Unique Mortality Profile in Japanese Patients with COPD: An Analysis from the Hokkaido COPD Cohort Study

Figures & data

Table 1 Baseline Characteristics of 10-Year Survivors and Non-Survivors

	Survivors	Non-Survivors	p value
Number of patients	153	112
Age, years old	67± 8	74 ± 5	<0.001^a
Female sex, N (%)	11 (7)	3 (3)	0.16^c
BMI, kg/m^2	23 ± 3	21 ± 3	0.001^a
Current smoker at entry, N (%)	45 (29)	28 (25)	0.46^c
Smoking index at entry, pack-years	66 ± 32	58 ± 25	0.07^a
Lung function
Post-BD FEV1, L	1.88 ± 0.67	1.54 ± 0.61	<0.001^a
Post-BD FEV1, % predicted	68 ± 22	59 ± 21	0.004^a
Post-BD FEV1/FVC	0.53 ± 0.13	0.48 ± 0.12	0.001^a
DLco, % predicted	81 ± 24	73 ± 26	0.009^a
Kco, % predicted	68 ± 23	57 ± 24	<0.001^a
Patient-reported outcomes
Chronic bronchitis, N (%)	17 (11)	12 (11)	1.00^c
mMRC dyspnea scale	1 (1–2)	2 (1–2)	0.04^b
SGRQ total score	30 ± 17	34 ± 18	0.13^a
Laboratory values
Leptin/adiponectin ratio	0.70 (0.35–1.62)	0.39 (0.17–0.87)	<0.001^b
CT emphysema score	1.00 (0.50–2.00)	1.50 (0.83–2.33)	<0.001^b
Comorbidities
Any cardiovascular disease	30 (20)	29 (26)	0.24^c
Ischemic heart disease	10 (7)	7 (6)	1.00^c
Diabetes	8 (5)	5 (4)	1.00^c
Charlson comorbidity index	0 (0–1)	0 (0–1)	0.29^b

Notes: Fourteen patients whose 10-year survival data were absent were not included in this table. Data are shown as means ± SD, median (interquartile range), or number (%). ^aStudent’s t-test, ^bMann–Whitney U-test, ^cFisher’s exact test.

Abbreviations: Post-BD, post-bronchodilator; DLco, carbon monoxide diffusion capacity; Kco, carbon monoxide transfer coefficient.

Figure 1 Kaplan–Meier curve for all-cause mortality for all patients.

Figure 2 Proportion of causes of death.

Table 2 Risk Factors of Baseline Variables for All-Cause Mortality (A) and Death from Respiratory Diseases (B)

A. All-Cause Mortality	Kco Excluded		CT Emphysema Score Excluded
	Hazard Ratio (95% CI)	p value	Hazard Ratio (95% CI)	p value
Sex (male)	2.20 (0.65–7.43)	0.19	2.23 (0.67–7.46)	0.19
Age (10 years older)	1.12 (1.08–1.16)	<0.001	1.12 (1.08–1.16)	<0.001
BMI (1 kg/m^2 increase)	0.92 (0.84–1.01)	0.08	0.94 (0.86–1.04)	0.23
Pack-years (10 pack-years increase)	0.93 (0.87–1.01)	0.07	0.94 (0.87–1.00)	0.07
mMRC dyspnea scale (1 grade increase)	0.92 (0.69–1.23)	0.59	0.88 (0.66–1.04)	0.39
Post-BD FEV1%predicted (10% increase)	0.97 (0.88–1.07)	0.54	0.93 (0.85–1.02)	0.22
Kco %predicted (10% increase)	-	-	0.89 (0.81–0.98)	0.01
CT emphysema score (1 point increase)	1.36 (1.08–1.72)	0.009	-	-
Charlson Comorbidity Index (1 point increase)	0.92 (0.69–1.46)	0.28	1.10 (0.86–1.40)	0.47
Leptin/adiponectin ratio (1 log10 increase)	1.00 (0.86–1.17)	0.96	0.99 (0.85–1.15)	0.92
B. Death From Respiratory Diseases	Kco Excluded		CT Emphysema Score Excluded
	Hazard Ratio (95% CI)	p value	Hazard Ratio (95% CI)	p value
Sex (male)	4.77e+07 (0-∞)	1.00	1.65e+07 (0-∞)	1.00
Age (10 years older)	1.17 (1.10–1.25)	<0.001	1.16 (1.10–1.23)	<0.001
BMI (1 kg/m^2 increase)	0.79 (0.68–0.92)	0.002	0.47 (0.72–0.99)	0.04
Pack-years (10 pack-years increase)	1.04 (0.93–1.15)	0.52	1.03 (0.93–1.14)	0.62
mMRC dyspnea scale (1 grade increase)	0.96 (0.58–1.59)	0.86	0.94 (0.57–1.55)	0.81
Post-BD FEV1%predicted (10% increase)	0.89 (0.75–1.06)	0.19	0.83 (0.70–0.99)	0.04
Kco %predicted (10% increase)	-	-	0.78 (0.67–0.92)	0.003
CT emphysema score (1 point increase)	1.94 (1.32–2.86)	<0.001	-	-
Charlson Comorbidity Index (1 point increase)	1.49 (1.05–2.11)	0.02	1.33 (0.93–1.88)	0.12
Leptin/adiponectin ratio (1 log10 increase)	1.16 (0.90–1.49)	0.25	1.10 (0.87–1.39)	0.41

