The asthma–COPD overlap syndrome: how is it defined and what are its clinical implications?

Figures & data

Table 1 Clinical features that when present suggest the diagnosis of asthma or COPD

	Asthma	COPD	ACOS	More compatible with asthma	More compatible with COPD
Age of onset	Usually at childhood, but can present at any age	Usually age ≥40 years	Usually age ≥40 years, but onset of symptoms may have been in childhood or early adulthood	• Onset before age 20 years	• Onset after age 40 years
Pattern of symptoms	May vary from day to day; often triggered by either non-specific stimuli such as exercise and laughter, or exposure specific inhaled allergens	Chronic usually continuous symptoms, particularly during exercise	Chronic respiratory symptoms including exertional dyspnea are present, but variability of symptoms may be prominent	• Variation in symptoms over minutes, hours, or days • Symptoms worse during night or early morning • Symptoms triggered by exercise, emotions including laughter, dust or exposure to allergens	• Persistence of symptoms despite treatment • Good and bad days but always symptoms and exertional dyspnea • Chronic cough and sputum preceded onset of dyspnea, unrelated to triggers
Lung function • Persistence of airflow Obstruction • Variability of lung function • Course of lung function over time	• Lung function may be normal between symptoms • Current and/or historical variability of airflow obstruction, bronchodilator reversibility, BHR • Often improves with treatment and remains stable over time, but fixed airflow obstruction can develop in a subset of asthmatics	• Persistent airflow obstruction • Airflow obstruction may improve to some extent, but airflow obstruction defined as either post-bronchodilator FEV1/FVC <0.7 or LLN persists • Generally slowly progressive over years despite treatment	• Persistent airflow obstruction • Airflow obstruction is not fully reversible, but often with current or historical bronchodilator reversibility, and/or BHR • Generally slowly progressive decline over years, but to lesser extent than in COPD alone	• Record of variable airflow obstruction documented with spirometry or peak flow • Lung function normal between symptoms • No worsening of symptoms over time • May improve spontaneously or after treatment with a bronchodilator or ICS	• Record of persistent airflow limitation • Persistent airflow limitation • Symptoms slowly worsening over time • R apid-acting bronchodilator treatment provides only limited relief
Past history or family history of asthma	Many patients have a history of allergy and asthma in childhood and/or a family history of asthma	History of exposure to noxious particles and gases (mainly tobacco smoke and biomass fuels)	Frequently a history of allergy and asthma in childhood and/or a family history of asthma, and/or exposure to noxious particles and gases (mainly tobacco smoke and biomass fuels)	• Previous doctor’s diagnosis of asthma • Family history of asthma and allergy	• Previous doctor’s diagnosis of COPD or emphysema • History of exposure to noxious particles and gases (mainly tobacco smoke and biomass fuels)
Chest X-ray Exacerbations	Usually normal Exacerbations occur, but can be considerably reduced by treatment	Often shows hyperinflation Exacerbations occur and are often related to co-morbidities. Exacerbation frequency can be reduced by treatment	Often shows hyperinflation Exacerbations occur more frequently than in asthma or COPD alone, but are reduced by treatment. Co-morbidities can also contribute to exacerbations	• Normal	• Shows hyperinflation
Type of airway inflammation	Characterized by increased numbers of eosinophils in blood, sputum, and bronchial biopsies	Characterized mainly by neutrophils in sputum lymphocytes in bronchial biopsies	Elevated numbers of eosinophils and/or neutrophils can be present in sputum

Note: When a patient displays clinical features of both diseases, the diagnosis of ACOS is considered.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroids; ACOS, asthma–COPD overlap syndrome; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; BHR, bronchial hyperresponsiveness; LLN, lower limit of normal.

Figure 1 Relationship between Th2 Signature Score at baseline and improvement of hyperinflation after 30 months of treatment with inhaled fluticasone with or without added formoterol. Increased baseline Th2 score predicts a greater decrease in RV/TLC % predicted in the treatment group compared to placebo, t-value −2.43, P=0.019.

Notes: Reprinted with permission of the American Thoracic Society. Copyright © 2015 American Thoracic Society. Christenson SA, Steiling K, van den Berge M, et al. 2015. Asthma -COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. Volume 191(7), pages 758–766.³ The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
Abbreviations: RV, residual volume; TLC, total lung capacity.

Table 2 Overview of studies investigating patients with the asthma–COPD overlap syndrome (ACOS)

