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Interleukin-13 (IL-13) is expressed by airway structural cells in paalready been licensed and are suggested as first line therapy for severe tients with asthma and has an active role in airway hyperresponsiveness, inflammation, mucous metaplasia and airway remodeling [1] while it seems to be an important biomarker in severe asthma [2]. Thus, blockade of IL-13 should plausibly alter airway inflammation and hyperresponsiveness, making this cytokine a possible target for the development of novel therapies. Recent studies using anti-IL-13 antibodies, lebrikizumab [3] and tralokinumab [4], failed to provide consistent improvement in patientswith severe T2 high asthma, despite some initial promising results in patients with evidence of T2 high inflammation, as expressed by increased serum periostin [5]. Since the promising Phase II results for lebrikizumab [5] and tralokinumab [4] were not confirmed in Phase III trials, a better understanding of the responder population for anti-IL-13 blockade is necessary. In this issue, the study of Burgess et al. [6] provide data of the administration of a humanized, high-affinity, neutralizing, anti-human-IL-13 antibody fragment, administered through the inhaled route, giving an alternative to the systemic administration of monoclonal antibodies for the therapy of asthma andmimicking the usual practice of drug delivery in asthmatic patients. This study has a proof-of-concept element, as the observed FeNO suppression shows an anti-inflammatory effect of this agent, while the numerical increase of FEV1 (with a mean difference of 150–200 mL versus placebo) shows an important treatment efficacy, both these improvements need to be confirmed in later phase trials. The difference in efficacy of this inhaled anti IL-13 antibody compared to injectable anti-IL-13 medicines is something that needs to be considered, as this potential option moves along its development pathway. The fact that in the study of Burgess et al. [6] there is a lack of a doseresponse relationship for both FeNO and FEV1 is a potential issue that needs to be considered in future trials of this agent. Approximately 10% of asthmatic patients are suffering from severe asthma that requires treatment with high doses of inhaled corticosteroids and bronchodilators in order to achieve disease control, or remain uncontrolled despite this treatment [7]. Historically, patients with severe uncontrolled asthmaweremainly treated with oral corticosteroids which are known to be associated with severe adverse events. Therefore, in the latest years there is an effort to replace oral corticosteroid therapywith biological agents, mainlymonoclonal antibodies, targeting specific inflammatory pathways. Some of these agents have been

Revisiting IL-13 blockade: can we reach the wonderland the inhaled way?