20 | 59.0 | 13/7 | Mechanical ventilation | ALI | LIS | BALF | 6 days | 6 days | 7 |
Quesnel [17] | France | 2012 | Retrospective | 122 | 49.0 | 79/43 | Critically ill | ALI/ARDS | AECC | BALF | NA | 28 days | 6 |
Osaka [18] | Japan | 2011 | Prospective | 27 | 50.0 | 12/15 | Pneumonia | ALI | PaO2/FiO2 | Blood | 1 day | 10 days | 8 |
Guervilly [19] | France | 2011 | Prospective | 74 | 58.0 | 53/21 | Critically ill | ALI | AECC | Blood/BALF | 1 day | 28 days | 7 |
Jabaudon [20] | France | 2011 | Prospective | 64 | 59.0 | 41/23 | Severe Sepsis | ALI | AECC | Blood | 1 day | 28 days | 7 |
Aman [21] | Netherlands | 2010 | Prospective | 83 | 60.0 | 65/18 | Mechanical ventilation | ALI/ARDS | AECC | Blood | 1 day | NA | 7 |
Kohno [22] | Japan | 2011 | Prospective | 20 | 71.0 | 15/5 | Thoracic aortic aneurysm repair | ARDS | PaO2/FiO2 | Blood | 1–4 days | 22 days | 7 |
Determann [23] | Netherlands | 2010 | Prospective | 36 | 58.0 | 22/14 | Mechanical ventilation | ALI/ARDS | LIS | Blood | 2 days | 2 days | 8 |
Determann [24] | Netherlands | 2010 | Prospective | 150 | 61.0 | 99/51 | Mechanical ventilation | ALI | LIS | Blood/BALF | 1 day | 4 days | 8 |
Fremont [25] | U.S | 2010 | Retrospective | 192 | 39.0 | 131/61 | Traumatic injuries | ALI | PaO2/FiO2 | Blood | 3 days | 6–10 days | 7 |
Determann [26] | Netherlands | 2009 | Retrospective | 22 | 65.0 | 17/5 | Ventilator-associated pneumonia | ALI/ARDS | AECC | BALF | 1 day | 8 days | 7 |
Chi [27] | China | 2009 | Prospective | 27 | NA | NA | Orthotopic liver transplantation | ALI | PaO2/FiO2 | Blood | 1 day | 7 days | 6 |
Kropski [28] | U.S | 2009 | Prospective | 32 | 43.0 | 15/17 | Mechanical ventilation | ARDS | AECC | Blood/BALF | 1 day | 2–14 days | 7 |
Calfee [29] | U.S | 2009 | Prospective | 67 | 51.0 | 40/27 | Hydrostatic pulmonary edema | ALI | AECC | Blood/BALF | 4 h | 3 days | 8 |
Van der Heijden [30] | Netherlands | 2008 | Prospective | 112 | 56.0 | NA | Critically ill | ALI/ARDS | AECC/LIS | Blood | 1 day | NA | 7 |
Kurzius-Spencer [31] | U.S | 2008 | Prospective | 21 | NA | 20/1 | Smoke inhalation injury | ARDS | AECC/PaO2/FiO2 | BALF | 36 h | 72 h | 8 |
Nathani [32] | U.K | 2008 | Prospective | 42 | 62.0 | 24/18 | ARDS risk population | ARDS/ALI | AECC | Blood/BALF | 1 day | 4 days | 7 |
Ganter [33] | U.S | 2008 | Prospective | 208 | 41.0 | 155/53 | Traumatic injuries | ALI | AECC | Blood | 1 day | 28 days | 7 |
