Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD

Figures & data

Figure 1 Study flowchart.

Table 1 Demographics and clinical characteristics of the study population

Variable	All participants (n=141)	Eosinophilica (n=45)	Noneosinophilicb (n=96)	P-value*
Age (years)	69.8±7.7	68.5±8.0	70.3±7.6	0.20
Sex (male)	89 (63)	30 (67)	59 (61)	0.58
Postbronchodilator FEV1 (% predicted)	57.5±17.9	58.3±18.8	57.1±17.6	0.72
Postbronchodilator FEV1 (L)	1.5 (1.12, 1.79)	1.56 (1.09, 1.79)	1.48 (1.12, 1.78)	0.48
Postbronchodilator FEV1/FVC ratio (%)	56.55 (43.31, 65.57)	55.26 (44.4, 62.65)	57.12 (42.56, 65.92)	0.46
Reversibility (L)	0.04 (0.006, 0.10)	0.04 (0, 0.08)	0.05 (0.008, 0.11)	0.48
Reversibility (%)	4.46 (0.63, 10.22)	3.9 (0.0, 7.5)	4.67 (0.9, 11.0)	0.48
CCI score	3.9±1.1	3.8±1.0	3.9±1.1	0.71
Frequent vs nonfrequent exacerbatorsc	74 vs 67 (52.5 vs 47.5)	23 vs 22 (51.1 vs 48.9)	51 vs 45 (53.1 vs 46.9)	0.86
GOLD grade				1.00
I	11 (7.8)	3 (6.7)	8 (8.3)
II	74 (52.4)	24 (53.3)	50 (52.1)
III	45 (31.9)	15 (33.3)	30 (31.3)
IV	11 (7.8)	3 (6.7)	8 (8.3)
GOLD quadrant				0.003
A	9 (6.4)	5 (11.1)	4 (4.2)
B	35 (24.8)	7 (15.6)	28 (29.2)
C	21 (14.9)	13 (28.9)	8 (8.3)
D	76 (53.9)	20 (44.4)	56 (58.3)
BMI (kg/m^2)	30.2 (25.5, 34.7)	30.4 (24.5, 33.3)	30.2 (26.1, 35.9)	0.32
Ex-smokers	116 (82.3)	36 (80)	80 (83.3)	0.64
Pack years	37.5 (13.8, 62.5)	35.3 (9.8, 61.3)	38.4 (13.9, 63.4)	0.51
SGRQ	49.7±16.9	45.7±18.0	51.6±16.1	0.052
BODEx	2 (1, 5)	2 (1, 3)	3 (2, 5)	0.003
mMRC score ≥2	96 (68.1)	24 (53.3)	72 (75.0)	0.01
ICS or ICS/LABA combination use	128 (90.8)	41 (91.1)	87 (90.6)	0.60
ICS dosed (μg/d)	500 (250, 500)	500 (250, 500)	500 (250, 500)	0.74
LAMA use	110 (78.0)	35 (77.8)	75 (78.1)	0.56
Prior history of asthma	69 (48.9)	23 (51.1)	46 (47.9)	0.86

Notes:

a Participants with sputum eosinophil count ≥3%;

b participants with sputum eosinophil count <3%;

c Frequent exacerbators: ≥2 exacerbations in the previous year, and nonfrequent exacerbators: <2 exacerbations in the previous year;

d ICS dose calculated as beclomethasone equivalents where 1 μg of beclomethasone =1 μg budesonide =0.5 μg fluticasone;

* P-value for the comparison of eosinophilic vs noneosinophilic COPD. Data expressed as mean ± SD, median (interquartile range) or as number (%).

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; CCI, Charlson comorbidity index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; BMI, body mass index; SGRQ, St George Respiratory Questionnaire; BODEx, body mass index, airflow obstruction, dyspnea, severe exacerbation; mMRC, modified Medical Research Council; ICS, inhaled corticosteroids; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonists; SD, standard deviation.

Table 2 Blood cell count parameters and blood cell ratios

Blood cell counts/ratios	All participants (n=141)	Eosinophilica (n=45)	Noneosinophilicb (n=96)	P-value*
Blood eosinophils (×10^9/L)	0.20 (0.10, 0.30)	0.30 (0.20, 0.40)	0.15 (0.10, 0.20)	<0.0001
Blood eosinophils (%)	2.70 (1.56, 3.92)	3.95 (2.94, 5.08)	2.07 (1.35, 3.25)	<0.0001
Blood neutrophils (×10^9/L)	5.08±1.67	4.60±1.53	5.30±1.70	0.02
White blood cells (×10^9/L)	7.62±1.95	7.38±1.77	7.73±2.03	0.32
Blood lymphocytes (×10^9/L)	1.78±0.65	1.76±0.58	1.78±0.68	0.84
Blood NLR	2.84 (2.15, 3.85)	2.59 (2.07, 3.23)	3.00 (2.24, 4.00)	0.04
Blood ELR	0.12 (0.07, 0.18)	0.15 (0.13, 0.24)	0.09 (0.06, 0.16)	<0.0001
Blood ENR	0.04 (0.02, 0.06)	0.07 (0.04, 0.08)	0.03 (0.02, 0.05)	<0.0001

Notes:

a Participants with sputum eosinophil count ≥3%;

b participants with sputum eosinophil count <3%;

* P-value for the comparison of eosinophilic vs noneosinophilic COPD. Data expressed as mean ± SD, median (interquartile range) or as number (%).

Abbreviations: NLR, neutrophil/lymphocyte ratio; ELR, eosinophil/lymphocyte ratio; ENR, eosinophil/neutrophil ratio; SD, standard deviation.

