Associated Factors and Comorbidities of Airflow Limitation in Subjects Undergoing Comprehensive Health Examination in Japan – Survey of Chronic Obstructive Pulmonary Disease Patients Epidemiology in Japan (SCOPE- J)

Figures & data

Table 1 Subject Characteristics by Presence or Absence of Airflow Limitation, Chronic Cough/Phlegm or Currently Treated Respiratory Diseases

Variable		Total	Having At least One of Airflow Limitation, Chronic Cough/Phlegm, and Currently Treated Respiratory Diseases	Having Neither Airflow Limitation, Chronic Cough/Phlegm, nor Currently Treated Respiratory Diseases
		N = 22,293	n = 1520	n = 20,773
Age (years)		54.6 ± 9.6	60.0 ± 10.7	54.3 ± 9.4
Sex	Male	14,013 (62.9)	1162 (76.4)	12,851 (61.9)
	Female	8280 (37.1)	358 (23.6)	7922 (38.1)
BMI (kg/m^2)		23.0 ± 3.3	23.0 ± 3.2	23.0 ± 3.3
Smoking history	None	11,212 (50.5)	525 (34.7)	10,687 (51.7)
	Past	6696 (30.2)	570 (37.7)	6126 (29.6)
	Current	4285 (19.3)	417 (27.6)	3868 (18.7)
	Missing data	100	8	92
Pack-years		11.2 ± 17.6	20.0 ± 22.1	10.6 ± 17.0
FEV1 (L)		2.82 ± 0.68	2.41 ± 0.68	2.84 ± 0.67
%FEV1 (%)		96.0 ± 14.4	82.6 ± 17.0	97.0 ± 13.7
FEV1/FVC (%)		81.0 ± 6.3	70.1 ± 9.4	81.8 ± 5.2
FVC (L)		3.48 ± 0.82	3.44 ± 0.86	3.49 ± 0.82
%FVC (%)		99.2 ± 13.6	97.4 ± 16.2	99.3 ± 13.4
WBC (/μL)		5385 ± 1,762	5683 ± 1588	5364 ± 1772
CRP (mg/dL)		0.11 ± 0.31	0.15 ± 0.40	0.11 ± 0.31
HbA1c (%)		5.65 ± 0.62	5.75 ± 0.67	5.65 ± 0.61
eGFR (mL/min/1.73m^2)		73.8 ± 13.0	72.1 ± 13.6	73.9 ± 12.9
CAT score		6.5 ± 4.9	9.0 ± 6.4	6.3 ± 4.7
Comorbidity
Myocardial infarction		80 (0.4)	10 (0.7)	70 (0.3)
Angina pectoris		188 (0.8)	23 (1.5)	165 (0.8)
Cerebrovascular disease		141 (0.6)	13 (0.9)	128 (0.6)
Osteoporosis		234 (1.0)	25 (1.6)	209 (1.0)
Fracture		48 (0.2)	6 (0.4)	42 (0.2)
Depression		233 (1.0)	14 (0.9)	219 (1.1)
Anxiety disorder		180 (0.8)	18 (1.2)	162 (0.8)
Sleep disorder		428 (1.9)	49 (3.2)	379 (1.8)
Diabetes mellitus		1,131 (5.1)	80 (5.3)	1,051 (5.1)
Lung cancer		59 (0.3)	14 (0.9)	45 (0.2)

Notes: Data are shown as numbers (%) or mean ± SD. Among the 22,293 subjects, 100 had no smoking data. Each comorbidity was defined as the number of examinees under treatment at the time of examination except for lung cancer. For lung cancer, it was defined as the number of diagnosed examinees, regardless of whether they were under treatment at the time of examination.

Abbreviations: BMI, body mass index; CAT, chronic obstructive pulmonary disease assessment test; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; FEV1, forced expiratory volume in 1 s; %FEV1, percent predicted FEV1; FVC, forced vital capacity; %FVC, percent predicted FVC; HbA1c, hemoglobin A1c; SD, standard deviation; WBC, white blood cell.

