The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia

Figures & data

Figure 1 Flow chart of patients.

Abbreviations: PBE, peripheral blood eosinophil; LTOT, long-term oxygen therapy; NLR, neutrophil-to-lymphocyte ratio; PLT/MPV, platelet-to-mean platelet volume ratio.

Table 1 Patients’ characteristics and laboratory findings on admission

Variables	Group 1 Eosinophilic (n=351)	Group 2 Non-eosinophilic (n=1,353)	P-value
Number of patients	351	1,353
Male, %	66.9	65.1
Age, years (median)	70 (61–80)	71 (63–78)	0.70
Comorbidities, n (%)
Diabetes mellitus	45 (12.8)	124 (9.2)	0.60
Hypertension	44 (12.5)	166 (12.3)	0.89
Ischemic heart disease	16 (4.6)	59 (4.4)	0.87
Chronic renal failure	7 (2)	17 (1.3)	0.29
Anemia	3 (0.9)	9 (0.7)	0.70
Anxiety/depression	2 (0.9)	16 (1.2)	0.60
Heart failure	54 (15.4)	223 (16.5)	0.62
Arrhythmia	6 (1.7)	32 (2.4)	0.45
Pleurisy	19 (1.6)	6 (1.2)	0.53
Emboli	60 (5.0)	19 (3.8)	0.27
Pneumothorax	1 (0.1)	1 (0.2)	0.52
LTOT, n (%)	177 (50.4)	696 (51.4)	0.73
Hemogram values
Leukocyte count, 10^9 L	7.7 (6.2–9.5)	9.9 (7.5–13.01)	0.001
Neutrophil, %	68.6 (62.1–73.8)	82.21 (74.10–88.90)	0.001
Monocyte, %	7.19 (5.6–9.02)	5.2 (3.1–7.2)	0.001
Lymphocyte, %	19.3 (14.9–24.32)	10.3 (6.3–17.1)	0.001
Eosinophil, %	3.0 (2.4–3.99)	0.8 (0.11–1.1)	0.001
Basophil, %	0.5 (0.29–0.9)	0.3 (0.1–0.6)	0.001
Erythrocyte count, 10^12 L	4.31 (3.9–4.74)	4.36 (3.93–4.8)	0.15
Hemoglobin, g/dL	12 (10.94–13.59)	12.35 (11.04–13.64)	0.11
Hematocrit, %	36.89 (33–41.1)	37.25 (33.6–41.41)	0.23
MCV, fL	86.99 (82–91)	86.51 (81.9–90.25)	0.50
Platelet count, 10^9 L	247 (194–311.8)	247.6 (198–313)	0.84
Mean platelet volume, fL	8.6 (7.9–9.2)	8.63 (7.95–9.3)	0.22
Biochemistry values
Blood glucose, mg/dL	110 (93–142)	136 (103–186)	0.001
BUN, mg/dL	22 (15–37)	25 (18–39)	0.002
Serum creatinine, mg/dL	0.81 (0.7–1.12)	0.83 (0.7–1.05)	0.90
Sodium, mmol/L	139 (137–141)	138 (136–140)	0.005
Potassium, mmol/L	4.2 (3.8–4.7)	4.2 (3.8–4.7)	0.63
SGOT, U/L	19.5 (14–26)	19 (14–26)	0.47
SGPT, U/L	16 (10–25)	17 (11–27)	0.06
Protein, g/dL	6.6 (6–7)	6.5 (6–7.1)	0.60
Albumin, g/dL	3.1 (2.7–3.4)	3.1 (2.7–3.5)	0.92
Inflammatory markers
CRP, mg/dL	19.3 (6.76–57.10)	35.15 (11.7–95.9)	0.001
Neutrophil-to-lymphocyte ratio	3.63 (2.57–4.95)	7.99 (4.36–13.87)	0.001
Platelet-to-mean platelet volume ratio	29.86 (21.37–38.29)	28.85 (21.87–37.47)	0.65

Note: Median (25%–75%).

Abbreviations: BUN, blood urea nitrogen; MCV, mean corpuscular volume; MPV, mean platelet volume; LTOT, long-term oxygen therapy; SGOT, serum glutamic-oxalacetic transaminase; SGPT, serum glutamic-pyruvic transaminase.

