Association of blood eosinophils and plasma periostin with FEV₁ response after 3-month inhaled corticosteroid and long-acting beta₂-agonist treatment in stable COPD patients

Figures & data

Figure 1 Study flow diagram.

Abbreviations: ICS, inhaled corticosteroids; LABA, long-acting beta₂-agonist.

Table 1 Baseline characteristics of 130 COPD patients

Characteristics	Median (IQR) or no (%)
Age, years	67 (61–70)
Male	126 (96.9)
Body mass index, kg/m^2	23.4 (21.5–25.1)
Body mass index ≥25 kg/m^2	33 (25.4)
Smoking status
Current smoker	53 (40.8)
Ex-smoker	77 (59.2)
Smoking pack-years	45 (35–59)
Comorbidities, overlapping
Chronic heart disease	55 (42.3)
Diabetes	9 (7.0)
Malignant disease	1 (0.8)
Cerebrovascular disease	1 (0.8)
Chronic kidney disease	1 (0.8)
Dyspnea (mMRC ≥2)	50 (38.5)
Lung function test
FVC (L)	3.3 (2.6–3.7)
FVC (% pred)	74.1 (64.4–87.1)
FEV1 (L)	1.5 (1.1–1.8)
FEV1 (% pred)	49.5 (38.8–60.8)
6-minute walk test (distance, m)	445 (403–486)
Positive bronchodilator response	47 (36.2)
Exacerbation (% of subjects)	17 (13.1)
Emphysema index	17.6 (8.0–30.9)
Laboratory findings
White blood cell count (/µL)	7,240 (6,000–8,450)
Neutrophil count (/µL)	3,921 (3,094–4,811)
Eosinophil count (/µL)	200.0 (120.6–345.6)
C-reactive protein (mg/L) (n=63)	1.5 (0.6–3.7)
Plasma periostin (ng/mL)	9.0 (1.0–41.3)

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IQR, interquartile range; mMRC, modified Medical Research Council; pred, predicted.

Table 2 Clinical findings of 130 COPD patients with and without ICS/LABA response

Characteristics of 130 COPD patients with and without ICS/LABA response	FEV1 non-responders (n=88)	FEV1 responders (n=42)	P-value
Age, years	68 (62–72)	65 (61–69)	0.046
Male	86 (97.7)	40 (95.2)	0.594
Smoking status
Current smoker	33 (37.5)	20 (47.6)	0.272
Smoking pack-years	46 (30–58)	45 (40–61)	0.587
Body mass index, kg/m^2	23.1 (20.5–25.3)	24.1 (22.7–25.0)	0.063
Dyspnea (mMRC ≥2)	33 (37.5)	17 (40.5)	0.744
Baseline FEV1 (% pred)			0.045
FEV1 50 to 80% pred	48 (54.5)	15 (35.7)
FEV1 <50% pred	40 (45.5)	27 (64.3)
Positive bronchodilator response	24 (27.3)	23 (54.8)	0.002
6-minute walk test (distance, m)	443 (404–487)	449 (401–483)	0.897
Chronic heart disease	34 (39.1)	21 (50.0)	0.240
Exacerbation (% of subjects)	14 (15.9)	3 (7.1)	0.166
Emphysema index	17.8 (8.4–30.3)	16.3 (7.3–32.2)	0.968

Note: The data are presented as numbers (%) or as medians and interquartile ranges.

Abbreviations: FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; LABA, long-acting beta₂-agonist; mMRC, modified Medical Research Council; pred, predicted.

Figure 2 Comparison of high blood eosinophils and high plasma periostin between FEV₁ responders and FEV₁ non-responders.

Abbreviation: FEV₁, forced expiratory volume in 1 second.

Table 3 Adjusted odds ratio of blood eosinophils >260/µL and plasma periostin >23 ng/mL for FEV₁ responders

Variables	Adjusted state
	OR	95% CI	P-value
Model 1
Age	0.96	0.90–1.03	0.268
Blood eosinophils >260/µL	3.52	1.37–8.99	0.009
Positive bronchodilator response at baseline	2.85	1.15–7.10	0.024
Baseline FEV1 <50% pred	3.12	1.18–8.27	0.022
Model 2
Age	0.96	0.89–1.02	0.181
Plasma periostin >23 ng/mL	3.52	1.31–9.49	0.013
Positive bronchodilator response at baseline	2.91	1.17–7.21	0.021
Baseline FEV1 <50% pred	2.74	1.05–7.15	0.040
Model 3
Age	0.95	0.89–1.02	0.150
Combined high blood eosinophils >260/µL and high plasma periostin >23 ng/mL	6.40	1.60–25.55	0.009
Positive bronchodilator response at baseline	3.21	1.29–7.98	0.012
Baseline FEV1 <50% pred	2.98	1.12–7.94	0.029

Note: Body mass index, smoking status, exacerbation, and emphysema index were entered into the logistic analysis in all models.

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; OR, odds ratio; pred, predicted.

Table 4 Area under the curve values from receiver operator characteristics generated for variables with blood eosinophils >260/µL and plasma periostin >23 ng/mL for the prediction of FEV₁ responders

Variables	AUC (95% CI)
Age	0.608 (0.509–0.707)
Baseline FEV1 <50% pred	0.594 (0.504–0.684)
Positive bronchodilator response at baseline	0.637 (0.548–0.726)
High blood eosinophils >260/µL	0.639 (0.549–0.728)
High plasma periostin >23 ng/mL	0.595 (0.507–0.683)
Positive bronchodilator response at baseline	0.637 (0.548–0.726)
Positive bronchodilator response at baseline + age	0.685 (0.587–0.783) (P=0.093)*
Positive bronchodilator response at baseline + age + baseline FEV1 <50% pred	0.700 (0.602–0.800) (P=0.527)*
Positive bronchodilator response at baseline + age + baseline FEV1 <50% pred + high blood eosinophils >260/µL	0.771 (0.688–0.853) (P=0.045)*
Positive bronchodilator response at baseline + age + baseline FEV1 <50% pred + high plasma periostin >23 ng/mL	0.729 (0.636–0.823) (P=0.346)‡
Positive bronchodilator response at baseline + age + baseline FEV1 <50% pred + combined high blood eosinophils >260/µL and high plasma periostin >23 ng/mL	0.769 (0.682–0.856) (P=0.064)‡

Notes:

* P-value for comparison with model of previous step.

‡ P-value for comparison with model of positive bronchodilator response at baseline + age + baseline FEV₁ <50% pred.

Abbreviations: AUC, area under the curve; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; pred, predicted.