Eosinophilic and Neutrophilic Airway Inflammation in the Phenotyping of Mild-to-Moderate Asthma and Chronic Obstructive Pulmonary Disease

Figures & data

Table 1. Clinical characteristics of patients with asthma and chronic obstructive pulmonary disease participating in the study.

	Asthma (n = 24)	COPD (n = 33)	p
Male/female (n)	11/13	20/13	0.347
Age (years)	51 (31–60.5)	68 (61–72)	<0.001  1.90E-07
BMI (kg/m^2)	27.1 (25.5–31.2)	26.3 (23.5–29.5)	0.173
Never smokers/ex-smokers/current smokers, n (%)	21(87.5)/3(12.5)/0	0/18(55.5)/15(44.5)	<0.001  3.0E-05
Smoking history (pack-years)	0 (0.0)	45 (35–57)	<0.001  2.07E-14
Duration of symptoms (months)	60 (33–120)	54 (24–120)	0.537
Pre-bronchodilator FEV^1% of predicted	88.5 (75.5–97)	67 (54–75)	<0.001  1.27E-06
Pre-FEV^1/VC ratio (%)	63.5 (61.5–71)	50 (44–56)	<0.001  1.11E-07
Post-bronchodilator FEV^1% of predicted	98.5 (74–121)	70 (61.9–80)	<0.001  4.36E-08
Post-FEV^1/VC ratio (%)	70.5 (64–75.5)	52 (47–56)	<0.001  3.73E-08
RV % of predicted	128.5 (116–150.5)	168 (141.187)	<0.001  4.51E-05
TLC % of predicted	117.04 (106.5–127)	124.5 (114.5–131)	0.072
Positive skin prick tests, n (%)	17 (71)	10 (30)	0.003  3.34E-03

Results are presented as median and IQR. Analyses were made using Fisher's exact test, Mann–Whitney U test; The bolded values are statistically significant (p < 0.05); COPD, chronic obstructive pulmonary disease; BMI, body mass index; FEV¹, forced expiratory volume in 1 second; VC, vital capacity; TLC, total lung capacity; RV, residual volume.

Table 2. Mediator concentrations and cell numbers in serum/blood and induced sputum from asthma and COPD patients.

	Asthma (n = 24)	COPD (n = 33)	p
IL-6 serum (pg/mL)	2.02 (0.86–2.5)	3.7 (1.97–4.92)	0.001  1.10E-03
IL-6 IS (pg/mL)	12.7 (7.32–15.78)	16.46 (13.38–17.45)	0.011  1.09E-02
MMP-9 serum (ng/mL)	560.19 (220.33–825.74)	485.59 (263.82–832.37)	0.791
MMP-9 IS (ng/mL)	136.91 (35.08–256.68)	323.35 (129.33–872.38)	0.010  9.79E-03
NE serum (pg/mL)	22.6 (17.26–35.93)	30.26 (14.93–36.93)	0.558
NE IS (pg/mL)	256.36 (210.9–347.27)	329.09 (256.36–656.36)	0.007  6.98E-03
IL-17 serum (pg/mL)	3.68 (2.13–9.93)	4.0 (0.88–9.15)	0.580
IL-17 IS (pg/mL)	1.85 (0–4.54)	3.0 (0.7–6.07)	0.356
ECP serum (ng/mL)	10.77 (8.85–12.21)	9.64 (6.57–11.23)	0.158
ECP IS (ng/mL)	0.01 (0–0.2)	0 (0–0.16)	0.277
IL-33 serum (pg/mL)	0.06 (0–0.7)	0.006 (0–0.54)	0.917
IL-33 IS (pg/mL)	0.75 (0.5–3.01)	0.7 (0.14–2.32)	0.907
Eosinophils blood (%)	4 (2–7)	2 (1–4)	0.01 9.63E-03
[×10^9cells/L]	[0.22 (0.16–0.37)]	[0.14 (0.1–0.21)]	[0.015] 1.58E-02
Granulocytes blood (%)	55.5 (44–61.5)	56 (52–61)	0.446
[×10^9cells/L]	[3.36 (2.54–4.41)]	[4.03 (3.15–4.55)]	[0.108]
Eosinophils IS (%)	10 (2–32)	1 (0–4)	<0.001  2.91E-04
[×10^6cells/g sputum]	[0.21 (0.04–0.83)]	[0.04 (0–0.17)]	[0.003]  2.96E-03
Neutrophils IS (%)	38 (25–55)	75.5 (58–91)	<0.001   4.16E-05
[×10^6cells/g sputum]	[1.08 (0.66–1.82)]	[2.1 (0.95–2.92]	[0.030] 3.01E-02

Results are presented as median and IQR. Analyses were made using Mann–Whitney U test; p-value: COPD, chronic obstructive pulmonary disease; IS, induced sputum; ECP, eosinophil cationic protein; MMP-9, matrix metalloproteinase 9; NE, neutrophil elastase.

Figure 1. Correlations between blood and sputum eosinophils (red triangles) and blood and sputum neutrophils (black circles) in asthma and COPD patients.

Figure 2. Receiver operating characteristic (ROC) curve analysis of the diagnostic accuracy of different blood/serum (a) and induced sputum (b) biomarkers (IL-6, IL-17, IL-33, MMP-9, ECP, NE, eosinophil and neutrophil percentages and combined model) in the differentiation between asthma and COPD.

Figure 3. Hierarchical clustering of asthma and COPD patients. Single set of clinical and laboratory data per one patient was used for clustering. (a) Patients clustered according to peripheral blood eosinophil percentage, FEV¹%, FEV¹/VC, RV%, pack-years, and atopy. (b) Patients clustered according to data from sputum samples (eosinophil and neutrophil percentages, IL-6, NE and MMP-9 concentrations) and clinical data (FEV¹/VC, FEV¹%, RV%, pack-years, and atopy status). Patient IDs are given at the bottom of the plot. The color scale codes the value of a variable with the brightest shade corresponding to the highest value.