The Value of Impulse Oscillometric Parameters and Quantitative HRCT Parameters in Differentiating Asthma–COPD Overlap from COPD

Figures & data

Figure 1 Enrollment flow chart of study.

Figure 2 Quantitative measurement of airways by HRCT.

Figure 3 Quantitative measurement of emphysema and air trapping by HRCT.

Table 1 Comparison of General Information Among the Healthy Control, COPD Patients, and ACO Patients

General Information	COPD (n=40)		ACO (n=26)		Control (n=44)	P value
Age, years	61.28±10.73		58.62±11.06		54.07±12.62*	0.019
Males	35(87.50)		16(61.54)		24(54.55) *^@	0.004
BMI, kg.m^−2	22.66±3.07		21.00±3.92		23.75±3.32^#	0.011
BSA,m^Citation2	1.61±0.18		1.53±0.15		1.63±0.22	0.180
Smokers, n (%)	21(52.50)		14(53.85)		13(29.55)	0.052
Atopy or allergic rhinitis, n (%)	2(5.00)		6(23.08)		1(2.27) ^#@	0.006
0 exacerbation, n (%)	31(77.50)		12(46.15)		NT	0.028
1 exacerbation, n (%)	6(15.00)		8(30.77)		NT
≥2 exacerbations, n (%)	3(7.50)		6(23.08)		NT
LAMA, n (%)	8(20.00)		2(7.70)		NT	0.293
ICS/LABA, n (%)	27(67.50)		20(76.92)		NT	0.579
ICS/LABA/LAMA, n (%)	5(12.50)		4(15.38)		NT	0.730

Notes: Exacerbations were defined as the number of respiratory exacerbations that resulted in a hospitalization or an emergency room visit in the year preceding enrolment. Data are presented as number (%) or mean ± standard deviation%), unless otherwise stated. Bold indicates P-values less than 0.05. *P<0.05, health control vs COPD group; ^#P<0.05, health control vs ACO group; ^@P<0.05, COPD group vs ACO group. BSA = 0.20247 × height^0.725 × weight^0.425, BMI= weight/ height², where height was measured in meters and weight was measured in kilograms.

Abbreviations: n, number; COPD, chronic obstructive pulmonary disease; ACO, asthma–COPD overlap; BSA, body square area; BMI, body mass index; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroids.

Table 2 Pulmonary Function Test Results Among the Healthy Control, COPD Patients, and ACO Patients

Parameters	COPD	ACO	Control	P
FVC (%pred)	89.13±17.87	79.39±19.80	105.01±15.75 *^#	<0.001
FEV1 (%pred)	64.00 (42.25–82.25)	57.40 (34.35–67.25)	98.75 (94.05–110.00) *^#	<0.001
FEV1/FVC (%)	53.97 (42.14–66.66)	53.92 (43.29–61.02)	78.28 (75.47–81.84) *^#	<0.001
MEF75 (% pred)	35.90 (14.30–58.05)	19.60 (12.35–42.75)	92.70 (81.55–115.48) *^#	<0.001
MEF50 (% pred)	22.30 (11.85–46.75)	16.60 (9.05–29.70)	81.15 (63.08–99.50) *^#	<0.001
MEF25 (% pred)	23.65 (19.78–32.65)	20.30 (12.50–27.60)	55.35 (46.13–74.15) *^#	<0.001
MMEF (%pred)	22.45 (13.03–39.20)	16.10 (9.25–26.20)	69.65 (57.50–89.18) *^#	<0.001
Fres (Hz)	19.95 (13.15–25.74)	23.27 (16.37–28.20)	13.00 (9.25–16.26) *^#	<0.001
R5(kpa·L^−1·s^−1)	0.46 (0.36–0.59)	0.58 (0.53–0.66)	0.37 (0.31–0.46) *^#@	<0.001
R20(kpa·L^−1·s^−1)	0.32 (0.28–0.37)	0.30 (0.26–0.46)	0.33 (0.27–0.38) *^#@	0.918
R5-R20(kpa·L^−1·s^−1)	0.14 (0.06–0.22)	0.31(0.19–0.37)	0.06 (0.02–0.08) *^#@	<0.001
X5(kpa·L^−1·s^−1)	−0.17 (−0.30 to −0.10)	−0.26(−0.45 to −0.20)	−0.11 (−0.15 to −0.07) *^#@	<0.001
AX (kpa·L^−1)	1.18 (0.40–2.62)	1.49 (0.81–4.00)	0.34 (0.15–0.68) *^#	<0.001

Notes: Data are presented as mean ± standard deviation or medians (interquartile range). Bold indicates P-values less than 0.05. *P<0.05, health control vs COPD group; ^#P<0.05, health control vs ACO group; ^@P<0.05, COPD group vs ACO group.

