Different Smoking Statuses on Survival and Emphysema in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Demographic and Baseline Characteristics

Characteristics	Never Smokers	Former Smokers	Current Smokers	P-value
	(n=83)	(n=118)	(n=156)
Age, years	71 (64~79)	71.5 (65~79)	63.5 (58~70) *^#	<0.001
Gender
Male (%)	49 (59%)	114 (96.6%) *	153 (98.1%) *	<0.001
Female (%)	34 (41%)	4 (3.4%) *	3 (1.9%) *	<0.001
Comorbidities	1 (0~2)	1 (0~2)	1 (0~1)	0.238
Exacerbations/year	0 (0~1)	0 (0~2)	0 (0~1)	0.049
CAT	19 (14~26.5)	19 (14~25)	20.5 (12~25)	0.712
mMRC	1 (0~2)	2 (1~3)	1 (0~2) ^#	0.002
BMI (kg/m^2)	23.5±3.9	22.8±3.6	23.1±3.9	0.448
WBC, (×10^9/L)	6.5 (5.02~7.79)	6.84 (5.47~9.38)	6.84 (5.31~8.68)	0.091
Neutrophils, (%)	71.21±12.07	73.25±11.19	70.35±11.9	0.124
Lymphocytes, (%)	21.3 (13.25~27.1)	18.85 (10.8~23.9)	20.6 (14.2~27.65)	0.11
Eosinophils, (%)	1.4 (0.4~2.9)	1.5 (0.5~3.3)	1.55 (0.35~3)	0.813
PLT, (×10^9/L)	163 (131.5~209.5)	161.5 (124~227)	167.5 (134~212)	0.977
FIB (g/L)	3.93 (3.26~5.16)	3.84 (3.19~5.07)	3.95 (3.13~4.81)	0.829
D-Dimer(ug/ml)	0.91 (0.61~1.28)	0.9 (0.67~1.46)	0.9 (0.66~1.28)	0.963
CRP (mg/L)	6.99 (3.28~23.15)	9.64 (3.28~38.2)	6 (3.28~24.8)	0.164
PCT(ng/ml)	0.05 (0.05~0.05)	0.05 (0.05~0.05)	0.05 (0.05~0.05)	0.475
PH	7.42 (7.4~7.44)	7.42 (7.39~7.44)	7.41 (7.38~7.44)	0.067
PaO2 (mmHg)	78 (67.5~89)	73 (65~88)	73 (64~83)	0.123
PaCO2 (mmHg)	40 (36~44)	42 (38~47)	42 (37~48)	0.074

Notes: *P < 0.05 compared with NS; ^#P < 0.05 compared with FS.

Abbreviations: BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; COPD, chronic obstructive pulmonary disease; WBC, white blood cell count; N, neutrophil; E, eosinophils; PLT, blood platelet count; FIB, fibrinogen; CRP, C-reactive protein; PCT, procalcitonin; PaO₂, arterial oxygen partial pressure; PaCO₂, arterial carbon dioxide partial pressure.

Table 2 PFT Parameters

Parameters	Never Smokers	Former Smokers	Current Smokers	P-value
	n=83	n=118	n=156
FEV1 (L)	1.14 (0.77~1.56)	1.18 (0.84~1.59)	1.37 (0.95~1.77) *^#	0.005
FEV1%pred	49.6 (37~66.35)	45.75 (31.2~57)	45.4 (35.6~58.4)	0.089
FVC% pred	70.2 (55.5~86.3)	68.3 (51.8~79.5)	67.05 (56.4~79.9)	0.376
FEV1/FVC (%)	58.78 (48.63~63.74)	52.38 (44.23~60.27) *	53.68 (45.07~60.32) *	0.007
PEF %pred	39.2 (28.25~51.2)	37.5 (28~46.1)	39 (29.85~48.8)	0.599
MMEF25–75%	19.4 (14~28.9)	18.6 (12.8~25)	19.25 (13.7~27)	0.598
DLCO/VA (%)	89.5±22.27	78.29±25.86*	75.63±23.98*	<0.001
RV/TLC (%)	57.09±10.48	58.44±11.2	55.14±10.84	0.051
Z5%pred	182.1 (144.5~219.6)	175.6 (143.1~207.4)	169.6 (142.8~205.8)	0.483
R5 (kPa/L/s)	0.58 (0.48~0.67)	0.49 (0.42~0.58) *	0.47 (0.39~0.56) *	<0.001
R20 (kPa/L/s)	0.36 (0.32~0.42)	0.32 (0.28~0.36) *	0.32 (0.29~0.37) *	<0.001
R5-R20 (kPa/L/s)	0.21 (0.12~0.28)	0.16 (0.11~0.22)	0.14 (0.09~0.2) *	0.001
X5	−0.26 (−0.38~-0.17)	−0.22 (−0.32~-0.14)	−0.2 (−0.29~-0.14) *	0.009
Fres (Hz)	23.34±5.79	22.73±5.07	21±5.23*^#	0.002
Ax (kPa/L)	2.18 (1.27~3.09)	1.88 (1.06~2.57)	1.49 (0.89~2.36) *	0.003

