Therapeutic approaches to asthma-COPD overlap syndromes

While asthma and chronic obstructive pulmonary disease (COPD) are distinct clinical entities, they are often treated with the same medications. There are many patients who present with features of both diseases, a condition called asthma-COPD overlap syndrome (ACOS). ACOS is currently poorly defined or understood, and it encompasses several phenotypes that require specific therapeutic approaches. For example, there are patients with COPD who have eosinophilic inflammation that may respond to inhaled corticosteroids (ICS), or severely asthmatic patients who smoke cigarettes and have COPD inflammation. Barnes summarizes three ACOS phenotypes and addresses the therapies currently available and those in development (J Allergy Clin Immunol 2015; 136(3): 531-545).

 The range of phenotypes is a challenge in treating ACOS patients, and the selection of appropriate therapy requires biomarkers that are predictive of a patient’s response to them. These include blood biomarkers such as eosinophil counts and fractional exhaled nitric oxide (F_ENO). In specialized centers, a patient’s sputum cell count can be useful to determine the cause of inflammation. Whether a patient has asthma, COPD, or both, a predominance of eosinophilic inflammation can be treated with bronchodilators, ICS, or more specific anti-eosinophilic therapies, many of which are in development. Macrolides offer a current therapy, with CXCR2 antagonists and antibodies to block interleukins and TNF under current study, for those with increased neutrophilic inflammation. Patients with largely fixed airway obstruction with little inflammation, the paucigranulocytic phenotype, may benefit from long-acting inhaled bronchodilators including LABA and LAMA, and triple inhalers containing an ICS, LABA, and LAMA are in clinical development.

Corticosteroid resistance is common in ACOS patients, and the molecular mechanisms that contribute to it may differ among ACOS phenotypes. Promising work with patients with severe asthma, smoking asthma, and COPD suggests, however, therapies that can restore responsiveness. These include existing, well-tolerated drugs such as theophylline, nortriptyline, and macrolides, or novel therapies such as inhaled PI3Kσ or p38 MAPK inhibitors.

There is little information about the long-term stability of inflammatory phenotypes of airway disease and some evidence the patterns of inflammation described above can vary within the same patient from time to time. Much remains to be learned. At the same time, the recognition that patients with ACOS present a range of phenotypes and require the development of specific treatments is an important one.