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Editorial |

Asthma-COPD Overlap FREE TO VIEW

Peter J. Barnes, Master FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

CORRESPONDENCE TO: Peter J. Barnes, Master FCCP, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, England


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(1):7-8. doi:10.1016/j.chest.2015.08.017
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Published online

Most clinicians can easily distinguish asthma and COPD. Asthma usually has an early onset with intermittent symptoms, a good response to inhaled therapy, and is often associated with other allergic diseases, whereas COPD is of late onset, slowly progressive symptoms, poor response to inhaled therapy, and is usually associated with long-term smoking. However, patients can sometimes have features of both diseases, and this condition has been termed asthma-COPD overlap syndrome (ACOS). Some overlap may be predicted because asthma and COPD are both common, and there is no evidence that one disease protects against the other. To call this overlap a syndrome is misleading, however; it includes different phenotypes, such as patients with COPD and eosinophilic inflammation, patients with asthma and severe disease or who smoke in whom there is predominantly neutrophilic inflammation, and patients with asthma who have largely irreversible airway obstruction due to structural changes. Thus, it may be better to refer to asthma-COPD overlap (ACO), rather than ACOS. Indeed, the patients who receive a primary diagnosis of asthma who have some features of COPD are better considered as phenotypes of asthma. The “Dutch hypothesis,” first proposed in the 1960s, suggested that there was a common genetic background to airway obstruction with a spectrum of clinical disease from asthma to COPD. Although the validity of the Dutch hypothesis has been fiercely debated, recent genetic studies indicate that there is very little, if any, common genetic background of asthma and COPD. ACO is now recognized in several national and international guidelines.

It is important to recognise whether a patient has ACO because this determination may influence the clinical course, long-term outlook, and response to therapy. There is uncertainty about the prevalence of ACO; it depends on the populations that are studied and tends to be higher in patients referred to specialists because they may be more difficult to manage. There is general agreement from several studies that 10% to 20% of patients with COPD have features of asthma. In the study published in this issue of CHEST (see page 45), ACO was found in approximately 15% of a Spanish cohort of > 800 patients with COPD, in good agreement with the 13% of 3,500 patients with ACO in the COPD Gene consortium. Among a population of patients with asthma, a higher proportion are likely to have ACO because many will be current smokers, about 5% will have severe asthma, and a higher proportion will have irreversible airway obstruction. Patients with ACO identified among those who receive a primary diagnosis of asthma or COPD will likely be of different phenotypes.

Most studies have reported that patients with COPD who have features of asthma have a worse prognosis, in terms of more frequent and severe exacerbations, more frequent symptoms, worse quality of life, more comorbidities, and less emphysema as noted on CT scans.,, A greater degree of airway reversibility in response to bronchodilators has been used as a criterion of ACOS; it is therefore not surprising that this factor is more frequently found in these patients. Surprisingly, in the study by Cosio et al, there were no significant clinical differences apart from reversibility and the fact that patients with ACOS had a better survival, at least 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.

The patterns of airway inflammation in asthma and COPD are markedly different, with mast cell activation, infiltration of eosinophils driven by activation of T-helper type 2 cells and type 2 innate lymphoid cells in asthma; in COPD, there is typically no mast cell activation (which accounts for the lack of reversibility), infiltration of neutrophils and macrophages, and driven by T-helper types 1 and 17 cells, and CD8+ T cells. COPD patients with asthma may have infiltration of eosinophils in the airways, and this may be driven by type 2 innate lymphoid cells, which secrete IL-5 but are not activated by allergens. There is an increased concentration of IL-5 in the sputum of patients with COPD who have increased eosinophils, and both are reduced by oral prednisolone. By contrast, patients with asthma and features of COPD may have predominantly neutrophilic inflammation or no increase in inflammatory cells.