Gallagher [34] | U.S | 2008 | Prospective | 63 | 67.0 | 35/28 | Critically ill | ALI/ARDS | AECC | Blood | 1 day | 2 months | 7 |
Calfee [35] | U.S | 2007 | Prospective | 1451 | 52.0 | 609/839 | Trauma | ALI | Defined | Blood | 1 day | 180 days | 7 |
Ware [36] | U.S | 2007 | Prospective | 878 | 52.0 | 514/364 | Acute cardiogenic pulmonary edema | ALI/ARDS | Defined | Blood | 1 day | 3 days | 7 |
Perkins [37] | UK | 2007 | Prospective | 54 | NA | NA | ARDS risk population | ALI/ARDS | AECC | BALF | 1 day | 4 days | 6 |
El Solh [38] | U.S | 2006 | Prospective | 51 | 36.6 | 22/29 | Aspiration pneumonitis | ALI | AECC | Blood/BALF | 1 day | 28 days | 8 |
Parsons [39] | U.S | 2005 | Prospective | 49 | NA | NA | Critically ill | ALI | AECC | Blood | 1 day | 180 days | 8 |
Bouros [40] | Greece | 2004 | Prospective | 59 | 51.7 | 43/16 | Critically ill | ALI | AECC | Blood/BALF | 1 day | NA | 7 |
Nakae [41] | Japan | 2003 | Prospective | 21 | 62.0 | 15/6 | Sepsis | ARDS | Defined | Blood | NA | NA | 7 |
Sato [42] | UK | 2004 | Prospective | 37 | 39.5 | 32/5 | Mechanical ventilation | ARDS | AECC | Blood | 1 day | 6.5 days | 8 |
Nys [43] | Belgium | 2003 | Prospective | 67 | 54.0 | 43/24 | Pneumonia | ARDS | PaO2/FiO2 | BALF | 1–2 days | NA | 7 |
Gessner [44] | Germany | 2003 | Prospective | 35 | 60.0 | 16/19 | Acute respiratory failure | ARDS | AECC | BALF | 1 day | 6 months | 7 |
Ishizaka [45] | Japan | 2004 | Prospective | 35 | 68.0 | 27/8 | Cardiogenic pulmonary edema | ALI | AECC | BALF | 1 day | NA | 6 |
Prabhakaran [46] | U.S | 2003 | Prospective | 51 | 50.0 | 29/22 | Hydrostatic edema | ARDS | AECC | Blood/BALF | 1 day | NA | 7 |
Grissom [47] | U.S | 2003 | Prospective | 39 | 51.0 | 16/17 | ARDS risk population | ARDS | AECC | Blood/BALF | 96 h | 42 days | 8 |
Agouridakis [48] | Greece | 2002 | Prospective | 65 | 44.0 | 40/25 | Mechanical ventilation | ARDS | AECC | Blood/BALF | 1 day | 15 days | 8 |
Agouridakis [49] | Greece | 2002 | Prospective | 34 | 49.0 | 23/11 | Mechanical ventilation | ARDS | AECC | Blood/BALF | 1 day | 6 months | 8 |
Thickett [50] | UK | 2002 | Prospective | 68 | 65.0 | 45/23 | ARDS risk population | ARDS | AECC | BALF | 1 day | 4 days | 6 |
Hamacher [51] | France | 2002 | Prospective | 36 | 43.0 | 28/8 | ARDS risk population | ARDS | AECC | BALF | 1 day | 21 days | 7 |
Takala [52] | Finland | 2002 | Prospective | 52 | 54.0 | 29/19 | Critically ill | ARDS | AECC | Blood | 1 day | 7 days | 8 |
