The added value of targeting airway hyperresponsiveness by blocking TSLP in the management of severe asthma.

Summary: Airways hyperresponsiveness (AHR) is a pathognomonic event of asthma in which the airways are reactive to various bronchoconstrictor stimuli at 'doses' that normally have no bronchoconstrictor effect in non-asthmatics. AHR is an objective measure of clinical efficacy, and the introduction of biologics revived interest as a marker of disease and its pathophysiologic mechanism. This article aims to discuss the mechanisms of AHR, focusing on the role of epithelial damage and TSLP production, and promote its correct assessment for the evaluation of patients with severe asthma, to predict the risk of exacerbations and outcomes, and the eligibility for treatment with an anti-TSLP agent. AHR is a complex trait of asthma, induced by the concurrence of many pathophysiological factors and related to different clinical manifestations. Recent evidence demonstrates the important role of airway epithelial damage and TSLP production in many of these events. A therapeutic response based on AHR control could be considered as a condition of disease remission and seems a promising new goal for the management of patients with severe asthma.