Defining the role of neutrophil-to-lymphocyte ratio in COPD: a systematic literature review

Figures & data

Table 1 Characteristics of included articles and population

Author, year	Study design	Age, years (SD)	Gender		Number of patients
			Male	Female	Control	COPD			Total patients
						Stable	Exacerbated	Total COPD
Günay et al, 2014^Citation22	Retrospective	65.76 (7.62)	216	103	50	178	91	269	319
Tanrıverdi et al, 2015^Citation36	Prospective	71.70 (9.50)	56	21	–	–	77	77	77
Sørensen et al, 2015^Citation29	Prospective	70.13 (3.16)	191	195	–	386	–	386	386
Taylan et al, 2015^Citation10	Retrospective	63.97 (11.60)	117	63	80	100	100	100	180
Saltürk et al, 2015^Citation19	Retrospective	67.75 (6.05)	523	124	–	647	647	647	647
Duman et al, 2015^Citation20	Retrospective	70.50 (4.90)	1,116	588	–	1,704	1,704	1,704	1,704
Kurtipek et al, 2015^Citation9	Prospective	64.66 (9.79)	94	0	–	48	46	94	94
Bilir et al, 2016^Citation23	Retrospective	54.90 (13.97)	519	98	215	216	186	402	617
Furutate et al, 2016^Citation30	Prospective	71.20 (7.46)	137	4	–	141	49	141	141
In et al, 2016^Citation24	Retrospective	65.67 (9.17)	112	31	40	56	47	103	143
Duyar, 2016^Citation31	Retrospective	67 (NS)	39	0	–	39	–	39	39
van de Geijn et al, 2016^Citation32	Retrospective	67.55 (2.45)	22	18	–	17	23	40	40
Lee et al, 2016^Citation33	Prospective	70.85 (7.70)	809	76	–	885	233	885	885
Lee et al, 2016^Citation25	Prospective	70.4 (6.13)	139	9	28	61	59	120	148
Yousef and Alkhiary, 2017^Citation26	Prospective	48.9 (8.29)	188	0	60	60	68	128	188
Xiong et al, 2017^Citation27	Prospective	69.65 (7.15)	252	412	296	368	–	368	664
Rahimirad et al, 2017^Citation37	Retrospective	69.89 (10.87)	174	141	–	–	315	315	315
Kumar et al, 2017^Citation21	Retrospective	71 (10)	93	88	–	181	181	181	181
Mohamed-Hussein et al, 2017^Citation34	Retrospective	58.1 (16.95)	107	41	–	74	74	148	148
Yao et al, 2017^Citation38	Retrospective	61 (10)	200	103	–	–	303	303	303
Farah et al, 2017^Citation28	Prospective	58.1 (10.70)	72	28	15	13	72	85	100
Acartürk et al, 2017^Citation35	Retrospective	66 (13)	636	430	–	993	73	1,066	1,066

Note: Values are given as geometric mean ± SD.

Abbreviation: NS, not specified.

Figure 1 Flowchart of the systematic review.

Table 2 Study quality assessment using the Newcastle-Ottawa scale

Studies	Selection	Comparability	Outcome	Total stars
Cohort studies
Sørensen et al, 2015^Citation29	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Saltürk et al, 2015^Citation19	⋆⋆⋆⋆	⋆	⋆⋆⋆	8
Duman et al, 2015^Citation20	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Lee et al, 2016^Citation33	⋆⋆⋆⋆	⋆⋆	⋆⋆	8
Kumar et al, 2017^Citation21	⋆⋆⋆⋆	⋆	⋆⋆⋆	8
Studies	Selection	Comparability	Exposure	Total stars
Cross-sectional studies
Tanrıverdi et al, 2015^Citation36	⋆⋆⋆	⋆	⋆⋆⋆	7
Kurtipek et al, 2015^Citation9	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Bilir et al, 2016^Citation23	⋆⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	10
Furutate et al, 2016^Citation30	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Duyar, 2016^Citation31	⋆⋆	–	⋆⋆⋆	5
Acartürk et al, 2017^Citation35	⋆⋆⋆⋆	⋆	⋆⋆⋆	8
Studies	Selection	Comparability	Exposure	Total stars
Case-control studies
Günay et al, 2014^Citation22	⋆⋆⋆⋆	⋆	⋆⋆⋆	8
Taylan et al, 2015^Citation10	⋆⋆⋆⋆	⋆⋆	⋆⋆	8
In et al, 2016^Citation24	⋆⋆⋆⋆	⋆	⋆⋆⋆	8
van de Geijn et al, 2016^Citation32	⋆⋆⋆	⋆	⋆⋆⋆	7
Lee et al, 2016^Citation25	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Yousef and Alkhiary, 2017^Citation26	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Xiong et al, 2017^Citation27	⋆⋆⋆⋆	⋆⋆	⋆⋆⋆	9
Rahimirad et al, 2017^Citation37	⋆⋆⋆	⋆⋆	⋆⋆⋆	8
Mohamed-Hussein et al, 2017^Citation34	⋆⋆⋆	–	⋆⋆⋆	6
Yao et al, 2017^Citation38	⋆⋆⋆	⋆	⋆⋆⋆	7
Farah et al, 2017^Citation28	⋆⋆⋆	⋆	⋆⋆⋆	7

