Impact of combined pulmonary fibrosis and emphysema on surgical complications and long-term survival in patients undergoing surgery for non-small-cell lung cancer

Figures & data

Table 1 Preoperative characteristics of lung cancer patients

Characteristics	CPFE group (n=11)	Emphysema group (n=108)	IP group (n=7)	Normal group (n=124)	P-value
Sex (M/F)	11 (100%)/0	96 (88.9%)/12	5 (71.4%)/2	62 (50%)/62	<0.0001
Age (year)	72.4±10.3	70.8±7.1	71.7±6.1	69.8±8.2	ns
BMI (kg/m^2)	23.1±3.8	22.1±3.1	20.1±2.3	22.4±3.7	ns
Smoking index (pack-year)	46.8±31.7a	57.5±31.3a	37.9±36.6	20.4±30.1
Pulmonary function tests
FVC	2.90±0.69	3.30±0.67a	2.65±0.73	2.90±0.71
%FVC	93.7±18.4	103.8±16.1	91.5±20.5	105.5±19.7	ns
FEV1.0	2.05±0.51	3.58±10.67	2.04±0.40	2.15±0.54	ns
%FEV1.0	87.8±22.7a	92.1±22.1a	95.1±18.7	109.9±22.2
FEV1.0/FVC	71.2±9.8b	65.5±11.0^a,b	86.8±30.1^a,c	74.5±8.8^b,c
%DLCO	71.3±20.8a	84.3±24.0a	99.9±39.6	108.2±27.0c
%DLCO/VA	69.2±19.7a	70.5±20.8^a,b	88.8±22.4c	94.4±18.2c
PaO2	92.8±23.7	83.1±12.6	86.3±9.9	87.9±13.3	ns
PaCO2	38.1±5.1	39.1±3.9	40.9±3.8	39.0±3.1	ns

Notes: Data are presented as mean ± SD.

a P<0.05 for Tukey–Kramer test with data from normal group.

b P<0.05 for Tukey–Kramer test with data from IP group.

c P<0.05 for Tukey–Kramer test with data from emphysema group.

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia; M, male; F, female; BMI, body mass index; %FVC, percentage of forced vital capacity; FEV_1.0, forced expiratory volume in 1 second; %DL_CO, percentage of diffusion capacity of the lung for carbon monoxide; V_A, alveolar volume; PaO₂, partial pressure of arterial oxygen; PaCO₂, partial pressure of arterial carbon dioxide; SD, standard deviation; ns, not significant.

Table 2 Perioperative characteristics of lung cancer patients

Characteristics	CPFE group (n=11)	Emphysema group (n=108)	IP group (n=7)	Normal group (n=124)	P-value
Types of procedure					0.959
Pneumonectomy	0 (0%)	4 (3.7%)	0 (0%)	4 (3.2%)
Lobectomy	8 (72.3%)	87 (80.5%)	5 (71.4%)	98 (79.0%)
Segmentectomy/partial resection	3 (27.2%)	17 (15.7%)	2 (28.5%)	22 (17.7%)
Tumor size (cm) (maximal diameter)	2.86±0.68	3.24±1.94	2.28±1.06	2.71±1.83	ns
Histologic diagnosis
Ad/Sq/Oth	4/7/0	51/45/12	4/2/1		<0.001
%	36.4/63.6/0	47.2/41.6/11.1	57.1/28.5/14.2	82.2/10.4/7.2
Pathological T status
T1/2/3/4	5/5/0/1	49/48/10/1	3/3/0/1	72/37/8/7	0.138
%	45.4./45.4/0/9.0	45.3/44.4/9.2/0.9	42.8/42.8/0/14.2	58.0/29.8/6.4/5.6
Pathological nodal status
N0/1/2/3	8/3/0/0	87/8/13/0	5/1/1/0	101/12/10/1	0.569
%	72.7/27.7/0/0	80.5/7.4/12.0/0	71.4/14.2/14.2/0	81.4/9.6/8.0/0.8
Pathological staging
I/II/III/IV	8/2/1/0	70/23/12/3	4/1/2/0	91/13/17/3	0.589
%	72.7/18.1/9.0/0	64.8/21.3/11.1/2.7	57.1/14.2/28.5/0	73.3/10.4/13.7/2.4

Note: Data presented as mean ± SD.

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; ns, not significant; IP, interstitial pneumonia; Ad, adenocarcinoma; Sq, squamous cell carcinoma; Oth, other histology; SD, standard deviation.

Table 3 Postoperative pulmonary complications and mortality

	CPFE group (n=11)	Emphysema group (n=108)	IP group (n=7)	Normal group (n=124)	P-value
Pneumonia	1 (9.0%)	2 (1.8%)	1 (14.2%)	0 (0%)	0.004
ALI	0 (0%)	4 (3.7%)	1 (14.2%)	2 (1.6%)	0.197
Prolonged mech vent	1 (9.0%)	2 (1.8%)	1 (14.2%)	0 (0%)	0.004
HOT	1 (9.0%)	1 (0.9%)	0 (0%)	0 (0%)	0.014
30-day mortality	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1.000
90-day mortality	1 (9.0%)	3 (2.7%)	0 (0%)	0 (0%)	0.064
Causes of death
Primary cancer	4 (36.4%)	16 (14.8%)	1 (14.2%)	12 (9.6%)	0.08
Respiratory failure	3 (27.2%)	2 (0.9%)	2 (28.5%)	1 (0.8%)	<0.0001
Others	0 (0%)	6 (5.5%)	0 (0%)	2 (1.6%)	0.315

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia; ALI, acute lung injury; mech vent, mechanical ventilation; HOT, home oxygen therapy.

