Asthma vs COPD: What's the Difference?

Editor's Note: The recently published CHAIN study^[1] examined a cohort of patients with chronic obstructive pulmonary disease (COPD) to find out how many of these patients met newly proposed criteria for asthma-COPD overlap syndrome (ACOS) and whether the prognosis for ACOS differed from that for COPD. The CHAIN study and its implications were addressed by two Medscape pulmonary medicine experts, in a recent viewpoint by Dr Nicholas Gross and in the following commentary by Dr Aaron Holley.

Challenging Conventional Wisdom

In medical school, we are taught that there is a clear difference between asthma and COPD. Asthma is an allergic disease, and COPD is not. COPD is related to smoking, and asthma is not. Perhaps of greatest importance, at least to the medical student trying to decipher the difference, patients with asthma have reversible airway obstruction on spirometry, whereas those with COPD do not. Symptoms and spirometry values vary over time with asthma, whereas COPD is associated with a slow, steady decline.

Not so fast. The CHAIN study,^[1] recently published in Chest, found that 125 of 831 patients (15%) diagnosed with COPD have features of asthma. They labeled these patients as having ACOS. The author of the accompanying editorial prefers the term asthma-COPD overlap (ACO).^[2] Patients were labeled as having ACO if they had a previous diagnosis of asthma or a robust bronchodilator response (BDR), defined as >400 cc and 15%. They also met ACO criteria if they had two of the following: blood eosinophils >5%, immunoglobulin E >100 IU/mL, or two separate bronchodilator tests with a positive BDR (>200 cc and 12%).

Within the pulmonary community at least, the concept of an overlap syndrome isn't novel. Pulmonary researchers have been debating the taxonomy and relationship between asthma and COPD for years. The "Dutch hypothesis" argues in favor of a new taxonomy with less dichotomy between the two entities. It has been around since 1961 and was the focus of a symposium published in Chest in 2004.^[3,4] Several ACOS reviews have been published, and several organizations have suggested criteria for diagnosis.^[5]

It's not surprising to see confusion and debate here. Just look at the current definitions for the two diseases. The National Asthma Education and Prevention Program Expert Panel Report states that asthma "is a complex disorder characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation."^[6] The executive summary for the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) defines COPD as "a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response."^[7] Asthma and COPD are both inflammatory diseases characterized by airflow obstruction.

Blurring the Lines

Most of the guidelines separate asthma from COPD by demographics, clinical history, and spirometry results.^[5] Asthma symptoms begin by early adulthood, whereas disease onset for COPD is after age 40 years. Asthma has variability in symptoms and disease course, whereas COPD shows a stable, progressive clinical decline. Those with asthma have BDR, whereas those with COPD do not.

In reality, however, adult-onset asthma is a well-recognized phenomenon. Patients with COPD have variability in their symptoms and often experience repeated exacerbations.^[7] In the long term, patients with asthma are at risk for airway remodeling and fixed deficits on spirometry,^[8] and more than 50% of patients with COPD will have a significant BDR at least once over time.^[9] In short, age of onset, disease course, and BDR are helpful in distinguishing one disease from the other, but they are not definitive.

Eventually there may by cellular, histologic, or genetic profiles that help with disease identification, but we are not there yet. To test cellular and histologic airway characteristics, one group enrolled 50 patients, 25 with COPD and 25 with asthma by clinical criteria. There was no clinical evidence of ACO in either group. They performed endobronchial biopsy on each patient and had blinded pathologists identify the type of airway disease. Although there were some histologic and cellular differences, the pathologists ended up assigning too much weight to the presence of eosinophils and subsequently mislabeled the patients.^[10]

Genetic studies have not identified profiles that reliably allow differentiation. Smolonska and colleagues^[11] recently published the results of a genome-wide association study (GWAS) conducted on a Dutch cohort with either asthma or COPD. They concluded that there is no common genetic predisposition to both diseases; or if there is, it is being obscured by environmental factors.^[11] Admittedly, however, the clinical phenotypes were poorly defined; for example, those with a physician diagnosis of "asthma ever" were labeled as having asthma. Another GWAS study with a detailed definition of phenotypes identified three gene polymorphisms that were associated with ACO.^[12]

Treatments and Outcomes

Given that the treatments are so similar, does it really matter how patients with airway disease are labeled? We think it does. For patients with asthma, inhaled corticosteroids (ICSs) are essential components of treatment. According to the GOLD guidelines, ICSs are only useful in COPD for reducing acute exacerbations in specific subgroups (those with forced expiratory volume in 1 second [FEV₁] <50% or a history of repeated acute exacerbations).^[7] In fact, chronic ICS use may be associated with pneumonia and osteoporosis in the COPD population. Data from COPD patients with elevated sputum or blood eosinophil counts have shown improvements in FEV₁ and a reduction in exacerbations with ICS treatment,^[13,14,15] prompting some to suggest that ACO should be added to the 2013 GOLD treatment algorithm.^[16]

Long acting beta-agonists (LABAs) appear to be safe in COPD, but LABA use without ICS is associated with an increase in mortality for patients with asthma.^[17] That said, no one really knows whether LABA monotherapy is dangerous for patients with ACO. Because randomized controlled trials have tended to focus exclusively on asthma or COPD, patients with ACO have been excluded. Few prospective treatment data are available to guide therapy.

The jury is still out as to whether the clinical outcomes are worse in ACO. Studies to date indicate that ACO, compared with COPD alone, is associated with worse outcomes. The recent study by Cosio and colleagues^[1] found that patients with ACO actually did better. Summary data show variability.^[1,2,3,12]

In summary, ACO is increasingly recognized as a distinct clinical entity. Some 10%-20% of asthma patients will have features of COPD, and 10%-20% of COPD patients will have features of asthma.^[5] Although cellular, genetic, spirometric, and histologic testing cannot reliably identify a patient as having asthma, COPD, or ACO, clinical features are sufficient to alert the physician to the presence of overlap. ICSs are an important component of management, even if the primary diagnosis is COPD; and, for now, LABA monotherapy should probably be avoided. With the exception of the recent Chest study,^[1] most data indicate that ACO is associated with a worse prognosis. Future treatment trials should enroll patients with ACO to establish evidence-based, therapeutic guidelines.

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