The term asthma chronic obstructive pulmonary disease (COPD) overlap (ACO) has been popularized to describe people who simultaneously have features of both diseases. Analysis of the basis of disease classification and comparison of the clinical, pathophysiological, and therapeutic features of asthma and COPD concludes that it is not useful to use the term ACO. Rather, it is important to make the individual diagnoses, recognizing that both diseases may coexist. If a concurrent diagnosis of COPD is suspected in people with asthma, pharmacotherapy should primarily follow asthma guidelines, but pharmacologic and nonpharmacologic approaches also may be needed for COPD.
Key points
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Patients may be diagnosed with asthma, chronic obstructive pulmonary disease (COPD), or both diseases.
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Patients with both diseases are generally excluded from clinical trials.
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It is not known if patients with both diseases have a different prognosis or need different treatment to those with either disease alone.
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The existence of an overlap condition or syndrome has been postulated, but there is no agreement on the definition of such a condition and definitive evidence to support its existence or the need for it as a diagnosis is lacking.
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The 2020 GOLD report has abandoned the concept and no longer refers to asthma and COPD overlap (ACO), instead it emphasizes that asthma and COPD are different disorders, although they may share some common traits and clinical features.
When I use a word,” Humpty Dumpty said, in rather a scornful tone, “it means just what I choose it to mean—neither more nor less. —Lewis Carroll (Charles L. Dodgson), Through the Looking-Glass , see Claus F. Vogelmeier and Peter Alter’s article, “ Assessing Symptom Burden ,” in this issue.
Making a diagnosis has always been central to the doctor-patient relationship. Diagnoses guide patients’ treatment, help set expectations about prognosis, and facilitate communication between doctors. In examining the current controversies about what is asthma chronic obstructive pulmonary disease (COPD) overlap (ACO) and whether it is a useful concept at all, it is helpful to consider how our current concepts of diseases evolved, what is meant by the term “disease,” and how we identify the extent and boundaries of diseases to differentiate one from another.
Diseases and diagnoses
Our current approach to the classification of diseases developed in the late seventeenth century when Sydenham urged physicians to organize illnesses into groups and hierarchies similar to those recently introduced by botanists to classify plants. Disease names, like the names of species, gave clinicians and patients terms that facilitated communication, even though specific treatments were not available in most cases. The only way categorize diseases at that time was according to their external characteristics, as the causes and pathophysiology could not be determined, and de Sauvages suggested grouping diseases by their symptoms. To be useful in classifying diseases, he said these had to be manifest, essential, and constant , that is, they had to be observable, not occur by accident, and always present; considerations still relevant today.
Much thought was given to how best to identify groups of symptoms and put boundaries around them to define specific diseases. This was necessary to make classification systems useful in practice and establish a set of terms that everyone associated with the same meanings. In the early eighteenth century, Drummond emphasized the importance of these boundaries but cautioned on taking it too far. He offered good and bad examples of this process, beginning the debate between “lumpers” and “splitters” that continued into the twentieth century. Drummond wrote that no two cases of disease are “strictly parallel in every circumstance but every case should not therefore have a new name.”
As pathologic and anatomic knowledge developed in the nineteenth century, new approaches to disease classification emerged and classification of disease, as promoted by Osler, relied on both the clinical presentation and pathologic findings. Over the past 100 years, this approach has gradually evolved with the introduction of definitive laboratory tests, physiologic and radiological investigations, and, most recently, molecular genetics. In many fields, more and more “precise” histopathological, radiological, and molecular characterization of a disease has become possible, but in other fields, notably psychiatry, clinical features remain the most important.
Modern disease classification reflects the inexorable progression, but not necessarily triumph, of “splitting.” By the end of the twentieth century, many broad disease syndromes had been split into more specific diseases, reflecting different causes, mechanisms, and responses to therapy. The continual elaboration of disease classification has led to advances in management, including more accurate prediction of prognosis, and splitting is fundamental to the concept of personalized medicine. Treatment using contemporary therapy often depends on maximal specificity in the diagnosis, as has been seen to great effect with the refinement of the classification of lung cancer and the use of targeted agents and checkpoint inhibitors. However, there is a point at which splitting stops defining different diseases and moves to defining subtypes of a disease that benefit in some ways from being considered the same, whilst benefit in other ways of being considered distinct.
