[ Editorial ]

ACO is now recognized in several national and

Asthma-COPD Overlap international guidelines.1
Peter J. Barnes, Master FCCP It is important to recognise whether a patient has ACO
London, England because this determination may influence the clinical
course, long-term outlook, and response to therapy.
There is uncertainty about the prevalence of ACO; it
Most clinicians can easily distinguish asthma and
depends on the populations that are studied and tends
COPD. Asthma usually has an early onset with
to be higher in patients referred to specialists because
intermittent symptoms, a good response to inhaled
they may be more difficult to manage. There is general
therapy, and is often associated with other allergic
agreement from several studies that 10% to 20% of
diseases, whereas COPD is of late onset, slowly
patients with COPD have features of asthma.2 In the
progressive symptoms, poor response to inhaled
study published in this issue of CHEST (see page 45),4
therapy, and is usually associated with long-term
ACO was found in approximately 15% of a Spanish
smoking. However, patients can sometimes have
cohort of > 800 patients with COPD, in good agreement
features of both diseases, and this condition has been
with the 13% of 3,500 patients with ACO in the COPD
termed asthma-COPD overlap syndrome (ACOS).1
Gene consortium.5 Among a population of patients with
Some overlap may be predicted because asthma and
asthma, a higher proportion are likely to have ACO
COPD are both common, and there is no evidence that
because many will be current smokers, about 5% will
one disease protects against the other. To call this
have severe asthma, and a higher proportion will have
overlap a syndrome is misleading, however; it includes
irreversible airway obstruction. Patients with ACO
different phenotypes, such as patients with COPD
identified among those who receive a primary diagnosis
and eosinophilic inflammation, patients with asthma
of asthma or COPD will likely be of different
and severe disease or who smoke in whom there is
phenotypes.
predominantly neutrophilic inflammation, and patients
with asthma who have largely irreversible airway Most studies have reported that patients with COPD
obstruction due to structural changes. Thus, it may be who have features of asthma have a worse prognosis,
better to refer to asthma-COPD overlap (ACO), rather in terms of more frequent and severe exacerbations,
than ACOS.2 Indeed, the patients who receive a primary more frequent symptoms, worse quality of life, more
diagnosis of asthma who have some features of COPD comorbidities, and less emphysema as noted on CT
are better considered as phenotypes of asthma. The scans.2,5,6 A greater degree of airway reversibility in
“Dutch hypothesis,” first proposed in the 1960s, response to bronchodilators has been used as a criterion
suggested that there was a common genetic background of ACOS; it is therefore not surprising that this factor
to airway obstruction with a spectrum of clinical disease is more frequently found in these patients. Surprisingly,
from asthma to COPD. Although the validity of the in the study by Cosio et al,4 there were no significant
Dutch hypothesis has been fiercely debated, recent clinical differences apart from reversibility and the fact
genetic studies indicate that there is very little, if any, that patients with ACOS had a better survival, at least
common genetic background of asthma and COPD.3 after 1 year of study. However, because of a lack of
longitudinal studies, it is unknown whether patients
with COPD and features of asthma have a more rapid
progression of disease.
AFFILIATIONS: From the National Heart and Lung Institute,
Imperial College London.
The patterns of airway inflammation in asthma and
FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.
CORRESPONDENCE TO: Peter J. Barnes, Master FCCP, National
COPD are markedly different, with mast cell activation,
Heart and Lung Institute, Dovehouse St, London SW3 6LY, England; infiltration of eosinophils driven by activation of
e-mail: [email protected] T-helper type 2 cells and type 2 innate lymphoid cells
Copyright Ó 2016 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved. in asthma; in COPD, there is typically no mast cell
DOI: http://dx.doi.org/10.1016/j.chest.2015.08.017 activation (which accounts for the lack of reversibility),

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 infiltration of neutrophils and macrophages, and driven and may reflect airway eosinophilia and predict
by T-helper types 1 and 17 cells, and CD8þ T cells.7 corticosteroid responsiveness.12 Sputum neutrophilia is
COPD patients with asthma may have infiltration of not reflected by circulating neutrophils and can only be
eosinophils in the airways, and this may be driven by detected by examination of induced sputum, however.
type 2 innate lymphoid cells, which secrete IL-5 but A formal trial of oral corticosteroids (prednisolone or
are not activated by allergens.8 There is an increased prednisone 30 mg daily for 2 weeks) may be useful for
concentration of IL-5 in the sputum of patients with identifying an asthmatic component in patients with
COPD who have increased eosinophils, and both are COPD (with improvement in FEV1 > 15% or 200 mL).
reduced by oral prednisolone.9 By contrast, patients with
ACO is a clinical reality and is important to identify,
asthma and features of COPD may have predominantly
but more research is needed to define these overlap
neutrophilic inflammation or no increase in inflammatory
phenotypes, to identify them in the clinic, and to
cells.
understand the best way of managing these patients.
An important reason for identifying ACO is to select
the most appropriate therapy. There is scant References
information on the therapy of overlap because these 1. Global Initiative for Asthma. Asthma, COPD and asthma-COPD
overlap syndrome (ACOS). Global Initiative for Asthma website.
patients are often excluded from large clinical trials of http://www.ginasthma.org/local/uploads/files/ACOS_2015.pdf.
asthma and COPD. Although most patients with COPD Accessed October 2, 2015.