Abbreviations: COPD, chronic obstructive pulmonary disease; ACO, asthma–COPD overlap; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FEV1/FVC (%), forced expiratory volume in the first second/forced vital capacity; FEF75%, forced expiratory flow at 75% of the FVC; FEF50%, forced expiratory flow at 50% of the FVC; FEF25%, forced expiratory flow at 25% of the FVC; FEF25-75%, forced expiratory flow between 25–75% of the FVC; Fres, resonant frequency; R5, resistance at 5 Hz; R20, resistance at 20 Hz; R5-R20, difference between R5 and R20; X5, reactance at 5 Hz; AX, area under the reactance curve.

Table 3 Quantitative HRCT Parameters Among the Healthy Control, COPD Patients, and ACO Patients

Parameters	COPD	ACO	Control	P
LAA% Whole lung	5.20(1.55–13.10)	3.50(0.95–14.80)	0.30(0.10–0.68) *^#	<0.001
RL	3.60(1.10–11.75)	3.50(0.65–13.45)	0.20(0.10–0.50) *^#	<0.001
LL	5.50(1.55–15.30)	2.90(1.20–14.95)	0.25(0.13–0.70) *^#	<0.001
RUL	3.30(0.65–9.70)	2.90(0.55–12.75)	0.10(0.03–0.40) *^#	<0.001
RML	5.70(1.70–12.10)	3.40 (1.05–7.30)	0.30(0.13–0.90) *^#	<0.001
RLL	3.40 (0.60–8.90)	4.30 (0.50–11.75)	0.15 (0.10–0.50) *^#	<0.001
LUL	4.80(1.15–13.30)	2.30(1.30–17.40)	0.30 (0.10–0.78) *#	<0.001
LLL	4.60(1.75–12.40)	3.70(0.90–13.65)	0.20(0.10–0.60) *#	<0.001
WT4/BSA (mm/m^2)	0.64±0.14	0.65±0.17	0.49±0.16 *#	<0.001
WT5/BSA (mm/m^2)	0.38(0.27–0.49)	0.37(0.29–0.49)	0.28(0.19–0.37) *#	<0.001
WT6/BSA (mm/m^2)	0.25 (0.19–0.34)	0.29 (0.22–0.35)	0.17 (0.13–0.22) *#	<0.001
WA4/BSA (mm^2/m^2)	9.00(7.57–11.42)	8.70(6.61–11.07)	7.91 (5.73–9.67) *	0.030
WA5/BSA (mm^2/m^2)	4.39(2.80–6.56)	4.77(2.86–5.44)	2.88(1.91–4.66) *^#	0.004
WA6/BSA (mm^2/m^2)	2.09 (1.43–2.95)	2.44 (1.84–2.90)	1.55(1.05–1.86) *^#	<0.001
LA4/BSA (mm^2/m^2)	6.85±3.21	5.95±2.83	8.54±4.13 *^#	0.013
LA5/BSA (mm^2/m^2)	3.89 (2.77–5.63)	3.69 (2.77–4.75)	3.88 (3.24–5.24)	0.575
LA6/BSA (mm^2/m^2)	2.36(1.71–3.93)	2.58(1.97–3.36)	2.91(2.29–3.86)	0.335
WA4% (%)	0.59±0.10	0.61±0.11	0.48±0.10 *^#	<0.001
WA5% (%)	0.52±0.11	0.54±0.13	0.41±0.12 *^#	<0.001
WA6% (%)	0.45(0.35–0.54)	0.52(0.37–0.56)	0.34(0.29–0.40) *^#	<0.001
RVC−856 to −950	−0.32(−0.39 to −0.27)	−0.25(−0.30 to −0.16)	−0.50(−0.63 to −0.35) *^#@	<0.001
MLDE/I	0.92(0.88–0.96)	0.92(0.85–0.95)	0.83(0.79–0.89) *^#	<0.001

Notes: Data are presented as mean ± standard deviation or medians (interquartile range). Bold indicates P-values less than 0.05. *P<0.05, health control vs COPD group; ^#P<0.05, health control vs ACO group; ^@P<0.05, COPD group vs ACO group.