Table 3 NLR value of healthy controls, and stable and exacerbated COPD patients

Author, year	NLR, mean (SD)
	Control	Stable COPD	Exacerbated COPD	P-value
Günay et al, 2014^Citation22	1.71 (0.41)	2.59 (1.05)	4.28 (2.38)	<0.001
Tanrıverdi et al, 2015^Citation36	–	–	18.5 (16.60)	–
Sørensen et al, 2015^Citation29	–	3.08 (0.76)	–	–
Taylan et al, 2015^Citation10	1.7 (0.90)	3.1 (2.50)	7.1 (5.40)	<0.001
Saltürk et al, 2015^Citation19	–	5.86 (1.80)	9.45 (2.80)	–
Duman et al, 2015^Citation20	–	5.18 (1.39)	6.12 (1.73)	–
Kurtipek et al, 2015^Citation9	–	2.75 (1.11)	7.99 (5.72)	0.001
Bilir et al, 2016^Citation23	1.9 (0.66)	2.41 (2.90)	4.22 (2.51)	<0.001
Furutate et al, 2016^Citation30	–	2.56 (0.23)	–	<0.001
In et al, 2016^Citation24	1.68 (0.41)	2.67 (1.13)	5.78 (3.14)	<0.05
Duyar, 2016^Citation31	–	2.14 (0.40)	–	–
van de Geijn et al, 2016^Citation32	–	3.08 (1.51)	5.89 (4.92)	<0.001
Lee et al, 2016^Citation33	–	2.4 (0.27)	–	–
Lee et al, 2016^Citation25	1.4 (0.50)	2.4 (0.70)	12.4 (10.60)	<0.001
Yousef and Alkhiary, 2017^Citation26	1.45 (0.21)	2.36 (0.55)	4.44 (1.61)	<0.001
Xiong et al, 2017^Citation27	2.02 (1.92)	2.98 (1.89)	–	–
Rahimirad et al, 2017^Citation37	–	–	10.22 (11.19)	–
Kumar et al, 2017^Citation21	–	–	10 (9)	–
Mohamed-Hussein et al, 2017^Citation34	–	1.2 (0.70)	3.7 (0.30)	<0.05
Yao et al, 2017^Citation38	–	–	7.92 (8.79)	–
Farah et al, 2017^Citation28	1.9 (0.60)	3.8 (2.20)	6.3 (5.40)	<0.001

Note: Values are given as geometric mean ± SD.

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

Figure 2 Neutrophil-to-lymphocyte ratio in healthy controls, and stable and exacerbated COPD patients.

Note: Box plots represent median, interquartile range, and range with outliers plotted separately.

Table 4 Accuracy data of NLR for detecting COPD global and bacterial infection exacerbation

Author, year	Cut-off	Sensitivity (%)	Specificity (%)	AUC (95% CI)
Kurtipek et al, 2015^Citation9,a	3.30	87	82	0.88 (NS)
Tanrıverdi et al, 2015^Citation36,b	11.50	61	52	0.58 (0.45–0.71)
Taylan et al, 2015^Citation10,a	3.29	80.80	77.70	0.89 (0.84–0.94)
Bilir et al, 2016^Citation23,a	3.35	69	59	0.68 (0.63–0.73)
In et al, 2016^Citation24,a	3.34	78.70	73.20	0.86 (0.79–0.93)
van de Geijn et al, 2016^Citation32,b	4.52	91	46	0.75 (0.60–0.91)
Yousef and Alkhiary, 2017^Citation26,a	3.12	86.70	76.70	0.88 (0.90–1.00)
Mohamed-Hussein et al, 2017^Citation34,a	1.50	93	90	0.68 (0.54–0.81)
Farah et al, 2017^Citation28,b	7.30	76.80	73.10	0.79 (NS)
Acartürk et al, 2017^Citation35,a	3.54	78	69	–

Notes:

a NLR for detecting COPD global exacerbation

b NLR for detecting COPD bacterial infection exacerbation.