Table 2 Laboratory findings, length of stay, and steroid use on hospital discharge

Variables	Group 1 Eosinophilic (n=351)	Group 2 Non-eosinophilic (n=1,353)	P-value
Hemogram values
Leukocyte count, 10^9 L	8.1 (6.5–10.11)	9.69 (7.6–12.2)	0.001
Neutrophil, %	69.71 (62.4–74.6)	78.4 (70.6–86.0)	0.001
Monocyte, %	7.0 (5.48–8.98)	5.8 (4.0–7.76)	0.19
Lymphocyte, %	18.75 (14.07–23.93)	13.1 (8–19.4)	0.001
Eosinophil, %	2.8 (2.2–3.84)	0.9 (0.34–1.42)	0.001
Basophil, %	0.46 (0.23–0.86)	0.30 (0.10–0.60)	0.001
Erythrocyte count, 10^12 L	4.34 (3.89–4.77)	4.37 (3.93–4.82)	0.13
Hemoglobin, g/dL	12.02 (10.99–13.60)	12.35 (11.04–13.70)	0.08
Hematocrit, %	36.8 (33.29–41.31)	37.4 (33.7–41.33)	0.019
MCV, fL	86.95 (82–91)	86.27 (82–90.23)	0.64
Platelet count, 10^9 L	253.3 (209–314)	258.5 (204–324)	0.64
Mean platelet volume, fL	8.46 (7.9–9.14)	8.47 (7.9–9.2)	0.89
Biochemistry values
Blood glucose, mg/dL	109 (90–139)	123 (95–166)	0.001
BUN, mg/dL	23 (15–37)	26 (18–41)	0.001
Serum creatinine, mg/dL	0.73 (0.63–0.91)	0.76 (0.64–0.92)	0.12
Sodium, mmol/L	139 (137–140)	138 (136–140)	0.019
Potassium, mmol/L	4.1 (3.8–4.6)	4.2 (3.8–4.6)	0.23
SGOT, U/L	19 (15–27)	18 (14–25)	0.040
SGPT, U/L	16 (11–28)	19 (12–30)	0.005
Protein, g/dL	6.5 (6.0–7.0)	6.5 (5.9–7.0)	0.83
Albumin, g/dL	3.3 (2.9–3.6)	3.2 (2.8–3.6)	0.20
Length of hospital stay, days, median	6.6 (4.6–8.0)	7.0 (5.5–9.0)	0.001
Steroid use, n (%)	216 (61)	1,097 (81)	0.001
Inflammatory markers
CRP, mg/dL	12.2 (5.7–26.4)	12.2 (4.3–31.6)	0.91
Neutrophil-to-lymphocyte ratio	3.73 (2.6–5.15)	6.0 (3.65–10.6)	0.001
Platelet-to-mean platelet volume ratio	30.3 (22.87–38.31)	29.97 (22.89–39.67)	0.89

Note: Median (25%–75%).

Abbreviations: BUN, blood urea nitrogen; MCV, mean corpuscular volume; SGOT, serum glutamic-oxalacetic transaminase; SGPT, serum glutamic-pyruvic transaminase.

Table 3 Hospital readmission for treatment of COPD exacerbation, and mortality within 6 months after discharge

