Journal Club - Asthma/Chronic Obstructive Pulmonary Disease Overlap: Fact or Fiction?

Abstract

With the development of biologics and the advent of “precision medicine” there is great interest in defining phenotypes and indeed endotypes that may identify responders based on clinical characteristics and/or underlying biological mechanisms. Recently, the Food and Drug Administration (FDA) voted against approval of mepolizumab for use in chronic obstructive pulmonary disease (COPD) stating that there was insufficient evidence to support mepolizumab as an add-on therapy for COPD patients guided by eosinophil levels. The FDA committee pointed to a lack of consensus over the definition and possible relevance of a so-called “eosinophilic COPD phenotype.” They pointed to the variability in blood eosinophils making it a challenge to use it as a potential marker to identify appropriate candidates for therapeutic trials. The committee recommended greater research with larger numbers and better patient characterization, including more female patients, (an important recommendation particularly given that women are known to have higher rates of airway hyper-responsiveness than men). Refining the characterization of the asthma/COPD overlap (ACO) group is key to moving forward in studying the use of biologics in this population. Recent studies have pointed to the benefits of long-acting muscarinic antagonists (LAMA) bronchodilators, originally only indicated for COPD, to be efficacious in some asthma patients (tiotropium has been approved by the FDA for asthma and COPD).1,2 Conversely, there have been several trials that have looked at the use of TH-2 pathway biologics typically reserved for asthma patients, (omalizumab,3 mepolizumab4-6and benralizumab7), in COPD patients thought to demonstrate potential overlap features (history of allergies, elevated immunoglobulin E [IgE], high eosinophil counts, asthma history, smoking history, partial reversibility). The various criteria used to define the ACO group have typically utilized some combination of these features. This is the backdrop for reviewing several recent papers that have focused on assessing the prevalence of ACO according to different ACO criteria and/or examined various potential clinical characteristics and/or biomarkers that may lead to greater discrimination in defining the potential endotypes within the ACO group. I present this particular collection of recent studies from this year mostly to demonstrate the highly variable, (and in some instances questionable), criteria for defining ACO patients. With more biologics for airway disease in the pipeline it is critical that we further refine our precision in defining the heterogeneity of the endotypes (or treatable traits) within the ACO group for better patient selection in clinical trials. Note: Abstracts are presented in their original, published format and have not been edited to match JCOPDF style.