Concept of ‘Asthma-COPD Overlap’ Still Alive Despite Detractors

HONOLULU — Pulmonologists couldn’t agree whether it was time to drop asthma/chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct airway disease, allowing no end to this controversy during a debate at the CHEST annual meeting hosted by the American College of Chest Physicians.

The discussion came as a response to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) moving away from the term “ACO” in its 2022 guideline update. Since then, GOLD has emphasized that asthma and COPD are different disorders and has preferred a new classification of COPD: COPD and asthma, or COPD-A.

At CHEST, Garbo Mak, MD, of UW Medicine-University of Washington Medical Center in Seattle, agreed with dropping “ACO,” stressing the distinct risk factors, environmental exposures, and pathophysiologies that argue against an overlap between asthma and COPD.

What’s more, she said, there is no standardized definition of ACO. Over the years, various attempts have been made to define ACO by the presence of specific asthma- or COPD-like variables. This leaves practitioners swimming around several proposed definitions.

“Recognizing ACO as a distinct entity is important but is often challenging,” argued Nicola Hanania, MD, MS, of Baylor College of Medicine in Houston, who took the position that ACO does exist separately from asthma and COPD. “Patients with ACO share some physiological and pathological features with patients with asthma and COPD but have other distinct features.”

Some believers of ACO say that asthma and COPD may represent opposite ends of a spectrum of airway disease, asthma being characterized by type 2 inflammation and co-occurring with allergies and a rise in eosinophils whereas COPD tends to feature airflow obstruction with type 1 inflammation, with an accompanying rise in neutrophils, after exposure to smoke or pollution.

Sitting somewhere in between, with affected individuals showing a mix of these characteristics, would be the ACO population — an understudied group often excluded from trials.

Hanania cited estimates that ACO has a 2% to 3% prevalence in the general population, up to a 31% prevalence in the asthma population, and a 25% prevalence in the COPD population.

He stressed that the clinical approach to ACO starts with initial inhaled corticosteroid (ICS) therapy, differentiating this from COPD’s long-acting beta-agonist (LABA)- or long-acting muscarinic antagonist (LAMA)-first strategy.

Reflecting on the overprescribing of corticosteroids in the COPD population, he cautioned against putting an ACO label on COPD patients that should really not be on ICS. “When you talk to primary care colleagues, it’s important to advocate that these two diseases may be separated,” he urged the audience.

Hanania said large longitudinal studies are needed to understand the clinical and natural history of ACO. The molecular mechanisms of ACO and its related phenotypes also remain to be clarified. Finally, he urged the development of novel biomarkers that may identify people with ACO, not asthma or COPD alone.

“It is very tempting to clump together asthma and COPD because they have common features. However, in the practice of medicine, we recognize that it’s very important to recognize separate entities [in reaching a] diagnosis,” Mak maintained.

She emphasized the value of a diagnosis to help guide a patient’s treatment, set expectations about prognosis, and facilitate communication between clinicians. She also highlighted the heterogeneous phenotypes within asthma and COPD (e.g., “eosinophilic COPD” or “neutrophilic asthma”).

“Asthma-COPD overlap is confusing as it implies the existence of a homogenous entity. Oversimplification makes it challenging to determine the most effective therapy for an individual patient,” Mak argued.

In any case, whether for COPD, ACO, or asthma, advanced therapy means ICS plus LABA plus LAMA. If symptoms are still uncontrolled, the patient may then go the route of treatable traits, Hanania said.

“Management of patients with ACO should be based on treatable traits, and strategies include both those of asthma to target airway inflammation and those of COPD to target airway obstruction and symptoms,” he explained. “Managing comorbidities and controlling exposures and triggers are extremely important.”

Mak was in agreement with treating specific traits in trying to help patients.

After all, regardless of whether one believes ACO is a separate entity or not, you still have to treat the patient, said Peter Gibson, MBBS, DMed, of University of Newcastle and John Hunter Hospital in Australia, during the session.

Gibson described the treatable traits model as one that identifies the relevant individual problems within each person to come up with an individualized treatment approach — an alternative to traditional stepped care for asthma.

As an example, he called type 2 inflammation a “supertrait” in asthma and COPD. This is supported by the recent BOREAS trial revealing that people with COPD with type 2 inflammation, indicated by eosinophil counts, are responders to the biologic dupilumab (Dupixent) in terms of fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms.

BOREAS finally showed that biologic therapy can work for COPD, in contrast to asthma, for which biologics have long been around.

During the session Q&A, Hanania’s position — that there is an advantage to having ACO as a clinical diagnosis — was challenged yet again.

“It seems to me that wet lungs that are related to heart failure and wet lung from ARDS [acute respiratory distress syndrome] go in different directions. You wouldn’t say there is a spectrum of pulmonary edema,” said William Calhoun, MD, of the University of Texas at Galveston, from the audience.

Hanania maintained that an ACO diagnosis does help patients by letting them know what condition they have, which has treatment implications and prognostic implications.

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