Sputum cell count: biomarkers in the differentiation of asthma, COPD and asthma–COPD overlap

Figures & data

Table 1 Patient demographics and baseline characteristics

Demographic parameter	Asthma (N=142)	COPD (N=160)	ACO (N=72)	p-value
Mean age, years (SD)	46.2 (16.45)	71.8 (8.50)	59.5 (15.78)	<0.001
Male, n (%)	56 (39.4)	132 (82.5)	53 (73.6)	<0.001*
Race, Chinese, n (%)	100	100	100
Mean height, cm (SD)	161 (8.42)	160 (7.46)	163 (7.83)	0.840
Mean weight, kg (SD)	59.8 (10.58)	52.5 (10.20)	59.8 (10.36)	0.999
Mean body mass index, kg/m^2 (SD)	23.19 (3.78)	20.51 (3.51)	22.36 (3.16)	0.270
Smokers, n (%)	24 (16.9)	112 (70)	37 (51.4)	<0.007
GOLD stage, n (%)
1	–	2 (1.25)	8 (11.11)
2	–	49 (30.62)	50 (69.45)
3	–	58 (36.25)	14 (19.44)
4	–	51 (31.88)	0 (0)
BHR stage, n (%)
Very mild	36 (25.35)	–	–
Mild	37 (26.06)	–	–
Moderate	48 (33.8)	–	–
Severe	21 (14.79)	–	–

Notes: N refers to the total population; n refers to the subgroup population.

* Difference between two groups was not statistically significant (p>0.05).

Abbreviations: ACO, asthma–COPD overlap; BHR, bronchial hyperresponsiveness; GOLD, Global Initiative for Chronic Obstruction Lung Disease.

Table 2 Spirometry results of the patients

Variable	Asthma (N=142) (baseline)	COPD (N=160) (postbronchodilator)	ACO (N=72) (postbronchodilator)	p-value
FVC (L), mean (SD)	3.21 (0.82)	1.97 (0.66)	3.04 (0.82)	<0.001*
FEV1 (L), mean (SD)	2.34 (0.68)	0.93 (0.41)	1.66 (0.58)	<0.001
FEV1 %predicted, mean (SD)	85.55 (12.83)	42.39 (18.90)	61.97 (15.33)	<0.001
FEV1/FVC (%), mean (SD)	73 (9.58)	46.85 (11.44)	54.04 (9.61)	<0.001
PEF (L/min), mean (SD)	6.04 (1.85)	2.53 (1.25)	4.15 (1.62)	<0.001
MMEF (L/sec), mean (SD)	1.87 (0.45)	0.47 (0.24)	0.87 (0.45)	<0.001
MEF50% (L/sec), mean (SD)	2.22 (1.01)	0.54 (0.31)	1.07 (0.54)	<0.001
MEF25% (L/sec), mean (SD)	1.02 (1.08)	0.24 (0.12)	0.4 (0.21)	<0.001

Note:

* Difference between two groups was not statistically significant (p>0.05).

Abbreviations: ACO, asthma–COPD overlap; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; MEF, maximal expiratory flow; MMEF, maximum mid-expiratory flow; PEF, peak expiratory flow.

Table 3 Results of induced sputum cells of the patients

Variables	Asthma (N=142)	COPD (N=160)	ACO (N=72)	p-value
Eosinophil (%)	3.93 (1.05, 21.18)	1.5 (0.38, 4.01)	5.12 (1.37, 18.86)	<0.001*
Neutrophil (%)	71.09 (42.9, 90.74)	92.18 (85.35, 96.08)	80.5 (61.2, 91.1)	<0.001
Lymphocyte (%)	0.87 (0.2, 1.62)	1.3 (0.58, 2.7)	1.1 (0.4, 1.82)	0.005*
Macrophage (%)	9.8 (3.16, 30.15)	2.3 (0.95, 5.95)	5.74 (2.07, 16.08)	<0.001

Notes: Values are expressed as median (interquartile range).

* Difference between two groups was not statistically significant (p>0.05), p-value for the differences was analyzed by Kruskal–Wallis test.

Abbreviation: ACO, asthma–COPD overlap.