Park [53] | Switzerland | 2001 | Prospective | 69 | 43.8 | 41/28 | ARDS risk population | ARDS | AECC | BALF | 1 day | 21 days | 7 |
Hirani [54] | UK | 2001 | Prospective | 56 | 48.0 | NA | Major trauma | ARDS | AECC | BALF | 1 day | 36 months | 8 |
Geerts [55] | Belgium | 2001 | Prospective | 26 | 52.0 | 19/7 | ARDS risk population | ARDS | AECC | BALF | 1 day | NA | 7 |
Siemiatkowski [56] | Poland | 2000 | Prospective | 36 | 44.3 | 27/9 | Major trauma | ARDS | LIS | Blood | 1 day | 10 days | 7 |
Armstrong [57] | UK | 2000 | Prospective | 67 | 62.0 | 44/23 | Critically ill | ARDS/ALI | AECC | BALF | 48 h | NA | 7 |
Bauer [58] | Spain | 2000 | Prospective | 66 | 57.2 | NA | Pneumonia | ARDS | AECC | Blood | 1 day | NA | 8 |
Gando [59] | Japan | 1999 | Prospective | 58 | 58.0 | 37/21 | Critically ill | ARDS | Defined | Blood | 1 day | 4 days | 7 |
Donnelly [60] | Scotland | 1999 | Prospective | 61 | NA | NA | Trauma | ARDS | Defined | BALF | NA | NA | 6 |
Parsons [61] | U.S | 1997 | Prospective | 77 | 37.5 | 53/24 | ARDS risk population | ARDS | Defined | Blood | 1 day | 2 days | 7 |
Schutte [62] | Germany | 1996 | Prospective | 56 | 54.5 | 45/11 | Pneumonia | ARDS | AECC | Blood/BALF | 2 days | 10 days | 7 |
Chollet-Martin [63] | France | 1996 | Prospective | 14 | 61.0 | NA | Pneumonia | ARDS | LIS | Blood/BALF | 3 days | 7 days | 8 |
Ricou [64] | U.S | 1996 | Prospective | 33 | 48.0 | 24/9 | Critically ill | ARDS | LIS | Blood/BALF | 3 days | 2 weeks | 8 |
Schwartz [65] | U.S | 1996 | Prospective | 12 | 45.0 | 7/5 | Mechanical ventilation | ARDS | LIS | BALF | 1 day | NA | 7 |
Jorens [66] | UK | 1995 | Prospective | 35 | 56.6 | 31/4 | Cardiopulmonary bypass | ARDS | Defined | BALF | 1 day | 3 days | 7 |
Fuchs-buder [67] | Switzerland | 1996 | Prospective | 21 | NA | NA | Critically ill | ARDS | LIS | BALF | 2 days | 10 days | 8 |
Leff [68] | U.S | 1993 | Prospective | 26 | NA | NA | Sepsis | ARDS | Defined | Blood | 1 day | 2 days | 7 |
Sakamaki [69] | Japan | 1995 | Prospective | 48 | 49.0 | 29/19 | Sepsis | ARDS | Defined | Blood | 1 day | 15 days | 7 |
Donnelly [70] | U.S | 1994 | Prospective | 82 | 49.5 | NA | ARDS risk population | ARDS | LIS | Blood | 1–3 days | NA | 8 |
Moalli [71] | U.S | 1989 | Prospective | 47 | 66.0 | NA | ARDS risk population | ARDS | Defined | Blood | 1 day | 22 days | 7 |
Rubin [72] | U.S | 1990 | Prospective | 45 | NA | NA | Sepsis | ARDS | LIS | Blood | 1 day | 3 days | 8 |
