Research Article: ACO: Time to move from the description of different phenotypes to the treatable traits

Date Published: January 24, 2019

Publisher: Public Library of Science

Author(s): Nuria Toledo-Pons, Job F. M. van Boven, Miguel Román-Rodríguez, Noemí Pérez, Jose Luis Valera Felices, Joan B. Soriano, Borja G. Cosío, Konstantinos Kostikas.


Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL. The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.

We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015. Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.

We included 603 patients. Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%. Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources. Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources. Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.

ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together. Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended.

Partial Text

The GOLD-GINA consensus recommends combining three characteristics of asthma and three of chronic obstructive pulmonary disease (COPD) to make a diagnosis of overlap between asthma and COPD (ACO). The assumption that patients with ACO are all similar, irrespectively if the diagnosis comes from an asthma patient that smokes or from a COPD patient with clinical characteristics of asthma, has led to consider ACO as an homogeneous condition. However, recent studies have shown that ACO is actually an heterogeneous condition with clinical and inflammatory differences between smoking asthmatics and eosinophilic COPD [1, 2].

We included 603 patients who fulfilled all criteria, of which 165 were considered ACO according to the aforementioned diagnostic algorithm. ACO patients were younger, relatively more often female, showed less cardiovascular comorbidities and more osteoporosis and rhinitis, with more FEV1 reversibility, reduced rates of health resources use and more frequently treated with ICS and short-acting beta agonists (SABA) compared to COPD without ACO criteria (Table 1).

In this study, we have validated a new proposed algorithm to differentiate a specific phenotype of COPD in a population cohort. Using the aforementioned algorithm we identified that 27.4% of all COPD patients fulfilled the definition of ACO, and these patients were more frequently treated with ICS and showed a better prognosis in terms of healthcare utilization (emergency visits and all-cause hospitalizations). Moreover, we have addressed the heterogeneity of this group of patients classified under the umbrella of ACO, and differentiate eosinophilic COPD from those patients with COPD with a previous diagnosis of asthma as different entities with different clinical characteristics and prognosis in terms of hospital admissions and visits to emergency department. This findings remark a change of perspective when approaching this topic. Maybe, is time to abandon the search of phenotypes and to start finding treatable traits and specific biomarkers, to guide clinicians to customize the treatment of the patients.

ACO is a prevalent and heterogeneous disorder that generates confusion because includes patients with different pathophysiology and prognosis, namely smoking asthmatics and eosinophilic COPD. This important heterogeneity leads us to think that probably using the term ACO to define all these patients can be confusing. From the practical point of view, the eosinophilic COPD (COPD-Eo group) identifies those COPD patients that would benefit the most from ICS. Moreover, the role of HBR is negligible and should not be used to identify this condition. We propose to abandon this term, and modify treatment of COPD by using a treatable trait such as the Th2 signature, using the blood eosinophil count as a marker. We should investigate now what is the best eosinophil cut-off point to predict the effective response to ICS.




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