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Table 1 Characteristics of studies included in the meta-analysis Study

From: Association between tumor necrosis factor alpha and obstructive sleep apnea in adults: a meta-analysis update

Study Year Country Sample size Sample mean age Gender (male/female) BMI (kg/m2) TNF (pg/ml) NOS
Case Control Case Control Case Control Case Control Case Control
Ming 2019 China 876 684 192 51.34 ± 5.16 52.18 ± 4.51 446/238 128/64 24.1 to 30.5 NR 31.2 ± 5.3 12.1 ± 1.1 9
Sundbom 2018 Sweden 333 109 224 55.6 ± 8.8 47.7 ± 11.3 0/109 0/224 28.2 ± 4.8 25.4 ± 4.1 Mean (95%CI) 2.1 (1.8, 2.4) Mean (95%CI) 2.0 (1.8, 2.2) 7
Bhatt 2018 India 240 47 (without NAFLD) 25 (without NAFLD) 44.2 ± 9.1 41 ± 8.5 25/22 17/8 32.5 ± 6.9 28.5 ± 8.6 Log (3.6 ± 0.14) Log(2.86 ± 0.2) 8
124 (with NAFLD) 44 (with NAFLD) 44.8 ± 9.1 39.5 ± 10.5 64/60 26/18 33.3 ± 7.9 31.0 ± 8.3 Log (3.86 ± 0.18) Log(3.2 ± 0.06)
Kong 2018 China 90 50 (Mild 10, Moderate 15, Severe 25) 40 54.34 ± 14.38 (Mild 59.60 ± 15.13, Moderate 56.73 ± 15.93, Severe 52.27 ± 13.54) 50.42 ± 8.35 34/16 31/9 26.86 ± 3.12 (Mild 27.04 ± 2.58, Moderate 26.81 ± 3.80, Severe 27.28 ± 3.16) 22.26 ± 3.54 327.34 ± 46.81 (Mild 274.64 ± 4.91, Moderate 308.75 ± 42.48, Severe 341.28 ± 44.80) 307.95 ± 27.15 7
Bozic 2018 Croatia 75 50 (Moderate 25, Severe 25) 25 Moderate 53.92 ± 10.75, Severe 52.04 ± 13.11 52.52 ± 10.18 50/0 25/0 Moderate 28.42 ± 2.57, Severe 29.30 ± 2.74 27.78 ± 2.23 Moderate 5.79 ± 1.44, Severe 8.67 ± 2.41 2.35 ± 1.25 7
Ugur 2018 Turkey 108 63 45 median (range) 46 (20–81) median (range) 45 (20–70) NR NR median (range) 25 (17–49) median (range) 24.8 (15–33) median (range) 2710 (80–59,520) median (range) 660 (80–23,140) 8
Heizati 2017 China 159 28 54 44.00 ± 8.26 44.94 ± 8.33 28/0 54/0 26.09 ± 1.75 25.30 ± 1.79 median (interquartile) 0.302 (0.177–0.436) median (interquartile) 0.298 (0.182–0.481) 8
40 (obese) 37 (obese) 44.40 ± 8.47 47.35 ± 6.75 40/0 37/0 30.69 ± 2.03 30.30 ± 1.97 median (interquartile) 0.281 (0.149–0.470) median (interquartile) 0.281 (0.185–0.426)
Jin 2017 China 150 100 50 55.284 ± 7.128 56.131 ± 6.210 82/18 37/13 26.746 ± 3.500 25.196 ± 2.449 37.67 ± 0.21 29.15 ± 1.74 6
Hirotsu 2017 Brazil 1042 193 275 47.0 ± 1.0 36.2 ± 0.8 193/0 275/0 29.0 ± 0.4 24.9 ± 0.2 10.91 ± 0.44 10.84 ± 0.38 5
149 425 55.7 ± 1 39.5 ± 0.6 0/149 0/425 30.4 ± 0.5 25.8 ± 0.2 10.95 ± 0.52 9.2 ± 0.29
Tirado* 2017 Spain 66 Mild 20, Moderate 16, severe 30 NO Mild 35.8 ± 8.43 Moderate 45.6 ± 9.08 Severe 44.5 ± 11.0 NO Mild 2/18, Moderate 2/14, Severe 8/22 NO Mild 46.3 ± 7.05, Moderate 43.1 ± 4.43, Severe 46.4 ± 6.18 NO Mild 2.33 ± 0.72, Moderate 3.57 ± 2.55, Severe 2.33 ± 1.04 NO 5
