Prevalence and characteristics of asthma–COPD overlap syndrome identified by a stepwise approach

Figures & data

Table 1 Features favoring asthma or COPD for syndromic diagnosis of airway disease based on the Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease report

Feature	Asthma	COPD
Age of onset	Before age 20 years	After age 40 years
Pattern of respiratory symptoms	Variation in symptoms over time Symptoms worsen during the night or early morning Symptoms triggered by exercise, emotional change (including laughter), or exposure to dust/allergens	Persistence of symptoms despite treatment Good and bad days but always daily respiratory symptoms and exertional dyspnea Chronic cough and sputum preceded by onset of dyspnea, unrelated to triggers
Lung function	Record of variable airflow limitation (spirometry, peak flow)	Record of persistent airflow limitation (post-bronchodilator FEV1/FVC <0.7)
Lung function between symptoms	Normal	Abnormal
Past history or family history	Previous doctor diagnosis of asthma Family history of asthma and other allergic conditions (allergic rhinitis, dermatitis)	Previous doctor diagnosis of COPD, chronic bronchitis, or emphysema Heavy exposure to a risk factor: tobacco smoke and biomass fuels
Time course	No worsening of symptoms over time. Symptoms vary either seasonally or from year to year May improve spontaneously or have a response to bronchodilator immediately or to ICS over weeks	Symptoms slowly worsen over time (progressive course over years) Rapid-acting bronchodilator treatment provides only limited symptom relief
Chest X-ray	Normal	Severe hyperinflation

Notes: Adapted with permission from Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease. Diagnosis of diseases of chronic airflow limitation: asthma, COPD, and asthma-COPD overlap syndrome (ACOS).¹

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid.

Table 2 Characteristics of patients with or without asthma–COPD overlap syndrome

Characteristics	Total (n=1,008)	ACOS defined by syndromic features and FEV1 variability ≥12% and ≥200 mL			ACOS defined by syndromic features and FEV1 variability ≥12% and ≥400 mL
		ACOS (n=93)	COPD alone (n=915)	P-value	ACOS (n=42)	COPD alone (n=966)	P-value
Sex (male)	937 (93.0)	84 (90.3)	853 (93.2)	0.288*	38 (90.5)	899 (93.1)	0.531*
Age at enrollment (years)	73.5±8.3	69.2±9.8	73.9±8.0	<0.001#	66.9±11.1	73.8±8.0	<0.001#
Height (cm)	163.0±6.9	164.4±7.9	162.9±6.8	0.071#	166.4±8.2	162.9±6.8	0.001#
Weight (kg)	59.4±10.9	62.0±11.2	59.1±10.8	0.014#	63.4±12.3	59.2±10.8	0.015#
BMI (kg/m^2)	22.3±3.5	22.8±3.4	22.2±3.5	0.092#	22.8±3.7	22.3±3.4	0.329#
COPD duration (months)	69.0±51.4	54.0±52.0	70.5±51.1	0.003#	39.3±31.1	70.3±51.7	<0.001#
Smoking status
Current smoker	146 (14.5)	14 (15.1)	$\begin{array}{l}132(14.4)\\ 783(85.6)\end{array}]$	0.877*	8 (19.0)	$\begin{array}{l}138(14.3)\\ 828(85.7)\end{array}]$	0.372*
Ex-smoker	862 (85.5)	79 (84.9)			34 (81.0)
Pack-years	56.9±31.3	46.0±27.7	58.1±31.5	<0.001#	40.6±21.9	57.7±31.5	<0.001#
Lung function
FEV1/FVC (%)	50.9±12.9	54.8±10.9	50.4±13.0	<0.001#	56.5±11.4	50.6±12.9	0.004#
% predicted FEV1	56.7±21.1	64.2±18.2	56.0±21.2	<0.001#	69.6±20.1	56.2±21.0	<0.001#
% predicted FVC	87.5±20.8	94.0±17.8	86.8±21.0	<0.001#	98.8±16.1	87.0±20.9	<0.001#
GOLD stage
I	148 (14.7)	17 (18.3)	$\begin{array}{l}131(14.3)\\ 405(44.3)\\ 270(29.5)\\ 109(11.9)\end{array}]$	<0.001‡	13 (31.0)	$\begin{array}{l}135(14.0)\\ 441(45.7)\\ 279(28.9)\\ 111(11.5)\end{array}]$	<0.001‡
II	463 (45.9)	58 (62.4)			22 (52.4)
III	285 (28.3)	15 (16.1)			6 (14.3)
IV	112 (11.1)	3 (3.2)			1 (2.4)
Treatment for COPD or asthma
Any treatment	988 (98.0)	91 (97.8)	897 (98.0)	0.706*	42 (100.0)	946 (97.9)	1.000*
SAMA	10 (1.0)	1 (1.1)	9 (1.0)		0 (0.0)	10 (1.0)
SABA	120 (11.9)	12 (12.9)	108 (11.8)		5 (11.9)	115 (11.9)
LAMA	578 (57.3)	50 (53.8)	528 (57.7)		22 (52.4)	556 (57.6)
LABA	140 (13.9)	6 (6.5)	134 (14.6)		2 (4.8)	138 (14.3)
LABA/LAMA	199 (19.7)	10 (10.8)	189 (20.7)		5 (11.9)	194 (20.1)
ICS	75 (7.4)	8 (8.6)	67 (7.3)		3 (7.1)	72 (7.5)
ICS/LABA	404 (40.1)	64 (68.8)	340 (37.2)		31 (73.8)	373 (38.6)
Expectorant	250 (24.8)	10 (10.8)	240 (26.2)		6 (14.3)	244 (25.3)
Xanthine derivatives	166 (16.5)	13 (14.0)	153 (16.7)		7 (16.7)	159 (16.5)
Leukotriene receptor antagonist	95 (9.4)	23 (24.7)	72 (7.9)		12 (28.6)	83 (8.6)
Anti-IgE antibody	4 (0.4)	0 (0.0)	4 (0.4)		0 (0.0)	4 (0.4)
Systemic steroid (oral/injection)	32 (3.2)	2 (2.2)	30 (3.3)		2 (4.8)	30 (3.1)
Oxygen therapy	132 (13.1)	2 (2.2)	130 (14.2)		1 (2.4)	131 (13.6)
Ventilatory support/surgical therapy	5 (0.5)	0 (0.0)	5 (0.5)		0 (0.0)	5 (0.5)
Other	66 (6.5)	5 (5.4)	61 (6.7)		3 (7.1)	63 (6.5)

