Inspiratory and Expiratory Computed Tomography Imaging Clusters Reflect Functional Characteristics in Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 The percentage of three DPM parameters for the five imaging clusters in 131 subjects. Bars show the percentage of DPM_Normal (green), DPM_GasTrap (yellow), and DPM_Emph (red). The number of subjects comprised 32, 20, 33, 32, and 14 in the NL, NL-GT, GT, GT-EM, and EM clusters, respectively.

Abbreviations: DPM, disease probability measure; DPM_Normal, normal lesion recognized by DPM; DPM_GasTrap, gas-trapping lesion recognized by DPM; DPM_Emph, emphysematous lesion recognized by DPM; NL, normal cluster; NL-GT, Normal-GasTrap cluster; GT, GasTrap cluster; GT-EM, GasTrap-Emphysema cluster; EM, emphysema cluster.

Table 1 Characteristics of the Five Imaging Clusters

	NL	NL-GT	GT	GT-EM	EM
Subjects (n)	32	20	33	32	14
Age (years)	67.4 ± 8.8	72.5 ± 6.7	73.7 ± 7.5*	74.8 ± 6.9*	72.5 ± 8.6
Sex (M / W)	30 / 2	20 / 0	25 / 8	32 / 0	13 / 1
Height (cm)	167.3 ± 6.7	165.2 ± 6.3	160.2 ± 6.3*^†‡	165.7 ± 7.5	163.1 ± 7.6
BMI (kg/m^2)	24.1 ± 2.6	24.5 ± 2.9	23.7 ± 4.1	22.4 ± 2.8^†	20.5 ± 2.3*^†⁑‡
Smoking history
Current / former	11 / 21	2 / 18	5 / 27 ^a	8 / 24	2 / 12
Pack-years	49.5 ± 24.6	64.8 ± 48.4	54.5 ± 22.6	62.0 ± 25.7*	76.1 ± 36.6*
mMRC score^b	0.9 ± 0.9	1.1 ± 1.1	0.9 ± 0.9	1.3 ± 1.0	2.1 ± 1.0*^†⁑‡
Total CAT score^c	11.2 ± 8.0	8.3 ± 6.3	8.2 ± 6.0	11.8 ± 7.7	13.6 ± 8.4^⁑
GOLD airflow limitation severity (1 / 2 / 3 / 4)	22 / 10 / 0 / 0	8 / 12 / 0 / 0	2 / 18 / 3 / 0	5 / 17 / 10 / 0	1 / 5 / 3 / 5
Treatments (n)
None	12	9	8	5	1
Monotherapy (ICS / LAMA / LABA)	1 / 11 / 2	0 / 2 / 2	0 / 12 / 4	0 / 6 / 4	0 / 1 / 1
Combination (ICS + LABA / LAMA + LABA)	5 / 1	2 / 3	1 / 2	2 / 8	0 / 6
Triple (LAMA + LABA + ICS)	0	2	6	7	5

Notes: Data are presented as the mean ± standard deviation unless otherwise stated and were analyzed by Wilcoxon’s rank-sum test. ^ainhalation biomass (n = 1); ^bn = 32 / 20 / 32 / 32 / 13; ^cn = 32 / 19 / 33 / 32 / 14; *p < 0.05 vs NL; ^†p < 0.05 vs NL-GT; ^⁑p < 0.05 vs GT; ^‡p < 0.05 vs GT-EM.

Abbreviations: BMI, body mass index; CAT, COPD assessment test; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; LAMA, long-acting muscarinic antagonist; M, men; mMRC, modified Medical Research Council dyspnea scale; W, women.

Table 2 Pulmonary Functions and FeNO Among the Five Imaging Clusters

	NL	NL-GT	GT	GT-EM	EM
VC (% predicted)	107.0 [97.3, 114.9]	104.1 [97.3, 110.9]	102.9 [95.0, 114.9]	104.3 [92.8, 119.8]	96.1* [83.2, 104.2]
FVC (% predicted)	107.4 [97.8, 115.5]	102.4 [96.4, 113.4]	104.0 [93.7, 113.9]	107.3 [92.1, 121.0]	94.5* [83.4, 108.7]
RV / TLC (%)	35.3 [31.9, 37.3]	36.6 [33.6, 39.6]	41.7*^† [37.4, 46.1]	38.2* [33.3, 46.4]	46.0*^†‡ [39.9, 51.9]
FEV1 (L)	2.36 [2.14, 2.88]	2.19* [1.86, 2.39]	1.63*^† [1.38, 2.09]	1.65*^† [1.29, 2.01]	1.16*^†⁑‡ [0.72, 1.48]
FEV1 (% predicted)	83.9 [76.1, 91.0]	77.5 [72.5, 88.5]	73.3* [57.8, 90.4]	60.6*^†⁑ [45.4, 74.5]	42.5*^†⁑‡ [25.9, 60.5]
DLco/VA (mL/min/mmHg/L)	3.38 [3.11, 3.74]	3.44 [2.90, 3.98]	3.30 [2.62, 3.94]	2.27*^†⁑ [1.72, 2.92]	1.56*^†⁑‡ [1.20, 2.03]
FeNO value (ppb) ^a	22 [16, 32]	28 [16, 47]	25 [15, 34]	20 [15, 35]	25 [9.5, 55]

Notes: Data are presented as the median [interquartile range] and were analyzed by Wilcoxon’s rank-sum test. ^an = 32 / 20 / 32 / 29 / 13; *p < 0.05 vs NL; ^†p < 0.05 vs NL-GT; ^⁑p < 0.05 vs GT; ^‡p < 0.05 vs GT-EM.

