Clinical characteristics of the asthma–COPD overlap syndrome – a systematic review

Figures & data

Figure 1 Consort diagram.

Note: This diagram illustrates the flow of the identified publications leading to the final inclusion of eleven publications in this systematic review.

Table 1 Characteristics with regard to design and methods, sample size, proportion, and definition of patients regarded as having the asthma–COPD overlap syndrome, and comparison groups for the studies (n=11) included in the present review

	Study design	Subjects no	Prevalence of overlap subjects n (%)	Division of groups	Method	Definition of overlap group
Brzostek and Kokot^Citation20 (Poland)	Retrospective noninterventional patient study	12,103 smoking patients (current or past) >45 years	12,103 (100%)	ACOS (~A+C)	Questionnaire completed by the physician based on medical record and paraclinical history Excl: Nonsmokers	A mixed phenotype with a combination of features of both asthma and COPD
Chung et al^Citation24 (Korea)	Used data from an cross-sectional population study (observational)	9,104 >19 years	210 (2.3%)	A, C, NOD, ACOS	Questionnaires, triglyceride and high-density lipoprotein (HDL) cholesterol levels, and lung function test Excl: no available wheezing history, unavailable respiratory symptoms, unacceptable spirometry (unacceptable flow-volume loop or nonreproducible)	FEV1/FVC <0.7 and a history of self-reported wheezing
de Marco et al^Citation8 (Italy)	Cross-sectional population study using data of a multicenter study	8,360 Aged 20–84 years	(1.6) aged 20–44 years (2.1) aged 45–64 years (4.5) aged 65–84 years	A, C, NOD, ACOS (~A+C)	Random sample by telephone calls and email Questionnaires, MRC dyspnea scale as the only parameter for dyspnea	Physician diagnosis of both asthma and COPD
Fu et al^Citation25 (Australia)	Cohort study (from 2006/07 to 2011)	99 OAD patients (75 data available, 59 for follow-up) >55 years	55 (55.5%)	A, C, ACOS	Questionnaire, lung function test, 6MWT, CCI, BODE index (and other measurements irrelevant for this review) Excl: current or recent smoking history or a history of other respiratory diseases	Respiratory symptoms, increased airflow variability and incompletely reversible airflow obstruction Post-BD FEV1<80% of predicted FEV1/FVC <0.7
Hardin et al^Citation26 (USA)	Cross-sectional study analyzing data from a prospective cohort study	3,570 current or former smokers with COPD aged 45–80 years	450 (12.6%)	C, ACOS	Questionnaire, lung function test, chest CT scan, BODE index, genome-wide association studies among others Excl: patients with late-onset asthma, COPD patients with <10 pack-years	COPD patient with physician diagnosis of asthma (self-reported) before the age of 40 years
Kauppi et al^Citation18 (Finland)	Retrospective patient study (annually follow- up for 10 years)	1,546 discharged patients 18–75 years	225 (14.5%)	A, C, ACOS (~A+C)	Medical record with spirometry results, and questionnaire Excl: insufficient documentation on the disease	Physician diagnosis of both asthma and COPD FEV1/FVC <0.7
Lee et al^Citation28 (Korea)	Retrospective patient study	256 asthmatics (both admitted and nonadmitted patients) 41–79 years	97 (37.9%)	A, ACOS	Lung function test, allergy tests, eosinophil counts, total IgE counts inter alia Medical records were retrospectively reviewed Excl: patients with other respiratory diagnoses than OLD COPD-only patients. Patients without respiratory symptoms in the last 3 months or without follow-up	Asthma patients (post-BD increase (in FEV1 of 200 mL and 12% or positive metacholine/mannitol provocation test) with an incompletely reversible airflow obstruction post-BD FEV1/FVC <0.7
Menezes et al^Citation29 (Latin America)	Cross-sectional study using data a population study	5,044	89 (1.8%) (11.6% of OAD patients)	A, C, NOD, ACOS	Questionnaire and lung function test (answering affirmatively to the question about dyspnea as the only parameter for dyspnea)	A combination of asthma (wheezing in the last 12 months plus post-BD increase) (or self- reported doctor diagnosis of asthma) and COPD Post-BD FEV1/FVC <0.70
Milanese et al^Citation7 (Italy)	Observational study of elderly asthmatics	350 asthmatics (≥65 years)	101 (28.8%)	A, ACOS	Medicine prescriptions were recorded (obtained from the patients’ medical records) Questionnaire, mMRC as the only parameter for dyspnea, lung function test	Diagnosis of asthma and chronic bronchitis or/and impaired diffusion capacity (DLCO result of <80% of the predicted value)
Miravitlles et al^Citation22 (Spain)	Using data from a cross-sectional population study	3,885 subjects (focus is the 385 COPD subjects with and without overlap) 40–80 years	67 (17.7% of COPD patients)	C, ACOS	Questionnaire, mMRC (plus answering affirmatively to the question about dyspnea), CCI, lung function test, 6MWD test among others Excl: of asthma subjects	Spirometric-defined COPD (post- BD FEV1/FVC <0.7) and physician diagnosis of asthma before the age of 40 years
Pleasants et al^Citation30 (USA)	Retrospective study using data from a cross-sectional population survey	24,073 18–74 years	807 (3.3%)	Former A, current A, C, NOD, ACOS (~A+C)	Random sample by telephone questionnaire	Affirmative answer to questions about physician diagnosis of COPD and asthma