exhibit little or no therapeutic response to even high 2. Gibson PG, McDonald VM. Asthma-COPD overlap 2015: now we
are six. Thorax. 2015;70(7):683-691.
doses of inhaled corticosteroids, patients with COPD 3. Smolonska J, Koppelman GH, Wijmenga C, et al. Common genes
and increased sputum eosinophil counts display a underlying asthma and COPD? Genome-wide analysis on the Dutch
hypothesis. Eur Respir J. 2014;44(4):860-872.
greater improvement in FEV1.10 Increasing the dose of
4. Cosio BG, Soriano JB, López-Campos JL, et al. Defining the asthma-
inhaled corticosteroids when sputum eosinophil counts COPD overlap syndrome in a COPD cohort. Chest. 2016;149(1):
increase > 3% significantly reduces exacerbations.11 45-52.
A recent post hoc analysis of a COPD trial showed that 5. Hardin M, Cho M, McDonald ML, et al. The clinical and genetic
features of COPD-asthma overlap syndrome. Eur Respir J. 2014;
an inhaled corticosteroid was more effective in reducing 44(2):341-350.
exacerbations in those with blood eosinophil counts 6. Barrecheguren M, Esquinas C, Miravitlles M. The asthma-chronic
> 2%, particularly in those with > 6% eosinophils.12 obstructive pulmonary disease overlap syndrome (ACOS):
opportunities and challenges. Curr Opin Pulm Med. 2015;21(1):74-79.
These studies suggest that patients with COPD and
7. Barnes PJ. Immunology of asthma and chronic obstructive
increased eosinophil counts may benefit from triple pulmonary disease. Nat Immunol Rev. 2008;8(3):183-192.
therapy with the addition of an inhaled corticosteroid 8. Hammad H, Lambrecht BN. Barrier epithelial cells and the control
to long-acting b2-agonist and anticholinergic inhalers. of type 2 immunity. Immunity. 2015;43(1):29-40.
9. Bafadhel M, Saha S, Siva R, et al. Sputum IL-5 concentration is
Similarly, asthmatic patients with COPD features may associated with a sputum eosinophilia and attenuated by
benefit from the addition of a long-acting anticholinergic corticosteroid therapy in COPD. Respiration. 2009;78(3):256-262.
agent to an inhaled corticosteroid/long-acting b2-agonist 10. Brightling CE, McKenna S, Hargadon B, et al. Sputum eosinophilia
and the short term response to inhaled mometasone in chronic
combination.13 Several new treatments are in development obstructive pulmonary disease. Thorax. 2005;60(3):193-198.
that may be suitable for the future management of 11. Siva R, Green RH, Brightling CE, et al. Eosinophilic airway
patients with ACO, including anti-eosinophil-directed inflammation and exacerbations of COPD: a randomised controlled
trial. Eur Respir J. 2007;29(5):906-913.
monoclonal antibodies and kinase inhibitors.14 However,
12. Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood
benralizumab, an antibody that blocks the IL-5 receptor, eosinophil counts, exacerbations, and response to the addition of inhaled
was ineffective in patients with COPD and eosinophilia.15 fluticasone furoate to vilanterol in patients with chronic obstructive
pulmonary disease: a secondary analysis of data from two parallel
randomised controlled trials. Lancet Respir Med. 2015;3(6):435-442.
To manage patients with overlap effectively, it is
13. Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly
necessary to make the diagnosis. This is currently controlled with standard combination therapy. N Engl J Med. 2012;
done by clinical assessment, including history, exposure, 367(13):1198-1207.
and bronchodilator reversibility, which are imprecise.1 14. Barnes PJ. Therapeutic approaches to asthma-chronic obstructive
pulmonary disease overlap syndromes. J Allergy Clin Immunol.
Airway eosinophilia may be measured by using sputum 2015;136(3):531-545.
eosinophil counts or fractional exhaled nitric oxide, but 15. Brightling CE, Bleecker ER, Panettieri RA Jr, et al. Benralizumab for
chronic obstructive pulmonary disease and sputum eosinophilia: a
these tests are usually not available in routine clinical randomised, double-blind, placebo-controlled, phase 2a study.
practice. Blood eosinophil counts are easy to perform Lancet Resp Med. 2014;2(11):891-901.

8 Editorial [ 149#1 CHEST JANUARY 2016 ]

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