Abbreviations: VC, vital capacity; FVC, forced vital capacity; RV, residual volume; TLC, total lung capacity; FEV₁, forced expiratory volume in 1 s; DL_co/V_A, carbon monoxide diffusing capacity divided by the alveolar volume; FeNO, fractional exhaled nitric oxide.

Table 3 FOT Parameters Among the Five Imaging Clusters

	NL	NL-GT	GT	GT-EM	EM
R5 (kPa/L/s)	0.17 [0.13, 0.23]	0.22 [0.17, 0.26]	0.25* [0.20, 0.31]	0.23* [0.17, 0.30]	0.31* [0.17, 0.40]
R20 (kPa/L/s)	0.15 [0.13, 0.18]	0.18 [0.15, 0.21]	0.21* [0.16, 0.25]	0.17 [0.14, 0.22]	0.21* [0.15, 0.27]
R5-R20 (kPa/L/s)	0.02 [0.0, 0.05]	0.04 [0.01, 0.06]	0.05* [0.03, 0.07]	0.06* [0.03, 0.09]	0.09*^† [0.01, 0.14]
X5 (kPa/L/s)	−0.02 [−0.05, −0.01]	−0.04 [−0.05, −0.01]	−0.06*^† [−0.10, −0.04]	−0.07*^† [−0.13, −0.03]	−0.09*^† [−0.20, −0.03]
ΔX5 (kPa/L/s)	0.00 [−0.01, 0.02]	0.01 [0.00, 0.04]	0.01 [−0.01, 0.05]	0.02* [0.00, 0.07]	0.04* [0.00, 0.14]
Fres (Hz)	0.67 [0.59, 0.95]	0.82 [0.60, 1.16]	1.01*^† [0.86, 1.50]	1.22*^† [0.82, 1.89]	1.50*^† [0.80, 2.07]
ALX (kPa/L/s·Hz)	0.08 [0.04, 0.19]	0.15 [0.06, 0.24]	0.25*^† [0.16, 0.68]	0.32*^† [0.12, 1.08]	0.64*^† [0.10, 1.77]

Notes: Data are presented as the median [interquartile range] and were analyzed by Wilcoxon’s rank-sum test. Each oscillatory index is expressed as the mean value of five entire respiratory cycles. *p < 0.05 vs NL; ^†p < 0.05 vs NL-GT.

Abbreviations: FOT, forced oscillation technique; R5, Rrs at 5 Hz; R20, Rrs at 20 Hz; R5-R20, difference from R5 to R20; X5, Xrs at 5 Hz; Fres, resonant frequency; ΔX5, difference in X5 between inspiratory and expiratory phases; ALX, low-frequency reactance area.

Figure 2 Comparison of computed tomography imaging biomarkers among the imaging clusters. Box plot of (a) LAV% and (b) √Aaw at Pi10 according to imaging clusters. The x mark shows the mean value. The Wilcoxon rank-sum test was used to compare computed tomography imaging biomarkers among clusters. *p < 0.05 compared with NL; ^†p < 0.05 compared with NL-GT; ^⁑p < 0.05 compared with GT; ^‡p < 0.05 compared with GT-EM.

Abbreviations: LAV%, percentage of low attenuation volume; √Aaw at Pi10, square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm; NL, normal cluster; NL-GT, Normal-GasTrap cluster; GT, GasTrap cluster; GT-EM, GasTrap-emphysema cluster; EM, emphysema cluster.

Figure 3 Longitudinal changes in DPM parameters of the imaging clusters. The baseline data and the 3-year follow-up data of 84 subjects are shown side-by-side. Bars show the mean percentage data of DPM_Normal (green), DPM_GasTrap (yellow), and DPM_Emph (red). The number of subjects comprised 19, 14, 23, 20, and 8 in the NL, NL-GT, GT, GT-EM, and EM clusters, respectively.

Abbreviations: DPM, disease probability measure; DPM_Normal, normal lesion recognized by DPM; DPM_GasTrap, gas-trapping lesion recognized by DPM; DPM_Emph, emphysematous lesion recognized by DPM; NL, normal cluster; NL-GT, Normal-GasTrap cluster; GT, GasTrap cluster; GT-EM, GasTrap-Emphysema cluster; EM, emphysema cluster.