Asthma and chronic obstructive pulmonary disease
How do these concepts relate to current understanding and usage of the terms asthma and COPD? The term asthma was used somewhat imprecisely from antiquity up to the middle of the past century to describe a condition of breathlessness. Its use was refined in the early nineteenth century to describe a condition associated with intermittent narrowing of the airways. Emphysema was described as a postmortem finding by Bonet in the late seventeenth century and the term chronic bronchitis was introduced by Badham in the early nineteenth century. Emphysema was linked with chronic bronchitis by Laennec, but the association with airflow obstruction was not recognized until the mid-twentieth century and the term COPD was not introduced until the mid-1960s.
The 1959 CIBA symposium attempted to develop definitions of asthma, chronic bronchitis, and emphysema, which included the presence of airflow obstruction and the extent of its reversibility. Two umbrella terms were proposed: chronic nonspecific lung disease (CNSLD) for the whole spectrum of these diseases, and generalized obstructive lung disease for asthma and what was subsequently termed COPD. CNSLD was adopted by the Netherlands, reflecting their reluctance to divide this group of patients into those with and without asthma. Most other countries continue to divide patients into those with and without asthma, but precise criteria dividing patients into those with COPD and those with asthma were not set out originally or subsequently. The terminology and definitions established at this period were provisional and expected to evolve, but although there have been many publications on these topics in the following 60 years, few modifications have been established. Yet, despite the difficulties of defining the terms of asthma and COPD, clinicians seemed to regard these terms as useful in clinical practice.
In 1991, the National Asthma Education Program guidelines for the diagnosis and management of asthma produced a working definition of asthma that combined immunopathological with physiologic and clinical features. Similar definitions of asthma have subsequently been proposed by the Global Initiative for Asthma (GINA) and definitions of COPD proposed by Global Initiative for Chronic Obstructive Lung Disease (GOLD), including the most recent, also combine pathologic and physiologic abnormalities with clinical features ( Box 1 ).
2019 GINA definition of asthma
Asthma is 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.
2020 GOLD definition of COPD
COPD is a heterogeneous disease/syndrome that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases and influenced by host factors, including abnormal lung development. Significant comorbidities may have an impact on morbidity and mortality.
The importance of definitions
In 1959, Scadding wrote, “These terminological matters are of great importance, for our choice of words inevitably influences our subsequent thought.” In later work, he discussed the difficulty in defining respiratory diseases with reference to philosophic thinking on definitions. In the 1940s, Popper had drawn attention to two fundamentally different philosophic types of definition used in science: essentialist and nominalist. Regarding essentialist definitions he wrote:
I use the name methodological essentialism to characterise the view, held by Plato and many of his followers, that it is the task of pure knowledge or science to discover and to describe the true nature of things, i.e. their hidden reality or essence. …. And a description of the essence of a thing they all called a definition.
Essentialist definitions imply the a priori existence of something that can be identified and characterized by the identification of a shared and unique essence. Essentialist thinking underpins the idea that diseases are causes of illness and that diagnosis simply consists of identifying the disease that is causing the illness. In contrast, nominalists believe that diseases have no existence apart from that of patients with them. Nominalists see definitions as merely introducing a name, the defined term, as an abbreviation or convenient way of briefly stating the end point of a diagnostic process, without introducing unjustified assumptions about pathophysiology or causation.
Popper criticized the essentialist view of knowledge because it implied finality and certainty. He believed we can never be sure to have reached the truth and that in the empirical sciences there are no proofs that establish once and for all the truth, or the complete characterization of a disease. To him, all definitions used in medicine were nominalist. In reality, I believe we have both. For example, streptococcal pneumonia is an essentialist definition, as the essence is a histopathological finding caused by a defined external agent, whereas asthma and COPD have nominalist definitions. Scadding also believed that most respiratory diagnoses were nominalist and, for example, wrote the following:
The physician should know that in applying the diagnostic term ‘asthma’ he is claiming no more than that the wheezy breathlessness is due to wide variations in resistance to expiratory air-flow in the lungs. He may be able to show that the patient’s bronchi are abnormally reactive to a variety of stimuli, but can only speculate about the causes of this abnormal reactivity. He will try to identify factors causing increases in resistance. In many instances, he will fail.
Asthma chronic obstructive pulmonary disease overlap
What then should we make of the term asthma COPD overlap (ACO)? From an essentialist’s perspective, are there 3 distinct diseases, asthma, COPD, and ACO, 2 diseases that may occur in the same patient, or all subtypes of a single disease? If ACO is simply the coincident occurrence of 2 diseases, does the coexistence of the 2 conditions modify the prognosis or management sufficiently to justify a specific label or lead to distinct treatment recommendations? From a nominalist perspective, are they simply convenient labels to describe groups of patients who have certain characteristics? The GINA and GOLD definitions of asthma and COPD appear to be essentialist, but are both flawed, they are simply descriptions of the diseases and neither identifies the essence or defining characteristics that separate them from each other and other diseases. This would not matter a great deal if there was consensus among doctors when making a differential diagnosis, and this is at the root of the difficulty in addressing ACO.
