The link between chronic obstructive pulmonary disease phenotypes and histological subtypes of lung cancer: a case–control study

Figures & data

Table 1 Characteristics of cases and controls

	Lung cancer cases (n=2,283)	Non-lung cancer controls (n=2,323)	P-value
Age, years (mean ± SD)	60.3±9.5	59.8±9.7	0.110
Sex, n (%)			0.061
Male	1,719 (75.3)	1,804 (77.7)
Female	564 (24.7)	519 (22.3)
BMI, kg/m^2 (mean ± SD)	24.2±3.5	23.4±3.4	<0.001
Smoking status, n (%)			0.745
Current and ex-smokers	1,225 (53.7)	1,258 (54.2)
Nonsmokers	1,058 (46.3)	1,065 (45.8)
COPD, n (%)
No	1,535 (67.2)	1,952 (84.0)	<0.001
Yes	748 (32.8)	371 (16.0)	<0.001
Mild	554 (24.3)	305 (13.1)	<0.001
Moderate	163 (7.1)	62 (2.7)	<0.001
Severe/extremely severe	31 (1.4)	4 (0.2)	<0.001
Histologic subtype, n (%)
Adenocarcinoma	1,120 (49.1)	NA
Squamous carcinoma	792 (34.7)	NA
Neuroendocrine carcinoma	192 (8.4)	NA
SCLC	152 (6.6)	NA
LCNC	20 (0.9)	NA
Carcinoid tumors	20 (0.9)	NA
Large-cell carcinoma	58 (2.5)	NA
Adenosquamous carcinoma	46 (2.0)	NA
Other subtypes@	14 (0.6)	NA
Unclassified carcinoma	61 (2.7)	NA
Lung cancer stage, n (%)
I	1,651 (72.3)	NA
II	467 (20.5)	NA
III–IV	165 (7.2)	NA

Note:

@ Other subtypes include sarcomatoid carcinoma and pulmonary melanoma.

Abbreviations: BMI, body-mass index; SCLC, small-cell lung cancer; LCNC, large-cell neuroendocrine carcinoma; NA, not applicable.

Table 2 Characteristics of COPD phenotypes

	Emphysema-predominant (n=110)	Non-emphysema-predominant (n=898)	P-value
Age, years (mean ± SD)	64.6±7.8	62.6±8.4	0.024
Sex, n (%)			0.028
Male	104 (94.5)	785 (87.4)
Female	6 (5.5)	113 (12.6)
BMI, kg/m^2 (mean ± SD)	23.0±3.7	23.3±3.4	0.348
Smoking status, n (%)			0.445
Current and ex-smokers	72 (65.5)	622 (69.3)
Nonsmokers	38 (34.5)	276 (30.7)
AC (mean ± SD)	129.2±6.9	150.9±7.1	<0.001
FEV1, L (mean ± SD)	1.4±0.4	2.1±0.6	<0.001
FVC, L (mean ± SD)	2.9±0.7	3.3±0.8	<0.001
FEV1/FVC, % (mean ± SD)	50.0±9.6	63.2±5.5	<0.001
Lung cancer subtype, n (%)	82 (74.5)	596 (66.4)
Adenocarcinoma	17 (15.5)	229 (25.5)	0.533
Squamous carcinoma	41 (37.3)	270 (30.1)	0.033
Neuroendocrine carcinoma	12 (10.9)	54 (5.9)	0.027
SCLC	11 (10.0)	46 (5.1)	0.028
LCNC	1 (0.9)	4 (0.4)	0.366
Carcinoid tumors	NA	4 (0.4)	NA
Large-cell carcinoma	3 (2.7)	17 (1.9)	0.404
Adenosquamous carcinoma	1 (0.9)	7 (0.8)	0.516
Other subtypes@	1 (0.9)	4 (0.4)	0.366
Unclassified carcinoma	7 (6.4)	15 (1.7)	0.044
Non-lung cancer, n (%)	28 (25.5)	302 (33.6)	0.086

Note:

@ Other subtypes include sarcomatoid carcinoma and pulmonary melanoma.