Gamsiz-Isik 2016 Turkey 163 83 (Mild 16, Moderate to severe 67) 80 46.87 ± 8.21 44.23 ± 9.83 65/18 57/23 30.91 ± 3.31 31.53 ± 3.44 11.5 ± 3.11 (Mild 11.5 ± 4.60, Moderate to severe 10.3 ± 2.59) 11.25 ± 4.0 6
Vicente 2016 Spain 115 89 (Mild to Moderate 42 Severe 47) 26 median (interquartile) 44(36–56) median (interquartile) 44(38–53) 62/27 16/10 median (interquartile)29.1 (27.1, 33.9) median (interquartile) 27.9 (25.2, 31.1) median (interquartile) Mild to Moderate: Plasma 4.54 (4.09–5.25), Lavage 1.8 (1.1–3.2); Severe: Plasma 4.46 (4.21–5.06), Lavage 2.1 (1.7–4.2) median (interquartile) Plasma 4.35 (4.01–4.99); Lavage 1.2 (0.8–2.1) 5
Ifergane 2016 Israel 43 21 22 66.0 ± 9.9 66.1 ± 13.1 8/13 5/17 29.6 ± 4.3 26.8 ± 4.3 6.39 ± 5.00 3.57 ± 1.87 5
Nizam 2015 Turkey 52 39 (Mild to Moderate 17, Severe 22) 13 Mild to Moderate 49.88 ± 11.47, Severe 45.36 ± 9.81 43.23 ± 9.08 Mild to Moderate 9/8, Severe 18/4 5/8 Mild to Moderate 31.85 ± 5.32 Severe34.18 ± 7.24 31.71 ± 4.56 Mild to Moderate: Serum 86.7 ± 40.5, Saliva 10.6 ± 10.1; Severe Serum 99.5 ± 64.63, Saliva 10.2 ± 9.8 Serum 91.3 ± 64.6; Saliva 6.8 ± 2.2 9
Leon-Cabrera 2015 Mexico 39 29 10 37.2 ± 11.4 43.4 ± 11.5 4/25 8/2 45.2 ± 8.4 23.6 ± 2.1 337.9 ± 67.8 270.2 ± 31.7 9
Jiang 2015 China 229 135 94 48.7 ± 12.1 47.2 ± 13.5 80/55 55/39 27.48 ± 2.56 27.52 ± 2.58 765.77 ± 64.04(Mild 545.36 ± 54.06, Moderate 764.48 ± 63.28; Severe 836.72 ± 71.06) 232.24 ± 31.5 6
Thunström 2015 Sweden 329 Moderate to Severe 234 95 65.3 ± 7.1 61.4 ± 9.5 204/30 71/24 26.8 ± 2.1 25.2 ± 2.5 median (interquartile) 5.0 (3.4–7.0) median (interquartile) 4.2 (3.0–6.0) 8
De Santis 2015 Italy 50 26 24 41.8 ± 7.4 43.7 ± 8.2 17/9 16/8 33.0 ± 5.2 30.8 ± 4.3 122.2 ± 12.0 80.2 ± 18.3 4
Salord 2014 Spain 39 26 13 median (interquartile) 45(39–51) median (interquartile) 39(31–46) 6/20 4/9 median (interquartile) 45.1(42–45) median (interquartile) 44.4(41–47) median (interquartile) 9.8 (8.0, 12.3) median (interquartile) 9.1 (7.5, 11.5) 5
Ciccone 2014 Italy 120 80 (Mild26,moderteto Severe 54) 40 Mild 53.65 ± 11.47, Moderate to Severe 52.33 ± 10.19 52.27 ± 10.52 Mild 23/3, Moderate to Severe 45/9 34/6 Mild 28.13 ± 2.7, Moderate to Severe 28.8 ± 3.03 28.24 ± 2.7 Mild 14.42 ± 3.29, Moderate to Severe 22.83 ± 3.85 12.53 ± 3.48 5
Yadav 2014 UK 41 20 21 49 ± 10 45 ± 9 3/17 5/16 52 ± 6 50 ± 8 median (interquartile) 87.2 (12.4, 133.8) median (interquartile) 15.5 (7.2, 38.2) 6
Chen 2013 China 64 44 (Mild23; Moderate 21) 20 Mild 40 ± 11, Moderate 45 ± 13 42 ± 11 Mild 17/6, Moderate 16/5 15/5 Mild 27.5 ± 4.2, Moderate 26.7 ± 2.8 26 ± 3.3 median (interquartile) Mild 2.8 (0.8, 4.1), Moderate 3.8 (2.5, 9.9) median (interquartile) 1.2 (0.5,1.7) 7