An important reason for identifying ACO is to select the most appropriate therapy. There is scant information on the therapy of overlap because these patients are often excluded from large clinical trials of asthma and COPD. Although most patients with COPD exhibit little or no therapeutic response to even high doses of inhaled corticosteroids, patients with COPD and increased sputum eosinophil counts display a greater improvement in FEV1. Increasing the dose of inhaled corticosteroids when sputum eosinophil counts increase > 3% significantly reduces exacerbations. A recent post hoc analysis of a COPD trial showed that an inhaled corticosteroid was more effective in reducing exacerbations in those with blood eosinophil counts > 2%, particularly in those with > 6% eosinophils. These studies suggest that patients with COPD and increased eosinophil counts may benefit from triple therapy with the addition of an inhaled corticosteroid to long-acting β2-agonist and anticholinergic inhalers. Similarly, asthmatic patients with COPD features may benefit from the addition of a long-acting anticholinergic agent to an inhaled corticosteroid/long-acting β2-agonist combination. Several new treatments are in development that may be suitable for the future management of patients with ACO, including anti-eosinophil-directed monoclonal antibodies and kinase inhibitors. However, benralizumab, an antibody that blocks the IL-5 receptor, was ineffective in patients with COPD and eosinophilia.

To manage patients with overlap effectively, it is necessary to make the diagnosis. This is currently done by clinical assessment, including history, exposure, and bronchodilator reversibility, which are imprecise. Airway eosinophilia may be measured by using sputum eosinophil counts or fractional exhaled nitric oxide, but these tests are usually not available in routine clinical practice. Blood eosinophil counts are easy to perform and may reflect airway eosinophilia and predict corticosteroid responsiveness. Sputum neutrophilia is not reflected by circulating neutrophils and can only be detected by examination of induced sputum, however. A formal trial of oral corticosteroids (prednisolone or prednisone 30 mg daily for 2 weeks) may be useful for identifying an asthmatic component in patients with COPD (with improvement in FEV1 > 15% or 200 mL).

ACO is a clinical reality and is important to identify, but more research is needed to define these overlap phenotypes, to identify them in the clinic, and to understand the best way of managing these patients.

Supplementary Data

Global Initiative for Asthma. Asthma, COPD and asthma-COPD overlap syndrome (ACOS). Global Initiative for Asthma website.http://www.ginasthma.org/local/uploads/files/ACOS_2015.pdf. Accessed October 2, 2015.
 
Gibson P.G. .McDonald V.M. . Asthma-COPD overlap 2015: now we are six. Thorax. 2015;70:683-691 [PubMed]journal. [CrossRef] [PubMed]
 
Smolonska J. .Koppelman G.H. .Wijmenga C. .et al Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis. Eur Respir J. 2014;44:860-872 [PubMed]journal. [CrossRef] [PubMed]
 
Cosio B.G. .Soriano J.B. .López-Campos J.L. .et al Defining the asthma-COPD overlap syndrome in a COPD cohort. Chest. 2016;149:45-52 [PubMed]journal. [CrossRef] [PubMed]
 
Hardin M. .Cho M. .McDonald M.L. .et al The clinical and genetic features of COPD-asthma overlap syndrome. Eur Respir J. 2014;44:341-350 [PubMed]journal. [CrossRef] [PubMed]
 
Barrecheguren M. .Esquinas C. .Miravitlles M. . The asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges. Curr Opin Pulm Med. 2015;21:74-79 [PubMed]journal. [CrossRef] [PubMed]
 
Barnes P.J. . Immunology of asthma and chronic obstructive pulmonary disease. Nat Immunol Rev. 2008;8:183-192 [PubMed]journal. [CrossRef]
 
Hammad H. .Lambrecht B.N. . Barrier epithelial cells and the control of type 2 immunity. Immunity. 2015;43:29-40 [PubMed]journal. [CrossRef] [PubMed]
 
Bafadhel M. .Saha S. .Siva R. .et al Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD. Respiration. 2009;78:256-262 [PubMed]journal. [CrossRef] [PubMed]
 
