Smoking history and emphysema in asthma–COPD overlap

Figures & data

Table 1 Characteristics of the subjects

Characteristics	COPD	ACO	Asthma/CAO	P-value
	N=537	N=256	N=64
Age (years)	69.4±7.8	66.5±8.3	63.7±9.5	<0.0001
Female sex	21 (3.9%)	33 (12.8%)	37 (57.8%)	<0.0001
Body mass index (kg/m^2)	21.1±3.5	22.0±4.0	22.6±3.7	<0.0001
Never smoker	0	0	59 (92.2%)	<0.0001
Smoking index (pack-years)	66.9±34.3	52.1±28.4	0.4±1.5	<0.0001
Post-bronchodilator FVC (% predicted)	85.3±19.4	86.5±18.8	84.5±19.2	NS
Post-bronchodilator FEV1 (% predicted)	60.5±24.2	59.4±22.6	66.5±22.2	NS
GOLD stage, 1/2/3/4	117/217/159/44	30/40/12/3	20/28/14/2	0.0045
Post-bronchodilator FEV1/FVC	44.3±12.5	47.3±12.3	52.9±10.3	<0.0001
Reversibility of FEV1 (%)	8.2±8.1	17.6±12.6	17.5±11.4	<0.0001
Annual change in FEV1 (mL/year)	−40.0 (−70.0 to −10.0)	−45.0 (−81.0 to −20.0)	−25.0 (−59.0 to 10.0)	0.016
Any vascular diseases	115 (21.4%)	46 (18.0%)	12 (18.8%)	NS
De novo malignant tumor	86 (16.0%)	32 (12.5%)	1 (1.6%)	0.0051
Observation period (years)	6.6 (3.5–9.7)	8.3 (5.1–11.8)	9.2 (6.5–12.9)	NS

Note: Data are shown as the mean ± standard deviation, median (interquartile range), or number (%).

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction; GOLD, Global Initiative for Chronic Obstructive Lung Disease; NS, not significant.

Table 2 Characteristics of the subjects classified by emphysema

Characteristics	COPD			ACO
	With emphysema	Without emphysema	P-value	With emphysema	Without emphysema	P-value
	N=452	N=85		N=161	N=95
Age (years)	69.2±7.9	70.2±7.3	NS	67.5±7.7	64.2±9.3	0.001
Female sex	14 (3.1%)	7 (8.2%)	0.034	18 (11.2%)	15 (15.8%)	<0.001
Body mass index (kg/m^2)	20.8±3.5	22.6±2.8	<0.001	21.4±4.1	23.0±3.7	0.005
Never smoker	0	0	NS	0	0	NS
Smoking index (pack-years)	68.7±35.3	57.0±26.8	0.002	60.6±28.9	37.7±20.6	<0.001
Post-bronchodilator FVC (% predicted)	85.2±19.5	85.5±18.9	NS	85.9±19.3	87.6±18.1	NS
Post-bronchodilator FEV1 (% predicted)	58.5±24.3	70.6±21.8	<0.001	55.3±21.6	66.2±22.7	<0.001
GOLD stage, 1/2/3/4	87/177/147/41	30/40/12/3	0.002	25/59/64/13	21/50/23/1	NS
Post-bronchodilator FEV1/FVC	44.3±12.5	53.3±10.3	<0.001	44.0±12.1	52.9±10.8	<0.001
Reversibility of FEV1 (%)	8.2±8.2	8.2±7.9	NS	17.6±12.4	17.7±12.7	NS
Annual change in FEV1 (mL/year)	−44.0 (−71.0 to −14.5)	−30.0 (−61.0 to 20.0)	0.016	−43.0 (−79.0 to −20.0)	−45.0 (−82.0 to −20.0)	NS
Any vascular diseases	89 (19.7%)	26 (30.6%)	0.025	26 (16.1%)	20 (21.1%)	NS
De novo malignant tumor	81 (17.9%)	5 (5.9%)	0.006	24 (14.9%)	8 (8.4%)	NS
Observation period (years)	6.4 (3.4–9.5)	7.2 (4.2–10.2)	NS	8.1 (4.9–11.6)	8.4 (5.5–12.6)	NS

Note: Data are shown as the mean ± standard deviation, median (interquartile range), or number (%).

