Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database

Figures & data

Figure 1 Study flow chart and outcome assessment flow using KNHANES and NHI reimbursement database.

Note: Vertical arrows in the rectangle box indicate the year of enrollment from KNHANES. Dashed arrows in the rectangle box represent the retrospective assessment of NHI data and solid arrows in the rectangle box represent the prospective assessment of NHI data.
Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; KNHANES, Korean National Health and Nutrition Examination Survey; NHI, National Health Insurance.

Table 1 Baseline characteristics (n=2,397)

	N (%) or mean ± SD
Age, years	63.5±11.9
Sex, male	1,692 (70.6)
Body mass index, kg/m^2	23.5±2.9
Body mass index ≥25 kg/m^2	689 (28.7)
Smoking historya
Nonsmoker	747 (31.2)
Current or ex-smoker	1,621 (67.6)
Pack-years	23.9±23.3
Previous pulmonary tuberculosis	323 (13.5)
Comorbidities
Hypertension	847 (35.3)
Diabetes mellitus	331 (13.8)
Depression	296 (12.3)
Bronchial asthma	261 (10.9)
Coronary heart diseaseb	96 (4.0)
Atopic dermatitis	69 (2.9)
Stroke	66 (2.8)
Physical activity
Days of moderate active physical activity per week	2.3±2.1
Days of high active physical activity per week	1.8±1.7
Baseline pulmonary function test
FVC, L	3.6±0.9
FVC, % predicted	90.9±13.6
FEV1, L	2.3±0.6
FEV1, % predicted	78.6±13.7
FEV1/FVC	0.6±0.07
COPD severity
FEV1% predicted ≥80%	1,075 (44.8)
65%≤ FEV1% predicted <80%	924 (38.6)
50%≤ FEV1% predicted <65%	398 (16.6)
EQ-5D index values	0.9±0.1
EQ-5D index values ≥0.9	1,611 (67.2)
Use of inhalers	141 (5.9)
LAMA	82 (3.4)
LABA	0 (0)
ICS/LABA	98 (4.1)

Notes: The data are presented as number (%) or mean and SD.

a Data of 29 patients are missed.

b Coronary heart disease includes myocardial infarction and angina pectoris.

Abbreviations: EQ-5D, The EuroQoL five dimensions questionnaire; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; LABA, long-acting beta₂-agonist; LAMA, long-acting muscarinic antagonist; SD, standard deviation.

Figure 2 Number of severe exacerbations in overall population over 6-year follow-up.

Table 2 Comparison of characteristics between patients with and without severe exacerbations

	Patients without severe exacerbations (n=2,286, 95.4%)	Patients with severe exacerbations (n=111, 4.6%)	P-value
Age, yearsa	63.2±11.9	69.5±8.2	<0.001
Sex, male	1,633 (71.4)	59 (53.2)	<0.001
Body mass index, kg/m^2a	23.5±2.8	23.5±2.9	0.821
Body mass index ≥25 kg/m^2	659 (28.8)	30 (27.0)	0.682
Smoking historyb
Nonsmoker	699 (30.6)	48 (43.2)	0.005
Current or ex-smoker	1,559 (68.2)	62 (55.9)
Pack-yearsa	24.0±23.0	20.9±28.9	0.310
Previous pulmonary tuberculosis	304 (13.3)	19 (17.1)	0.250
Comorbidities
Diabetes mellitus	308 (13.5)	23 (20.7)	0.031
Hypertension	801 (35.0)	46 (41.4)	0.168
Depression	276 (12.1)	20 (18.0)	0.063
Bronchial asthma	233 (10.2)	28 (25.2)	<0.001
Coronary heart diseasec	92 (4.0)	4 (3.6)	0.825
Atopic dermatitis	65 (2.8)	4 (3.6)	0.640
Stroke	61 (2.7)	5 (4.5)	0.248
Physical activity
Days of moderate active physical activity per weeka	2.3±2.1	2.3±2.1	0.862
Days of high active physical activity per weeka	1.8±1.7	1.5±1.4	0.008
Baseline pulmonary function test
FVC, La	3.6±0.9	3.1±0.9	<0.001
FVC, % predicteda	91.0±13.6	87.8±14.0	0.016
FEV1, La	2.3±0.6	1.8±0.6	<0.001
FEV1, % predicteda	78.8±13.6	74.2±14.4	<0.001
FEV1/FVC, %a	0.6±0.1	0.6±0.1	<0.001
COPD severity			<0.001
FEV1, % predicted ≥80%	1,034 (45.2)	41 (36.9)
65%≤ FEV1, % predicted <80%	888 (38.9)	36 (32.5)
50%≤ FEV1, % predicted <65%	364 (15.9)	34 (30.6)
EQ-5D index values ≥0.9	1,578 (69.0)	33 (29.7)	<0.001
Use of inhalers	100 (4.4)	41 (36.9)	<0.001

Notes: The data are presented as number (%) or mean and standard deviation.

a These data are analyzed by using Student’s t-test.

b Data of 29 patients are missed including 28 patients without severe exacerbations and one patient with severe exacerbation.

c Coronary heart disease includes myocardial infarction and angina pectoris.

Abbreviations: EQ-5D, The EuroQoL five dimensions questionnaire; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 3 The comparison of severe exacerbation between COPD patients with coexisting self-reported physician-diagnosed bronchial asthma and those with COPD only.

Notes: (A) Percentage of patients with severe exacerbations and (B) number of severe exacerbations/person-year.

Table 3 Multivariate analysis for factors associated with severe exacerbations in mild-to-moderate COPD patients

	All patients (n=2,397)
	aOR (95% CI)	P-value
Age, years	1.04 (1.02–1.06)	<0.001
Sex, female	1.82 (1.01–3.33)	0.045
Body mass index, kg/m^2	1.0 (0.93–1.07)	0.954
Smoking historya
Nonsmokerc	1.0
Current or ex-smoker	1.02 (0.57–1.82)	0.961
Comorbidities
Diabetes mellitus	1.44 (0.87–2.38)	0.157
Cardiovascular diseaseb	0.89 (0.42–1.86)	0.752
Bronchial asthma	1.67 (1.002–2.77)	0.049
Severity of airflow limitation
FEV1, % predicted ≥80%c	1.0
65%≤ FEV1, % predicted <80%	1.14 (0.70–1.85)	0.599
50%≤ FEV1, % predicted <65%	1.93 (1.15–3.24)	0.013
Quality of life
EQ-5D index values ≥0.9c	1.0
EQ-5D index values <0.9	3.47 (2.22–5.43)	<0.001
Use of inhalers	2.34 (1.25–4.38)	0.008

Notes:

a Data of 29 patients are missed.

b Cardiovascular disease includes stroke, myocardial infarction, and angina pectoris.

c Subjects in this category served as the reference group.

Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; EQ-5D, The EuroQoL five dimensions questionnaire; FEV₁, forced expiratory volume in 1 second.

Figure 4 Association between asthma and severe exacerbations in mild-to-moderate COPD patients. Diamonds and whiskers show odds ratio and 95% CI values, respectively. Model 1 was adjusted for age, sex, and BMI; Model 2 was additionally adjusted for pulmonary-related variables generally considered to be important in severe exacerbations in COPD (smoking history and severity of airflow limitation); Model 3 additionally included extrapulmonary-related variables generally considered to be important in severe exacerbations in COPD or extrapulmonary-related variables with P<0.05 in the univariate analyses with considering multicollinearity (diabetes mellitus, cardiovascular disease [stroke, myocardial infarction, and angina pectoris], and quality of life); finally, Model 4 was additionally adjusted for use of inhalers with all of the above mentioned variables.

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