COMMENTARY

Asthma-COPD Overlap -- A New Clinical Entity

Nicholas Gross, MD, PhD

Disclosures

February 01, 2016

The Asthma-COPD Overlap Syndrome

Postma DS, Rabe KF
N Engl J Med. 2015;373:1241-1249

Dual-Airway Disorders

Asthma and chronic obstructive pulmonary disease (COPD) are both common and well-recognized airway disorders. They have usually been considered discrete entities with treatments that are described by different guidelines (GINA[1] and GOLD,[2] respectively), but with considerable overlap. Recently, however, allergists and pulmonologists, believing that the two disease categories overlap, have designated a new category of airways disorder known as asthma-COPD syndrome (ACOS). Postma and Rabe recently published a discussion of ACOS, including its principal features and suggestions for its management.

Asthma is an inflammatory disorder that typically develops in childhood and is often accompanied by allergies. Reversible airways obstruction is a typical feature of asthma that is amenable to corticosteroid administration. Inflammation in asthma is characterized by the presence of eosinophils and type 2 helper T lymphocytes. COPD is an inflammatory disorder that typically develops in cigarette smokers in middle age. Airways obstruction is a hallmark of COPD disorder, and the response to corticosteroids is modest or absent. COPD-related inflammation is predominantly the result of neutrophils and involves CD8 lymphocytes.

Both asthma and COPD have several phenotypes, which adds to the challenge of precise identification.[3] Reversibility of airways obstruction by bronchodilators has often been taken as a feature of asthma that is not present in COPD, but this has been shown to be incorrect because the two disorders cannot be differentiated by their response to bronchodilators. Postma and Rabe address the issue of whether and when it is appropriate to apply the diagnosis of ACOS to a patient with some features of both airway disorders. They also discuss what treatment should be administered to patients with ACOS. As they state, "the answer to these questions cannot be evidence-based because studies addressing ACOS as a disease entity have yet to be conducted."

Lung function declines over decades in both asthma and COPD. It is believed that this is largely owing to airway remodeling secondary to inflammation. Asthma that begins at an early age and is moderate to severe tends, in mid-life, to resemble COPD clinically, particularly if it has not been well controlled by corticosteroids. The presence of eosinophils in sputum, blood, and airway histology has long been recognized as a feature of asthma, yet eosinophils are commonly found in patients with COPD, particularly during acute exacerbations. Similarly, exhaled nitric oxide (FENO), once described as a marker for asthma, is often absent in asthma and can be present in the exhaled breath of smokers with COPD. The diagnosis of ACOS may be useful and, if better described by research, suggests appropriate treatments.

Viewpoint

The fact that no clinical trials have been conducted specifically for potential cases of ACOS is unfortunate and is mostly owing to the regulatory requirement that studies of drugs destined for US Food and Drug Administration approval have been required to exclude participants with ambiguous diagnoses. Presumably, trials of patients with potential ACOS will be performed soon. The authors of the present review believe that it is premature to recommend the designation of ACOS until more research can better characterize the patient with ACOS.

Several points can be made. Because both asthma and COPD are common disorders, some patients will have both conditions purely by chance. Furthermore, both asthma and COPD are heterogeneous disorders. Research is now busy describing the various phenotypes of asthma and COPD, particularly their molecular differences. Biomarkers of both asthma and COPD are needed and are being sought. When each clinical disorder has been sufficiently described, it is hoped that the identity and appropriate management of ACOS will emerge.

For the present, patients with ACOS should be treated empirically, and bronchospasm should be treated with bronchodilators. Patients with a history of episodes of dyspnea early in life should receive anti-inflammatory agents. Acute exacerbations should be managed with the medications currently being used to avoid acute exacerbations—primarily corticosteroids, a PDE4 inhibitor, and low-dose azithromycin. And, of course, cigarette smoking and exposure to irritant dusts and fumes should be eliminated.

Abstract

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