Association of Total Airway Count on Computed Tomography with Pulmonary Function Decline in Early-Stage COPD: A Population-Based Prospective Cohort Study

Figures & data

Figure 1 Study flow chart.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; CT, computer tomography.

Table 1 Characteristics of the Subjects at Baseline

Characteristic	Healthy Control (n=41)	GOLD I (n=76)	GOLD II(n=59)
Age, years	59.8±8.4	62.3±7.8	65.3±6.5^†
Male sex, n (%)	20 (48.8)	59 (77.6)*	46 (78.0)*
Body-mass index, kg/m^Citation2	23.0±3.7	22.3±3.9	21.8±3.6
Smoking status, n (%)
Never smoked	27 (65.9)	24 (31.6)*	17 (28.8)*
Current smoking	13 (31.7)	42 (55.3)*	31 (52.5)*
Former smoking	1 (2.4)	10 (13.2)*	11 (18.6)*
Smoking index, pack-year	11.1 (19.5)	33.2 (33.5)*	32.2 (28.0)*
Biomass use, n (%)	33 (80.5)	52 (68.4)	32 (54.2)*
Family history of respiratory diseases, n (%)	3 (7.3)	14 (18.4)	10 (16.9)
Spirometry values at baseline
Before bronchodilator use
FEV1, L	2.10±0.46	2.17±0.53	1.50±0.41*^†
FEV1, % predicted	94.4±16.6	88.9±12.6	62.9±9.9*^†
FVC, L	2.81±0.66	3.44±0.77*	2.71±0.48^†
FEV1/FVC, %	75.5±6.0	63.1±4.9*	55.8±8.2*^†
After bronchodilator use
FEV1, L	2.17±0.47	2.28±0.50	1.61±0.38*^†
FEV1, % predicted	96.2±16.2	93.6±11.4	67.9±8.0*^†
FVC, L	2.82±0.69	3.52±0.75*	2.87±0.64^†
FEV1/FVC, %	77.7±6.3	61.1±5.5*	56.7±7.9*^†
Bronchodilator response, n (%)	4 (9.8)	10 (13.2)	10 (16.9)

Notes: Data are mean ± standard deviation or n (%) as required. *Significantly different from healthy control (p<0.05). †Significantly different from GOLD I (p<0.05).

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Table 2 Quantitative CT Parameters of the Subjects at Baseline

Characteristic	Healthy Control (n=41)	GOLD I (n=76)	GOLD II (n=59)
Imaging features
LAA−950, %	5.2 (4.4)	8.8 (7.8)*	11.4 (7.4)*
LAA−856, %	22.1 (18.0)	28.9 (18.4)	44.4 (24.1)*^†
Inspiratory Pi10, mm	3.59 (3.54–3.78)	3.65 (3.56–3.89)	3.70 (3.57–3.93)
Perc 15, HU	−926(−935-−896)	−931 (−944-−917)	−942 (−953-−927)*^†
TAC, n	240 (132)	195 (116)	155 (101)*

Notes: Data are mean ± standard deviation or median (interquartile range) as required. *Significantly different from healthy control (p<0.05). †Significantly different from GOLD I (p<0.05).

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; LAA₋₉₅₀, the percentage of low-attenuation area below −950 Hounsfield units on full-inspiration computed tomography; LAA₋₈₅₆, the percentage of low-attenuation area below −856 Hounsfield units on full-expiration computed tomography; Pi10 the square root of the airway wall area for a theoretical airway with 10-mm internal perimeter; Perc 15, the Hounsfield units at which 15% of the voxels fall below at full-inspiration; HU, Hounsfield units; TAC, total airway count.

Figure 2 The reconstruction of the airway tree.

Figure 3 Computed tomography-visible total airway count by generation, average lumen diameter and average inner area. *Significantly different from healthy control (p<0.05). † Significantly different from GOLD I (p<0.05).

