Blood eosinophil count as a prognostic biomarker in COPD

Figures & data

Table 1 Baseline characteristics of the patients of each cohort

Variables	KOLD	CODA	P-value
Total number	395 (62.8%)	234 (37.2%)
Age (years)	66.9±7.5	72.7±7.0	<0.001
Gender (male)	385 (97.5%)	230 (98.3%)	0.499
Smoking (pack-years)	46.8±26.5	26.3±22.6	<0.001
BMI (kg/m^2)	23.1±3.2	22.7±3.2	0.202
Dyspnea (mMRC scale)	1.7±1.1	1.5±1.1	0.049
Leukocyte (×10^3/μL)	7.3±2.0	6.9±1.8	0.006
Eosinophil count (%)	3.7±3.3	2.8±3.2	0.001
Post-bronchodilator pulmonary function
FVC (%)	83.3±16.0	96.0±19.0	<0.001
FEV1 (%)	54.2±16.1	77.8±19.4	<0.001
FEV1/FVC (%)	46.8±11.2	53.3±8.8	<0.001

Abbreviations: BMI, body mass index; CODA, COPD in Dusty Area; KOLD, Korean Obstructive Lung Disease; mMRC, modified Medical Research Council.

Figure 1 Flow diagram illustrating patient enrollment.

Abbreviations: CODA, COPD in Dusty Area; KOLD, Korean Obstructive Lung Disease.

Table 2 Baseline characteristics of the patients with COPD according to blood eosinophil count

Variables	High eosinophil group (blood eosinophil ≥5%)		Middle eosinophil group (blood eosinophil 2%–5%)	Low eosinophil group (blood eosinophil <2%)	P-value
Total number		123	301	205
Eosinophil count (%)		8.1±4.6	3.0±0.8	1.0±0.5	<0.001
Age (years)		69.1±8.5	68.4±7.8	69.92±7.3	0.100
Gender (male)		98.4% (121/123)	97.7% (294/301)	97.6% (200/205)	0.665
Current smoker vs former smoker		46.3%	39.2%	37.1%	0.238
BMI (kg/m^2)		23.3±3.1	23.1±3.1	22.5±3.2	0.042
SGRQ		33.7±17.0	31.1±17.5	34.6±18.7	0.225
Dyspnea (mMRC scale)		1.74±1.07	1.45±1.10	1.69±1.10	0.010
Serum laboratory finding
Leukocyte (×10^3/μL)		7.0±2.0	6.8±1.7	7.4±2.2	0.003
hs-CRP (mg/dL)		1.02±0.13	1.01±0.09	1.02±0.14	0.670
Hemoglobin (g/dL)		14.8±1.3	14.8±1.4	14.8±1.4	0.909
Platelet (×10^3/μL)		236.7±63.1	234.3±59.2	240.2±65.2	0.725
Protein (g/dL)		7.06±0.52	7.10±0.47	7.03±0.52	0.486
Albumin (g/dL)		4.13±0.36	4.19±0.34	4.18±0.31	0.249
Cholesterol (mg/dL)		182.5±36.5	180.3±36.9	182.3±37.5	0.831
Creatinine (mg/dL)		1.03±0.22	0.99±0.38	0.93±0.21	0.009

Abbreviations: BMI, body mass index; SGRQ, St George Respiratory Questionnaire; hs-CRP, high-sensitivity C-reactive protein; mMRC, modified Medical Research Council; SGRQ, St George Respiratory Questionnaire.

Table 3 Physiological and radiological findings of patients with COPD according to blood eosinophil count