Abbreviations: AC, airway collapse; BMI, body-mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LCNC, large-cell neuroendocrine carcinoma; SCLC, small-cell lung cancer; NA, not applicable.

Table 3 Risk factors for lung cancer

	Univariate analysis			Logistic regression@
	OR	95% CI	P-value	OR	95% CI	P-value
COPD	2.56	2.23–2.95	<0.001	2.88	2.48–3.34	<0.001^a
COPD grading	2.06	1.84–2.29	<0.001	2.24	1.99–2.51	<0.001^b
Emphysema-predominant COPD	3.72	2.41–5.75	<0.001	4.43	2.85–6.88	<0.001^c
Non-emphysema-predominant COPD	2.51	2.15–2.93	<0.001	2.82	2.40–3.31	<0.001^d
Age	1.01	0.99–1.01	0.110	1.00	0.99–1.00	0.605^a
BMI	1.07	1.05–1.09	<0.001	1.08	1.06–1.11	<0.001^a
Sex	1.14	0.99–1.31	0.059	1.32	1.12–1.56	0.001^a
Smoking status	0.98	0.87–1.10	0.735	1.00	0.87–1.15	0.988^a

Notes:

@ There were four multivariable logistic regression models: COPD (dichotomous, referent non-COPD), COPD grading (continuous, increase), emphysema-predominant COPD phenotype (dichotomous, referent non-COPD), and non-emphysema-predominant COPD phenotype (dichotomous, referent non-COPD) distributed in models 1–4, respectively. Age (continuous, increase), BMI (continuous, increase), sex (dichotomous, referent male) and smoking status (dichotomous, referent nonsmoking) were common variables of models 1–4,^a model 1,^b model 2,^c model 3,^d and model 4.

Abbreviation: BMI, body-mass index.

Table 4 Risk factors for different histological subtypes of lung cancer@

	Squamous carcinoma&	Adenocarcinoma&	Neuroendocrine carcinoma&	SCLC&	LCNC&
COPD^a	3.51 (2.90–4.23)#	2.11 (1.74–2.55)#	4.28 (3.20–5.73)#	5.14 (3.58–7.39)#	4.35 (1.68–11.3)#
COPD grading^b	2.53 (2.20–2.29)#	1.72 (1.49–2.00)#	2.92 (2.41–3.61)#	3.32 (2.61–4.22)#	3.69 (2.04–6.68)#
Emphysema-predominant phenotype^c	5.96 (3.44–9.41)#	2.01 (1.07–3.79)#	8.73 (4.47–17.1)#	11.9 (5.58–25.5)#	9.80 (1.10–82.3)#
Non-emphysema-predominant phenotype^d	3.40 (2.78–4.17)#	2.26 (1.85–2.77)#	3.68 (2.76–5.08)#	4.31 (2.89–16.8)#	2.80 (0.85–9.18)*
Age^a	1.02 (1.01–1.03)#	0.99 (0.99–1.00)*	0.97 (0.96–0.98)#	0.96 (0.95–0.98)#	0.99 (0.93–1.01)*
BMI^a	1.08 (1.05–1.10)#	1.09 (1.07–1.12)#	1.07 (1.03–1.11)#	1.07 (1.02–1.12)#	0.99 (0.87–1.12)*
Sex^a	0.45 (0.33–0.61)#	1.78 (1.48–2.16)#	1.27 (0.87–1.87)*	1.59 (0.99–2.55)*	1.20 (0.36–3.98)*
Smoking status^a	1.51 (1.23–1.85)#	0.70 (0.58–0.83)#	1.16 (0.84–1.61)*	1.11 (0.73–1.68)*	0.77 (0.27–2.19)*
	Carcinoid tumors&	Large-cell carcinoma&	Adenosquamous carcinoma&	Other subtypes&	Unclassified&
COPD^a	1.75 (0.74–6.16)*	3.41 (1.94–5.98)#	2.04 (1.01–4.11)#	5.26 (1.84–18.1)#	3.09 (1.78–5.35)#
COPD grading^b	1.47 (0.63–3.45)*	2.27 (1.53–2.71)#	1.69 (1.03–2.79)#	2.44 (1.17–5.09)#	2.52 (1.78–3.59)#
Emphysema-predominant phenotype^c	NA	5.56 (1.55–19.9)#	2.45 (0.27–16.8)*	8.29 (0.88–78.5)*	9.03 (3.16–25.8)#
Non-emphysema-predominant phenotype^d	2.10 (0.67–6.63)*	3.37 (1.84–6.17)#	1.51 (0.65–3.54)*	3.26 (0.90–11.8)*	2.74 (1.48–5.04)#
Age^a	0.98 (0.94–1.02)*	0.99 (0.96–1.02)*	1.01 (0.98–1.05)*	0.99 (0.94–1.05)*	1.02 (0.99–1.05)*
BMI^a	1.06 (0.94–1.19)*	1.07 (1.00–1.16)#	1.12 (1.03–1.21)#	0.87 (0.74–1.03)*	1.00 (0.93–1.08)*
Sex^a	NA	0.66 (0.25–1.72)*	3.03 (1.34–6.86)#	2.17 (0.41–11.5)*	1.20 (0.56–2.55)*
Smoking status^a	0.86 (0.31–2.45)*	1.73 (0.89–3.35)*	1.97 (0.90–4.33)*	2.35 (0.52–10.6)*	1.30 (0.70–2.43)*