Doufas 2013 USA 48 33 15 median (range) 34(19–54) median (range) 31(19–52) 33/0 15/0 median (range) 26(20–33) median (range) 24(20–32) median (range) 7.88 (5.39, 31.69) median (range) 7.77 (4.57,14.57) 5
Hargens 2013 USA 30 12 (obese) 18 (obese) 22.8 ± 0.8 22.5 ± 0.7 12/0 18/0 32.4 ± 1.0 31.6 ± 1.1 0.95 ± 0.07 0.86 ± 0.05 6
Yang 2013 China 50 25 25 54 ± 7 53 ± 7 23/2 23/2 27.39 ± 2.91 26.27 ± 1.9 12.55 ± 8.09 5.12 ± 1.23 7
Fornadi 2012 Germany 100 25 75 54 ± 12 50 ± 13 20/5 60/15 29 ± 5 26 ± 5 median (interquartile) 2.2 (1.5–2.8) median (interquartile) 1.9 (1.3–2.6) 6
Medeiros 2012 Brazil 65 50 (Mild to Moderate 15; Severe 35) 15 Mild to Moderate 62.62 ± 9, Severe 65 ± 7.2 62.5 ± 8.4 Mild to Moderate 11/4;Severe 20/15 6/9 Mild to Moderate 24.5 ± 3.8, Severe25.9 ± 4.1 25.81 ± 4.04 Mild to Moderate 0.84 ± 1.8, Severe 2.09 ± 7.3 0.32 ± 0.77 6
Qian 2012 China 110 70 (40 with hypertension; 30 without) 40 With hyperten 46.9 ± 7.0, without 45.0 ± 9.0 46.3 ± 8.1 70/0 40/0 With hyperten 28.2 ± 2.5, without 29.4 ± 2.1 24.1 ± 2.3 With hyperten 1290 ± 220, without 1150 ± 370 1140 ± 400 6
Kim 2010 Korea 59 37 (Moderate 9, Severe 28) 22 Moderate 38 ± 15.04, Severe 42 ± 10.77 26 ± 6.91 37/0 22/0 Moderate 24.43 ± 2.45, Severe 28.69 ± 4.05 23.88 ± 2.30 Moderate 14.56 ± 5.61, Severe 15.32 ± 6.8 14.4 ± 4.13 5
Li 2010 China 417 Normotensive 113; hypertension 134 97; 73 45.45 ± 8.63; 46.10 ± 9.41 44.16 ± 8.59; 45.97 ± 9.06 85/28; 101/33 74/23; 54/19 27.84 ± 3.44;28.91 ± 3.24 26.85 ± 3.78;27.7 ± 3.01 19,980 ± 8480; 22,850 ± 8980 13,100 ± 4280; 17,320 ± 7020 8
Steiropoulos 2010 Greece 61 38 23 45.5 ± 10.5 43.7 ± 6.7 33/5 17/6 36.4 ± 7.4 34.5 ± 3.7 6.72 ± 3.72 3.94 ± 1.34 8
Tamaki 2009 Japan 46 33 (Mild to Moderate 13, Severe 20) 13 Mild to Moderate 56.1 ± 8.7, Severe 50.5 ± 12.2 35.5 ± 9.7 Mild to Moderate 11/2, Severe 19/1 12/1 Mild to Moderate 24.6 ± 2.7, Severe 30.7 ± 5.8 23.6 ± 2.6 Mild to Moderate 22,700 ± 4100, Severe 30,200 ± 6900 17,300 ± 4400 6
Sahlman 2009 Finland 124 84 40 50.4 ± 9.3 45.6 ± 11.5 64/20 25/15 32.5 ± 3.3 31.5 ± 3.5 1.54 ± 1.75 1.17 ± 1.58 8
Bhushan 2009 India 207 104 103 46.18 ± 10.7 44 ± 10 84/20 65/38 31.48 ± 4.26 30.94 ± 4.27 Log (3.6 ± 0.8) Log (3.3 ± 0.6) 7
Carneiro 2009 Brazil 29 16 13 40.1 ± 2.8 38.8 ± 3.3 16/0 13/0 46.9 ± 2.0 42.8 ± 1.3 10.7 ± 0.44 7.5 ± 0.44 7
Thomopoulos 2009 Greece 132 62 (hypertension) 70 (hypertension) 48.1 ± 7.6 48.1 ± 3.9 49//13 56/14 31.9 ± 4.9 32.1 ± 3.0 Log(0.33 ± 0.27) Log(0.10 ± 0.23) 5
Li 2009 China 90 68 (Mild 22, Moderate 22, Severe 24) 22 Mild 48 ± 12, Moderate 44 ± 13, Severe 44 ± 8 43 ± 9.3 Mild 15/7, Moderate 18/4, Severe 17/7 14/8 Mild 25.7 ± 4.2, Moderate 28.8 ± 5.3, Severe 28.67 ± 4.2 23.3 ± 2.0 Serum: Mild 102.3 ± 11.3, Moderate 125 ± 11.9, Severe 132.1 ± 10.8 EBC: Mild 96.1 ± 8.2, Moderate 116.7 ± 11.1, Severe 128.2 ± 8.8 Serum: 87.3 ± 6.1; EBC: 83.7 ± 4.1 9