Roten [73] | Switzerland | 1990 | Prospective | 50 | 49.0 | 31/19 | Critically ill | ARDS | Defined | Blood | 1 day | 5 days | 7 |
Parsons [74] | U.S | 1992 | Prospective | 103 | 46.0 | 77/26 | ARDS risk population | ARDS | Defined | Blood | 1 day | 2 days | 7 |
Inflammatory biomarkers and ARDS/ALI
Factors | No. of studies | Groups | SMD | 95% CI | P value | Heterogeneity (%) | P for heterogeneity |
---|---|---|---|---|---|---|---|
Albumin | 1 | Blood | −0.82 | −1.79 to 0.14 | 0.095 | – | – |
2 | BALF | 2.15 | 0.51 to 3.79 | 0.010 | 82.2 | 0.018 | |
ANG‑1 | 1 | Blood | 0.80 | 0.28 to 2.30 | 0.676 | – | – |
1 | BALF | 4.60 | 3.09 to 6.12 | < 0.001 | – | – | |
CC16 | 3 | Blood | −0.31 | −2.7 to 2.08 | 0.799 | 96.8 | < 0.001 |
4 | BALF | −0.44 | −3.06 to 2.18 | 0.742 | 96.1 | < 0.001 | |
CRP | 3 | Blood | 1.64 | −0.31 to 3.59 | 0.100 | 92.2 | < 0.001 |
Endotoxin | 2 | BALF | 0.30 | −0.15 to 0.75 | 0.191 | 0.0 | 0.887 |
G‑CSF | 2 | Blood | −0.49 | −1.47 to 0.49 | 0.326 | 93.9 | < 0.001 |
ICAM | 4 | Blood | −0.14 | −2.47 to 2.20 | 0.909 | 99.4 | < 0.001 |
2 | BALF | 0.79 | −1.61 to 3.18 | 0.520 | 96.3 | < 0.001 | |
IL‑2 | 2 | Blood | 0.01 | −0.26 to 0.28 | 0.934 | 0.0 | 0.817 |
1 | BALF | −0.36 | −1.16 to 0.44 | 0.380 | – | – | |
IL‑4 | 2 | Blood | 0.69 | −0.16 to 1.54 | 0.111 | 81.1 | 0.022 |
1 | BALF | 0.30 | −0.38 to 0.99 | 0.387 | – | – | |
IL-12 | 1 | Blood | −0.8 | −1.09 to −0.50 | < 0.001 | – | – |
1 | BALF | −1.47 | −2.18 to −0.75 | < 0.001 | – | – | |
KL‑6 | 3 | Blood | 3.36 | 2.50 to 4.21 | < 0.001 | 49.5 | 0.138 |
3 | BALF | 2.23 | 0.06 to 4.41 | 0.044 | 93.0 | < 0.001 | |
LDH | 2 | Blood | 1.82 | −0.23 to 3.87 | 0.082 | 85.9 | < 0.001 |
MPO | 1 | Blood | 2.58 | 2.20 to 2.97 | < 0.001 | – | – |
1 | BALF | 1.75 | 0.90 to 2.60 | < 0.001 | – | – | |
NF-κβ | 2 | BALF | 0.86 | −0.45 to 2.17 | 0.198 | 67.1 | 0.081 |
PCT | 2 | Blood | 0.41 | 0.02 to 0.80 | 0.038 | 23.7 | 0.252 |
Protein C | 2 | Blood | −2.00 | −7.15 to 3.16 | 0.447 | 99.9 | < 0.001 |
RAGE | 4 | Blood | 1.64 | 0.15 to 3.14 | 0.031 | 96.3 | < 0.001 |
1 | BALF | 0.16 | −0.68 to 1.00 | 0.704 | – | – | |
sE-selectin | 3 | Blood | 0.55 | 0.13 to 0.97 | 0.011 | 15.2 | 0.307 |
SP‑D | 4 | Blood | −0.05 | −1.65 to 1.55 | 0.950 | 98.5 | < 0.001 |
1 | BALF | −1.17 | −2.08 to −0.25 | 0.012 | – | – | |
TGF-β1 | 4 | BALF | 0.83 | 0.17 to 1.49 | 0.013 | 81.2 | < 0.001 |
TF | 1 | Blood | 3.55 | 2.71 to 4.39 | < 0.001 | – | – |
1 | BALF | 5.57 | 3.55 to 7.60 | < 0.001 | – | – | |
TNFR‑1 | 2 | Blood | 1.61 | −4.42 to 7.64 | 0.601 | 98.9 | < 0.001 |