Notes:

@ There were four multivariable logistic regression models, and each lung cancer subtype was analyzed respectively. COPD (dichotomous, referent non-COPD), COPD grading (continuous, increase), emphysema-predominant COPD phenotype (dichotomous, referent non-COPD), and non-emphysema-predominant COPD phenotype (dichotomous, referent non-COPD) distributed in models 1–4, respectively. Age (continuous, increase), BMI (continuous, increase), sex (dichotomous, referent male) and smoking status (dichotomous, referent non-smoking) were common variables of models 1–4,^a model 1,^b model 2,^c model 3,^d and model 4.

& Adjusted OR (95% CI);

# P<0.05;

* P>0.05.

Abbreviations: BMI, body-mass index; SCLC, small-cell lung cancer; LCNC, large-cell neuroendocrine carcinoma; NA, not applicable.

Table 5 Risk of specific lung cancer subtypes in the presence of emphysema-predominant phenotype of COPD relative to non-emphysema-predominant phenotype

	Emphysema-predominant phenotype of COPD@
	OR	95% CI	P-value
All subtypes	1.61	1.02–2.54	0.043
Adenocarcinoma	0.89	0.46–1.71	0.721
Squamous carcinoma	1.73	1.03–2.89	0.038
Neuroendocrine carcinoma	3.09	1.50–6.35	0.002
SCLC	3.74	1.64–8.53	0.002
LCNC	2.94	0.31–28.1	0.349
Carcinoid tumors	NA	NA	NA
Large-cell carcinoma	2.24	0.60–8.37	0.230
Adenosquamous carcinoma	1.89	0.21–16.7	0.567
Other subtypes	3.28	0.29–37.6	0.340
Unclassified carcinoma	2.54	0.85–7.61	0.096

Notes:

@ Each lung cancer subtype was analyzed separately. Multivariable logistic regression model variables: emphysema-predominant phenotype of COPD (dichotomous, referent non-emphysema-predominant phenotype), age (continuous, increase), BMI (continuous, increase), sex (dichotomous, referent male), and smoking status (dichotomous, referent nonsmoking).

Abbreviations: BMI, body-mass index; SCLC, small cell-lung cancer; LCNC, large-cell neuroendocrine carcinoma; NA, not applicable.