The Value of Inflammatory Biomarkers in Differentiating Asthma–COPD Overlap from COPD

Figures & data

Table 1 Characteristics of the Study Patients (n=182)

Characteristics	COPD (n = 134)	ACO (n = 48)	P-value
Sex (M/F)	91/43	26/22	0.114
Age (years)	67.66±8.63	61.13±9.41	<0.001*
BMI (kg/m^2)	22.57±3.24	23.03±3.47	0.703
Smoking history	79 (59.0%)	20 (41.7%)	0.044*
Smoking status
Current smoking	48(25.8%)	8(40.0%)	0.094
Ex-Smoking	31(74.2%)	12(60.0%)
ICS use	61 (45.5%)	24 (50.0%)	0.617
Comorbidity
Hypertension	47 (35.1%)	13 (27.1%)	0.373
Diabetes mellitus	10 (7.5%)	3 (6.3%)	0.998
Cardiovascular disease	25 (18.7%)	3 (6.3%)	0.060
Neutrophils (10^9/L)	4.80 (3.60, 7.06)	4.55 (3.28, 6.47)	0.426
Lymphocyte (10^9/L)	1.33 (0.97, 1.70)	1.47 (1.03, 1.89)	0.432
Platelet (10^9/L)	192.00 (170.00, 236.00)	211.50 (181.25, 301.5)	0.028*
EOS (10^9/L)	0.10 (0.04, 0.21)	0.20 (0.07, 0.45)	0.004*
NLR	3.99 (2.31, 6.12)	3.27 (2.16, 4.59)	0.287
PLR	148.35 (112.54, 206.23)	142.67 (118.43, 251.62)	0.563
CRP (mg/L)	5.20 (3.10, 20.85)	5.21 (3.20, 17.23)	0.804
FVC (L)	2.06 (1.52,2.69)	2.00 (1.51, 2.41)	0.356
FEV1(L)	1.03 (0.78, 1.30)	1.12 (0.79, 1.41)	0.382
FEV1/FVC (%)	52.35±10.63	50.66±8.22	0.009*
FEV1%pred (%)	38.00 (29.00, 52.00)	39.00 (32.25, 52.25)	0.484
FeNO (ppb)	24.50 (16.75, 33.50)	37.50 (23.00, 60.75)	<0.001*

Notes: Data are shown as number (%) or medians (interquartile range) or means±SD, *P<0.05 value indicates statistical significance.

Abbreviations: COPD, chronic obstructive pulmonary disease; ACO, asthma–COPD overlap; BMI, body mass index; ICS, inhaled corticosteroids; EOS, blood eosinophils count; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; CRP, c-reactive protein; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; FEV₁%pred, forced expiratory volume in one second/prediction; FeNO, fractional exhaled nitric oxide.

Figure 1 Inflammatory biomarkers levels in COPD and ACO.

Notes: (A) FeNO levels; (B) EOS levels; (C) NLR levels. All of them are shown as medians (interquartile range). Mann–Whitney U-test were used to assess the differences between groups. P<0.05 indicates statistical significance.

Abbreviations: FeNO, fractional exhaled nitric oxide; EOS, blood eosinophils count; NLR, neutrophil to lymphocyte ratio; ICS, inhaled corticosteroids.

Figure 2 Correlation of FeNO with EOS in patients with ACO.

Notes: (A) overall patients; (B) patients without ICS use; (C) patients with ICS use; (D) patients without smoking history; (E) patients with smoking history. P<0.05 indicates statistical significance.

Abbreviations: FeNO, fractional exhaled nitric oxide; EOS, blood eosinophils count; NLR, neutrophil to lymphocyte ratio; ICS, inhaled corticosteroids.

Figure 3 Correlation of inflammatory biomarkers with FEV₁%pred in patients with ACO.

Notes: (A) FeNO with FEV₁%pred; (B) EOS with FEV₁%pred; (C) NLR with FEV₁%pred; P<0.05 indicates statistical significance.