Notes: A, asthma COPD-overlap syndrome; (~A+C), concomitant doctor diagnosed asthma and COPD as an expression for ACOS.

Abbreviations: COPD, chronic obstructive pulmonary disease; ACOS, asthma–COPD overlap syndrome; Excl, remarkable exclusions; NOD, no obstructive lung disease; MRC, Medical Research Council; CCI, Charlson Comorbidity Index; BD, bronchodilator; CT, computed tomography; OLD, obstructive lung disease; OAD, obstructive airway disease; mMRC, Modified Medical Research Council dyspnea scale; DL_co, total diffusion capacity; 6MWD, 6 minutes walking distance test; BODE, Body mass index, airflow Obstruction, Dyspnea and Exercise capacity, FEV₁, forced expiratory volume in 1st second; FVC, forced vital capacity.

Table 2 Spirometric parameters among patients classified as ACOS, COPD only, and asthma only

	FEV1% predicted			FVC% predicted			FEV1/FVC%
	ACOS	COPD	Asthma	ACOS	COPD	Asthma	ACOS	COPD	Asthma
Milanese et al^Citation7	78±20 P<0.001	–	85±20	91±16 P<0.02	–	95±16	85±11 P<0.005	–	89±12
Lee et al^Citation28	58.0±1.2 P<0.01	–	69.4±1.2	82.4±1.4a NS	–	80.8±1.1a	ms	–	ms
Chung et al^Citation24	69.4±1.5 P<0.001	77.2±0.7 P<0.001	90.4±0.7	86.2±1.4 P<0.05	90.0±0.7	90.9±0.7	0.60±0.06 P<0.001	0.64±0.07 P<0.001	0.81±0.08
Fu et al^Citation25	54.6±18.2a P<0.001	55.9±16.2a P<0.001	81.6±6.8	82.2±20.2 NS	77.5±16.1	90.7±10.4	52.1±11.3a <0.001	57.8±14.6a P<0.001	73.1±3.2
Menezes et al^Citation29	63.5±18.9 P<0.001a	81.4±20.0	79.9±17.2	83.5±17.8 NS	98.0±18.8	85.3±18.4	57.7%±11.1% P<0.01	62.3%±9.6% NS	73.7%±7.9%
Kauppi et al^Citation18	67.4±18.0	61.4±19.4	86.5±15.6	83.1±17.4	76.1±18.3	90.5±14.8	65.8±13.2	65.3 ±14.6	78.5±9.3
Miravitlles et al^Citation22	P<0.001 Pre-BD 67.6±16.4 Post-BD 72.7±17.7 NS	P<0.001 71.2±18.6 75.6±18.1		P<0.001 82.2±18.1 86.9±19.8 NS	P<0.001 83.3±19.0 88.1±18.3 NS		P<0.001 0.60±0.08 0.61±0.07 NS	P<0.001 0.62±0.08 0.62±0.07

Note:

a COPD and/or ACOS vs asthma.