First author	Definition	Number	Design	Characteristics of included subjects	Main study outcome
Benayoun^Citation32	1. Post-BD FEV1/FVC <70% and FEV1 <80% predicted, and 2. Patient reports previous doctor’s diagnosis of asthma before the age of 40	ACOS, n=119 COPD, n=796	Observational cross-sectional study in (ex) smokers with >10 packyears between 45 and 80 years old	• ACOS: 51% male, age 61 yrs, 0% never-smokers, mean FEV1/FVC 61%, mean FEV1 73% predicted •COPD: 53% male, age 65 yrs, 0% never-smokers, mean FEV1/FVC 62%, mean FEV1 76% predicted	• Worse health-related quality of life and more exacerbation in ACOS vs COPD • No difference in % emphysema measured with CT
Lim^Citation37	1. Post-BD FEV1/FVC <70%, and 2. Patient reports previous diagnosis of asthma	ACOS, n=67 COPD, n=318	Epidemiological population based study in 385 subjects between 40 and 80 years old with airflow obstruction defined as post-BD FEV1/FVC <70%	• ACOS: 45% male, age 64 yrs, 45% never-smokers, mean FEV1/FVC 48%, mean FEV1 49% predicted • COPD: 76% male, age 64 yrs, 20% never-smokers, mean FEV1/FVC 48%, mean FEV1 49% predicted	• More symptoms of dyspnea and wheezing in ACOS vs COPD • Higher number of exacerbations in ACOS vs COPD
Kauppi^Citation34	1. Post-BD FEV1/FVC <70% and FEV1 <80% predicted, and 2. One of the following criteria: • post-BD increase in FEV1 ≥200 mL and 12% • decrease in FEV1 ≥15% during exercise test	ACOS, n=55 COPD, n=36 Asthma, n=8	Prospective cohort study with 4-year follow-up	• ACOS: 49% male, age 69 yrs, 25% never-smokers, mean FEV1/FVC 52%, mean FEV1 55% predicted • COPD: 33% male, age 70 yrs, 38% never-smokers, mean FEV1/FVC 58%, mean FEV1 56% predicted Asthma: 38% male, age 66 yrs, 75% never-smokers, mean FEV1/FVC 73%, mean FEV1 82% predicted	During the 4-year follow-up patients with COPD but not those with ACOS or asthma, experienced a significant decline in their FEV1, 6-minute walking distance, and health status when compared to baseline. The decline in 6-minute walking distance during the 4-year follow-up was significantly larger for COPD than ACOS
Hardin^Citation33	1. Post-BD FEV1/FVC <70%, and 2. One of the following criteria: • post-BD increase in FEV1 ≥12%: • post-BD increase in PEF ≥15% • diurnal PEF variation ≥20% • decrease in FEV1 ≥15% during exercise test	ACOS, n=225 COPD, n=237 Asthma, n=1,084	Observational study in patients diagnosed with asthma or COPD at the Helsinki University Hospital between 1996 and 2006	• ACOS: 48% male, age 61 yrs, 54% never-smokers, mean FEV1/FVC 66%, mean FEV1 67% predicted • COPD: 64% male, age 64 yrs, 1% never-smokers, mean FEV1/FVC 65%, mean FEV1 60% predicted • Asthma: 26% male, age 53 yrs, 4% never-smokers, mean FEV1/FVC 79%, mean FEV1 87% predicted	Lower health-related quality of life in ACOS vs asthma and COPD
Tashkin^Citation36	1. Post-BD FEV1/FVC <70%, and 2. One of the following criteria: • post-BD increase in FEV1 ≥200 mL and 12% • PC20 methacholine ≤16 mg/mL	ACOS, n=125
Jones^Citation38	Patient-reported doctor’s diagnosis of both asthma and COPD	ACOS 4.5%* COPD 13.3%* Asthma 2.9%*	Epidemiological population based study	ACOS? COPD? Asthma?	More symptoms and exacerbations in ACOS vs COPD and asthma
Kitaguchi^Citation13	1. Post-BD FEV1/FVC <70% in subjects who smoked >30 packyears, and 2. Asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning	ACOS, n=89 COPD, n=17	Cross-sectional observational study	• ACOS: 46% male, age 60 yrs, 0% never-smokers, mean FEV1/FVC 51%, mean FEV1 51% predicted • COPD: 87% male, age 71 yrs, 0% never-smokers, mean FEV1/FVC 46%, mean FEV1 48% predicted	Compared to COPD, patients with ACOS had: • A lower diffusion capacity • Thicker airway walls measured with CT • A higher percentage of sputum eosinophils (12.3%±3.3% vs 2.0%±0.5%) Better improvement in FEV1 after 2–3 months of treatment with 400 µg fluticasone/day
Pascoe^Citation39	1. Post-BD FEV1/FVC <70%, and 2. Patient-reported symptoms of wheezing during last 12 months plus post-BD increase in FEV1 or FVC >200 mL and 12%	ACOS, n=89 COPD, n=594 Asthma, n=84	Population survey (PLATINO study)	• ACOS: 46% male, age 60 yrs, 35% never-smokers, mean FEV1/FVC 58%, mean FEV1 58% predicted • COPD: 48% male, age 64 yrs, 31% never-smokers, mean FEV1/FVC 62%, mean FEV1 81% predicted • Asthma: 25% male, age 55 yrs, 40% never-smokers, mean FEV1/FVC 74%, mean FEV1 80% predicted	More respiratory symptoms, worse general health status, and more exacerbations in ACOS vs asthma and COPD

Note:

* Subjects aged 64–84 years.

Abbreviations: BD, bronchodilator; CT, computed tomography; COPD, chronic obstructive pulmonary disease; yrs, years; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; BHR, bronchial hyperresponsiveness; LLN, lower limit of normal; PEF, peak expiratory flow.

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