Associations Between Morphological Phenotypes of COPD and Clinical Characteristics in Surgically Resected Patients with COPD and Concomitant Lung Cancer

Figures & data

Table 1 Baseline Clinical Characteristics of the Three Phenotypes in Surgically Resected Patients with COPD and Concomitant Lung Cancer

	All Subjects (n=132)	Non-Emphysema Phenotype (n=36)	Emphysema Phenotype (n=49)	Mixed Phenotype (n=47)
Age, years	70.50±7.93	71.86±6.10	69.67±8.99	70.32±8.03
Gender, female/male	7/125	4/32	1/48	2/45
BMI, kg/m^2	22.99±3.45	24.82±3.18	22.28±3.32 **	22.32±3.33 **
Smoking index, pack-years	61.28±36.38	51.87±42.91	66.56±32.85	60.11±36.31
Smoking status, Former/current smoker	85/47	28/8	24/25 *	33/14
GOLD stage, 1/2/3/4	66/58/8/0	24/12/0/0	24/24/1/0	18/22/7/0
PS	0.70±0.52	0.53±0.65	0.59±0.50	0.96±0.29 **^††
mMRC dyspnea scale	1.02±0.69	0.81±0.71	0.94±0.69	1.26±0.64 **^†
Chest CT findings
LAA score	7.12±7.33	0±0	8.80±6.54 **	10.83±7.18 **
WA% of right B1, %	50.49±10.05	48.08±6.84	46.27±8.94	56.74±10.23 **^††
WA% of right B10, %	48.90±7.68	47.50±6.95	43.12±4.67 **	56.00±4.46 **^††
ESMCSA, mm^2	3203.51±751.68	3236.52±742.26	3217.38±655.10	3163.77±859.88
Pulmonary function tests
VC, L	3.52±0.73	3.46±0.66	3.74±0.72	3.37±0.76^†
%VC, %	102.48±16.74	102.47±14.17	105.61±16.87	99.08±18.14
FVC, L	3.36±0.74	3.25±0.72	3.58±0.73	3.20±0.74^†
%FVC, %	99.73±17.66	99.85±17.03	103.28±17.33	95.94±18.06
FEV1, L	2.03±0.54	2.04±0.48	2.14±0.52	1.91±0.58
%FEV1, %	75.68±17.08	78.11±14.49	76.83±17.15	72.62±18.68
FEV1/FVC, %	60.34±7.53	62.79±5.17	59.86±7.21	58.96±0.94
TLC, L	5.97±0.99	5.74±0.96	6.14±0.91	5.98±1.07
%TLC, %	114.63±15.14	112.97±14.61	115.50±13.41	115.03±17.35
RV, L	2.43±0.54	2.24±0.61	2.39±0.39	2.62±0.57 **
%RV, %	142.55±31.22	131.56±35.32	138.49±20.25	155.49±33.49 **^†
FRC, L	3.58±0.76	3.28±0.71	3.67±0.74 *	3.71±0.76 *
%FRC, %	102.66±19.68	102.78±21.55	100.09±18.27	105.3±19.67
DLCO, mL/min/mmHg	16.67±5.30	20.07±4.02	15.41±4.65 **	15.36±5.73 **
%DLCO, %	69.97±21.49	85.90±15.62	63.62±18.71 **	64.28±22.16 **
DLCO/VA, mL/min/mmHg/L	3.75±1.26	4.68±0.97	3.40±1.09 **	3.39±1.27 **
%DLCO/VA, %	85.68±29.43	107.76±23.10	77.43±26.16 **	77.19±28.62 **
Prognostic indices for lung cancer
PNI	49.76±5.08	50.82±4.26	49.88±5.45	48.82±5.19
NLR	2.40±1.60	2.37±1.78	2.35±1.69	2.48±1.38
PLR	131.82±71.45	141.22±100.64	120.22±55.93	136.66±56.67
ALI	50.10±23.42	57.20±26.25	47.25±18.59	47.48±24.93
mGPS	0.10±0.35	0.03±0.17	0.06±0.24	0.19±0.50
PI	0.11±0.34	0.06±0.23	0.10±0.31	0.17±0.43
Regular treatment for COPD before surgery
LAMA	39 (29.5%)	11 (30.6%)	14 (28.6%)	14 (29.8%)
LABA	36 (27.3%)	14 (38.9%)	11 (22.4%)	11 (23.4%)
ICS	18 (13.6%)	9 (25.0%)	5 (10.2%)	4 (8.5%)
Comorbidities before surgery
Hypertension	51 (38.6%)	19 (52.8%)	14 (28.6%)	18 (38.3%)
Diabetes mellitus	20 (15.2%)	7 (19.4%)	5 (10.2%)	8 (17.0%)
Cardiovascular disease	13 (9.8%)	3 (8.3%)	4 (8.2%)	6 (12.8%)
Arrhythmia	6 (4.5%)	2 (5.6%)	2 (4.1%)	2 (4.3%)
Peptic ulcer and/or Gastoroesophageal reflux disease	12 (9.1%)	3 (8.3%)	5 (10.2%)	4 (8.5%)

