Phenotyping COPD Patients with Emphysema Distribution Using Quantitative CT Measurement; More Severe Airway Involvement in Lower Dominant Emphysema

Figures & data

Figure 1 Flow diagram of the subjects enrolled in the study.

Abbreviations: KOLD, Korean Obstructive Lung disease; COPD, chronic obstructive pulmonary disease; CT, computed tomography; EI, emphysema index.

Table 1 Comparison of Baseline Characteristics of the Study Subjects

	UD (N = 141)	LD (N = 107)	HD (N = 177)
Age, Years, Mean – SD	67.7–8.5	68.7–7.5	67.1–7.8
Male, N (%)	136 (96.5)	104 (97.2)	173 (97.7)
BMI, Kg/m,^2 Mean – SD	22.4–2.7	22.3–3.0^b	23.3–3.2^c
Current smokers, N (%)	50 (35.5)	34 (31.8)	65 (36.7)
6MWD, Meter, Median (IQR)	420.0 (360.0–480.0)	424.5 (360.0–488.3)	430.0 (380.0–480.0)
Exertional desaturation, N (%)	35 (24.8)	17 (15.9)	19 (10.7)^c
mMRC score, Mean – SD	1.87–1.01^a	1.54–1.03	1.52–1.05^c
mMRC score ≥2, N (%)	78 (55.3)^a	46 (43.0)	63 (35.6)^c
SGRQ score, Median (IQR)	29.6 (19.9–46.3)	29.8 (17.5–47.6)^b	22.5 (15.3–37.1)^c
BODE index, Mean – SD	2.88–2.06	2.86–1.95^b	2.18–2.03^c
Charlson comorbidity index, Mean – SD	1.19–0.53	1.36–0.76	1.28–0.61
Presence of chronic bronchitis, N (%)	53 (37.6)	39 (36.4)	70 (39.5)
Presence of chronic bronchitis symptoms assessed by SGRQ, N (%)	55 (39.0)	48 (44.9)	71 (40.1)
Pulmonary functions
Post-BD FEV1, % predicted, Mean – SD	54.5–16.5^a	49.5–14.9^b	59.3–16.5
Bronchodilator responsiveness, N (%)	37 (41.1)	27 (31.2)	60 (33.9)
DLCO, % predicted, Mean – SD	58.7–19.3^a	68.9–21.7^b	74.8–22.4
TLC, % predicted, Mean – SD	110.1–22.0	114.4–23.7^b	100.2–21.3
RV, % predicted, Mean – SD	124.4–57.7^a	141.6–63.6^b	104.4–54.7
RV/TLC, %, Mean – SD	42.5–14.2^a	47.8–13.0^b	38.6–14.3^c
Chest CT measures
EI of the whole lung, %, Median (IQR)	26.3 (15.8–39.0)	21.0 (14.0–33.1)^b	14.5 (8.2–24.8)^c
EI of the upper lung, %, Median (IQR)	38.4 (26.6–51.5)^a	12.3 (7.4–21.9)	14.0 (8.3–25.1)^c
EI of the lower lung, %, Median (IQR)	20.2 (11.7–32.2)^a	24.3 (16.2–37.7)^b	14.3 (8.3–24.6)^c
ATI, Median (IQR)	0.955 (0.937–0.969)	0.953 (0.933–0.973)^b	0.945 (0.915–0.969)^c
WA%, Median (IQR)	62.3 (57.5–66.9)^a	68.3 (61.7–73.5)	66.1 (58.4–71.8)^c
Pi10, Median (IQR)	3.71 (3.34–4.09)^a	4.24 (3.70–4.74)	4.06 (3.46–4.52)^c
Presence of BE/BWT, N (%)	16 (11.3)^a	38 (35.5)^b	32 (18.1)
Patients who experienced exacerbations in the previous year, N (%)	29 (20.5)	29 (27.1)^b	25 (14.1)

Notes: P value < 0.05, ^aUD vs LD, ^bLD vs HD, ^cHD vs UD.

Abbreviations: UD, upper dominant emphysema group; LD, lower dominant emphysema group; HD, homogeneous group; SD, standard deviation; BMI, body mass index; 6MWD, 6 min walk distance; IQR, interquartile range; mMRC, modified Medical Research Council; SGRQ, Saint George Respiratory Questionnaire; BODE, Body mass index, degree of airflow Obstruction and Dyspnea and Exercise capacity; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s; DL_CO, diffusing capacity of carbon monoxide; TLC, total lung capacity; RV, residual volume; CT, computed tomography; EI, emphysema index; ATI, air trapping index; WA%, mean wall area percent; Pi10, square root of the wall area for a theoretical airway with an internal perimeter of 10 mm; BE, bronchiectasis; BWT, bronchial wall thickening.

Table 2 Long-Term Clinical Outcomes in Terms of Emphysema Distribution

	UD (N = 141)	LD (N = 107)	HD (N = 177)
Duration of follow-up, Days, Median (IQR)	1699 (792–3243)	1689 (1010–2938)	1831 (966–3276)
Annual decline of post-BD FEV1, mL, Mean – SD	30.8–20.5	28.7–20.6	33.4–20.2
Number of patients experienced exacerbation during the follow-up duration, N (%)	51 (36.2)^a	55 (51.4)	76 (42.9)
Mortality, N (%)	26 (18.4)	17 (15.9)	20 (11.3)

Notes: P value < 0.05, ^aUD vs LD.

Abbreviations: UD, upper dominant emphysema group; LD, lower dominant emphysema group; HD, homogeneous group; IQR, interquartile range; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s; SD, standard deviation.

Figure 2 Kaplan-Meier curves for the time to first exacerbation (A) and the probability of survival (B) concerning the emphysema distribution.