Table 4 Comparison of cause of death between CPFE and emphysema groups

	CPFE group (n=11)	Emphysema group (n=108)	P-value
Cause of death
Primary cancer	4 (36.4%)	16 (14.8%)	0.068
Respiratory failure	3 (27.3%)	1 (0.9%)	<0.0001
Others	0 (0%)	6 (5.6%)	0.422

Abbreviation: CPFE, combined pulmonary fibrosis and emphysema.

Figure 1 Overall survival in the four groups: Kaplan–Meier curves for OS after surgery.

Notes: The cumulative survivals at 3 years and 5 years were 50.0% and 18.7% in the CPFE group, 76.0% and 67.1% in the emphysema group, 44.4% and 44.4% in the IP group, and 85.9% and 77.5% in the normal group, respectively. Comparing with the CPFE group, there was significant difference in the normal group (P<0.0001, log-rank test) and the emphysema group (P=0.0027, log-rank test).
Abbreviations: OS, overall survival; CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia.

Figure 2 Disease-specific survival in the four groups: Kaplan–Meier curves for disease-specific survival.

Notes: The disease-specific survival at 5 years was 48.6% in the CPFE group, 81.7% in the emphysema group, 80% in the IP group, and 88.6% in the normal group. Comparing with the CPFE group, there was significant difference in the normal group (P=0.0003, log-rank test) and the emphysema group (P=0.0076, log-rank test).
Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia.

Figure 3 Overall survival in the four groups with pathological stage I disease: Kaplan–Meier curves for overall survival with pathological stage I disease.

Notes: The cumulative survival at 5 years was 21.4% in the CPFE group, 81.1% in the emphysema group, 50% in the IP group, and 84.9% in the normal group, respectively. Comparing with the CPFE group, there was significant difference in the normal group (P<0.0001, log-rank test) and the emphysema group (P<0.0001, log-rank test) but no difference in the IP group (P=0.2428, log-rank test).
Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia.

Table 5 Univariate analysis of prognostic factors using Cox proportional hazard model

Variable	Hazard ratio	95% CI	95% CI	P-value
Age	1.054804	1.000	1.0007	0.002
Sex
Female	Reference
Male	2.830	1.452	6.203	0.0015
BMI	0.965	0.893	1.038	0.350
Smoking index	1.000	1.000	1.000	0.010
Pulmonary function data
%FVC	0.979	0.969	0.990	0.0007
%FEV1.0	0.993	0.982	1.004	0.263
FEV1.0/FVC	1.007	0.984	1.029	0.511
%DLCO	0.982	0.969	0.994	0.004
%DLCO/VA	0.983	0.968	0.997	0.023
Type of procedure
Segmentectomy/partial resection	Reference
Lobectomy	1.441	0.716	3.309	0.322
Pneumonectomy	4.200	1.265	12.634	0.021
Pathological stage
I	Reference
II	2.498	1.209	4.878	0.014
III	3.829	1.974	7.167	0.0002
IV	2.087	0.336	6.979	0.365
Group
Normal	Reference
CPFE	6.147	2.515	13.730	0.0002
Emphysema	2.021	1.126	3.720	0.018
IP	2.843	0.665	8.425	0.139

Abbreviations: CI, confidence interval; BMI, body mass index; %FVC, percentage of forced vital capacity; FEV_1.0, forced expiratory volume in 1 second; %DL_CO, percentage of diffusion capacity of the lung for carbon monoxide; V_A, alveolar volume; CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia.

Table 6 Multivariate analysis of prognostic factors using Cox proportional hazard model

Variable	Hazard ratio	95% CI	95% CI	P-value
Age	1.087	1.022	1.16	0.007
Sex
Female	Reference
Male	2.495	0.720	12.26	0.160
Smoking index	1.000	0.999	1.000	0.305
Pulmonary function data
%FVC	0.968	0.946	0.99	0.006
%DLCO	0.989	0.966	1.012	0.377
%DLCO/VA	0.995	0.966	1.026	0.791
Type of procedure
Segmentectomy/partial resection	Reference
Lobectomy	2.731	0.857	10.24	0.091
Pneumonectomy	3.656	0.612	21.89	0.152
Pathological stage
I	Reference
II	2.288	0.766	6.302	0.132
III	3.370	1.308	8.510	0.012
IV	36.35	4.241	234.6	0.002
Group
Normal	Reference
CPFE	8.004	1.712	34.62	0.009
Emphysema	1.562	0.635	4.146	0.337
IP	5.996	1.079	27.79	0.041

Abbreviations: CI, confidence interval; %FVC, percentage of forced vital capacity; %DL_CO, percentage of diffusion capacity of the lung for carbon monoxide; V_A, alveolar volume; CPFE, combined pulmonary fibrosis and emphysema; IP, interstitial pneumonia.