Notes: *P < 0.05 compared with NS group; ^#P < 0.05 compared with FS group. Abbreviations: PFT pulmonary function test, FEV1 forced expiratory volume in 1 second, FVC forced vital capacity, FEV1/FVC forced expiratory volume in 1 sec/forced vital capacity, MMEF_25–75% maximal mid expiratory flow, RV/TLC residual volume/total lung capacity, DL_CO/VA ratio of carbon monoxide diffusion capacity to alveolar ventilation, %Pred, of the predicted value, Z5 total respiratory impedance, R₅ resistance at 5 Hz, R₂₀ resistance at 20 Hz, X₅ reactance at 5 Hz, Fres response frequency, Ax reactance area.

Figure 1 Comparison of two lung function test parameters and imaging parameters. (A) Comparison of FEV1/FVC and DL_CO/VC. (B) Comparison of R₅, R₂₀, R₅-R₂₀. (C) Comparison of Fres and Ax. (D) Comparison of X₅. (E) Comparison of LC and EI of whole lungs. (F) Comparison of MED and MLD of whole lungs. Notes: *P < 0.05 compared with NS (no smoking); ^#P < 0.05 compared with FS (quit smoking).

Abbreviation: FEV1/FVC the ratio of forced expiratory volume occupancy in the first second, KCO the ratio of carbon monoxide diffusion to alveolar ventilation, R₅ resistance at 5 Hz, R₂₀ resistance at 20 Hz, R₅-R₂₀ resistance at 5Hz-resistance at 20Hz, X₅ reactance at 5 Hz, Fres resonant frequency, A_X reactance area, EI emphysema index, MED mean emphysema density, MLD mean lung density, LC lung capacity, NS, no significance.

Table 3 Imaging Characteristics

Parameters	Never Smokers	Former Smokers	Current Smokers	P-value
	n=65	n=83	n=115
LC Whole (ml)	4594.28±1332.85	5663.81±1305.35*	6004.53±1252.95*	<0.001
LC Right lung (ml)	2495.24±712.45	3033.31±700.95*	3201.49±655.4*	<0.001
LC Left lung (ml)	2099.03±643.76	2630.5±644.48*	2824.56±605.5*	<0.001
%LAA−950 Whole lung	14.94±7.93	21.45±9.25*	20.54±9.5*	<0.001
%LAA−950 Right lung	13.89 (9.26~18.75)	21.93 (15.17~28.45) *	20.73 (13.53~26.48) *	<0.001
%LAA−950 Left lung	13.67 (8.96~19.85)	22.11 (14.33~27.57) *	21.35 (12.29~26.83) *	<0.001
MED Whole lung (HU)	−980.44 (−982.54~-979.23)	−983 (−984.8~-981.15) *	−982.23 (−984.3~-980.35) *	<0.001
MED Right lung (HU)	−980.06 (−982.64~-978.72)	−982.84 (−984.71~-980.875) *	−981.69 (−984.24~-980.07) *	<0.001
MED Left lung (HU)	−980.78 (−982.94~-979.9)	−983.3 (−984.74~-981.2) *	−982.6 (−984.79~-980.21) *	0.001
MLD Whole lung (HU)	−839.68 (−856.24~-817.42)	−852.92 (−871.94~-835.07) *	−857.25 (−873.4~-834.18) *	0.005
MLD Right lung (HU)	−841.27 (−856.14~-818.25)	−855.27 (−871.74~-835.4) *	−855.12 (−873.67~-834.98) *	0.004
MLD Left lung (HU)	−838.08 (−864.02~-815.32)	−852.12 (−870.95~-831.11)	−858.67 (−874.93~-836.64) *	0.005
HI Whole lung	0.08±0.25	0.14±0.28	0.13±0.27	0.398
HI Right lung	0.08±0.29	0.16±0.3	0.17±0.29	0.16
HI Left lung	−0.1±0.29	−0.09±0.28	−0.12±0.32	0.75