Table 3 Multivariable Linear Regression Analysis for Pulmonary Function Measurements with Imaging Measurements

Parameter	Unstandardized Coefficients	SE	Standardized Coefficients	VIF	P values
Pre-bronchodilator FEV1*, L
TAC	0.002	0.0003	0.402	2.245	<0.001
LAA−950	−0.001	0.007	−0.013	3.954	0.888
LAA−856	−0.004	0.002	−0.156	1.703	0.009
Inspiratory Pi10	−0.079	0.166	−0.031	2.160	0.637
Perc 15	0.003	0.002	0.126	3.988	0.166
Pre-bronchodilator FVC*, L
TAC	0.001	0.0005	0.208	2.245	0.004
LAA−950	0.010	0.010	0.089	3.954	0.340
LAA−856	−0.004	0.002	−0.121	1.703	0.050
Inspiratory Pi10	0.090	0.242	0.026	2.160	0.709
Perc 15	0.001	0.003	0.040	3.988	0.670
Post-bronchodilator FEV1*, L
TAC	0.002	0.000	0.343	2.226	<0.001
LAA−950	−0.001	0.007	−0.016	3.932	0.869
LAA−856	−0.004	0.002	−0.170	1.693	0.007
Inspiratory Pi10	−0.049	0.171	−0.020	2.174	0.776
Perc 15	0.002	0.002	0.094	3.964	0.330
Post-bronchodilator FVC*, L
TAC	0.001	0.0005	0.121	2.226	0.094
LAA−950	0.015	0.010	0.140	3.932	0.143
LAA−856	−0.006	0.002	−0.153	1.693	0.015
Inspiratory Pi10	0.006	0.242	0.002	2.174	0.979
Perc 15	−0.00006	0.003	−0.002	3.964	0.985
Post-bronchodilator FEV1/FVC*, %
TAC	0.038	0.007	0.440	0.449	<0.001
LAA−950	−0.343	0.157	−0.249	0.254	0.030
LAA−856	−0.032	0.036	−0.067	0.591	0.373
Inspiratory Pi10	−3.582	3.804	−0.080	0.460	0.348
Perc 15	0.093	0.048	0.221	0.252	0.056

Note: *Both models were adjusted by age, sex, body mass index, smoking status, and pack-years.

Abbreviations: SE, standard error; VIF, variance inflation factor; FEV1, forced expiratory volume in 1 second; TAC, total airway count; LAA₋₉₅₀, the percentage of low-attenuation area below −950 Hounsfield units on full-inspiration computed tomography; LAA₋₈₅₆, the percentage of low-attenuation area below −856 Hounsfield units on full-expiration computed tomography; Pi10, the square root of the airway wall area for a theoretical airway with 10-mm internal perimeter; Perc 15, the HU at which 15% of the voxels fall below at full inspiration; FVC, forced vital capacity.

Figure 4 Relationship between total airway count (n) and inspiratory Pi10 (mm). CT-visible TAC was strongly related to inspiratory Pi10 (ρ=0.750; p<0.001).

Table 4 Multivariable Linear Regression Analysis Exploring Factors Independently Associated with the Annual Decline in Pulmonary Function

Parameter	Unstandardized Coefficients	95% CI	Standardized Coefficients	P values
Pre-bronchodilator FEV1*, L
TAC	−0.098	−0.182 to −0.014	−0.234	0.023
LAA−950	1.457	0.217 to 2.698	0.216	0.022
Baseline pre-bronchodilator FEV1	44.889	21.940 to 67.837	0.500	<0.001
Pre-bronchodilator FVC*, L
TAC	−0.30	−0.153 to 0.094	−0.044	0.634
LAA−950	0.634	−1.322 to 2.589	0.057	0.523
Baseline pre-bronchodilator FVC	55.916	28.604 to 83.229	0.538	<0.001
Post-bronchodilator FEV1*, L
TAC	−0.093	−0.169 to −0.016	−0.228	0.018
LAA−950	1.358	0.192 to 2.524	0.208	0.023
Baseline post-bronchodilator FEV1	46.251	24.600 to 69.902	0.519	<0.001
Post-bronchodilator FVC*, L
TAC	−0.012	−0.025 to 0.001	−0.186	0.048
LAA−950	0.110	−0.088 to 0.307	0.102	0.273
Baseline post-bronchodilator FVC	−0.992	−3.764 to 1.780	−0.098	0.480
Post-bronchodilator FEV1/FVC*, %
TAC	−0.005	−0.007 to −0.003	−0.408	<0.001
LAA−950	0.055	0.014 to 0.096	0.280	0.009
Baseline post-bronchodilator FEV1/FVC	0.061	0.027 to 0.095	0.383	<0.001

Note: *Both models were adjusted for age, sex, body mass index, smoking status, and pack-years.

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; TAC, total airway count; LAA₋₉₅₀, the percentage of low-attenuation area below −950 Hounsfield units on full-inspiration computed tomography; FVC, forced vital capacity.

Koo H-K, Vasilescu DM, Booth S, et al. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. Lancet Respir Med. 2018;6(8):591–602. doi:10.1016/S2213-2600(18)30196-6

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