Notes: 261 subjects who had 10-year mortality data as well as data of all variables were analyzed. All variables listed were included into the multivariate Cox proportional hazards models. Covariate selection for inclusion in the models was based on potential confounding variables known to affect COPD mortality. CT emphysema score and Kco %predicted were treated separately, because they were mutually correlated.

Abbreviations: CI, confidence interval; Post-BD, post-bronchodilator; Kco, carbon monoxide transfer coefficient.

Table 3 Risk Factors of Longitudinal Variables During the First 5 Years for All-Cause Mortality (A) and Death from Respiratory Diseases During the Last 5 Years (B)

A. All-Cause Mortality	Model 1			Model 2
	Hazard Ratio (95% CI)		p value	Hazard Ratio (95% CI)	p value
Annual body weight change (1 kg/year increase)	0.31 (0.16–0.53)		<0.001	0.36 (0.19–0.69)	0.002
Annual post-BD FEV1 change (1 mL/year increase)	0.99 (0.98–0.997)		0.007	0.99 (0.97–0.998)	0.02
Exacerbation frequency (per 1 prescription change event)	1.09 (0.50–2.39)		0.82	0.75 (0.33–1.69)	0.49
B. Death From Respiratory Diseases	Model 1			Model 2
	Hazard Ratio (95% CI)	p value		Hazard Ratio (95% CI)	p value
Annual body weight change (1 kg/year increase)	0.17 (0.07–0.42)	<0.001		0.26 (0.09–0.75)	0.01
Annual post-BD FEV1 change (1 mL/year increase)	0.98 (0.97–0.994)	0.004		0.98 (0.96–1.00)	0.05
Exacerbation frequency (per 1 prescription change event)	2.68 (1.11–6.44)	0.03		0.82 (0.33–2.06)	0.68

Notes: 231 subjects who survived during the first 5 years were analyzed. Model 1: Multivariate Cox proportional hazards models using the three longitudinal variables. Model 2: Multivariate Cox proportional hazards models using the three longitudinal variables adjusted by baseline variables (sex, age, BMI, pack-years, mMRC dyspnea scale, post-BD FEV₁%predicted, CT emphysema score, Charlson Comorbidity Index, leptin/adiponectin ratio).

Abbreviations: CI, confidence interval; Post-BD, post-bronchodilator.

Figure 3 Risk factors for all-cause mortality. (A) Kaplan–Meier curves for all-cause mortality according to the CT emphysema score at baseline. (B) Classification tree produced by CART analysis of risk factors for all-cause mortality during the last 5 years.

Abbreviation: BW, body weight.