Reviews and feature article
Treatment of overlapping asthma–chronic obstructive pulmonary disease: Can guidelines contribute in an evidence-free zone?

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In their most typical forms, asthma and chronic obstructive pulmonary disease (COPD) are clearly distinguishable, but many patients with chronic airflow limitation demonstrate features of both conditions and have worse health outcomes than those with either disease alone. This has been called the asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS), but as yet, it lacks a precise definition. However, given the different pathways by which a patient can come to demonstrate features of both asthma and COPD, ACOS is not thought to represent a single disease but to include several heterogeneous phenotypes with different underlying mechanisms. These issues have important implications for guidelines because some existing treatment recommendations for asthma and COPD are in conflict, and patients with both asthma and COPD have specifically been excluded from major pharmacologic trials. As a result, there is little evidence at present to support specific treatment recommendations for ACOS on the basis of efficacy or effectiveness, yet these patients continue to present for diagnosis and management, mainly in primary care. This article highlights the need for clinical guidance about ACOS, summarizes recommendations about its diagnosis and treatment from a sample of national asthma and COPD guidelines, and proposes a way forward, as suggested in a collaborative Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease report, to provide health professionals with interim recommendations about syndromic recognition and initial treatment based on both potential effectiveness and potential risk. Additional research in broad populations is urgently needed to develop a precise definition for ACOS, characterize its phenotypes, and identify opportunities for targeted treatment.

Section snippets

Definitions

The potential for confusion about asthma-COPD overlap is not surprising, considering the imprecise definitions for these diseases themselves. In the past, asthma has been described (rather than defined) as a disease characterized by chronic inflammatory cells, airway hyperresponsiveness, variable airflow limitation, and variable symptoms. However, there is now clear evidence that asthma is not a single disease, although most research about asthma phenotypes has been in patients with severe

Clinical patterns

Patients who satisfy the above description of overlap can have widely varying clinical histories. For example, they might include patients with childhood-onset asthma who accumulate a significant smoking history and often require higher-dose inhaled corticosteroids (ICSs),3 patients with airflow limitation that persists from childhood through to adult life,4 smokers with variable respiratory symptoms and a family history of asthma, life-long nonsmokers presenting for the first time in adult

Prevalence

The reported prevalence of asthma-COPD overlap varies widely, depending on the criteria used and the population studied. Among patients self-reporting a doctor's diagnosis of asthma or COPD, 15% to 20% report both diagnoses.12, 13, 14, 15 However, reported diagnoses are unreliable for both asthma16, 17, 18 and COPD,19 and when physician diagnosis is the standard, it is likely to be biased toward more familiar single phenotypes, such as childhood-onset allergic asthma and later-onset emphysema.

Diagnosis

Although the issue of overlapping asthma and COPD might appear to be an academic discussion, in reality, it is of intense importance to those involved in frontline patient care. Patients often present with nonspecific symptoms that can represent a life-threatening emergency, a short-term self-limiting problem, or an evolving chronic condition.26 Primary care environments rarely permit the luxury of in-depth diagnostic consultations, with diagnostic evaluation instead being carried out in a

The evidence framework

Clinical practice guidelines are intended to provide evidence-based recommendations for the management of patients in clinical practice. Over the past 10 years, there has been increasing emphasis on systematically evaluating the quality of research evidence, with the highest rating given to highly controlled randomized studies in well-defined populations. These studies are designed to establish the efficacy of the treatment under ideal conditions, and the process of grading the evidence allows

Guidelines: What do they say?

In the context of differential diagnosis, most asthma guidelines mention COPD, and most COPD guidelines mention asthma, and many provide a table of key clinical differences between asthma and COPD. However, recommendations about the diagnosis and management of patients with features of both asthma and COPD are generally only found in the most recently published or recently updated guidelines, reflecting the rapidly escalating interest in this topic. Some examples are given below, first from

Future implications

The key goals of management of airways disease include identification of specific treatment targets to optimize symptom control and reduce risk for individual patients, use medications where they will be most cost-effective, and reduce the risks of overtreatment. For this, predictors of treatment response are needed. Some evidence is available from selected populations that should also be investigated for ACOS. For example, increased exhaled nitric oxide levels are associated with greater

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    Disclosure of potential conflict of interest: H. K. Reddel is on advisory boards and a Data and Safety Monitoring Board for AstraZeneca, GlaxoSmithKline, and Novartis; was an advisory board member for Boehringer Ingelheim; is on a Data and Safety Monitoring Board for Merck; has provided consulting for AstraZeneca and GlaxoSmithKline; has received grants from AstraZeneca and GlaxoSmithKline; has received payment for lectures from Aerocrine, AstraZeneca, GlaxoSmithKline, Mundipharma, Novartis, and Teva; and is chair of the Global Initiative for Asthma (GINA) Science Committee.

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