Asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS): structured literature review and physician insights

Figures & data

Figure 1. Structured literature review–attrition of identified publications.

Table 1. Reported prevalence of ACOS within the published literature.

Source	Study design	Definition of ACOS	ACOS prevalence
Andersen et al. 2013[5]	Hospital discharge registry data in Finland, covering the whole Finnish population (5.35 million, 2009). Patients >34 years of age and treatment periods from 2000 to 2009, with a primary or secondary diagnosis of COPD or asthma were identified (n = 105,122).	ICD-10 COPD or asthma plus treatment for both within the study period.	16.1% in patients with primary or secondary diagnoses of COPD or asthma in Finland.
Miravitlles et al. 2013[6]	A total of 385 patients with COPD (FEV1/FVC < 0.7) identified in the cross-sectional EPI-SCAN study cohort (n = 3,885, 40–80-year-old participants, field work done from May 2006 to July 2007, Spain).	All participants with spirometric-defined COPD (defined by a post-bronchodilator FEV1/FVC ratio of <0.70) were classified as overlap COPD-asthma subjects if they confirmed that they had previously been diagnosed with asthma.	17.4% in subjects diagnosed with COPD in Spain (n = 3885).
De Marco et al. 2013[7]	A screening questionnaire on respiratory symptoms, diagnoses, and risk factors was administered by mail to a random sample of the general Italian population.	Self-reported physician diagnosis of ACOS.	1.6%, 2.1%, and 4.5% of a sample of the Italian general population, aged 20–44, 45–64, and 65–84, respectively.
Izquierdo-Alonso et al. 2013[8]	An observational multicenter study enrolling 331 COPD patients aged 40 or older from pulmonary outpatient centers.	Diffusion test with transfer factor of the lung for carbon monoxide (TLco) values ≥80%, absence of pulmonary emphysema demonstrated through imaging, and a history of asthma before the age of 40 without a current diagnosis of asthma.	12.1% of COPD patients (n = 331) in Spain.
Fu et al. 2014[9]	A 4 year prospective cohort study in adults aged >55 years with obstructive airway diseases in Australia (n = 99, mean age = 68.8 ± 7.6 years).	Respiratory symptoms, increased airflow variability (asthma, i.e. airway hyperresponsiveness), and incompletely reversible airway obstruction (COPD, i.e. post-bronchodilator FEV1/FVC <70%).	55.5% in patients >55 years of age with obstructive airway disease (n = 99) at baseline in Australia.
Milanese et al. 2014[10]	An observational multicenter survey enrolling patients >64 years old with a documented physician diagnosis of asthma between October 2012 and March 2013 in Italy (n = 350).	A diagnosis of asthma plus chronic bronchitis and/or impaired CO diffusion test.	29% in asthma patients >64 years of age (n = 350) in Italy.
Yon-Lee et al. 2014[11]	Retrospective medical record review of the clinical characteristics of asthma in- and outpatients aged 41‒79 years between September 2007 and March 2012 in South Korea(n = 256).	Overlap patients were defined as patients with physician-diagnosed asthma (a positive response to bronchodilator (>200 mL FEV1 and >12% baseline) and/or positive methacholine or mannitol provocation test) and incompletely reversible airflow obstruction (post-bronchodilator FEV1/FVC <70) at admission and for ≥3 months regardless of treatment.	38% in asthma patients aged 41–79 years (n = 256) in South Korea.
Marsh et al. 2008[12]	A randomized, population-based survey including questionnaires, pulmonary function tests, and chest CT scans.	Patients with COPD (post-bronchodilator FEV1/FVC <0.7) and asthma (post-bronchodilator increase in FEV1 ≥ 15% or peak flow variability ≥20% during 1 week of testing or physician-diagnosed asthma in conjunction with current symptoms).	55.2% in COPD patients >50 years of age (n = 96) in New Zealand.
Zeki et al. 2011[13]	A small cohort from the academic general pulmonary/asthma referral clinic was compared to patients from the severe asthma clinic (UC Davis Asthma Network (UCAN) Clinics).	ACOS was defined as one of two clinical phenotypes: Allergic disease consistent with asthma (variable airflow obstruction or AHR) that is incompletely reversible (with or without emphysema or reduced carbon monoxide diffusion capacity). COPD with emphysema accompanied by reversible or partially reversible airflow obstruction (with or without an allergic component or reduced carbon monoxide diffusion capacity).	Of the small cohort from the academic general pulmonary clinic/asthma referral clinic, 15.8% of patients were ACOS compared to 34.2% asthma and 43.4% COPD/emphysema. In the severe asthma clinic, 24.3% of patients were ACOS compared to 52.9% of asthma.

ACOS = Asthma and COPD overlap syndrome; AHR = Airway hyper responsiveness; CO = Carbon monoxide; COPD = Chronic obstructive pulmonary disease; CT = computed tomography; FVC = forced vital capacity; FEV1 = forced expiratory volume in 1 second; ICD-10 = international classification of disease criteria.

Figure 2. Terminology reported within the published literature to describe the overlap phenotype (n = 43).

Table 2. Clinical and physiological characteristics of asthma, ACOS,and COPD [1,2,4,13,24].

Measure	Asthma	ACOS	COPD
Symptoms	Intermittent, worse at night or in the morning	Progressively worsen	Progressively worsen
FEV1/FVC	≥70%	<70%	<70%
FEV1 %predicted*	>80%	<80%	<80%
AHR, PD15^	<12 ml	<12 ml	>12 ml
PB increase in FEV1	≥12% and 400 ml (marked reversibility)	≥12% and ≥200 ml (reversible)	≥12% and ≥200 ml (reversible)
FeNO	>50 ppb	25–50 ppb	<25 ppb
DLco	Normal, although smokers may present with a lower DLco	Normal–low	<80% predicted
Imaging	Usually normal	Bronchial wall thickening, emphysema, gas trapping on expiratory chest CT scans, greater segmental wall area on inspiratory CT scans, fibrosis, hyperinflation	Bronchial wall thickening, emphysema, fibrosis, hyperinflation
Inflammation	Eosinophils > neutrophils, mast cells, CD4+ T lymphocytes	Eosinophils and neutrophils, CD4+ and CD8+ T lymphocytes	Neutrophils > eosinophils, CD4+, CD8+ T lymphocytes
	IgE, IL-4/-5/-13, eotaxin	IgE, IL-4/-5/-13/-1β/-8/-6, TNF-α, eotaxin, proteases	IL-1β/-8/-6, TNF-α, proteases
Test for atopy, (MAST)	Commonly allergic to environmental allergens	Commonly allergic to environmental allergens	Do not rule out COPD, ACOS may be more likely
Exacerbations	>3/year, well controlled by treatment	More frequent than asthma and COPD alone	>2/year

*postbronchodilator, ^provocation dose of hypertonic saline that induces a 15% fall in FEV1.

AHR = airway hyperresponsiveness; COPD = Chronic obstructive pulmonary disease; CT = computed tomography; DLco = carbon monoxide diffusing capacity; FeNO = fraction of exhaled nitric oxide; FEV1 = forced expiratory volume in 1s; FVC = Forced vital capacity; IgE = immunoglobulin E; MAST= multiple allergens simultaneous test; PD = provocation dose; PB = post bronchodilator; TNF = tumour necrosis factor.

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