Abbreviations: FeNO, fractional exhaled nitric oxide; EOS, blood eosinophils count; NLR, neutrophil to lymphocyte ratio.

Table 2 Diagnostic Accuracy of Inflammatory Biomarkers

Biomarkers	AUC (95% CI)	Sen. (%)	Spe. (%)	PPV (%)	NPV (%)	P-value
Overall (n = 182)
FeNO≥39.5 ppb	0.683 (0.590–0.776)	50.0	83.6	52.2	82.4	<0.001*
EOS≥0.335×10^9/L	0.640 (0.542–0.738)	39.6	90.3	59.4	80.7	0.004*
FeNO + EOS	0.678 (0.580–0.775)	69.8	75.5	53.6	82.5	<0.001*
No ICS use history (n = 97)
FeNO≥39.5ppb	0.740 (0.610–0.870)	58.3	84.9	56.0	86.1	<0.001*
EOS≥0.285×10^9/L	0.693 (0.554–0.833)	41.7	94.5	71.4	83.1	0.005*
FeNO + EOS	0.740 (0.610–0.869)	75.7	80.2	56.3	90.7	<0.001*
ICS use history (n = 85)
FeNO≥40.5ppb	0.635 (0.506–0.765)	41.7	82.0	47.6	78.1	0.053
EOS≥0.335×10^9/L	0.588 (0.449–0.727)	41.7	80.3	45.5	77.8	0.208
FeNO + EOS	0.623 (0.482–0.764)	66.0	65.9	44.4	83.7	0.078
No smoking history (n = 83)
FeNO≥39.5ppb	0.632 (0.502–0.761)	46.4	80.0	22.8	42.3	0.051
EOS≥ 0.335×10^9/L	0.617 (0.479–0.755)	35.7	92.7	16.4	81.8	0.084
FeNO + EOS	0.638 (0.506–0.769)	65.5	74.2	56.3	80.4	0.050
Smoking history (n = 99)
FeNO≥31.5ppb	0.758 (0.631–0.886)	70.0	89.9	40.0	90.6	<0.001*
EOS≥0.360×10^9/L	0.692 (0.556–0.828)	45.0	73.4	52.9	86.6	0.008*
FeNO + EOS	0.742 (0.600–0.885)	83.5	66.0	38.6	94.6	<0.001*
No ICS use and smoking history (n = 39)
FeNO≥27.5ppb	0.744(0.579,0.908)	81.8	60.7	45.0	89.5	0.019*
EOS≥0.305×10^9/L	0.597(0.367,0.828)	54.5	71.4	42.9	80.0	0.349
FeNO + EOS	0.727(0.560,0.894)	91.7	43.3	38.5	92.3	0.029*
Both ICS use and smoking history (n = 41)
FeNO≥40.5pb	0.574(0.338,0.809)	42.9	79.4	30.0	87.1	0.782
EOS≥0.660×10^9/L	0.534(0.292,0.775)	28.6	94.1	50.0	86.5	0.544
FeNO + EOS	0.534(0.281,0.786)	59.2	74.7	30.8	89.3	0.782

Note: *P<0.05 value indicates statistical significance.

Abbreviations: AUC, area under curve; 95% CI, 95% confidence interval; Sen, sensitivity; Spe, specificity; PPV, positive predictive value; NPV, negative predictive value; ICS, inhaled corticosteroids; EOS, blood eosinophils count; FeNO, fractional exhaled nitric oxide.

Figure 4 ROC curve for inflammatory markers for differentiating ACO from COPD.

Notes: (A) overall patients; (B) patients without ICS use; (C) patients with ICS use; (D) patients with smoking history; (E) patients without smoking history; (F) patients without smoking and ICS use history; (G) patients with smoking and ICS use history.

Abbreviations: FeNO, fractional exhaled nitric oxide; EOS, blood eosinophils count; NLR, neutrophil to lymphocyte ratio; ICS, inhaled corticosteroids.