Notes: Values are given as mean±SD or n (%) unless otherwise noted. **p<0.01, *p<0.05 vs non-emphysema phenotype; ^††p<0.01, ^†p<0.05 vs emphysema phenotype.

Abbreviations: BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; PS, performance status; mMRC, modified British Medical Research Council; LAA, low attenuation area; WA%, percentage of airway wall area; ESM_CSA, cross-sectional area of erector spinae muscles; VC, vital capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 s; TLC, total lung capacity; RV, residual volume; FRC, functional residual capacity; DLCO, diffusing capacity for carbon monoxide; DLCO/VA, diffusing capacity for carbon monoxide corrected for alveolar volume; PNI, prognostic nutritional index; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; ALI, Advanced Lung Cancer Inflammation Index; mGPS, modified Glasgow Prognostic Score; PI, prognostic index; LAMA, long-acting muscarinic antagonist; LABA, long-acting β₂ agonist; ICS, inhaled corticosteroid.

Table 2 Histological Diagnosis, Pathological Stage, Type of Resection, Postoperative Complications Following Pulmonary Resection, and Postoperative Chemotherapy for the Three Phenotypes in Surgically Resected Patients with COPD and Concomitant Lung Cancer

	All Subjects (n=132)	Non-Emphysema Phenotype (n=36)	Emphysema Phenotype (n=49)	Mixed Phenotype (n=47)
Histological diagnosis
Small cell carcinoma	3 (2.3%)	1 (2.8%)	0 (0.0%)	2 (4.3%)
Squamous cell carcinoma	52 (39.4%)	4 (11.1%)	19 (38.8%) *	29 (61.7%) **^†
Adenocarcinoma	69 (52.3%)	28 (77.8%)	26 (53.1%) *	15 (31.9%) **
Large cell carcinoma	6 (4.5%)	2 (5.6%)	3 (6.1%)	1 (2.1%)
Other non-small cell carcinoma	2 (1.5%)	1 (2.8%)	1 (2.0%)	0 (0.0%)
Pathological stage (7th edition)
Stage I A, B	98 (74.2%)	30 (83.3%)	32 (71.4%)	36 (76.6%)
Stage II A, B	24 (18.2%)	3 (8.3%)	10 (20.4%)	11 (23.4%)
Stage III A, B	9 (6.8%)	2 (5.6%)	7 (14.3%)	0 (0.0%)^†
Stage IV	1 (7.6%)	1 (2.8%)	0 (0.0%)	0 (0.0%)
Advanced stage (IIIB, IV)	1 (7.6%)	1 (2.8%)	0 (0.0%)	0 (0.0%)
Type of resection
Segmentectomy	16 (12.1%)	3 (8.3%)	7 (14.3%)	6 (12.8%)
Lobectomy	114 (86.4%)	33 (91.7%)	41 (83.7%)	40 (85.1%)
Pneumonectomy	2 (1.5%)	0 (0.0%)	1 (2.0%)	1 (2.1%)
Postoperative complications following pulmonary resection
Acute exacerbation of COPD	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Bacterial pneumonia	8 (6.1%)	3 (8.3%)	3 (6.1%)	2 (4.3%)
Pyothorax	8 (6.1%)	3 (8.3%)	1 (2.0%)	4 (8.5%)
Hypoxemia (respiratory failure)	12 (9.1%)	1 (2.8%)	6 (12.2%)	5 (10.6%)
Prolonged air leak	12 (9.1%)	6 (16.7%)	3 (6.1%)	3 (6.4%)
Paroxysmal atrial fibrillation	12 (9.1%)	2 (5.6%)	7 (14.3%)	3 (6.4%)
Others	5 (3.8%)	1 (2.8%)	3 (6.1%)	1 (2.1%)
Surgery-related death	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Postoperative chemotherapy and radiation therapy
Adjuvant chemotherapy	32 (24.2%)	6 (16.7%)	16 (32.7%)	10 (21.3%)
Postoperative recurrence of lung cancer	43 (32.6%)	8 (22.2%)	16 (32.7%)	19 (40.4%)
Chemotherapy after developing recurrence	30 (22.7%)	5 (13.9%)	10 (20.4%)	15 (31.9%)
Chemotherapy-related death	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Radiation therapy after developing recurrence	8 (6.1%)	2 (5.6%)	2 (4.1%)	4 (8.5%)