Table 2 Associations of Participant Characteristics with Having at Least One of Airflow Limitation, Chronic Cough/Phlegm, and Currently Treated Respiratory Diseases (Logistic Regression Analysis)

(A) Participant Characteristics Other Than Comorbidities
Variables	Total (N = 22,293)				Ever-Smokers (n = 10,981)				Never-Smokers (n = 11,212)
	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value
Age (per 10 years)	1.79 (1.69–1.88)	<0.001	1.89 (1.77–2.01)	<0.001	1.93 (1.80–2.07)	<0.001	2.04 (1.86–2.23)	<0.001	1.72 (1.58–1.87)	<0.001	1.81 (1.65–1.99)	<0.001
Sex (male)	2.00 (1.77–2.26)	<0.001	1.42 (1.21–1.66)	<0.001	1.66 (1.32–2.10)	<0.001	1.06 (0.80–1.41)	0.677	1.46 (1.22–1.74)	<0.001	1.41 (1.15–1.72)	<0.001
Pack-years (per 10 pack-years)	—	—	—	—	1.25 (1.20–1.29)	<0.001	1.09 (1.04–1.13)	<0.001	—	—	—	—
BMI (per 1 kg/m^2)	1.00 (0.99–1.02)	0.651	0.96 (0.94–0.98)	<0.001	0.98 (0.96–1.00)	0.038	0.96 (0.94–0.99)	0.003	1.01 (0.98–1.03)	0.624	0.97 (0.94–1.01)	0.102
CRP (per 0.5 mg/dL)	1.13 (1.07–1.20)	<0.001	1.08 (1.01–1.16)	0.029	1.16 (1.07–1.27)	<0.001	1.11 (1.00–1.23)	0.041	1.11 (1.02–1.20)	0.015	1.05 (0.95–1.17)	0.310
CAT score (per 5 points)	1.59 (1.52–1.67)	<0.001	1.69 (1.60–1.78)	<0.001	1.48 (1.40–1.57)	<0.001	1.67 (1.56–1.79)	<0.001	1.68 (1.55–1.81)	<0.001	1.72 (1.58–1.87)	<0.001
Notes: Objective variable was having at least one of airflow limitation (FEV1/FVC < 70%), chronic cough and phlegm, and under treatment for respiratory disease. Among the 22,293 subjects, 100 had no smoking data. Adjusted odds ratios for age, sex, pack-years, BMI, CRP and CAT score were calculated by using these 6 explanatory variables (in never-smokers, 5 explanatory variables other than pack-years). Abbreviations: BMI, body mass index; CAT, chronic obstructive pulmonary disease assessment test; CI, confidence interval; CRP, C-reactive protein; OR, odds ratio.
(B) Comorbidities
Variables	Total (N = 22,293)				Ever-Smokers (n = 10,981)				Never-Smokers (n = 11,212)
	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value
Myocardial infarction	1.99 (1.02–3.86)	0.043	0.88 (0.43–1.80)	0.725	2.04 (0.99–4.18)	0.053	1.04 (0.48–2.26)	0.922	<0.01 (<0.01->999)	0.949	<0.01 (<0.01->999)	0.945
Angina pectoris	1.93 (1.24–3.00)	0.003	1.14 (0.72–1.79)	0.573	1.61 (0.93–2.78)	0.089	1.07 (0.60–1.89)	0.826	2.10 (0.96–4.59)	0.064	1.11 (0.50–2.46)	0.797
Cerebrovascular disease	1.39 (0.79–2.47)	0.257	0.85 (0.47–1.53)	0.583	1.11 (0.53–2.31)	0.778	0.77 (0.36–1.63)	0.493	1.52 (0.55–4.22)	0.419	0.86 (0.31–2.41)	0.776
Osteoporosis	1.65 (1.09–2.51)	0.018	1.23 (0.79–1.91)	0.364	2.31 (0.87–6.11)	0.092	0.90 (0.30–2.66)	0.844	2.25 (1.40–3.59)	<0.001	1.40 (0.86–2.28)	0.176
Fracture	1.96 (0.83–4.61)	0.125	1.59 (0.65–3.90)	0.313	2.90 (0.95–8.84)	0.060	2.08 (0.62–6.92)	0.234	1.51 (0.36–6.38)	0.572	1.17 (0.28–4.97)	0.833
Depression	0.87 (0.51–1.50)	0.622	1.20 (0.69–2.07)	0.525	0.57 (0.25–1.29)	0.175	0.84 (0.36–1.93)	0.677	1.50 (0.73–3.08)	0.275	1.76 (0.85–3.65)	0.130
Anxiety disorder	1.52 (0.93–2.49)	0.092	1.87 (1.13–3.10)	0.015	0.82 (0.36–1.89)	0.642	0.96 (0.41–2.26)	0.927	2.87 (1.56–5.28)	<0.001	2.13 (1.68–5.82)	<0.001
Sleep disorder	1.80 (1.33–2.43)	<0.001	1.49 (1.08–2.06)	0.015	1.87 (1.24–2.81)	0.003	1.35 (0.86–2.13)	0.187	1.96 (1.25–3.10)	0.004	1.70 (1.07–2.70)	0.025
Diabetes mellitus	1.04 (0.83–1.32)	0.724	0.64 (0.50–0.82)	<0.001	0.76 (0.56–1.02)	0.065	0.50 (0.36–0.69)	<0.001	1.56 (1.06–2.30)	0.025	1.06 (0.71–1.57)	0.782
Lung cancer	4.28 (2.34–7.82)	<0.001	2.46 (1.31–4.60)	0.005	4.53 (1.96–10.45)	<0.001	2.55 (1.06–6.10)	0.036	4.61 (1.89–11.20)	<0.001	2.56 (1.03–6.34)	0.043

