Interleukin-8 concentrations in obstructive sleep apnea syndrome: a systematic review and meta-analysis

Figures & data

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

Author, year	Country	Ethnicity	Ages (mean± SD)		BMI (kg/m^2)		AHI(events/h)		n		Sample
			OSA	Control	OSA	Control	OSA	Control	OSA	Control
Ohga E [31]	Japan	Asian	47.8 ± 2.2	48.9 ± 2.9	29.4 ± 1.4	28.4 ± 1.4	38.9 ± 3.1	3.1 ± 0.4	20	10	Serum
Alzoghaibi [17]	Saudi Arabia	Caucasian	49.5 ± 2.2	30.7 ± 1.5	36.3 ± 1.5	23.4 ± 0.7	73.5 ± 6.9	NA	25	17	Serum
Ryan S(mild to moderate), [32]	Ireland	Caucasian	42 ± 8	41 ± 8	32.9 ± 6.03	30.7 ± 3.1	15.9 ± 7.7	1.2 ± 1.0	35	30	Serum
Ryan S(severe) [32]	Ireland	Caucasian	43 ± 9	41 ± 8	32.1 ± 3.5	30.7 ± 3.1	56.6 ± 20.9	1.2 ± 1.0	31	30	Serum
Devouassoux G [25]	France	Caucasian	54 ± 11	45 ± 7	28.7 ± 5.4	18.2 ± 3.7	NA	NA	57	13	Sputum
Borel JC [21]	France	Caucasian	57 ± 10	56 ± 10	41.0 ± 5.2	40.9 ± 5.1	57 ± 54	NA	14	39	Serum
Carpagnano GE(obesity) [23]	Italy	Caucasian	47.3 ± 13.2	45.9 ± 9.9	42.6 ± 6.8	34.5 ± 5.5	48.8 ± 23.1	3.9 ± 1.0	12	10	Plasma
Carpagnano GE(non-obesity) [23]	Italy	Caucasian	53.9 ± 11.8	42 ± 4	25.9 ± 1.5	24.6 ± 2.6	37.5.04 ± 11.8	3.2 ± 0.9	10	8	Plasma
Kim J(moderate) [28]	Korea	Asian	38 ± 15.04	26 ± 6.91	24.43 ± 2.45	23.88 ± 2.3	14.4 ± 4.07	1.25 ± 1.25	9	22	Serum
Kim J(severe), [28]	Korea	Asian	42 ± 10.77	26 ± 6.91	28.69 ± 4.05	23.88 ± 2.3	52.71 ± 22.23	1.25 ± 1.25	28	22	Serum
Bouloukaki I [22]	Greece	Caucasian	48.5 ± 8.55	47.9 ± 7.9	32.4 ± 3.74	32.6 ± 3.21	48.09 ± 26.39	NA	31	15	Serum
Wang Y [39]	China	Asian	58.6 ± 5.9	60.5 ± 5.2	31.4 ± 2.1	30.4 ± 2.1	34.04 ± 14.76	1.74 ± 1.48	47	28	BAL fluid
Thunstrom E(non-obesity) [36]	Sweden	Caucasian	65.3 ± 7.1	61.4 ± 9.5	26.8 ± 2.1	25.2 ± 2.5	28.9 ± 13.7	3.1 ± 1.3	234	95	Serum
Thunstrom E(obesity) [36]	Sweden	Caucasian	62.9 ± 8.6	61.4 ± 9.5	33.5 ± 3.3	25.2 ± 2.5	31.5 ± 16.2	3.1 ± 1.3	110	95	Serum
Archontogeorgis K [18]	Greece	Caucasian	51.78 ± 11.55	51.40 ± 16.24	36.34 ± 13.18	33.73 ± 5.68	28.6 ± 11.2	NA	64	20	Serum