Abbreviations: AUC, area under the curve; NLR, neutrophil-to-lymphocyte ratio; NS, not specified.

Table 5 Correlation data between NLR and FEV₁

Author, year	Correlation coefficient	P-value
Furutate et al, 2016^Citation30	Rho=−0.387	<0.001
In et al, 2016^Citation24	r=−0.288	0.003
Lee et al, 2016^Citation33	r=−0.176	<0.001
Lee et al, 2016^Citation25	r=−0.285	0.071
Yousef and Alkhiary, 2017^Citation26	r=−0.176	<0.001
Mohamed-Hussein et al, 2017^Citation34	Rho=−0.498	<0.01

Abbreviations: r, Pearson’s correlation coefficient; Rho, Spearman’s rank correlation coefficient; NLR, neutrophil-to-lymphocyte ratio.

Table 6 NLR during stable and exacerbation periods according to GOLD stage

Author, year	Group	GOLD 1	GOLD 2	GOLD 3	GOLD 4	P-value
Günay et al, 2014^Citation22	Stable	2.44 (1.19)	2.90 (2.00)	2.46 (1.41)	3.16 (4.87)	0.254
	Exacerbation	2.29 (4.39)	4.28 (3.51)	4.35 (4.26)	6.15 (5.38)	0.178
Bilir et al, 2016^Citation23	Stable	1.64 (1.60)	2.33 (2.09)	2.60 (3.58)	2.66 (3.86)	<0.001
	Exacerbation	6.19 (2.94)	4.18 (4.48)	3.47 (3.53)	6.29 (6.38)	0.028
Duyar, 2016^Citation31	Stable	1.81 (0.33)		2.57 (0.34)		0.091

Note: Values are given as geometric mean ± SD.

Table 7 Correlation between NLR and other inflammatory parameters in COPD patients

Correlation	Author/year	COPD
		Stable	Exacerbated	Total
NLR/CRP	Günay et al, 2014^Citation22	Rho=0.485, P<0.001	Rho=0.665, P<0.001	–
	Taylan et al, 2015^Citation10	–	r=0.415, P<0.001	–
	Kurtipek et al, 2015^Citation9	–	r=0.512, P<0.001	–
	Bilir et al, 2016^Citation23	Rho=0.436, P<0.001	Rho=0.534, P<0.001	–
	Furutate et al, 2016^Citation30	Rho=0.209, P=0.015	–	–
	In et al, 2016^Citation24	–	–	r=0.641, P<0.001
	Yousef and Alkhiary, 2017^Citation26	–	r=0.609, P<0.000	–
	Yao et al, 2017^Citation38	–	r=0.281, P<0.001	–
	Farah et al, 2017^Citation28	–	–	r=0.556, P<0.000
NLR/ESR	Taylan et al, 2015^Citation10	–	r=0.275, P=0.035	–
	In et al, 2016^Citation24	–	–	r=0.276, P=0.005
	Yousef and Alkhiary, 2017^Citation26	–	r=0.714, P<0.000	–
	Mohamed-Hussein et al, 2017^Citation34	–	Rho=0.558, P<0.01	–
NLR/WBC	Taylan et al, 2015^Citation10	–	r=0.304, P=0.002	–
	Yousef and Alkhiary, 2017^Citation26	–	r=0.694, P<0.000	–
	Mohamed-Hussein et al, 2017^Citation34	–	Rho=0.330, P<0.01	–

Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; NLR, neutrophil-to-lymphocyte ratio; Rho, Spearman’s rank correlation coefficient; r, Pearson’s correlation coefficient; WBC, white blood cell.

Table 8 Predictive value of NLR in COPD patients’ mortality based on multivariate analysis

Author, year	Cut-off	Odds ratio	95% CI	P-value	Event
Saltürk et al, 2015^Citation19	NLR ≥16	1.96	1.13–3.39	0.016	In-hospital mortality (respiratory failure)
Duman et al, 2015^Citation20	NLR ≥7	1.79	1.37–2.34	0.001	Late mortality (within 6 months)
Xiong et al, 2017^Citation27	NLR ≥3.3	3.95	2.54–6.38	<0.001	Late mortality (within 24 months)
Rahimirad et al, 2017^Citation37	NLR ≥4	3.586	1.69–7.60	0.001	In-hospital mortality
Kumar et al, 2017^Citation21	–	0.95	0.84–1.08	0.46	Early mortality (at 90 days after hospital admission)

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

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