As they stand, neither of the definitions of asthma and COPD is mutually exclusive and the differential diagnosis is sometimes a challenge for clinicians. Nevertheless, we persevere in trying to differentiate asthma and COPD for the very reason splitting evolved: to guide the patient’s treatment, help set expectations about prognosis, and facilitate communication between doctors. However, for many years, clinicians have recognized that some patients share traits of the two conditions, and this was exemplified in the Venn diagram included in the 1995 American Thoracic Society COPD guidelines.
Consider a patient in his or her late 60s who had allergic asthma when younger and became tight chested and developed airflow obstruction when exposed to cats, who has smoked all his or her adult life, and now has daily breathlessness on exertion, fixed airflow obstruction on spirometry, and emphysema on computed tomography (CT), but who still bronchoconstricts on exposure to cats. Because of the history, it is clear that the patient has both asthma and COPD concurrently.
It is more difficult to make a firm diagnosis when assessing a patient with no prior history of respiratory symptoms who presents in his or her 50s with variable breathlessness, who has a significant bronchodilator response on spirometry but the post-bronchodilator forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) ratio remains abnormal and has mild emphysema on CT. This patient could have asthma or COPD or ACO.
The difficulty in separating asthma and COPD arises because there are no accepted unique defining characteristics, yet in most cases a diagnosis of one or the other can be made. A major cause of the confusion that reigns is the misinterpretation of the diagnostic labels as essentialist and to unthinkingly apply criteria as disease defining. For example, bronchodilator responsiveness is seen by many as the defining physiologic characteristic of asthma, yet it can be demonstrated in many patients with COPD, and markers of type 2 inflammation, thought to be common in asthma, are also found in people with COPD. Similarly, fixed airflow obstruction is seen by many as the defining physiologic characteristic of COPD yet it can be found in many patients with asthma, particularly those with longstanding disease. The reluctance to make a specific diagnosis also occurs in some cases because of laziness based on the perception that the treatment and prognosis are the same.
There is also a lack of clear and useful guidance from “experts” as to how the distinction can be made in clinical practice. A recent systematic review on the overlap syndrome provides an example of the tautology of the use of terms and the lack of precision in making the correct diagnosis. The investigators defined the overlap phenotype as any patients with COPD (defined as fixed airflow obstruction on post-bronchodilator spirometry) with at least 1 or more of the following findings :
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Physician-diagnosed asthma or self-reported physician diagnosis of asthma.
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Reversibility testing (≥12% and at least 200 mL change in FEV 1 from baseline).
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Peak expiratory flow (PEF) variability (≥20% change in PEF).
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Airway hyperresponsiveness to methacholine or histamine.
In reality, some of these patients may have fixed airflow obstruction as part of their asthma, in which case the presence of 1 or more of the 4 findings would simply confirm the diagnosis of asthma, or they may have had COPD but none of the physiologic findings prove they also have asthma. In particular, a previous physician diagnosis of asthma may simply reflect initial diagnostic uncertainty before a conclusive diagnosis of COPD was made, and up to 50% of patients with COPD have bronchodilator reversibility greater than 200 mL and greater than 12%. , Similarly problems arise in the Spanish effort to develop criteria for the diagnosis of asthma overlap in COPD without defining COPD itself.
The introduction of the term asthma COPD overlap syndrome (ACOS) in 2014 did not help with this confusion, particularly as it has essentialist pretensions implying the existence of a distinct entity not just an overlap of 2 common conditions. The dropping of the word syndrome helped undo some of the problems that had developed, but without an operational definition, the term ACO has continued to be problematic, particularly if viewed from an essentialist rather than nominalist perspective.
Much effort has been put into “defining” ACO. Many workshops have been convened, and a variety of definitions proposed by these groups as well as individual investigators ( Table 1 ). In many cases, it is not possible to determine how the separate diagnoses of asthma and COPD were made or whether they are describing patients with asthma with fixed airflow obstruction or patients with COPD with a significant bronchodilator response. The GINA/GOLD document stated that one of the objectives of publishing the report was to “stimulate further study of the character and treatments for this common clinical problem” ; however, without an agreed definition, confusion rather than clarity has emerged.
