Neutrophil-to-Lymphocyte Ratio Predicts Clinical Outcome of Severe Acute Exacerbation of COPD in Frequent Exacerbators

Figures & data

Figure 1 Flowchart of the study participants.

Abbreviations: AECOPD, acute exacerbation of chronic obstructive pulmonary disease; NLR, neutrophil-to-lymphocyte ratio; ICU, intensive care unit.

Table 1 Characteristics of Frequent Exacerbators and Non-Frequent Exacerbators During Severe AECOPD

Characteristics	Total (n=604)	Frequent Exacerbators (n=282)	Non-Frequent Exacerbators (n=322)	P value
Age, years	77.00 (67.00–84.00)	78.00 (68.00–84.00)	76.00 (67.00–84.00)	0.127
Male, n (%)	523 (86.59)	247 (87.59)	276 (85.71)	0.500
BMI, kg/m^2	21.91 (19.02–24.75)	21.54 (18.60–24.78)	22.03 (19.36–24.72)	0.630
Current smoker, n (%)	144 (23.84)	58 (20.57)	86 (26.71)	0.077
Comorbidities, n (%)
Diabetes	120 (19.87)	56 (19.86)	64 (19.88)	0.996
Hypertension	321 (53.15)	160 (56.74)	161 (50.00)	0.098
NYHA≥3	95 (15.73)	47 (16.66)	48 (14.91)	0.553
Arrhythmia	130 (21.52)	72 (25.53)	58 (18.01)	0.025*
Pulmonary Function Test^a
FEV1/FVC, %	52.08 (42.25–66.67)	49.09 (37.80–56.75)	60.24 (43.50–72.73)	0.007*
FEV1 pred, %	37.50 (27.25–53.78)	36.25 (26.78–49.69)	42.91 (27.80–57.03)	0.004*
FVC pred, %	57.40± 17.50	55.22± 16.18	59.57± 18.52	0.038*
GOLD grade, I/II/III/IV^b	18/68/102/91	7/27/55/51	11/41/47/40	0.030*
Therapy in stable stage, n (%)
LABA monotherapy	8 (1.32)	6 (2.13)	2 (0.62)	0.100
LAMA monotherapy	10 (1.66)	2 (0.71)	8 (2.48)	0.076
LABA+ICS	87 (14.40)	45 (15.96)	42 (13.04)	0.309
LAMA+LABA	2 (0.33)	1 (0.35)	1 (0.31)	1.000
LABA+LAMA+ICS	160 (24.69)	108 (38.30)	52 (16.15)	<0.001*
Blood cell count
Leukocytes, ×10^9/L	7.71 (5.95–10.25)	8.25 (6.15–10.84)	7.36 (5.80–9.83)	0.008*
Neutrophils, ×10^9/L	5.75 (3.87–8.18)	6.14 (4.20–8.82)	5.26 (3.73–7.69)	<0.001*
Lymphocytes, ×10^9/L	1.15 (0.84–1.59)	1.08 (0.78–1.48)	1.23 (0.93–1.63)	0.002*
NLR	5.05 (2.92–8.16)	5.93 (3.40–9.28)	4.41 (2.74–6.80)	<0.001*
Monocytes, ×10^9/L	0.53 (0.36–0.73)	0.55 (0.32–0.72)	0.52 (0.38–0.75)	0.348
Eosinophils, ×10^9/L	0.07 (0.01–0.19)	0.04 (0.00–0.17)	0.10 (0.01–0.21)	<0.001*
Haemoglobin, g/L	128.00 (115.00–141.00)	127.00 (116.00–139.75)	129.00 (114.00–142.00)	0.931
Platelet, ×10^9/L	189.00 (151.00–245.00)	188.00 (151.25–243.00)	191.50 (151.00–245.00)	0.726
Inflammatory parameters
CRP, mg/L^c	13.00 (4.00–48.40)	11.75 (3.73–46.43)	14.00 (4.15–52.50)	0.351
PCT, ng/mL^d	0.05 (0.05–0.14)	0.05 (0.05–0.14)	0.05 (0.05–0.14)	0.800
ESR, mm/h^e	14.00 (6.00–36.00)	13.50 (6.00–34.75)	14.00 (7.00–36.00)	0.300
LDH, IU/L^f	179.00 (143.00–212.00)	183.00 (145.25–225.25)	171.00 (141.25–201.00)	0.016*
Worse outcome (%)	96 (15.89)	58 (20.57)	38 (11.80)	0.003*
ICU admission (%)	77 (12.75)	47 (16.67)	30 (9.32)	0.007*
Invasive ventilation (%)	15 (2.48)	11 (3.90)	4 (1.24)	0.036*
Mortality (%)	32 (5.30)	23 (8.16)	9 (2.80)	0.003*

Notes: ^aPulmonary function test was available in 279 patients, among 140 in frequent exacerbation (FE) group and 139 in non-frequent exacerbation (non-FE) group; ^bGOLD grade was classified according to pulmonary function test; ^cCRP was available in 535 patients, among 248 in FE group and 287 in non-FE group; ^dPCT was available in 468 patients, among 225 in FE group and 243 in non-FE group; ^eESR was available in 405 patients, among 186 in FE group and 219 in non-FE group; ^fLDH was available in 512 patients, among 250 in FE group and 262 in non-FE group, *p<0.05.

Abbreviations: BMI, body mass index; NYHA, New York heart association; FEV₁, forced expiratory volume in 1s; FVC, forced vital capacity; LABA, long-acting beta-agonists; LAMA, long-acting antimuscarinic antagonists; ICS, inhaled corticosteroids; NLR, neutrophil to lymphocyte ratio; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; LDH, lactic dehydrogenase; ICU, intensive care unit.