Notes: Objective variable was having at least one of airflow limitation (FEV1/FVC < 70%), chronic cough and phlegm, and under treatment for respiratory disease. Among the 22,293 subjects, 100 had no smoking data. Adjusted odds ratios for each comorbidity was calculated by using 5 explanatory variables including each comorbidity, age, sex, pack-years and BMI (in never-smokers, 4 explanatory variables other than pack-years). In never smokers, all the participants with comorbid myocardial infarction did not have airflow limitation, chronic cough/phlegm or currently treated respiratory diseases.

Table 3 Odds Ratios for Comorbid Diabetes Mellitus with Different Objective Variable Settings (Logistic Regression Analyses)

(A) Objective Variable: Having at Least One of %FEV1 <80%, Chronic Cough/Phlegm, and Currently Treated Respiratory Diseases
Subjects	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value
Total	1.77 (1.52–2.06)	<0.001	1.19 (1.02–1.40)	0.028
Ever-smokers	1.54 (1.28–1.86)	<0.001	1.13 (0.93–1.37)	0.208
Never-smokers	1.81 (1.37–2.38)	<0.001	1.32 (1.00–1.75)	0.052
(B) Objective Variable: Having at Least One of %FVC < 80%, Chronic Cough/Phlegm, and Currently Treated Respiratory Diseases
Subjects	Crude OR (95% CI)	p value	Adjusted OR (95% CI)	p value
Total	1.85 (1.56–2.19)	<0.001	1.28 (1.07–1.53)	0.006
Ever-smokers	1.59 (1.28–1.97)	<0.001	1.18 (0.94–1.46)	0.149
Never-smokers	2.09 (1.57–2.77)	<0.001	1.51 (1.13–2.02)	0.006

Notes: Explanatory variables for calculating adjusted odds ratios were having comorbid diabetes mellitus, age, sex, pack-years and BMI in ever-smokers, and 4 variables other than pack-years in never-smokers.

Abbreviations: BMI, body mass index; CI, confidence interval; OR, odds ratio.

Figure 1 Cluster dendrogram of subjects by comorbidities. The “height” on the vertical axis indicates the dissimilarity/distance between clusters. The higher “height” represents less similarity between clusters. (A) Ever-smokers (n = 487) were first divided into SO cluster (overweight) and others, followed by SC (CKD) and SI (inflammation), in order. (B) Never-smokers (n = 276) were first divided into NC (CKD) and others, followed by NO (overweight) and NU (underweight), in order.

Figure 2 The prevalence of each comorbid disease sorted by the comorbid clusters (excluding no comorbidity cluster) among ever-smokers (A, n=487) and never-smokers (B, n=276). For example, among ever-smokers, 34.9% of SI cluster, 100% of SO cluster, 33.6% of SC cluster and 21.3% of SM cluster had OW (overweight).

