Experts Debate Terminology and Treatment of Asthma-COPD Overlap

Asthma and chronic obstructive pulmonary disease (COPD) are known to coexist in some patients, and the disorders can share some genetic and environmental mechanisms. Still, the term asthma-COPD overlap (ACO) is controversial and so is the optimal approach to treatment, with experts at the CHEST Annual Meeting 2023 coming together for a friendly debate over the merits of each argument.

Health and medicine - Young girl using blue asthma inhaler to prevent an asthma attack | Image credit: DALU11 - stock.adobe.com

Nicola Hanania, MD, MS, of Baylor College of Medicine in Houston, Texas, first took the podium to declare that ACO is a real entity with important treatment implications. He joked that he could prove it exists simply by citing the Wikipedia article on ACO or showing ChatGPT’s affirmative answer to the question, but more convincing evidence comes in the form of the known genetic and environmental components such as elevated eosinophils and inflammation (type 2 in asthma and type 1 in COPD) that are often prevalent in the area of overlap. Also, ACO is associated with greater symptom burden, frequency of exacerbations, and comorbidities.

While the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) have recently shied away from the term ACO due to the lack of a universal definition, Hanania noted that the GOLD 2023 guidelines now endorse the existence of the COPD-A, or COPD and asthma, phenotype. In fact, he said, there are many phenotypes of ACO, meaning it does exist and have an impact on outcomes, but not with a single face.

Hanania argued that ACO calls for a distinct treatment approach of controlling exposures and triggers, assessing inflammation biomarkers, and treating comorbidities. These interventions can include nonpharmacological components (eg, pulmonary rehabilitation, smoking cessation) as well as biologic medications that target airway inflammation, although the latter have limited evidence because patients with both asthma and COPD are often excluded from clinical trials.

“My take-home message is that I definitely believe ACO is a distinct entity compared to asthma and COPD. It is often challenging to diagnose, but it’s important for pulmonologists to understand and agree that this entity does exist…. It has treatment implications, and there may be some shared physiologic and pathologic features,” Hanania concluded. He emphasized the need for large longitudinal studies to help researchers understand the history, biomarkers, and molecular mechanisms of ACO, as well as for more enrollment of these patients in clinical trials.

Taking the contrarian view was his former mentee, Garbo Mak, MD, of University of Washington Medical Center in Seattle. She argued that as tempting as it may be to lump the 2 diseases together because of their shared features, they are distinct and we should retire the term ACO. They have different features, biometrics, risk factors, and phenotypes, she said, and distinguishing them is especially important given the recent advances in personalized medicine that hinge on pathophysiological markers like eosinophil levels. Asthma and COPD can coexist in some individuals, but after much research, the scientific community still can’t agree on whether they are separate circles or overlapping or instead on either end of a spectrum, she noted.

Furthermore, a precise diagnosis is important to guide a patient’s treatment, set expectations about their prognosis, and standardize communication across care providers, Mak emphasized, so the overly simplified diagnosis of ACO makes it more challenging to determine the most effective therapy and can also contribute to overprescription of inhaled corticosteroids.

“[Asthma and COPD] may coexist in an individual and there may be some shared common features as well; however, we should call a condition by what it is: asthma or COPD, with specific features and specific traits, and we should all be using the guidelines that we have for both of these conditions,” she summed up.

Whether or not a clinician buys into the term ACO, there remains the challenge of not just diagnosing but treating a patient with airway disease, noted Peter Gibson, MBBS, DMed, of John Hunter Hospital in New South Wales, Australia. That’s where the treatable traits model comes in, boosted by trial results showing a dramatic increase in the effectiveness of mepolizumab when focusing only on the subgroup of patients with asthma who show the trait of eosinophilic inflammation.

This model of treatment emphasizes addressing the pulmonary, extrapulmonary, and behavioral/risk factor traits that are clinically relevant, actionable, and treatable, Gibson explained, showing supporting evidence for this approach. For instance, a 2022 review by Sarwar and colleagues identified an association between treatable trait management of obstructive airway diseases and improvements in quality of life and reduced hospitalizations.¹ On the individual trial level, work by McDonald et al published in 2020 showed that a multidisciplinary intervention in severe asthma using a case manager resulted in 55.6% in the treatable traits group showing a significant improvement in quality of life compared with 22% in the arm receiving usual care with pharmacotherapy.²

In his own practice, obstruction, emphysema, and eosinophilic bronchitis are among the top-priority traits as determined by prevalence, treatability, impact, and importance to both the patient and clinician. “Treatable traits is a model of care…that’s more effective than standard care and is now the standard of care for severe asthma in GINA/GOLD,” Gibson noted, but also important is that it recognizes the advantages of personalized medicine and the individual heterogeneity of each patient.

To emphasize that point, he presented a poem that could be read top to bottom as the voice of the naysayers or bottom to top as a call to action:

It’s too hard

So don’t tell us that

Treatable traits is a new paradigm

Because the reality is

That regulators won’t support it

And don’t trust anyone who says

We need to demand better outcomes

Because I am living my life with breathlessness

Arjun Mohan, MBBS, of the University of Michigan in Ann Arbor, could be considered such a naysayer, he acknowledged, bemoaning his “awful task” of presenting an opposing view after Gibson had impressed the audience with that poem. In fact, Mohan said, he doesn’t necessarily disagree with the treatable traits approach, but he does feel that its shortcomings mean it’s not ready for prime time quite yet.

The pulmonology community wants treatable traits to be the answer because the current “one-size-fits-all” stepped approach to managing asthma with escalating treatments of corticosteroids, β₂ agonists, and biologics can sometimes fall short in producing a satisfactory response for some patients, Mohan said, but the current stepwise approach already addresses the reasons for uncontrolled asthma, so the treatable traits approach fits into that paradigm but doesn’t replace it.

“The evidence just doesn’t match the enthusiasm,” Mohan argued, noting that positive trials on treatable traits have had small sample sizes and took place before the biologic drug era. Not only do we need better quality of evidence before large-scale uptake, he said, but there also needs to be a clear-eyed assessment of the practicality of such a costly intervention. The treatable traits approach is so treatment intensive that he couldn’t make the case for employing a case manager in his own practice.

He concluded by calling treatable traits “novel and exciting” but not yet viable as an alternative to the stepped approach.

References

1. Sarwar MR, McDonald VM, Abramson MJ, McLoughlin RF, Geethadevi GM, George J. Effectiveness of interventions targeting treatable traits for the management of obstructive airway diseases: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2022;10(9):2333-2345.e21. doi:10.1016/j.jaip.2022.05.012

2. McDonald VM, Clark VL, Cordova-Rivera L, Wark PAB, Baines KJ, Gibson PG. Targeting treatable traits in severe asthma: a randomised controlled trial. Eur Respir J. 2020;55(3):1901509. doi:10.1183/13993003.01509-2019