Abbreviations: ACO, asthma–COPD overlap; GOLD, Global Initiative for Chronic Obstructive Lung Disease; NS, not significant.

Table 3 Risk of all-cause mortality in asthma/CAO, ACO, and COPD

Groups	Hazard ratio (95% CI)	P-value	Subgroups	Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value
Univariate analysis
Asthma/CAO	1.00 (reference)		Asthma/CAO	1.00 (reference)
ACO	10.64 (1.46–77.52)	0.020	ACO, emphysema (−)	5.74 (0.72–45.88)	0.099	1.00 (reference)
COPD	26.98 (3.77–192.91)	0.001	ACO, emphysema (+)	13.79 (1.88–101.16)	0.010	2.41 (1.11–5.26)	0.027
			COPD, emphysema (−)	15.59 (2.06–118.01)	0.008	1.00 (reference)
			COPD, emphysema (+)	29.55 (4.13–211.43)	0.001	1.86 (1.09–3.18)	0.023
Adjusted for age, sex and BMI
Asthma/CAO	1.00 (reference)		Asthma/CAO	1.00 (reference)
ACO	7.26 (0.95–55.34)	0.056	ACO, emphysema (−)	5.25 (0.63–43.47)	0.125	1.00 (reference)
COPD	14.28 (1.88–108.56)	0.010	ACO, emphysema (+)	10.02 (1.29–77.75)	0.028	1.96 (0.88–4.33)	0.098
			COPD, emphysema (−)	9.28 (1.163–73.98)	0.036	1.00 (reference)
			COPD, emphysema (+)	18.71 (2.43–143.84)	0.005	2.04 (1.18–3.53)	0.011

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; BMI, body mass index; CAO, chronic airflow obstruction.

Figure 1 Kaplan–Meier survival curves for COPD, ACO, and asthma/CAO.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction.

Figure 2 Kaplan–Meier survival curves for COPD, ACO, and asthma/CAO subclassified by the emphysema.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction.

Table 4 Causes of emergent admission

Causes	COPD			ACO			COPD total	ACO total	Asthma/CAO	P-value
	With emphysema	Without emphysema	P-value	With emphysema	Without emphysema	P-value
COPD exacerbation, N (N/person, year)	444 (0.20)	56 (0.11)	0.044	142 (0.13)	23 (0.05)	<0.001	500 (0.18)	165 (0.09)	5 (0.01)	<0.001
Asthma attack, N (N/person, year)	NA	NA	NA	26 (0.02)	32 (0.06)	0.014	NA	58 (0.03)	30 (0.04)	NA
Others, N (N/person, year)	149 (0.07)	23 (0.04)	NS	30 (0.03)	4 (0.01)	0.019	172 (0.06)	34 (0.02)	4 (0.01)	<0.001

Note: In ACO patients and asthma/CAO patients, admission with severe wheezing that required oral or parenteral corticosteroids was designated as an asthma attack, and admission with symptoms of airway infection, such as a fever, absence of severe wheezing, and increased serum C-reactive protein >1 mg/dL requiring antibiotics, was designated as COPD exacerbation according to the study criteria.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction; NA, not applicable.

Figure 3 Frequencies of emergent admission in the subgroups of COPD, ACO, and asthma with CAO.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction; NS, not significant.

Figure 4 Causes of emergent admission in the subgroups of ACO and asthma/CAO.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction.

Figure S1 Frequencies of total exacerbation events in the subgroups of COPD, ACO, and asthma/CAO.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction.

Figure S2 Frequencies of emergency visit in the subgroups of COPD, ACO, and asthma/CAO.

Abbreviations: ACO, asthma–COPD overlap; asthma/CAO, asthma with CAO; CAO, chronic airflow obstruction.