Current perspectives Treatment of overlapping asthma–chronic obstructive pulmonary disease: Can guidelines contribute in an evidence-free zone? Helen K. Reddel, MBBS, PhD Sydney, Australia 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. (J Allergy Clin Immunol 2015;136:546-52.) Key words: Asthma, chronic obstructive pulmonary disease, asthma-chronic obstructive pulmonary disease overlap syndrome, guidelines In their most typical forms (childhood-onset allergic asthma and emphysema in a heavy smoker), asthma and chronic obstructive pulmonary disease (COPD) can be readily distin- guished. However, there is substantial overlap between asthma and COPD, with many patients who have chronic airflow limitation demonstrating clinical features of both conditions. Yet these patients have mostly been studied in selected popula- tions, and they are specifically excluded from most major pharmacologic studies of asthma or COPD treatment. In such an evidence-free zone, can clinical practice guidelines make any recommendations about how such patients should be diagnosed and be managed? This article discusses the clinical problem of overlapping asthma and COPD (here called asthma-COPD overlap syndrome [ACOS]), highlights the need for clinical guidance, summarizes recommendations about ACOS from a sample of asthma and COPD guidelines, and proposes a way forward to provide health professionals with practical clinical advice while awaiting out- comes of research to identify specific treatment targets. DEFINITIONS The potential for confusion about asthma-COPD overlap is not surprising, considering the imprecise definitions for these dis- eases 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 asthma. To focus attention on the potential for targeting treatment, asthma is now defined strategically in the recent Global Initiative for Asthma (GINA) report as follows: ‘‘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 limita- tion.’’ 1 For COPD, the most commonly quoted definition, from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is as follows: ‘‘a common preventable and treatable dis- ease, . characterized by persistent airflow limitation that is usu- ally progressive and associated with an enhanced chronic inflammatory response in the airways and the lungs to noxious From the Woolcock Institute of Medical Research, University of Sydney. 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. Received for publication June 3, 2015; revised June 25, 2015; accepted for publication June 30, 2015. Corresponding author: Helen K. Reddel, MBBS, PhD, Woolcock Institute of Medical Research, University of Sydney, 431 Glebe Point Rd, Glebe, NSW 2037, Australia. E-mail: [email protected]. 0091-6749/$36.00 Ó 2015 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaci.2015.06.043 546
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