Asthma-COPD Overlap: What Is Known and What Is Not

37Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a complicated issue without the benefit of randomized, controlled research including patients who truly have an overlap. At a session during the ACAAI annual meeting, Nicola A. Hanania, MD, MS, FCCP, FERS, of the Baylor College of Medicine in Houston, reviewed the current knowledge base, clarified the condition, and presented knowledge gaps for future exploration.

Clinically, ACO can be defined as one of two phenotypes, Hanania said: (a) asthma with partially reversible airflow obstruction with or without emphysema or reduced DLCO and (b) COPD accompanied by reversible or partially reversible airflow obstruction with or without environmental allergies. An article in New England Journal of Medicine in 2015 categorized ACO into four groups of patients : those with “easy” asthma, those with “easy” COPD, those who have ACO stemming from asthma, and those having ACO stemming from COPD. Factors the authors considered for classification included age, presence of atopy, smoking behavior, presence of dyspnea or wheezing, reversible airway obstruction, and bronchial hyper-responsiveness.

“There is more to this story,” Hanania said, explaining that other COPD phenotypes (eosinophilic COPD, reversible COPD, and non-smoker COPD) and other asthma phenotypes (late-onset asthma, neutrophilic asthma, chronic remodeled asthma, and smoker with asthma) can complicate research and treatment.

Hanania said that there are several confirmed “knowns” about ACO, despite complexities of overlap. Its prevalence increases with age. The overlap is associated with significant impairment of health status, lower quality of life, more healthcare utilization, and higher costs. Patients with ACO experience more frequent exacerbations, comorbidities, wheezing, asthma attacks, anti-asthmatic drugs, allergic rhinitis, sinusitis, cough or phlegm, and hospitalizations than patients with asthma or COPD alone. Research has suggested that patients with ACO have increased eosinophils, neutrophils, or both in sputum.

In a recent collaboration, the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) wrote: “ACO is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. ACO is therefore identified in clinical practice by the features it shares with both asthma and COPD.” The organizations noted that this is not a definition, but rather a description of ACO for clinical use, as ACO includes several different clinical phenotypes and there are likely to be several different underlying mechanisms. They even went so far as to remove the S from the formerly used abbreviation ACOS, to avoid the impression that it is a single disease, Hanania noted. Those guidelines are available at https://goldcopd.org/asthma-copd-asthma-copd-overlap-syndrome/.

In CHEST in 2016, a Spanish group proposed diagnostic criteria for ACO, stratifying major and minor criteria (Cosio, et al.). ACO diagnosis results from the presence of one or more major criteria (history of asthma and marked reversibility with bronchodilators) or two minor criteria, as well as three or more of the usual features of COPD. However, the criteria are controversial, and it focuses on patients with COPD then asthma, not addressing the reverse. Another similar set of criteria was developed by a roundtable group (Sin et al., 2016). The variability “shows just how confusing it can be,” Hanania added.

Hanania called for a consensus definition, as well as research to elucidate the clinical context of ACO and the scope of the problem according to population data. He said that large longitudinal studies should be designed to discover the molecular mechanisms of ACO and its related phenotypes. Further research is needed to help clarify the clinical and natural history, as well as the role of corticosteroids in ACO.