Abbreviations: ACOS, asthma–chronic obstructive pulmonary disease overlap syndrome; COPD, chronic obstructive pulmonary disease; ms, missing value; NS, nonsignificant; BD, bronchodilator; FEV₁, forced expiratory volume in first second; FVC, forced vital capacity.

Table 3 Prevalence (P) and prevalence ratio (PR) of exacerbations among patients classified as having ACOS and comparison groups

	Study’s description of exacerbations	Prevalence of exacerbations in ACOS subjects	Prevalence of exacerbations in comparison group	ACOS subjects (n)	“Comparison subjects” in study (n) (either asthma or COPD or both)	PR of ACOS	PR of other group
Hardin et al^Citation26	Severe exacerbationsa	153 P<0.001	646 COPD P<0.001	450	COPD group: 3,120	–	–
Milanese et al^Citation7	1 SE ≥2 SE	(42%) (25%)	(18%) (7%)	101	Asthma group: 249 Asthma group: 249	– –	– –
Menezes et al^Citation29	Exacerbationsb unadjusted	14 P<0.001	31 COPD 11 asthma	89	Asthma: 84 COPD: 594	3.01c [95% CI: 1.74–5.21] P<0.001	Asthma 2.54c [95% CI: 1.42–4.52] P<0.001
	Exacerbationsb adjustedd	14 P<0.001	31 COPD 11 asthma P<0.001	89	Asthma: 84 COPD: 594	2.11c 95% CI: 1.08–4.12 P=0.06	Asthma 1.65c 95% CI: 0.93–2.92 P=0.06

Notes: SE, severe exacerbations defined as an exacerbation requiring a rescue course of systemic corticosteroids for at least three days and/or hospitalization;

a severe exacerbations defined as a history of exacerbations that resulted in an emergency room visit or hospital admission (%); n, number of subjects;

b exacerbations is based on subjects’ retrospective report of breathing symptoms,

c COPD is the reference, PR =1.0;

d adjusted for age, sex, BMI, schooling, education, comorbidity score, pack-years, and reported use of any inhaled therapy (bronchodilator or inhaled corticosteroids).

Abbreviations: ACOS, asthma–chronic obstructive pulmonary disease overlap syndrome; COPD, chronic obstructive pulmonary disease; CI, confidence interval; SE, standard error.

Figure 2 Frequency of exacerbations (per year) among patients classified as ACOS, COPD only, and asthma only.

Notes: *P<0.001; **P<0.002.
Abbreviations: ACOS, asthma–chronic obstructive pulmonary disease overlap syndrome; COPD, chronic obstructive pulmonary disease.

Figure 3 Prevalence of comorbidities among patients classified as ACOS, COPD only, and asthma only.

Notes: x, proportion having a comorbid condition; y, having two comorbid conditions; Pa, patient study, where comorbidities were inferred by recording concomitant drug prescriptions for other diseases (arterial hypertension, chronic heart disease, diabetes, gastroesophageal and osteoporosis); Po, population study with self-reported comorbidities; a, age adjusted (≥18 years). #Data from the comorbid condition; stroke is chosen to give a representative impression of tendency in the study, in the lack of data about all comorbidities together. ^{^}Asthma group only includes patients with current asthma. *P<0.02, **P<0.633, ***P<0.05.

Abbreviations: ACOS, asthma-chronic obstructive pulmonary disease overlap syndrome; COPD, chronic obstructive pulmonary disease.

Figure 4 Prevalence of the comorbidity diabetes in patients classified as having ACOS, COPD* only, and asthma only.

Notes: Pa, proportion of subjects with concomitant diabetes is inferred by recording concomitant drug prescriptions for diabetes. ^{^}Asthma group only include patients with current asthma. *P<0.32, **P<0.05, ***P≤0.001, ****P<0.349.
Abbreviations: ACOS, asthma–chronic obstructive pulmonary disease overlap syndrome; COPD, chronic obstructive pulmonary disease.

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