Notes: Data are presented as n (%) or mean ± standard deviation.

* Fisher’s exact test.

# Student’s t-test.

‡ Wilcoxon rank sum test.

Abbreviations: ACOS, asthma–COPD overlap syndrome; BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; IgE, immunoglobulin E; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting beta agonist; SAMA, short-acting muscarinic antagonist.

Figure 1 Identification of patients with ACOS using a stepwise approach.

Abbreviations: ACOS, asthma–COPD overlap syndrome; CI, confidence interval; FEV₁, forced expiratory volume in 1 second.

Table 3 COPD exacerbations during the past year

COPD exacerbation	Total (n=1,008)	ACOS defined by syndromic features and FEV1 variability ≥12% and ≥200 mL				ACOS defined by syndromic features and FEV1 variability ≥12% and ≥400 mL
		ACOS (n=93)	COPD alone (n=915)	Ratio*	P-value	ACOS (n=42)	COPD alone (n=966)	Ratio*	P-value
Any
No of patients (%)	284 (28.2)	25 (26.9)	259 (28.3)	–	0.810#	12 (28.6)	272 (28.2)	–	1.000#
No of events (rate)	502 (0.498)	53 (0.570)	449 (0.491)	1.161	0.502‡	31 (0.738)	471 (0.488)	1.514	0.176‡
Moderate or severe
No of patients (%)	265 (26.3)	24 (25.8)	241 (26.3)	–	1.000#	12 (28.6)	253 (26.2)	–	0.722#
No of events (rate)	452 (0.448)	48 (0.516)	404 (0.442)	1.169	0.497‡	29 (0.690)	423 (0.438)	1.577	0.147‡

Notes:

* ACOS:COPD alone.

# Fisher’s exact test.

‡ Negative binomial regression analysis.

Abbreviations: ACOS, asthma–COPD overlap syndrome; FEV₁, forced expiratory volume in 1 second; No, number.

Table 4 Symptoms and health status

Item	Total	ACOS defined by syndromic features and FEV1 variability ≥12% and ≥200 mL			ACOS defined by syndromic features and FEV1 variability ≥12% and ≥400 mL
		ACOS	COPD alone	P-value*	ACOS	COPD alone	P-value*
mMRC score	n=938	n=90	n=848		n=40	n=898
	1.4±1.1	1.0±1.0	1.5±1.2	<0.001	0.8±0.9	1.5±1.1	<0.001
CCQ	n=938	n=91	n=847		n=41	n=897
Symptoms	1.8±1.1	1.7±1.0	1.8±1.1	0.365	1.7±1.0	1.8±1.1	0.556
Functional state	1.8±1.4	1.3±1.2	1.8±1.4	0.002	1.4±1.2	1.8±1.4	0.066
Mental state	1.5±1.5	1.3±1.4	1.5±1.5	0.285	1.5±1.5	1.5±1.5	0.854
Total score	1.7±1.1	1.5±0.9	1.7±1.1	0.011	1.5±1.0	1.7±1.1	0.279

Notes: Data are presented as mean ± standard deviation.

* Student’s t-test.

Abbreviations: ACOS, asthma–COPD overlap syndrome; CCQ, Clinical COPD Questionnaire; FEV₁, forced expiratory volume in 1 second; mMRC, modified British Medical Research Council.

Table 5 Inflammatory biomarkers

Biomarker	Total	ACOS defined by syndromic features and FEV1 variability ≥12% and ≥200 mL			ACOS defined by syndromic features and FEV1 variability ≥12% and ≥400 mL
		ACOS	COPD alone	P-value*	ACOS	COPD alone	P-value*
Peripheral blood eosinophil count (cells/μL)	n=854	n=78	n=776		n=37	n=817
	239.1±234.6	368.3±362.8	226.1±213.6	0.001	450.4±448.6	229.5±215.7	0.005
Peripheral blood eosinophil rate (%)	n=854	n=78	n=776		n=37	n=817
	3.6±3.2	5.3±4.6	3.5±3.0	<0.001	6.7±5.5	3.5±3.0	0.001
FeNO (ppb)	n=224	n=36	n=188		n=19	n=205
	27.5±21.2	33.1±17.5	26.4±21.7	0.080	33.7±15.3	26.9±21.6	0.182

Notes: Data are presented as mean ± standard deviation.

* Student’s t-test.

Abbreviations: ACOS, asthma–COPD overlap syndrome; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second.

Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung DiseaseDiagnosis of diseases of chronic airflow limitation: asthma, COPD, and asthma-COPD overlap syndrome (ACOS) Available from: http://goldcopd.org/asthma-copd-asthma-copd-overlap-syndrome/Accessed July 6, 2016

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