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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