Taillé C [34]	France	Caucasian	51.2 ± 2.5	44.6 ± 2.2	29.6 ± 1.4	27.2 ± 0.8	14.2 ± 1.6	2.0 ± 0.2	14	11	Sputum
Vicente E [37]	Spain	Caucasian	45.41 ± 15.07	45.07 ± 11.77	30.08 ± 5.12	28.08 ± 4.63	28.12 ± 24.11	NA	89	26	Plasma/ pharyngeal lavage
Jin F [27]	China	Asian	55.28 ± 7.13	56.13 ± 6.21	26.75 ± 3.50	25.19 ± 2.44	38.01 ± 8.04	3.62 ± 1.54	100	50	Serum
Santamaria-Martos F(mild) [33]	Spain	Caucasian	57.59 ± 16.52	44.42 ± 11.39	28.05 ± 4.28	24.88 ± 3.22	9.35 ± 3.75	1.88 ± 1.73	109	132	Serum
Santamaria-Martos F(moderate to severe), [33]	Spain	Caucasian	65.06 ± 12.38	44.42 ± 11.39	28.68 ± 3.97	24.88 ± 3.22	28.75 ± 15.68	1.88 ± 1.73	119	132	Serum
Ming H [30]	China	Asian	51.34 ± 5.16	52.18 ± 4.51	27.01 ± 1.04	26.88 ± 1.12	31.15 ± 9.12	4.34 ± 2.01	684	192	Serum
Zhang D [40]	China	Asian	40.39 ± 9.58	37.73 ± 10.52	27.73 ± 2.93	24.41 ± 2.86	33.24 ± 32.65	1.16 ± 0.92	21	10	Nasal lavage
Bhatt SP [19]	India	Asian	10.71 ± 3.0	11.87 ± 2.66	27.1 ± 6.53	27.40 ± 4.88	8.45 ± 10.82	0.68 ± 1.13	190	57	Serum
Bilal N(mild) [20]	Turkey	Caucasian	42.7 ± 14.25	42.53 ± 9.81	30.65 ± 6.98	29.09 ± 4.52	9.70 ± 2.77	2.62 ± 1.34	10	30	Serum
Bilal N(moderate) [20]	Turkey	Caucasian	47 ± 9.63	42.53 ± 9.81	30.66 ± 7.76	29.09 ± 4.52	20.24 ± 4.40	2.62 ± 1.34	10	30	Serum
Bilal N(severe) [20]	Turkey	Caucasian	43 ± 7.42	42.53 ± 9.81	29.93 ± 3.71	29.09 ± 4.52	44.01 ± 10.07	2.62 ± 1.34	10	30	Serum
Tam CS [35]	Australia	Caucasian	7.3 ± 3.7	7.6 ± 4	19.4 ± 5.5	17.9 ± 3.9	3.6 ± 3.4	NA	44	69	Serum
Li AM [29]	China	Asian	11.02 ± 3.36	10.55 ± 3.46	NA	NA	17.71 ± 20.80	NA	47	95	Serum
Smith DF(mild) [8]	America	Caucasian	9.6 ± 2.5	9.7 ± 2.5	20.7 ± 4.6	19.4 ± 4.4	3.5 ± 1.1	0.4 ± 0.3	23	90	Plasma
Smith DF(moderate to severe) [8]	America	Caucasian	9.0 ± 2.7	9.7 ± 2.5	23.4 ± 13.5	19.4 ± 4.4	15.2 ± 11.7	0.4 ± 0.3	42	90	Plasma
Hirsch D [26]	Australia	Caucasian	10.0 ± 1.7	10.7 ± 1.2	NA	NA	12.1 ± 10.7	NA	23	17	Serum
Chen VG [24]	Brazil	Latino	7.5 ± 1.5	8.5 ± 1.4	NA	NA	NA	NA	17	17	Tonsil tissue
Wang W [38]	China	Asian	6.58 ± 0.61	5.69 ± 0.78	21.61 ± 2.28	18.98 ± 1.74	33.49 ± 5.6	1.16 ± 0.22	22	20	Plasma