Note: *P < 0.05 compared with NS group.

Abbreviations: LC, lung capacity; %LAA_−950, the extent of emphysema of CT attenuation value below −950 HU; MED, mean emphysema density; MLD, mean lung density; HI, emphysema heterogeneity index, when emphysema is equally distributed among the lobes or the full extent in the whole lung is < 1%, HI is near zero; otherwise, HI = (%LAA _upper -%LAA _lower)/(%LAA _upper+%LAA _lower)*100.

Figure 2 (A) A 65 years old male of NS: FEV1=1.65L, FEV1/FVC=65.36%, KCO=100.6%, Z5%_pred=99.7%, R₅=0.28, R₂₀=0.22, R₅-R₂₀=0.06, X₅=−0.11, Fres=15.38, Ax=0.49, EI=13.68%, MLD=−841.91HU, MED=−979.35HU, LC=4823mL. (B) A 66 years old male of FS: FEV1=0.92L, FEV1/FVC=44.37%, KCO=96.5%, Z5%_pred=174.3%, R₅=0.46, R₂₀=0.31, R₅-R₂₀=0.15, X₅=−0.27, Fres=20.07, Ax=1.62, EI=26.85%, MLD=−850.85HU, MED=−988.4HU, LC=6004mL. (C) A 65 years old male of CS: FEV1=1.16L, FEV1/FVC=46.03%, KCO=71.9%, Z5%_pred=242.5%, R₅=0.64, R₂₀=0.31, R₅-R₂₀=0.33, X₅=−0.38, Fres=27.17, Ax=3.63, EI=25.19%, MLD=−874.26HU, MED=−981.88HU, LC=6905mL.

Table 4 Logistic Regression Analysis of Smoking and EI

Characteristics	Univariable Analysis		Multivariable Analysis
	OR (95% CI)	P	OR (95% CI)	P
Smoking	4.185 (2.179~8.04)	<0.001	3.052 (1.342~6.938)	0.008
BMI, kg/m^2	3.448 (1.967~6.044)	<0.001	2.429 (1.192~4.949)	0.015
FEV1%pred	2.694 (1.63~4.451)	<0.001	1.954 (1.014~3.765)	0.045
KCO (60%≤KCO<80%)	4.22 (2.235~7.967)	<0.001	2.828 (1.386~5.769)	0.004
KCO (<60%)	18.739 (8.459~41.513)	<0.001	10.975 (4.716~25.544)	<0.001
PaCO2	2.332 (1.151~4.725)	0.019
Comorbidities	0.88 (0.538~1.44)	0.611
CAT	0.967 (0.596~1.572)	0.894
Exacerbations/year	1.181 (0.713~1.957)	0.518
mMRC	1.257 (0.77~2.053)	0.361
Age	0.978 (0.601~1.591)	0.927
PaO2	1.116 (0.574~2.17)	0.747

Notes: After adjusting age (>65 years), FEV1%pred (<50%), BMI (<21), and DLCO/VA (<80%), the factor of smoking was related to emphysema formation EI (≥20%).

Figure 3 Kaplan–Meier survival curves for AECOPD patients in the NS group (n=83; 29 deaths) and all smokers AECOPD group (n=274; 91 deaths). No significant difference between the two groups was observed (log rank test, 0.113; P=0.74).