Abbreviations: UD, upper dominant emphysema group; LD, lower dominant emphysema group; HD, homogeneous group.

Table 3 Variables Associated with Time to First Exacerbation

	OR [95% CI]	P value	Adjusted OR [95% CI]^a	P value
Age, Years	1.035 [1.017–1.052]	<0.001	1.021 [0.999–1.043]	0.066
BMI, Kg/m^2	0.973 [0.930–1.010]	0.238
Smoking status (Current over Ex-)	1.369 [1.050–1.784]	0.020	1.683 [1.229–2.304]	0.001
Post-BD FEV1, % predicted	1.009 [1.000–1.018]	0.042	1.001 [0.978–1.015]	0.925
DLco, % predicted	0.991 [0.984–0.997]	0.004	0.994 [0.986–1.002]	0.159
RV/TLC, % predicted	0.988 [0.978–0.998]	0.016	0.986 [0.975–0.997]	0.013
6MWD, Meter	0.995 [0.994–0.997]	<0.001	0.996 [0.994–0.998]	<0.001
Exertional desaturation	0.793 [0.557–1.130]	0.199
mMRC	1.134 [0.989–1.301]	0.072
SGRQ	1.001 [0.992–1.011]	0.771
Presence of chronic bronchitis symptoms assessed by the SGRQ	1.626 [1.243–2.127]	<0.001	1.226 [0.876–1.715]	0.234
History of exacerbations in previous year	1.523 [1.085–2.138]	0.015	1.298 [0.853–1.974]	0.223
EI of the whole lung, %	0.994 [0.184–1.004]	0.256
ATI	2.849 [0.065–123.570]	0.587
WA%	0.988 [0.962–1.014]	0.361
Presence of BE/BWT	1.389 [1.018–1.895]	0.038	0.996 [0.994–0.998]	0.025
EI distribution, LD		0.861

Notes: ^aAdjusted for age. smoking status, post-BD FEV₁, DLco, RV/TLC, 6MWD, presence of chronic bronchitis symptoms assessed by the SGRQ, history of exacerbations in previous year, and presence of BE/BWT.

Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s; DL_CO, diffusing capacity of carbon monoxide; RV/TLC, residual volume/total lung capacity; 6MWD, 6 min walk distance; mMRC, modified Medical Research Council; SGRQ, Saint George Respiratory Questionnaire; EI, emphysema index; ATI, air trapping index; WA%, mean wall area percent; BE, bronchiectasis; BWT, bronchial wall thickening; LD, lower dominant emphysema group.

Table 4 Response After 3 Months of ICS/LABA Treatment in Non-Severe COPD Patients

	UD (N = 82)	LD (N = 56)	HD (N = 134)
Pulmonary functions
Post-BD FEV1, % predicted, Mean – SD	57.9–16.4	51.4–15.3^b	61.2–16.5
DLCO, % predicted, Mean – SD	63.9–20.6	71.7–21.4	77.7–22.0^c
TLC, % predicted, Mean – SD	109.6–23.1	118.5–23.2^b	99.0–21.8^c
IC, % predicted, Mean – SD	73.5–21.1	76.3–21.1	76.0–20.3
RV, % predicted, Mean – SD	119.1–60.0^a	151.3–69.1^b	100.4–56.7
RV/TLC, %, Mean – SD	40.2–15.4^a	49.1–13.6^b	36.7–14.3
Chest CT measures
EI % of the whole lung, Median (IQR)	26.0 (14.8–38.0)	19.0 (13.1–32.3)^b	14.1 (8.0–21.9)^c
ATI, Median (IQR)	0.956 (0.936–0.968)	0.946 (0.932–0.971)^b	0.937 (0.909–0.962)^c
WA%, Median (IQR)	62.5 (57.0–67.9)^a	70.1 (64.6–75.7)^b	66.3 (58.5–72.1)^c
Pi10, Median (IQR)	3.71 (3.31–4.23)^a	4.34 (3.87–4.93)^b	4.06 (3.46–4.59)^c
Response after 3 months of ICS/LABA treatment
Pulmonary function
ΔFVC, mL, Mean – SD	122.6–404.9	232.4–438.0	190.1–398.3
ΔFEV1, mL, Mean – SD	80.7–332.7	111.7–311.6	142.8–311.0
ΔIC, mL, Mean – SD	180.4–444.4	214.6–327.5	108.1–455.1
ΔIC, % predicted, Mean – SD	7.04–17.03	8.32–13.29	4.00–17.00
ΔRV, mL, Mean – SD	−86.5–623.5^a	−531.1–936.5	−201.2–589.6
ΔRV, % predicted, Mean – SD	−5.47–28.30^a	−24.19–43.82	−12.76–25.44
ΔRV/TLC, %, Mean – SD	−1.56–7.40	−4.10–8.45	−3.00–6.68

Note: P value < 0.05, ^aUD vs LD, ^bLD vs HD, ^cHD vs UD.

Abbreviations: ICS, inhaled corticosteroid; LABA, long acting beta₂ agonist; UD, upper dominant emphysema group; LD, lower dominant emphysema group; HD, homogeneous group; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s; SD, standard deviation; DL_CO, diffusing capacity of carbon monoxide; TLC, total lung capacity; IC, inspiratory capacity; RV, residual volume; CT, computed tomography; EI, emphysema index; IQR, interquartile range; ATI, air trapping index; WA%, mean wall area percent; Pi10, square root of the wall area for a theoretical airway with an internal perimeter of 10 mm; ΔFVC, change in forced vital capacity; ΔFEV1, forced expiratory volume in 1 s; ΔIC, changes in inspiratory capacity; ΔRV, changes in residual volume; ΔRV/TLC, changes in residual volume/total lung capacity.