Neutrophil to lymphocyte ratio is a better indicator of COPD exacerbation severity in neutrophilic endotypes than eosinophilic endotypes

Figures & data

Figure 1 Flowchart of patient data.

Abbreviations: CBC, complete blood count; ICU, intensive care unit.

Table 1 Baseline characteristics of neutrophilic and eosinophilic acute exacerbation of COPD

	Neutrophilic COPD N=6,537	Eosinophilic COPD N=4,056	P-value
Age, median (IQR) yearsa	69 (61–77)	67 (59–75)	<0.001
Male, n (%)	4,325 (66)	2,931 (72)	<0.001
CBC, median (IQR) valuesa
Leucocyte count, 10^9 L	9.90 (7.80–12.80)	8.30 (6.90–9.99)	<0.001
Neutrophil count	7.90 (5.40–10.20)	5.10 (4.00–6.59)	<0.001
Lymphocyte count	1.50 (0.95–2.10)	1.91 (1.50–2.50)	<0.001
Monocyte count	0.60 (0.48–0.90)	0.62 (0.50–0.80)	0.036
Erythrocyte count, 10^12 L	4.64 (4.18–5.07)	4.76 (4.36–5.15)	<0.001
Hemoglobin, g/dL	13.0 (11.0–14.0)	14.0 (12.0–15.0)	<0.001
Hematocrit, %	40 (36–44)	41 (36–44)	0.25
MCV, fL	86.6 (82.5–90.4)	86.8 (82.9–90.3)	0.25
Platelet count, 10^9 L	256 (206–320)	252 (209–307)	0.08
Mean platelet volume	8 (8–9)	8 (8–9)	0.64
Biochemistry, median (IQR) valuesa
Blood glucose, mg/dL	132 (106–176)	112 (95–142)	<0.001
BUN, mg/dL	44 (33–62)	38 (30–51)	<0.001
Serum creatinine, mg/dL	0.78 (0.61–1.01)	0.80 (0.62–1.01)	0.92
AST, U/L	22 (17–33)	22 (17–29)	0.005
ALT, U/L	18 (12–29)	16 (12–24)	<0.001
Albumin, g/dL	3.6 (3.2–3.9)	3.7 (3.3–4.0)	<0.001
Sodium, mmol/L	138 (135–140)	138 (136–140)	<0.001
Potassium, mmol/L	4.4 (4.0–4.8)	4.4 (4.1–4.7)	0.049
Inflammatory markers, median (IQR) valuesa
Neutrophil to lymphocyte ratio	5.11 (2.92–9.64)	2.62 (1.88–3.80)	<0.001
Platelet to lymphocyte ratio	175.66 (118.46–281.11)	130.00 (98.66–175.38)	<0.001
Platelet to MPV ratio	31 (24–40)	30 (24–39)	0.18
CRP, mg/dL	11.6 (4.0–36.4)	7.7 (3.4–21.2)	<0.001
Admission to the hospital, n (%)
Outpatient clinic	4,367 (67)	3,497 (86)	<0.001
Ward	1,823 (28)	410 (10)
ICU	346 (5)	149 (4)
Mortality, n (%)	29 (0.4)	3 (0.1)	0.001

Note:

a Median (25%–75%), Mann–Whitney U test.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CBC, complete blood count; CRP, C-reactive protein; ICU, intensive care unit; IQR, interquartile range; MCV, mean corpuscular volume; MPV, mean platelet volume.

Table 2 Comparison of inflammatory markers in neutrophilic and eosinophilic COPD exacerbation

	Neutrophilic (PBE < 2%) N=6,537		Eosinophilic (PBE ≥2%) N=4,056		P-value
	N	Variables	N	Variables
Outpatient clinic
Patientsa	4,367	–	3,497	–
WBC (10^9 L)	4,367	9.70 (7.76–12.50)	3,497	8.30 (6.90–9.93)	<0.001
NLR	4,367	4.21 (2.58–7.47)	3,497	2.50 (1.83–3.62)	<0.001
CRP (mg/dL)	1,276	7.7 (3.4–22.7)	1,445	5.7 (3.3–12.7)	<0.001
PLT/MPV ×10^3	4,367	32 (24–41)	3,497	31 (24–39)	0.004
PLR	4,367	155.53 (110.50–236.67)	3,497	126.54 (97.53–169.09)	<0.001
Ward
Patientsa	1,823	–	410	–
WBC (10^9 L)	1,823	10.20 (8.00–13.10)	410	8.20 (6.60–10.20)	<0.001
NLR	1,823	7.57 (4.29–13.20)	410	3.43 (2.44–4.92)	<0.001
CRP (mg/dL)	1,788	14.0 (4.6–42.3)	402	19.0 (8.4–41.7)	<0.001
PLT/MPV	1,823	30 (23–40)	410	29 (22–40)	0.49
PLR	1,823	228.33 (145.38–366.67)	410	156.37 (114.21–216.67)	<0.001
ICU
Patientsa	346	–	149	–
WBC (10^9 L)	346	10.07 (7.70–13.40)	149	8.30 (7.00–9.81)	<0.001
NLR	346	8.60 (4.53–16.60)	149	3.42 (2.57–5.10)	<0.001
CRP (mg/dL)	337	20.4 (8.6–67.6)	147	25.1 (12.9–47.6)	0.90
PLT/MPV	346	28 (21–38)	149	27 (20–35)	0.19
PLR	346	246.88 (159.74–433.33)	149	143.85 (112.78–204.17)	<0.001

Note:

a Median and interquartile range (25th–75th percentile). Significant values are written bold.