Figure 1. Flow diagram of literature selecting process and results

Figure 2. Forest plot of random-effects analysis of IL-8 levels in the overall patients

Table 2. Subgroup analysis for serum and plasma levels of interleukin-8

Categories	Subgroup analysis	SMD (95%CI)	p-Value	I^2	Ph	meta-analysis model
Serum level	Overall	0.915(0.418,1.411)	<0.001	96.9%	<0.001	Random‐effects model
	Age
	Children	0.445(0.214,0.689)	0.01	0%	0.646	Fixed‐effect model
	Adult	1.013(0.437,1.587)	<0.001	97.2%	<0.001	Random‐effects model
	Ethnicity
	Asian	1.573(0.240,2.905)	0.021	98.6%	<0.001	Random‐effects model
	Caucasian	0.558(0.237,0.877)	0.001	87.7%	<0.001	Random‐effects model
	Mean BMI (kg/m^2)
	≤30	1.137(0.429,1.844)	<0.001	98.0%	<0.001	Random‐effects model
	>30	0.568(0.052,1.084)	0.031	87.5%	<0.001	Random‐effects model
	Mean AHI (events/h)
	≤30	0.275(0.077,0.473)	0.007	67.1%	<0.001	Random‐effects model
	>30	2.064(0.791,3.337)	0.001	98.4%	<0.001	Random‐effects model
	Total number of participants
	>100	1.883(0.925,2.841)	<0.001	98.8%	<0.001	Random‐effects model
	≤100	0.461(−0.020,0.950)	0.064	90.1%	<0.001	Random‐effects model
Plasma level	Overall	0.748(0.308,1.189)	0.001	82.3%	<0.001	Random‐effects model
	Age
	Children	0.440(0.120,0.760)	0.007	58.4%	0.048	Random‐effects model
	Adult	1.832(0.521,3.144)	0.006	91.0%	<0.001	Random‐effects model
	Ethnicity
	Asian	NA	NA	NA	NA
	Caucasian	0.837(0.345,1.328)	0.001	84.2%	<0.001	Random‐effects model
	Mean BMI (kg/m^2)
	≤30	0.589(0.177,1.001)	0.005	79.7%	<0.001	Random‐effects model
	>30	NA	NA	NA	NA
	Mean AHI (events/h)
	≤30	0.660(0.297,1.022)	<0.001	39.3%	0.193	Random‐effects model
	>30	0.936(0.240,1.631)	0.008	87.4%	<0.001	Random‐effects model

Figure 3. Meta-analysis for the association between serum IL-8 levels and OSAS: subgroup analysis by age

Figure 4. Meta-analysis for the association between serum IL-8 levels and OSAS: subgroup analysis by mean BMI

Figure 5. Meta-analysis for the association between serum IL-8 levels and OSAS: subgroup analysis by ethnicity

Figure 6. Meta-analysis for the association between serum IL-8 levels and OSAS: subgroup analysis by total number of participants

Figure 7. Meta-analysis for the association between serum IL-8 levels and OSAS: subgroup analysis by mean AHI

Table 3. Meta-regression analysis of variables predicting serum and plasma levels of IL-8

Age	R	Adjusted R^2	p
Serum	0.696	−0.049	0.749
Plasma	1.463	0.019	0.24
Mean BMI of OSAS	R	Adjusted R^2	p
Serum	−1.21	0.005	0.347
Plasma	1.775	0.952	0.205
Mean AHI of OSAS	R	Adjusted R^2	p
Serum	0.657	0.003	0.308
Plasma	0.691	0.404	0.625
Ethnicity	R	Adjusted R^2	p
Serum	0.458	−0.029	0.495
Plasma	−0.987	−0.352	0.638
Number of participants	R	Adjusted R^2	p
Serum	1.657	0.029	0.208
Plasma	NA	NA	NA

Table

Author	Selection				Comparability	Exposure			Score
	Case definition	Representativeness	Control selection	Control definition	Comparability in the design/statistical analysis of case and control	Ascertainment of exposure	Same method of ascertainment for cases and controls	Non-Response rate
Ohga E [31]	1	1	0	1	1	1	1	1	7
Alzoghaibi [17]	1	1	0	1	1	1	1	1	7
Ryan S [32]	1	1	0	1	2	1	1	1	8
Devouassoux G [25]	1	1	0	1	1	1	1	1	7
Borel JC [21]	1	1	1	1	1	1	1	1	8
Carpagnano GE [23]	1	1	1	1	1	1	1	1	8
Kim J [28]	1	1	1	1	2	1	1	1	9
Bouloukaki I [22]	1	1	1	1	1	1	1	1	8
Wang Y [39]	1	1	1	1	2	1	1	0	8
Thunstrom E [36]	1	1	0	1	1	1	1	1	7
Archontogeorgis K [18]	1	1	0	1	1	1	1	1	7
Taillé C [34]	1	1	1	1	1	1	1	1	8
Vicente E [37]	1	1	1	1	1	1	1	1	8
Jin F [27]	1	1	0	1	1	1	1	1	7
Santamaria-Martos F [33]	1	1	0	1	1	1	1	1	7
Ming H [30]	1	1	0	1	1	1	1	1	7
Zhang D [40]	1	1	0	1	2	1	1	1	8
Bhatt SP [19]	1	1	0	1	1	1	1	1	7
Bilal N [20]	1	1	1	1	1	1	1	1	8
Tam CS [35]	1	1	1	1	1	1	1	1	8
Li AM [29]	1	1	0	1	1	1	1	1	7
Smith DF [8]	1	1	0	1	1	1	1	1	7
Hirsch D [26]	1	1	0	1	1	1	1	1	7
Chen VG [24]	1	1	0	1	1	1	1	1	7
Wang W [38]	1	1	0	1	1	1	1	1	7

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Data availability statement

All relevant data in the study are included in the article/supplementary material. Further inquiries could be directed to the corresponding author.