1 | BALF | 5.40 | 4.22 to 6.58 | < 0.001 | – | – | |
TNFR‑2 | 1 | Blood | 3.82 | 2.80 to 4.83 | < 0.001 | – | – |
2 | BALF | 3.22 | −2.62 to 9.05 | 0.280 | 98.4 | < 0.001 | |
VEGF | 1 | Blood | 0.49 | −0.23 to 1.04 | 0.063 | – | – |
1 | BALF | −4.52 | −5.43 to −3.61 | < 0.001 | – | – | |
vWF | 6 | Blood | 0.81 | −0.94 to 2.54 | 0.365 | 99.2 | < 0.001 |
Meta-regression and subgroup analyses
Inflammatory factors | Groups | No. of studies | SMD | 95%CI | P value | Heterogeneity (%) | P for heterogeneity |
---|---|---|---|---|---|---|---|
ANG‑2 | Sample size | ||||||
≥ 100 | 5 | 1.30 | 0.47 to 2.13 | 0.002 | 97.8 | < 0.001 | |
< 100 | 1 | 1.59 | 0.97 to 2.20 | < 0.001 | – | – | |
Mean age (years) | |||||||
≥ 60.0 | 3 | 1.74 | 1.30 to 2.18 | < 0.001 | 51.1 | 0.129 | |
< 60.0 | 3 | 0.98 | −0.02 to 1.98 | 0.055 | 98.4 | < 0.001 | |
Patients’ status | |||||||
ARDS | 1 | 2.15 | 1.65 to 2.64 | < 0.001 | – | – | |
ALI | 3 | 1.38 | −0.19 to 2.93 | 0.085 | 98.3 | < 0.001 | |
ARDS/ALI | 2 | 0.91 | −0.34 to 2.16 | 0.152 | 93.7 | < 0.001 | |
Specimen source | |||||||
Blood | 6 | 1.34 | 0.59 to 2.10 | < 0.001 | 97.4 | < 0.001 | |
BALF | 0 | – | – | – | – | – | |
IL-1β | Sample size | ||||||
≥ 100 | 2 | −0.33 | −1.05 to 0.40 | 0.379 | 79.7 | 0.026 | |
< 100 | 8 | 1.26 | 0.48 to 2.04 | 0.002 | 89.9 | < 0.001 | |
Mean age (years) | |||||||
≥ 60.0 | 1 | −0.75 | −1.34 to −0.15 | 0.014 | – | – | |
< 60.0 | 7 | 1.33 | 0.43 to 2.23 | 0.004 | 94.4 | < 0.001 | |
Patients’ status | |||||||
ARDS | 6 | 1.39 | 0.41 to 2.37 | 0.005 | 91.8 | < 0.001 | |
ALI | 4 | 0.22 | −0.59 to 1.04 | 0.590 | 88.0 | < 0.001 | |
Specimen source | |||||||
Blood | 5 | 1.39 | 0.15 to 2.62 | 0.028 | 95.3 | < 0.001 | |
BALF | 6 | 0.73 | −0.19 to 1.66 | 0.121 | 90.2 | < 0.001 | |
IL‑6 | Sample size | ||||||
≥ 100 | 5 | 0.45 | −0.26 to 1.16 | 0.215 | 96.1 | < 0.001 | |
< 100 | 8 | 0.83 | 0.11 to 1.55 | 0.024 | 91.6 | < 0.001 | |
Mean age (years) | |||||||
≥ 60.0 | 3 | 1.49 | 0.37 to 2.61 | 0.009 | 92.1 | < 0.001 | |
< 60.0 | 10 | 0.43 | −0.06 to 0.92 | 0.088 | 93.1 | < 0.001 | |
Patients’ status | |||||||
ARDS | 7 | 0.80 | 0.03 to 1.57 | 0.043 | 92.6 | < 0.001 | |
ALI | 6 | 0.54 | −0.12 to 1.20 | 0.108 | 95.3 | < 0.001 | |
Specimen source | |||||||
Blood | 11 | 0.37 | −0.04 to 0.77 | 0.074 | 88.8 | < 0.001 | |
BALF | 7 | 1.33 | 0.24 to 2.42 | 0.016 | 93.2 | < 0.001 | |
IL‑8 | Sample size | ||||||
≥ 100 | 4 | 0.06 | −1.84 to 1.95 | 0.953 | 99.2 | < 0.001 | |
