The Evolving Role of Biologics and TSLP Inhibition in Severe Asthma and Upper Airway Disease - Episode 3
Asthma Phenotypes and Endotypes: Defining the Terms
Phenotype, endotype, and treatable trait are used loosely and often interchangeably. The panel defines each term and tests where the boundaries between them break down.
"Asthma Phenotypes and Endotypes: Defining the Terms" takes up a vocabulary problem the field has never fully settled.
Dr. Chupp notes that recognizing the epithelium as part of the immune system has forced clinicians to confront the disease's complexity, and that this complexity now shows up clinically as multiple subtypes. He asks each panelist to define the terms. Dr. Wechsler calls a phenotype the outward manifestation of a disease process, something a patient can describe: smoker or non-smoker, frequent exacerbator or not. Endotype refers to the underlying mechanism, which a patient cannot describe but a biomarker can reveal. He gives examples. Eosinophils identify an IL-5-driven eosinophilic endotype. High nitric oxide points to an IL-13-mediated process. Broadly, he says, there are two endotypes: type 2, mediated by IL-4, IL-5, and IL-13 and identified by allergies, eosinophils, or nitric oxide, and non-type 2, defined by the absence of those biomarkers and often neutrophilic or polygranulocytic. Phenotypes are useful because they point to endotypes; chronic rhinosinusitis with nasal polyps is a phenotype that flags type 2 biology.
Dr. Chupp presses on the disagreement, noting some clinicians classify eosinophils differently. Dr. Ross sees crossover rather than a clean line, using the phenotype as a marker for the biology underneath. She describes allergic asthma patients with very high IgE and seasonal presentation, and notes eosinophilic patients respond exceptionally well to steroid courses despite frequent exacerbations.
Dr. Hanania offers an iceberg analogy- above the water sits the clinical phenotype: early or late onset, allergic, smoke-related, obesity-related, exacerbation-prone. Below sits the endotype. He adds a third term, treatable traits, and argues it appeals to clinicians precisely because the available biomarkers remain limited and imperfect.
In "Treatable Traits in Asthma: Targeting Comorbidities Beyond the Lung," the panel will press Dr. Hanania for a concrete example of what a treatable trait actually is.