Table 4 Results of induced sputum cells in the stage of COPD, ACO and asthma

Variables	COPD					ACO				Asthma
	Stage 1	Stage 2	Stage 3	Stage 4	p-value	Stage 1	Stage 2	Stage 3	p-value	Very mild	Mild	Moderate	Severe	p-value
Eosinophil (%)	1.04 (0, 1.55)	1.71 (0.4, 4.66)	1.15 (0.3, 3.47)	1.84 (0, 5.2)	0.654	14.9 (1.2, 34.71)	5.12 (1.95, 17.89)	1.71 (0.4, 21.86)	0.603	1.79 (0.43, 19.98)	3.2 (1.06, 11.99)	5.09 (1.79, 31.65)	4.2 (1.16, 21.54)	0.474
Neutrophil (%)	92.78 (69.11, 70.06)	90.42 (80.18, 93.9)	93 (87.36, 96.23)	92.5 (86.69, 97.07)	0.16	82.46 (56.58, 91.1)	78.71 (60.26, 90.55)	87.06 (69, 95.43)	0.552	70.29 (42.7, 84.92)	81 (47.36, 92.22)	66 (37.3, 90.86)	70.1 (46.63, 93.82)	0.546
Lymphocyte (%)	2.24 (1.55, 1.8)	1 (0.4, 3)	1.36 (0.83, 4.94)	1.2 (0.7, 2.8)	0.631	1.1 (0.67, 1.69)	1.1 (0.2, 2.35)	0.9 (0.24, 1.41)	0.346	0.94 (0.33, 1.75)	1.21 (0.48, 2.29)	0.66 (0, 1.32)	0.68 (0, 1.68)	0.095
Macrophage (%)	3.96 (2.8, 3.14)	4 (1.55, 9.5)	2.24 (0.83, 4.94)	1.79 (0.76, 5)	0.078	4.37 (1.28, 6.1)	6.3 (2.88, 16.38)	2.96 (1.61, 10.44)	0.247	15.03 (7.09, 37.65)	6.4 (2.41, 19.75)	7.67 (3.06, 34.03)	8 (1.46, 25.66)	0.338

Note: Values are expressed as median (interquartile range).

Abbreviation: ACO, asthma–COPD overlap.

Figure 1 Scatter plots of correlations between sputum eosinophils, BHR and bronchodilator reversibility.

Notes: (A) Correlation between the percentage of sputum eosinophils and PD₂₀ (mg). (B) Correlation between the percentage of sputum eosinophils and ΔFEV₁ (mL); Δ, improvement in FEV₁ after 400 μg of salbutamol.
Abbreviations: BHR, bronchial hyperresponsiveness; FEV₁, forced expiratory volume in 1 second; PD₂₀, provocative dose.

Table 5 Results of ROC analysis of induced sputum cells in the discovery cohort

Discovery cohort	Eosinophil (%)	Neutrophil (%)	Lymphocyte (%)	Macrophage (%)
ACO versus COPD
AUC (95% CI)	0.708 (0.633–0.782)	0.271 (0.2–0.342)	0.433 (0.354–0.513)	0.660 (0.583–0.736)
Cutoff (%)	3.55	84.55	5.76	4.63
Sensitivity/specificity (%)	59.7/72.5	37.5/23.7	97/12	58.3/69.4
p-value	<0.001	<0.001	0.104	<0.001
Asthma versus COPD
AUC (95% CI)	0.673 (0.612–0.733)	0.234 (0.18–0.288)	0.393 (0.329–0.456)	0.746 (0.69–0.802)
Cutoff (%)	8.95	76.4	1.77	5.33
Sensitivity/specificity (%)	38.7/88.7	44.4/11.2	22.5/60	65.5/72.5
p-value	<0.001	<0.001	0.001	<0.001
ACO versus asthma
AUC (95% CI)	0.518 (0.438–0.598)	0.585 (0.508–0.661)	0.541 (0.458–0.623)	0.389 (0.312–0.466)
Cutoff (%)	1.11	70.66	1.64	7.16
Sensitivity/specificity (%)	84.7/25.4	69.4/50	34.7/76.1	36.1/43
p-value	0.668	0.43	0.33	0.008

Abbreviations: ACO, asthma–COPD overlap; AUC, area under the curve; ROC, receiver operating characteristic.

Figure 2 ROC curve for induced sputum cell counts in ACO versus COPD (A), asthma versus COPD (B), ACO versus asthma (C).

Abbreviations: ACO, asthma–COPD overlap; ROC, receiver operating characteristic.