< 100 | 10 | 0.74 | 0.15 to 1.33 | 0.014 | 87.7 | < 0.001 | |
Mean age (years) | |||||||
≥ 60.0 | 2 | 2.87 | −1.95 to 7.70 | 0.243 | 96.6 | < 0.001 | |
< 60.0 | 9 | 0.52 | −0.61 to 1.65 | 0.364 | 98.5 | < 0.001 | |
Patients’ status | |||||||
ARDS | 6 | 1.28 | 0.34 to 2.21 | 0.007 | 90.4 | < 0.001 | |
ALI | 7 | 0.13 | −1.13 to 1.40 | 0.834 | 98.6 | < 0.001 | |
ARDS/ALI | 1 | −0.37 | −0.93 to 0.20 | 0.201 | – | – | |
Specimen source | |||||||
Blood | 9 | 0.67 | −0.50 to 1.85 | 0.262 | 98.3 | < 0.001 | |
BALF | 8 | 0.78 | 0.08 to 1.48 | 0.029 | 86.1 | < 0.001 | |
IL-10 | Sample size | ||||||
≥ 100 | 2 | −0.90 | −7.01 to 5.21 | 0.772 | 99.6 | < 0.001 | |
< 100 | 5 | 1.89 | 0.59 to 3.19 | 0.004 | 93.4 | < 0.001 | |
Mean age (years) | |||||||
≥ 60.0 | 0 | – | – | – | – | – | |
< 60.0 | 6 | 1.29 | −0.75 to 3.32 | 0.216 | 98.6 | < 0.001 | |
Patients’ status | |||||||
ARDS | 3 | 1.62 | 0.05 to 3.19 | 0.043 | 91.7 | < 0.001 | |
ALI | 4 | 0.73 | −2.15 to 3.61 | 0.618 | 99.0 | < 0.001 | |
Specimen source | |||||||
Blood | 4 | 0.18 | −2.64 to 3.00 | 0.899 | 99.0 | < 0.001 | |
BALF | 4 | 1.90 | 0.12 to 3.68 | 0.037 | 94.3 | < 0.001 | |
PAI‑1 | Sample size | ||||||
≥ 100 | 3 | 0.42 | −0.78 to 1.61 | 0.497 | 98.8 | < 0.001 | |
< 100 | 4 | 0.89 | 0.52 to 1.27 | < 0.001 | 42.1 | 0.159 | |
Mean age (years) | |||||||
≥ 60.0 | 1 | 0.31 | −0.35 to 0.96 | 0.363 | – | – | |
< 60.0 | 6 | 0.77 | −0.04 to 1.57 | 0.063 | 97.6 | < 0.001 | |
Patients’ status | |||||||
ARDS | 2 | 0.68 | 0.06 to 1.29 | 0.030 | 61.1 | 0.109 | |
ALI | 4 | 0.77 | −0.54 to 2.08 | 0.250 | 98.1 | < 0.001 | |
ARDS/ALI | 1 | 0.66 | 0.45 to 0.87 | < 0.001 | – | – | |
Specimen source | |||||||
Blood | 6 | 0.44 | −0.34 to 1.22 | 0.267 | 97.2 | < 0.001 | |
BALF | 3 | 1.57 | 0.77 to 2.36 | < 0.001 | 69.6 | 0.037 | |
TNF‑α | Sample size | ||||||
≥ 100 | 4 | 1.66 | −0.10 to 3.43 | 0.065 | 98.3 | < 0.001 | |
< 100 | 12 | 0.76 | 0.27 to 1.24 | 0.002 | 85.5 | < 0.001 | |
Mean age (years) | |||||||
≥ 60.0 | 3 | 0.51 | 0.17 to 0.84 | 0.003 | 0.0 | 0.482 | |
< 60.0 | 10 | 1.36 | 0.52 to 2.20 | 0.002 | 96.0 | < 0.001 | |
Patients’ status | |||||||
ARDS | 9 | 1.05 | 0.11 to 1.99 | 0.028 | 94.7 | < 0.001 | |
ALI | 5 | 0.90 | −0.14 to 1.95 | 0.090 | 95.1 | < 0.001 | |
ARDS/ALI | 2 | 0.92 | −0.14 to 1.97 | 0.089 | 86.5 | 0.007 | |
Specimen source | |||||||
Blood | 9 | 1.00 | 0.12 to 1.89 | 0.026 | 95.7 | < 0.001 | |
BALF | 10 | 0.91 | 0.26 to 1.57 | 0.006 | 87.6 | < 0.001 |