Figure 2 Scatter dot plot comparing.

Notes: (A) Blood eosinophil count, (B) eosinophil/neutrophil ratio, (C) eosinophil/lymphocyte ratio, and (D) neutrophil/lymphocyte ratio between eosinophilic (≥3% sputum eosinophils) and noneosinophilic COPD (<3% sputum eosinophils). Graphs represent individual data points and a median as a bar (red).
Abbreviations: ENR, eosinophil/neutrophil ratio; ELR, eosinophil/lymphocyte ratio; NLR, neutrophil/lymphocyte ratio.

Figure 3 Scatter plots for correlations between sputum and blood eosinophil counts.

Notes: (A) Correlation between percentage sputum eosinophils and absolute blood eosinophil count (×10⁹/L). Vertical dotted line represents upper limit of normal for percentage sputum eosinophils. (B) Correlation between absolute sputum eosinophil counts (×10⁴/L) and absolute blood eosinophil count (×10⁹/L).

Table 3 Summary of sensitivity and specificity for different blood eosinophil cutoff points for detecting sputum eosinophilia

Blood eosinophil cutoff points (×10^9/L)	Sensitivity (%)	Specificity (%)	Correctly classified (%)	LR (+)	LR (−)
≥0.1	97.8	6.3	35.5	1.04	0.36
≥0.2	91.1	50.0	63.1	1.82	0.18
≥0.3	60.0	76.0	70.9	2.50	0.53
≥0.4	31.1	91.7	72.3	3.73	0.75
≥0.5	13.3	94.8	68.8	2.56	0.91
≥0.6	8.9	99.0	70.2	8.53	0.92
≥0.7	4.4	100.0	69.5	a	0.96

Note:

a The LR (+) at this cutoff point is incalculable (with 0 as a denominator).

Abbreviations: LR (+), positive likelihood ratio; LR (−), negative likelihood ratio.

Figure 4 Receiver operating characteristic (ROC) curve for absolute blood eosinophil count to predict sputum eosinophilia (≥3%).

Note: Points on the ROC curve are presented as (specificity %, sensitivity %).

Table 4 Demographics and clinical characteristics of participants with and without blood eosinophilia

Variable	Participants with blood eosinophilia (≥0.4×10^9/L)	Participants without blood eosinophilia (<0.4×10^9/L)	P-value*
Number	22 (15.6)	119 (84.4)	NA
Age (years)	70.1±7.5	69.7±7.8	0.84
Sex (male)	13 (59.1)	76 (63.9)	0.81
Postbronchodilator FEV1 (% predicted)	65.1±19.3	56.1±17.4	0.03
Postbronchodilator FEV1 (L)	1.56 (1.2, 1.88)	1.48 (1.12, 1.79)	0.31
Postbronchodilator FEV1 FVC ratio (%)	58.82±14.83	54.64±14.79	0.23
Reversibility (L)	0.025 (0, 0.12)	0.045 (0.01, 0.1)	0.51
Reversibility (%)	2.5 (0, 12.03)	4.55 (0.95, 9.66)	0.51
CCI score	4 (3, 5)	4 (3, 4)	0.14
Frequent vs nonfrequent exacerbatorsa	13 vs 9 (59.1, 40.9)	61 vs 58 (51.2, 48.8)	0.64
Number of severe exacerbation	0 (0, 1)	0 (0, 1)	0.60
GOLD grade			0.23
I	4 (18.2)	7 (5.9)
II	12 (54.5)	62 (52.1)
III	5 (22.7)	40 (33.6)
IV	1 (4.5)	10 (8.4)
GOLD quadrant			0.16
A	0 (0)	9 (7.6)
B	3 (13.6)	32 (26.9)
C	6 (27.3)	15 (12.6)
D	13 (59.1)	63 (52.9)
BMI (kg/m^2)	31.1 (26.7, 34.5)	30.2 (25.5, 34.9)	0.91
Ex-smokers	19 (86.4)	97 (81.5)	0.77
Pack years	22.3 (9, 42)	38.8 (15, 65)	0.06
SGRQ	44.2 (32.8, 66.6)	50.2 (38, 61.1)	0.89
BODEx	2 (1, 3)	3 (1, 5)	0.047
mMRC score ≥2	12 (54.5)	84 (59.6)	0.14
ICS or ICS/LABA combination use	22 (100)	106 (89.1)	0.22
ICS doseb (μg/d)	500 (400, 500)	500 (250, 500)	0.16
LAMA use	16 (72.7)	94 (79)	0.52
Prior history of asthma	12 (55)	57 (48)	0.65

Notes:

a Frequent exacerbators: ≥2 exacerbations in the previous year, and nonfrequent exacerbators: <2 exacerbations in the previous year;

b ICS dose calculated as beclomethasone equivalents where 1 μg of beclomethasone =1 μg budesonide =0.5 μg fluticasone. Data expressed as mean ± standard deviation, median (interquartile range) or as number (%);

* P-value for the comparison of participants with and without blood eosinophilia.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; CCI, Charlson Comorbidity Index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; BMI, body mass index; SGRQ, St George Respiratory Questionnaire; BODEx, body mass index, airflow obstruction, dyspnea, severe exacerbation; mMRC, modified Medical Research Council; ICS, inhaled corticosteroids; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonists; NA, not applicable.

Figure 5 Bland–Altman plot showing the difference between the absolute blood eosinophil counts of two measurements against the mean of the absolute blood eosinophil counts of the two measurements.

Notes: The blue line represents the mean of differences (bias line). Horizontal dotted lines represent the 95% limits of agreement (mean difference ±1.96 SD).
Abbreviation: SD, standard deviation.