Abbreviations: CRP, C-reactive protein; ICU, intensive care unit; NLR, neutrophil to lymphocyte ratio; PBE, peripheral blood eosinophilia; PLR, platelet to lymphocyte ratio; PLT/MPV, platelet to mean platelet volume; WBC, white blood cell count.

Table 3 Comparison of inflammatory markers in AECOPD patients on the day of admission to the ICU, ward, or outpatients’ clinic

	ICU		Ward		Outpatients’ clinic		P-valuea
	n	Median (25%–75%)	n	Median (25%–75%)	n	Median (25%–75%)
Total patient
CRP (mg/dL)	484	22.8 (9.9–55.3)	2,190	15.0 (5.2–42.2)	2,721	6.4 (3.4–16.8)	<0.001
NLR	495	5.94 (3.40–12.87)	2,233	6.33 (3.58–11.6)	7,864	3.20 (2.12–5.45)	<0.001
PLR	495	207.39 (134.68–348.57)	2,233	208.46 (136.39–337.78)	7,864	140.43 (103.64–202.35)	<0.001
PLT/MPV	495	27.9 (20.7–36.4)	2,233	29.6 (22.5–39.6)	7,864	31.1 (24.3–40.1)	<0.001
Neutrophilic
CRP (mg/dL)	337	20.4 (8.6–67.6)	1,788	14.0 (4.6–42.3)	1,276	7.7 (3.4–22.7)	<0.001
NLR	346	8.60 (4.53–16.60)	1,823	7.57 (4.29–13.20)	4,367	4.21 (2.58–7.47)	<0.001
PLR	346	246.88 (159.74–433.33)	1,823	228.33 (145.38–366.67)	4,367	155.53 (110.50–236.67)	<0.001
PLT/MPV	346	28.2 (21.1–37.7)	1,823	29.6 (22.5–39.6)	4,367	31.7 (24.2–40.9)	<0.001
Eosinophilic
CRP (mg/dL)	147	25.1 (12.9–47.6)	402	19.0 (8.4–41.7)	1,445	5.7 (3.3–12.7)	<0.001
NLR	149	3.42 (2.57–5.10)	410	3.43 (2.44–4.92)	3,497	2.50 (1.83–3.62)	0.82
PLR	149	143.85 (112.78–204.17)	410	156.37 (114.21–216.67)	3,497	126.54 (97.53–169.09)	<0.001
PLT/MPV	149	26.9 (19.6–35.0)	410	29.5 (22.2–39.9)	3,497	30.5 (24.3–39.0)	0.09

Note:

a Kruskal Wallis Test.

Abbreviations: AECOPD, acute exacerbation of Chronic Obstructive Pulmonary Disease; CRP, C-reactive protein; ICU, intensive care unit; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PLT/MPV, platelet to mean platelet volume.

Table 4 Area under the curve of inflammatory markers in patients with AECOPD who died in the hospital

Test result variable(s)	Area	Asymptotic 95% CI		P-values
		Lower bound	Upper bound
C-reactive protein	0.81	0.74	0.89	<0.001
Neutrophil to lymphocyte ratio	0.78	0.69	0.87	<0.001
Platelet to lymphocyte ratio	0.53	0.41	0.66	0.54
Platelet to mean platelet volume	0.35	0.24	0.46	0.006

Abbreviation: AECOPD, acute exacerbation of chronic obstructive pulmonary diseases.

Figure 2 ROC curves of inflammatory markers for mortality of hospitalized COPD acute exacerbation patients.

Note: Diagonal segments are produced by ties.
Abbreviations: ROC, receiver operating characteristic; PLR, platelet to lymphocyte ratio; PLT/MPV, platelet/mean platelet volume; CRP, C-reactive protein; NLR, neutrophil to lymphocyte ratio.

Table 5 The cutoff values of inflammatory markers in patients with AECOPD who died in the hospital

Variables	Cutoff	Sensitivity, %	Specificity, %
C-reactive protein	35.1	81	60
Neutrophil to lymphocyte ratio	8.01	78	60
Platelet to lymphocyte ratio	228.87	52	55
Platelet to mean platelet volume	19.3	66	16

Abbreviation: AECOPD, acute exacerbation of chronic obstructive pulmonary diseases.

Figure 3 A treatment approach for chronic obstructive pulmonary diseases with respect to endotypes.

Abbreviations: PBE, peripheral blood eosinophil; NLR, neutrophil to lymphocyte ratio.