Variables	High eosinophil group (blood eosinophil ≥5%)	Middle eosinophil group (blood eosinophil 2%–5%)	Low eosinophil group (blood eosinophil <2%)	P-value
Post-bronchodilator pulmonary function
FVC (%)	85.1±16.5	89.2±17.4	88.0±19.7	0.542
FEV1 (%)	62.4±19.4	63.8±19.6	62.1±23.2	0.625
FEV1/FVC (%)	52.3±11.4	51.5±11.6	49.7±11.2	0.108
DLCO	82.4±21.9 (83)	74.3±23.7 (163)	76.8±24.5 (118)	0.035
DLCO/VA	84.6±23.7 (81)	76.1±22.6 (161)	76.3±25.2 (115)	0.023
RV/TLC (%)	45.2±12.8 (81)	44.2±12.3 (167)	47.7±13.6 (118)	0.074
IC/TLC (%)	32.6±7.4 (79)	32.4±9.2 (158)	29.9±8.9 (112)	0.036
Six-minute walk test
6MWD (m)	445.8±81.4 (84)	428.5±88.0 (177)	414.7±86.3 (119)	0.029
Resting O2 Sat (%)	96.7±1.7 (84)	96.4±1.8 (175)	96.4±1.7 (119)	0.404
Minimum O2 Sat (%)	95.3±4.4 (84)	94.4±5.3 (174)	94.9±3.8 (119)	0.338
Radiological findings
Emphysema index	18.5±14.1 (77)	22.2±15.3 (155)	23.7±16.3 (106)	0.077
Wall area (%)	66.8±5.4 (77)	66.2±4.8 (155)	66.7±5.0 (106)	0.679
Air-trapping index	0.94±0.04 (75)	0.95±0.04 (152)	0.95±0.04 (104)	0.330
Frequent exacerbators	13.9%	14.0%	20.1%	0.176

Notes: The number of patients is noted within parenthesis if any of the values for an item are missing. Wall area% = wall area/(wall area + lumen area) ×100.

Abbreviations: D_LCO/VA, diffusing capacity for carbon monoxide/alveolar volume; IC, inspiratory capacity; O₂ Sat, oxygen saturation; RV, residual vol; 6MWD, six minute walk distance; TLC, total lung capacity.

Table 4 Factors associated with blood eosinophil count according to linear regression method

Variables	B	SE	t	P-value
Univariate analysis
Age (years)	−0.019	0.017	−1.133	0.258
R-square=0.002, adjusted R-square=0.001, F=1.284, P-value=0.258
Gender (male)	−0.333	0.894	−0.372	0.710
R-square=0.001, adjusted R-square=−0.001, F=0.139, P-value=0.710
Leukocyte (×10^3/μL)	0.036	0.067	0.535	0.593
R-square=0.001, adjusted R-square=−0.001, F=0.286, P-value=0.593
BMI (kg/m^2)	0.044	0.041	1.060	0.290
R-square=0.002, adjusted R-square=0.001, F=1.123, P-value=0.290
IC/TLC (%)	0.015	0.020	0.764	0.446
R-square=0.002, adjusted R-square=−0.001, F=0.583, P-value=0.446
DLCO (%)	0.017	0.007	2.414	0.016
R-square=0.015, adjusted R-square=0.012, F=5.827, P-value=0.016
Emphysema index	−0.034	0.012	−2.784	0.006
R-square=0.023, adjusted R-square=0.020, F=7.751, P-value=0.006
6MWD (m)	0.009	0.002	1.882	0.061
R-square=0.009, adjusted R-square=0.007, F=3.544, P-value=0.061
a Multivariate analysis by stepwise method
Emphysema index	−0.034	0.013	−2.689	0.008

Note:

a Adjustment for age, gender, BMI, 6MWD, D_LCO, and emphysema index.

Abbreviations: BMI, body mass index; D_LCO, diffusing capacity for carbon monoxide; IC, inspiratory capacity; SE, standard error; 6MWD, six minute walk distance; TLC, total lung capacity.

Figure 2 Survival analysis in the high eosinophil group (mean survival =9.52±0.23 years), middle group (mean survival =8.47±1.94 years), and low group (mean survival =7.42±0.27 years) (P<0.001) by using the Kaplan–Meier method.

Table 5 Prognostic factors for mortality in the total COPD group according to multivariate Cox regression analysis

Variables	Model 1		Model 2
	HR (95% CI)	P-value	HR (95% CI)	P-value
Age (years)	1.122 (1.076–1.169)	<0.001	1.102 (1.054–1.153)	<0.001
Gender (female)	0.441 (0.061–3.188)	0.417	0.919 (0.123–6.875)	0.934
Blood eosinophil count (%)	0.897 (0.802–0.996)	0.041	0.922 (0.839–1.013)	0.091
Dyspnea (mMRC scale)			1.459 (1.119–1.904)	0.005
BMI (kg/m^2)			0.827 (0.757–0.904)	<0.001
Post-BD FEV1 (%)			0.976 (0.959–0.994)	0.008

Abbreviations: BMI, body mass index; HR, Hazard ratio; mMRC, modified Medical Research Council; Post-BD FEV₁, post-bronchodilator FEV₁.