Review
The asthma–COPD overlap syndrome: towards a revised taxonomy of chronic airways diseases?

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Summary

Most research of treatments for airways diseases has been restricted to patients who meet standard definitions of either chronic obstructive pulmonary disease (COPD) or asthma, yet to distinguish COPD from asthma in adult patients who have clinical features of both can be challenging. Treatment guidelines provide scant advice on how such patients should be managed. With increasing recognition that asthma and COPD are heterogeneous diseases, attention has been directed to the needs of a group of patients with what is now termed asthma–COPD overlap syndrome (ACOS), particularly in view of the high morbidity in this population. This Review considers the epidemiology, mechanisms of disease, current attempts to define and diagnose ACOS, existing and potential treatment options, and new approaches to the phenotyping and taxonomy of airway diseases.

Introduction

In respiratory medicine, the term overlap syndrome has been applied both to the association between obstructive sleep apnoea and chronic obstructive pulmonary disease (COPD)1 and to patients with features of both asthma and COPD (asthma–COPD overlap syndrome [ACOS]).2, 3 In 2014, this syndrome was the topic of a joint publication by the Global Initiative for Asthma (GINA)4 and the Global initiative for Obstructive Lung Disease (GOLD),3, 5 and is beginning to appear in national clinical practice guidelines.6, 7, 8, 9 These developments have been prompted by the following considerations: the recognition that ACOS represents a form of airways disease that is associated with a disproportionate number of exacerbations,10, 11 hospital admissions, and use of health-care resources;12 the fact that patients with ACOS are generally excluded from most trials of new treatments for asthma or COPD; the realisation that asthma and COPD themselves are heterogeneous disorders and that new insights are emerging into the gene–environment interactions involved in different forms of airways diseases and resultant phenotypes; and the emergence of new treatments for asthma and COPD that target specific biological mechanisms of disease (ie, endotypes).13 However, some commentators question whether the description of ACOS as a clinical entity is valid or a useful concept. To address these concerns, this Review discusses the epidemiology, mechanisms of disease, current attempts to define and diagnose ACOS, existing and potential treatment options, and new approaches to the phenotyping and taxonomy of airway diseases.

Section snippets

Epidemiology of ACOS

The reported prevalence of ACOS in different studies varies according to how asthma and COPD were defined, the population sampled (random population samples vs asthma or COPD cohorts), and age group (all adults or older adults [eg, aged >40 years]). When ACOS is defined on the basis of a doctor diagnosis of both asthma and COPD, its prevalence in different cohorts of patients aged 40 years and older with chronic airways disease—including the US NHANES III study,14 the UK GP Research Database,15

Definitions and descriptions of asthma, COPD, and ACOS

When considering how to define ACOS, existing definitions of asthma and COPD would seem the logical place to begin, but they provide little help to the clinician. In 2014, GINA defined asthma as “a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation”.4 The GOLD

Diagnosis of ACOS

Until the past few years,5, 41, 42, 43 clinical practice guidelines have been relatively silent on how to diagnose and manage patients with features of both asthma and COPD (ie, ACOS), except to advise that the two disorders might coexist. Several groups have proposed a more structured approach.31, 44, 45 In 2013, Louie and colleagues44 suggested the diagnosis of ACOS be applied to patients with a doctor diagnosis of both asthma and COPD, a history or evidence of atopy (eg, hayfever or raised

A clinical approach to the diagnosis of chronic airway diseases, including ACOS

In clinical practice, for a clinician to make a diagnosis in patients with chronic airways disease, they need to weigh features of typical asthma or typical COPD that are present against those that are absent. Several of these features call for a quantitative judgment; for example, what level of smoking history (number of pack-years) would change the diagnosis from asthma to COPD if all other features favoured asthma? In the global context, how much exposure to biomass or other risk factors

Approach to treatment in ACOS

Although overlapping or mixed asthma and COPD are described in some recent national COPD guidelines6, 7, 9 and the GINA4 and GOLD5 strategy documents, almost no high quality data exist on which to base treatment recommendations, because patients with ACOS have been specifically excluded from trials investigating treatments for asthma or COPD. However, many clinicians have experience of empirical treatment of such patients with drugs approved for asthma or COPD. At present, the GINA–GOLD document

Need for a new taxonomy of airways diseases based on progress in endotyping and phenotyping

The argument for a new taxonomy for chronic airways diseases is compelling.61, 62 The creation of a new taxonomy is not an academic exercise, but is essential for an improved understanding of the natural histories and pathogenesis of these disorders, and as part of the personalised (precision) medicine approach to find treatments for unmet needs, particularly for severe forms of disease.59, 63, 64

The existing classification of airways disease into asthma and COPD involves a-priori assumptions

Pathways to ACOS and the Dutch hypothesis of chronic airways disease

ACOS is generally only used as a potential diagnosis in adults aged 40 years and older (midway through life). Detailed studies comparing elderly patients with chronic asthma and fixed airflow limitation with age-matched patients with COPD, confirm differences in airway morphology and inflammation, implying that lifelong asthma does not morph into the usual forms of COPD, but ageing inevitably plays a part in chronic airflow limitation.76, 77 The origins of airway diseases in adulthood can be

Conclusions and future research

The understanding of chronic airways disease in adults with features both of asthma and COPD (so-called ACOS) is incomplete, and its treatment omitted from previous regulatory studies and treatment guidelines. Existing descriptions of ACOS are intended, in the first instance, as interim advice to assist clinical management of airways disease by non-specialist physicians, not as definitive statement. Preliminary advice in most publications is to treat patients with suspected ACOS with both a

Search strategy and selection criteria

We searched the Cochrane Library (Jan 1, 2001, to Dec 31, 2015) and Medline (Jan 1, 1970, to Dec 31, 2015) for manuscripts published in English, using the medical subject heading (MeSH) search terms “Asthma” OR “COPD” OR “chronic obstructive airway disease” OR “chronic obstructive pulmonary disease” OR “chronic obstructive lung disease” AND “overlap”. We prioritised publications from the past 5 years. We also searched the reference lists of articles identified by this search strategy and

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