Brightling C.E. .McKenna S. .Hargadon B. .et al Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease. Thorax. 2005;60:193-198 [PubMed]journal. [CrossRef] [PubMed]
 
Siva R. .Green R.H. .Brightling C.E. .et al Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29:906-913 [PubMed]journal. [CrossRef] [PubMed]
 
Pascoe S. .Locantore N. .Dransfield M.T. .Barnes N.C. .Pavord I.D. . Blood eosinophil counts, exacerbations, and response to the addition of inhaled 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;3:435-442 [PubMed]journal. [CrossRef] [PubMed]
 
Kerstjens H.A. .Engel M. .Dahl R. .et al Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367:1198-1207 [PubMed]journal. [CrossRef] [PubMed]
 
Barnes P.J. . Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes. J Allergy Clin Immunol. 2015;136:531-545 [PubMed]journal. [CrossRef] [PubMed]
 
Brightling C.E. .Bleecker E.R. .Panettieri R.A. Jr..et al Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Resp Med. 2014;2:891-901 [PubMed]journal. [CrossRef]
 

Figures

Tables

References

Global Initiative for Asthma. Asthma, COPD and asthma-COPD overlap syndrome (ACOS). Global Initiative for Asthma website.http://www.ginasthma.org/local/uploads/files/ACOS_2015.pdf. Accessed October 2, 2015.
 
Gibson P.G. .McDonald V.M. . Asthma-COPD overlap 2015: now we are six. Thorax. 2015;70:683-691 [PubMed]journal. [CrossRef] [PubMed]
 
Smolonska J. .Koppelman G.H. .Wijmenga C. .et al Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis. Eur Respir J. 2014;44:860-872 [PubMed]journal. [CrossRef] [PubMed]
 
Cosio B.G. .Soriano J.B. .López-Campos J.L. .et al Defining the asthma-COPD overlap syndrome in a COPD cohort. Chest. 2016;149:45-52 [PubMed]journal. [CrossRef] [PubMed]
 
Hardin M. .Cho M. .McDonald M.L. .et al The clinical and genetic features of COPD-asthma overlap syndrome. Eur Respir J. 2014;44:341-350 [PubMed]journal. [CrossRef] [PubMed]
 
Barrecheguren M. .Esquinas C. .Miravitlles M. . The asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges. Curr Opin Pulm Med. 2015;21:74-79 [PubMed]journal. [CrossRef] [PubMed]
 
Barnes P.J. . Immunology of asthma and chronic obstructive pulmonary disease. Nat Immunol Rev. 2008;8:183-192 [PubMed]journal. [CrossRef]
 
Hammad H. .Lambrecht B.N. . Barrier epithelial cells and the control of type 2 immunity. Immunity. 2015;43:29-40 [PubMed]journal. [CrossRef] [PubMed]
 
Bafadhel M. .Saha S. .Siva R. .et al Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD. Respiration. 2009;78:256-262 [PubMed]journal. [CrossRef] [PubMed]
 
Brightling C.E. .McKenna S. .Hargadon B. .et al Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease. Thorax. 2005;60:193-198 [PubMed]journal. [CrossRef] [PubMed]
 
Siva R. .Green R.H. .Brightling C.E. .et al Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29:906-913 [PubMed]journal. [CrossRef] [PubMed]
 
Pascoe S. .Locantore N. .Dransfield M.T. .Barnes N.C. .Pavord I.D. . Blood eosinophil counts, exacerbations, and response to the addition of inhaled 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;3:435-442 [PubMed]journal. [CrossRef] [PubMed]
 
Kerstjens H.A. .Engel M. .Dahl R. .et al Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367:1198-1207 [PubMed]journal. [CrossRef] [PubMed]
 
Barnes P.J. . Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes. J Allergy Clin Immunol. 2015;136:531-545 [PubMed]journal. [CrossRef] [PubMed]
 
Brightling C.E. .Bleecker E.R. .Panettieri R.A. Jr..et al Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Resp Med. 2014;2:891-901 [PubMed]journal. [CrossRef]
 
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