Notes: Values are given as n (%). **p<0.01, *p<0.05 vs non-emphysema phenotype; ^†p<0.05 vs emphysema phenotype.

Table 3 Causes of Deaths in Surgically Resected Patients with COPD and Concomitant Lung Cancer

	All Subjects (n=132)	Non-Emphysema Phenotype (n=36)	Emphysema Phenotype (n=49)	Mixed Phenotype (n=47)
Number of deaths	68	10	21	37
Lung cancer	34 (50.0%)	6 (60.0%)	12 (57.1%)	16 (44.4%)
Pneumonia	13 (19.1%)	2 (20.0%)	1 (4.8%)	10 (27.8%)
Acute exacerbation of COPD	1 (1.5%)	0 (0.0%)	0 (0.0%)	1 (2.8%)
Chronic respiratory failure	3 (4.4%)	1 (10.0%)	0 (0.0%)	2 (5.6%)
Other causes	17 (25.0%)	1 (10.0%)	8 (38.1%)	8 (22.2%)

Note: Values are given as n (%).

Table 4 Univariate and Multivariate Cox Proportional Hazards Regression Analyses of the Risk of Death in Surgically Resected Patients with COPD and Concomitant Lung Cancer (n=132)

	Univariate Analysis			Multivariate Analysis
	HR	95% CI	p	HR	95% CI	p
Age	1.10181	0.98544–1.05187	0.2807	1.03828	1.00073–1.07723	0.0456
BMI	0.94708	0.87700–1.02276	0.1657	0.96791	0.88087–1.06355	0.4975
Smoking index	1.00441	0.99835–1.01051	0.1539	1.00048	0.99326–1.00775	0.8962
GOLD stage	1.10382	0.74794–1.62903	0.6189	0.91566	0.62399–1.34366	0.6525
mMRC dyspnea scale	1.48052	1.03362–2.12063	0.0323	1.31875	0.87771–1.98141	0.1829
LAA score	1.04538	1.01383–1.07792	0.0045	1.04791	1.00668–1.09083	0.0223
ESMCSA	0.99995	0.99963–1.00026	0.7511	1.00024	0.99984–1.00064	0.2341

Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council; LAA, low attenuation area; ESM_CSA, cross-sectional area of erector spinae muscles.

Figure 1 Kaplan-Meier curve of overall survival for non-emphysema phenotype (n=36, MST: 14.48 years), emphysema phenotype (n=49, MST: 10.38 years), and mixed phenotype (n=47, MST: 5.15 years). Differences in survival were assessed using the Log rank test.

Abbreviation: MST, median survival time.