Abbreviations: OW, overweight; UW, underweight; Inf, inflammation; CKD, chronic kidney disease; MI, myocardial infarction; AP, angina pectoris; Cer, cerebrovascular disease; OP, osteoporosis; Fra, fracture; Dep, depression; Anx, anxiety disorder; Sle, sleep disorder; DM, diabetes mellitus; LC, lung cancer.

Table 4 Characteristics of Comorbidity-Based Clusters

(A) Characteristics of Each Cluster in Ever-Smokers
	Cluster SN (None) n = 500	Cluster SI (Inflammation) n = 83	Cluster SO (Overweight) n = 130	Cluster SC (CKD) n = 110	Cluster SM (Mixed) n = 164	p value
Sex, female	39 (7.8)	6 (7.2)	9 (6.9)	6 (5.5)	22 (13.4)	0.116
Age (years)	58.7 ± 10.1	57.1 ± 10.2	56.2 ± 9.4	66.6 ± 8.9	63.1 ± 10.9	<0.001
BMI (kg/m^2)	22.2 ± 1.6	24.0 ± 3.3	27.2 ± 2.0	24.1 ± 2.8	22.5 ± 4.4	<0.001
CRP (mg/dL)	0.07 ± 0.06	0.54 ± 0.92	0.10 ± 0.07	0.10 ± 0.07	0.28 ± 0.66	<0.001
FEV1/FVC (%)	68.7 ± 8.9	68.9 ± 10.0	73.5 ± 9.1	67.3 ± 8.8	68.1 ± 8.3	<0.001
%FEV1 (%)	81.3 ± 16.0	77.2 ± 16.7	81.0 ± 15.2	82.7 ± 17.9	77.6 ± 16.9	0.019
%FVC (%)	98.4 ± 15.2	93.8 ± 16.4	92.5 ± 14.3	100.1 ± 16.9	93.5 ± 16.3	<0.001
CAT score	8.7 ± 6.0	11.3 ± 7.4	10.6 ± 6.4	8.0 ± 5.6	9.6 ± 6.8	<0.001
Note: Data are presented as numbers (%) or mean ± SD.
(B) Characteristics of Each Cluster in Never-Smokers
	Cluster NN (None) n = 249	Cluster NO (Overweight) n = 56	Cluster NC (CKD) n = 57	Cluster NU (Underweight) n = 29	Cluster NM (Mixed) n = 134	p value
Sex, female	132 (53.0)	29 (51.8)	24 (42.1)	25 (86.2)	65 (48.5)	0.002
Age (years)	57.8 ± 11.2	57.6 ± 10.5	66.2 ± 9.0	58.8 ± 10.3	63.8 ± 10.6	<0.001
BMI (kg/m^2)	21.7 ± 1.6	27.1 ± 2.0	22.0 ± 1.7	17.3 ± 1.0	24.0 ± 3.9	<0.001
CRP (mg/dL)	0.06 ± 0.05	0.10 ± 0.07	0.07 ± 0.05	0.06 ± 0.09	0.37 ± 0.72	<0.001
FEV1/FVC (%)	71.8 ± 10.0	74.6 ± 10.2	70.2 ± 8.7	69.6 ± 8.1	72.3 ± 9.8	0.175
%FEV1 (%)	88.2 ± 17.2	85.7 ± 16.3	86.1 ± 17.2	84.8 ± 18.6	84.1 ± 17.7	0.082
%FVC (%)	101.4 ± 16.1	95.2 ± 16.4	99.8 ± 18.1	99.5 ± 20.3	94.5 ± 15.8	0.001
CAT score	7.5 ± 5.9	10.5 ± 6.2	6.6 ± 5.0	8.3 ± 6.1	10.5 ± 7.6	<0.001

Note: Data are presented as numbers (%) or mean ± SD.

Abbreviations: BMI, body mass index; CKD, chronic kidney disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 s; %FEV1, percent predicted FEV1; FVC, forced vital capacity; %FVC, percent predicted FVC; CAT, chronic obstructive pulmonary disease assessment test; SD, standard deviation.