Table 2 Characteristics of Frequent Exacerbators with Different Outcome During Severe AECOPD

	With Worse Outcome (n=58)	Without Worse Outcome (n=224)	P value
Age, years	80.00 (71.25–84.75)	77.00 (67.00–84.00)	0.169
Male, n (%)	46 (79.31)	201 (89.73)	0.032*
BMI, kg/m^2	21.91 ± 5.00	22.03 ± 4.19	0.081
Current smoker, n (%)	7 (12.07)	51 (22.77)	0.072
Diabetes, n (%)	16 (27.59)	40 (17.86)	0.098
Hypertension, n (%)	42 (72.41)	118 (52.68)	0.007*
NYHA≥3, n (%)	21 (36.21)	26 (11.61)	<0.001*
Arrhythmia, n (%)	16 (27.59)	56 (25.00)	0.687
GOLD grade, I/II/III/IV^a	0/2/4/4	7/25/51/47	0.901
ICS+LABA+LAMA, n (%)	10 (17.24)	98 (43.75)	<0.001*
NLR	11.09 (7.74–16.49)	5.28 (2.93–7.93)	<0.001*
Monocytes, ×10^9/L	0.49 (0.23–0.66)	0.55 (0.34–0.73)	0.065
Eosinophils, ×10^9/L	0.01 (0.00–0.05)	0.06 (0.00–0.18)	<0.001*
Haemoglobin, g/L	122.00 (102.00–133.00)	129.00 (118.00–141.00)	0.002*
Platelet, ×10^9/L	179.50 (142.75–220.00)	191.00 (152.00–248.00)	0.102
CRP, mg/L^b	15.35 (5.33–72.08)	11.00 (3.10–42.75)	0.069
PCT, ng/mL^c	0.09 (0.05–0.55)	0.05 (0.05–0.10)	<0.001*
ESR, mm/h^d	10.00 (4.00–24.50)	15.00 (6.00–37.00)	0.172
LDH, IU/L^e	207.50 (176.75–266.25)	179.50 (142.25–213.75)	<0.001*

Notes: ^aGOLD grade was classified according to pulmonary function test in 140 frequent exacerbators; 10 subjects were with worse outcome and 130 subjects were without worse outcome; ^bCRP was available for 248 frequent exacerbators, among whom 58 were the ones with worse outcome and 190 were without worse outcome; ^cPCT was available for 225 frequent exacerbators, where 52 were with worse outcome and 173 were without worse outcome; ^dESR was available for 186 frequent exacerbators, where 43 were with worse outcome and 143 were without worse outcome; ^eLDH was available for 250 frequent exacerbators, among whom 56 were with worse outcome and 194 were without worse outcome. *p<0.05.

Abbreviations: BMI, body mass index; NYHA, New York heart association; LABA, long-acting beta-agonists; LAMA, long-acting antimuscarinic antagonists; ICS, inhaled corticosteroids; NLR, neutrophil to lymphocyte ratio; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; LDH, lactic dehydrogenase.

Figure 2 (A) NLR during severe AECOPD in frequent exacerbators with different outcome. Among the frequent exacerbators, the values of NLR in the ones with worse outcome were higher than in those without worse outcomes. (B) ROC curve of NLR for predicting the worse outcome of severe AECOPD in frequent exacerbators. The cut-off value of NLR was 10.23, with a sensitivity of 0.621, a specificity of 0.920 and an AUC of 0.833 (95% CI 0.771 −0.894; p<0.001).

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; ROC, receiver operating characteristic; AUC, area under the curve.

Table 3 Association Between NLR and Worse Outcome in Frequent Exacerbators During Severe AECOPD

		NLR Quartiles
	NLR (per unit)	Q1	Q2	Q3	Q4
Median of NLR		2.40	4.75	7.42	12.37
Interquartile range of NLR		1.90–2.84	4.02–5.34	6.72–8.38	10.28–16.35
adverse outcome, n (%)		2 (2.82)	7 (10.00)	11 (15.71)	38 (53.52)
OR (95% CI) for adverse outcome
Crude model	1.37 (1.26–1.50)***	1.00 (Ref)	3.83 (0.89–26.38)	6.43 (1.64–42.65)*	39.73 (11.24–253.52)***
Model 1^a	1.39 (1.27–1.54)***	1.00 (Ref)	4.01 (0.91–27.90)	6.51 (1.63–43.71)*	42.87 (11.74–279.01)***
Model 2^b	1.43 (1.29–1.60)***	1.00 (Ref)	3.83 (0.78–28.75)	5.94 (1.38–42.11)*	56.25 (13.86–401.90)***
Model 3^c	1.43 (1.28–1.63)***	1.00 (Ref)	3.96 (0.79–30.02)	4.76 (1.10–33.52)*	53.19 (12.39–387.45)***
Model 4^d	1.43 (1.28–1.64)***	1.00 (Ref)	4.10 (0.80–31.36)	3.79 (0.82–27.46)	41.85 (9.57–306.74)***

Notes: ^aModel 1 adjusted for age, sex, BMI and smoking status; ^bModel 2 further adjusted for comorbidities (including diabetes, hypertension, NYHA≥3 and arrhythmia); ^cModel 3 further adjusted for GOLD grade and triple inhaled therapy as maintenance strategy; ^dModel 4 further adjusted for inflammatory indicators (including CRP, PCT, ESR, LDH), *p<0.05; ***p<0.001.

Abbreviations: NLR, neutrophil to lymphocyte ratio; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; OR, Odd ratios; CI, confidence intervals; BMI, body mass index; NYHA, New York heart association; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; LDH, lactic dehydrogenase.