Antonopoulou 2008 Greece 70 45 25 52 ± 12 51 ± 7 37/18 18/7 33.5 ± 7 31 ± 3 1.4 ± 0.9 0.64 ± 0.3 7
Arias 2008 Spain 45 30 15 48 ± 10 52 ± 13 30/0 15/0 30.5 ± 4.0 28.7 ± 4.7 18.5 ± 13.4 11.4 ± 12.2 6
Constantinidis 2008 Greece 51 obses 13; overweighted 11 obses 12; overweighted 15 Mean (range) 45.1 (26–54) Matched 13/0; 11/0 12/0; 15/0 33.4 ± 1.5; 26.1 ± 1.1 34.9 ± 1.8; 27.4 ± 0.8 124.64 ± 96.7;105 ± 88.7 78.8 ± 50.1;48.5 ± 36.7 5
Kanbay 2008 Turkey 138 106 32 51.39 ± 10.37 44.79 ± 13.35 NR NR 31.06 ± 5.87 28.85 ± 5.49 114.15 ± 144.15 34.25 ± 13.1 7
Bravo 2007 Spain 70 with EDS 28; without EDS 22 20 51.3 ± 1.4;52.3 ± 2.4 47.4 ± 1.2 28/0; 22/0 20/0 33.3 ± 1.0; 30.9 ± 1.4 28.4 ± 0.6 0.82 ± 0.11;0.89 ± 0.37 0.42 ± 0.11 7
Kobayashi 2006 Japan 51 35 16 51.4 ± 13.1 41 ± 13.1 30/5 13/3 27.9 ± 3.6 27.4 ± 3.7 1.11 ± 0.46 0.62 ± 0.44 5
Ryan 2006 Ireland 96 66 (Mild to Moderate 35, Severe 31) 30 Mild to Moderate 42 ± 8, Severe 43 ± 9 41 ± 8 Mild to Moderate 35/0, Severe 31/0 30/0 Mild to Moderate 32.9 ± 6.03, Severe 32.1 ± 3.5 30.7 ± 3.1 median (interquartile)
Mild to Moderate 4.15 (2.71,6.05), Severe 6.19(4.9,7.99)
median (interquartile)3.21 (1.91,3.90) 5
Ciftci 2004 Turkey 65 obese 43 obese 22 49.6 ± 9.1 47.2 ± 10.3 43/0 22/0 31.86 ± 4.11 31.03 ± 3.1 4.6 ± 3.39 3.29 ± 2.13 5
Imagawa 2004 Japan 69 24 Severe 45 NR NR NR NR 28.5 ± 3.6 22.9 ± 2.9 AHI 70–89, 28.6 ± 27.9 25 ± 26.4 4
Minoguchi 2004 Japan 36 24 (Mild 12; Moderate to Severe 12) 12 Mild 51 ± 14.8; Moderate to Severe 49.2 ± 11.7 47.5 ± 11.2 Mild 12/0; Moderate to Severe 12/0 12/0 Mild 26.1 ± 1.3; Moderate to Severe 29.1 ± 2.2 22.3 ± 0.9 Mild 104.2 ± 139.2; Moderate to Severe 501.3 ± 378.8 61.7 ± 40.3 6
Teramoto 2003 Japan 80 40 40 NR NR 34/6 NR NR NR 9500 ± 2200 4400 ± 900 3
Alberti 2003 Italy 38 18 20 52.7 ± 12.0 51.3 ± 13.2 13/5 14/6 26.5 ± 2.2 22.1 ± 3.4 9.7 ± 8.5 6.3 ± 3.0 5
Liu 2000 China 38 22 16 47.4 ± 13.6 47.6 ± 14.7 15/7 11/5 27.58 ± 3.28 23.11 ± 2.96 Plasma 299.09 ± 43.57,
PBMC 4165.45 ± 1501.43
Plasma 101.88 ± 21.27,
PBMC 1596.25 ± 403.08
4
Vgotzas 1997 USA 22 12 10 40.9 ± 2.2 24.1 ± 0.8 11/1 10/0 40.5 ± 3.2 24.6 ± 0.7 2.51 ± 0.13 1.17 ± 0.1 4
  1. Abbreviations: NAFLD Non-alcoholic fatty liver disease, EDS Excessive daytime sleepiness, EBC Exhaled breath condensate, PBMC Peripheral blood mononuclear cell, PHAL pharyngeal lavage, GCF gingival crevicular fluid, NR not record, NOS Newcastle-Ottawa Scale
  2. *study without control group, data were only used in subgroup meta-analysis