Persistent airway obstruction in severe eosinophilic asthma: targeting interleukin-5 and eosinophils

A large proportion of patients (40-60%) with severe asthma present with persistent airway obstruction (PAO). Patients with severe eosinophilic asthma (SEA) and PAO appear to be an underrepresented group in clinical guidance, despite being associated with considerable healthcare and economic burden. High levels of eosinophils drive airway inflammation, obstruction and hyperresponsiveness, which are key characteristics of SEA and can increase the risk of PAO and subsequent irreversible worsening of lung function. Available clinical and real-world data must examine the effectiveness of biologic treatment targeting SEA in PAO to identify any data gaps that might help further define such patients and optimise their management. However, clinical trials of SEA frequently exclude the enrolment of patients with PAO. Eosinophils are activated and recruited to airways in response to different cytokines, particularly interleukin-5 (IL-5), produced via a complex molecular and cellular cascade. A few studies evaluating the effectiveness of benralizumab and mepolizumab were able to identify cohorts of patients with SEA and PAO who had a significant response to these IL-5/Rα-targeted biologics. PAO in patients with SEA represents a distinct clinical entity, one which could be referred to as "persistent eosinophilic airway obstruction". Patients with persistent eosinophilic airway obstruction are likely to be responsive to targeted biologic treatment, although additional clinical studies and real-world data are needed to further assess treatment efficacy and safety in this population and provide guidance to clinical practice.