Variables	Readmission			Mortality
	No (n: 1,200)	Yes (n: 504)	P-value	No (n: 1,448)	Yes (n: 256)	P-value
Eosinophilic patients, n (%)	266 (22.2)	85 (16.9)	0.014	301 (20.8)	50 (19.5)	0.64
Male, %	61.9	74	0.01	70 (62–77)	76 (67–82)	0.001
Age, years (median)	71 (63–79)	70 (62–76)	0.01	70 (62–77)	76 (67–82)	0.001
Comorbidities, n (%)
Diabetes mellitus	120 (10.0)	49 (9.7)	0.22	149 (10.3)	20 (7.8)	0.92
Hypertension	143 (11.9)	67 (13.3)	0.43	188 (13.0)	22 (8.6)	0.04
Ischemic heart disease	54 (4.5)	21 (4.2)	0.75	67 (4.6)	8 (3.1)	0.28
Chronic renal failure	22 (1.8)	2 (0.4)	0.02	18 (1.2)	6 (2.3)	0.16
Anemia	12 (1.0)	0 (0)	0.02	11 (0.8)	1 (0.4)	0.51
Depression/anxiety	1 (0.9)	8 (1.6)	0.23	16 (1.1)	3 (1.2)
Heart failure	202 (16.8)	75 (14.9)	0.31	213 (14.7)	64 (25.0)	0.001
Arrhythmia	29 (2.4)	9 (1.8)	0.42	32 (2.2)	6 (2.3)	0.89
Pleurisy	19 (1.6)	6 (1.2)	0.53	19 (1.3)	6 (2.3)	0.20
Emboli	60 (5.0)	19 (3.8)	0.27	63 (4.4)	16 (6.2)	0.18
Pneumothorax	1 (0.1)	1 (0.2)	0.52	1 (0.1)	1 (0.4)	0.16
LTOT, n (%)	605 (50.4)	268 (53.2)	0.11	743 (51.3)	130 (50.8)	0.88
Laboratory findings
Leukocyte count, 10^9 L	9.2 (7.2–11.6)	9.7 (7.6–12.0)	0.006	9.3 (7.3–11.7)	9.4 (7.2–11.8)	0.96
Hematocrit, %	37 (33.4–41.2)	38.2 (34.0–41.7)	0.013	37.7 (33.9–41.8)	35.5 (31.4–39.0)	0.001
Platelet count, 10^9 L	257 (208–323)	258 (202–319)	0.79	257 (208–321)	257 (192–328)	0.40
Mean platelet volume, fL	8.5 (7.9–9.2)	8.4 (7.8–9.1)	0.01	8.4 (7.8–9.2)	8.5 (7.9–9.2)	0.50
Blood glucose, mg/dL	121 (94–164)	118 (93–155)	0.21	120 (94–164)	119 (94–155)	0.61
BUN, mg/dL	26 (17–40)	25 (17–38)	0.25	25 (17–39)	28 (19–50)	0.001
Serum creatinine, mg/dL	0.8 (0.6–1.0)	0.7 (0.6–0.9)	0.012	0.8 (0.6–1.0)	0.8 (0.6–1.1)	0.48
Sodium, mmol/L	138 (136–140)	138 (136–141)	0.21	138 (136–140)	138 (135–141)	0.015
Potassium, mmol/L	4.2 (3.8–4.6)	4.2 (3.8–4.6)	0.19	4.2 (3.8–4.6)	4.1 (3.8–4.6)	0.39
Albumin, g/dL	3.0 (2.6–3.4)	3.1 (2.7–3.4)	0.1	3.1 (2.7–3.5)	2.8 (2.7–3.1)	0.001
Inflammatory markers
CRP, mg/dL	12.9 (5.0–32.1)	10.4 (4.0–27.7)	0.01	11.2 (4.3–27.9)	18.9 (7.2–48.7)	0.001
Neutrophil-to-lymphocyte ratio	4.9 (3.2–8.8)	5.8 (3.5–10.4)	0.004	4.9 (3.2–8.7)	6.7 (4.2–12.3)	0.001
Platelet-to-mean platelet volume ratio	30.0 (22.7–39.5)	30.2 (23.2–39.1)	0.79	30.2 (23.1–39.4)	29.6 (21.8–40.0)	0.41
Steroid use, n (%)	844 (70.3)	469 (93.1)	0.001	1,132 (78.2)	181 (70.7)	0.009
Length of stay, days (%)	7.0 (5.0–8.8)	7.0 (5.5–9.0)	0.03	7.0 (5.0–8.6)	7.5 (6.0–10.5)	0.00

Note: Median (25%–75%).

Abbreviations: BUN, blood urea nitrogen; LTOT, long-term oxygen therapy; SGOT, serum glutamic-oxalacetic transaminase; SGPT, serum glutamic-pyruvic transaminase.

Figure 2 Eosinophilic and non-eosinophilic COPD patient survival after hospital discharge (days) as determined by Kaplan–Meier analysis.

Table 4 Cox regression analysis of survival after hospital discharge

Variables	Odds ratio	95% CI: lower–upper limit	P-value
Readmission	1.93	1.45–2.57	0.001
NLR equal and ≥7 at discharge	1.79	1.37–2.34	0.001
CRP >19 mg/dL at discharge	1.32	1.01–1.71	0.035
Presence of heart failure	1.48	1.10–1.99	0.01
Length of stay	1.06	1.03–1.09	0.001
Steroid use	0.42	0.31–0.59	0.001

Abbreviations: CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio.

Figure 3 Survival functions of COPD patients according to CRP and NLR.

Notes: (A) CRP values above and below 19 mg/dL for 6-month survival after discharge. (B) CRP values >19 mg/dL and, (C) CRP ≤19 mg/dL had similar survival curves in both eosinophilic groups (eosinophils ≤2% and >2%) (P>0.36). (D) Kaplan–Meier survival curves show the neutrophil-to-lymphocyte ratio (NLR) <7 and ≥7 for all patients. (E) NLR ≥7 mg/dL and (F) NLR <7 had similar survival curves in both eosinophilic groups (eosinophils ≤2% and >2%) (P>0.98).