Eosinophils in asthma phenotypes: perpetrators or guilty by association?

25 years after publication of a clinical trial in The Lancet on the anti-IL-5 antibody mepolizumab in individuals with allergic asthma, evidence has accumulated that the pathogenetic role of eosinophils is fundamentally different between asthma phenotypes. In the allergen-driven form of asthma, often starting in childhood or during adolescence (ie, early onset asthma), blood eosinophil counts are variable, mainly dependent on allergen exposure, and play only a minor role (as a so-called sidekick) in allergen-induced asthma symptoms. By contrast, eosinophils are persistently elevated and are crucial drivers of the disease in the intrinsic (eosinophilic) form of asthma, which typically starts in adulthood (ie, adult-onset asthma). These data suggest that eosinophilia should not be considered a treatable trait in people with chronic airway diseases, but only a complement to an accurate clinical diagnosis. This evidence has major implications for the diagnosis of asthma phenotypes and the treatment of asthma (eg, choice of the right biologic).