Abbreviations: COPD, chronic obstructive pulmonary disease; ACO, asthma–COPD overlap; LAA%, the % area of low attenuate to the corresponding lung area= the percentage of low-attenuation areas lower than −950 Hounsfield units (HU) on inspiratory CT; RL, right lung; LL, left lung; RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; BSA, body surface area; WT, bronchial wall thickness; WA, wall area; LA, luminal area; WA%, wall area percent; BSA, body square area; RVC_−856—950, relative volume change −856HU to −950HU= change of the relative volume of voxels between −856 to −950 HU from inspiratory to expiratory CT; MLD_E/I, the expiration to inspiration ratio of mean lung density.

Table 4 Multivariate Analysis of the Association of RVC_{−856 to −950}, R5-R20, R5 and X5 with ACO Among COPD Patients

Parameters	Univariate Analysis		Multivariate Analysis
	OR (95% CI)	P	OR (95% CI)	P
RVC−856 to −950		<0.001	RVC−856 to −950	0.048
<-0.41	1.00 (reference)		1.00 (reference)
≥-0.41	3.365(1.541–7.344)		3.615(1.010–12.940)
R5-R20 (kpa·L^−1·s^−1)		<0.001	R5-R20 (kpa·L^−1·s^−1)	0.001
<0.24	1.00 (reference)		1.00 (reference)
≥0.24	3.269(1.656–6.453)		432.018(10.240–18,226.731)
R5 (kpa·L^−1·s^−1)		<0.001	R5 (kpa·L^−1·s^−1)	0.003
<0.46	1.00 (reference)		1.00 (reference)
≥0.46	1.789(1.331–2.404)		49.176(3.770–653.599)
X5 (kpa·L^−1·s^−1)		0.004	X5 (kpa·L^−1·s^−1)	0.017
≥-0.22	1.00 (reference)		1.00 (reference)
<-0.22	2.145(1.270–3.620)		5.364(1.347–21.353)

Notes: Adjusted for age, sex, BMI, history of smoking, exacerbation and atopy or allergic rhinitis.

Abbreviations: RVC_−856—950, relative volume change −856HU to −950HU; R5-R20, difference between R5 and R20; R5, resistance at 5 Hz; X5, reactance at 5 Hz; OR, odds ratio.

Table 5 ROC Curves for RVC_{−856 to −950} Combined with R5-R20 in Predicting ACO

Parameters	Cutoff Values	AUC (95% CI)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
RVC−856 to −950	> −0.41	0.803 (0.682–0.893) ^#	90.48	68.29	59.4	93.3
R5-R20(kpa·L^−1·s^−1)	>0.24	0.771(0.651–0.866) ^#	68.00	80.49	68.0	80.5
R5(kpa·L^−1·s^−1)	>0.46	0.758(0.636–0.855) ^#	92.00	53.66	54.8	91.7
X5(kpa·L^−1·s^−1)	≤-0.22	0.716(0.592–0.820) ^#	76.00	60.98	54.3	80.6
RVC−856 to −950 + R5-R20	RVC−856 to −950> −0.62 and R5-R20>0.09	0.909(0.808–0.967)	76.19	95.12	88.9	88.6

Note: ^#P<0.05, compared with AUC_{RVC-856 to −950 +R5-R20}; The cutoff points were obtained by maximizing the sum of sensitivity and specificity (maximum Youden index).

Abbreviations: RVC_{−856 to −950}, relative volume change −856HU to −950HU; R5-R20, difference between R5 and R20; R5, resistance at 5 Hz; X5, reactance at 5 Hz; AUC, Area under the curve; PPV, positive predictive value; NPV, negative predictive value.

Figure 4 ROC curves for RVC_{−856 to −950} combined with R5-R20 in predicting ACO.

Abbreviations: AUC, area under the curve; RVC_{−856 to −950}, relative volume change −856HU to −950HU; R5-R20, difference between R5 and R20.

Figure 5 Calibration curve of RVC_{−856 to-950} combined with R5-R20.

Global Initiative for Asthma [webpage on the Internet]. Global strategy for asthma management and prevention. Available from: http://www.ginasthma.org. Accessed April 30, 2018.

 Google Scholar