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The alarmin cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)‐33, and IL‐25 are epithelial cell‐derived mediators that contribute to the pathobiology and pathophysiology of asthma. Released from airway epithelial cells exposed to environmental triggers, the alarmins drive airway inflammation through the release of predominantly T2 cytokines from multiple effector cells. The upstream positioning of the alarmins is an attractive pharmacological target to block multiple T2 pathways important in asthma. Blocking the function of TSLP inhibits allergen‐induced responses including bronchoconstriction, airway hyperresponsiveness, and inflammation, and subsequent clinical trials of an anti‐TSLP monoclonal antibody, tezepelumab, in asthma patients demonstrated improvements in lung function, airway responsiveness, inflammation, and importantly, a reduction in the rate of exacerbations. Notably, these improvements were observed in patients with T2‐high and with T2‐low asthma. Clinical trials blocking IL‐33 and its receptor ST2 have also shown improvements in lung function and exacerbation rates; however, the impact of blocking the IL‐33/ST2 axis in T2‐high versus T2‐low asthma is unclear. To date, there is no evidence that IL‐25 blockade is beneficial in asthma. Despite the considerable overlap in the cellular functions of IL‐25, IL‐33, and TSLP, they appear to have distinct roles in the immunopathology of asthma. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroids (ICS) are a mainstay of treatment in eosinophilic asthma. Many studies have explored the dose‐response effect of different formulations of ICS through direct or indirect bronchoprovocation testing. Such studies are important for investigating efficacy and identifying the relative potency between formulations. However, lack of consistency in methods and designs has hindered the comparability of study findings. This review discusses current knowledge of the dose‐response, or lack thereof, of different formulations of ICS through direct and indirect bronchoprovocation testing. The strengths and weaknesses of past studies inform recommendations for future methodological considerations in this field, such as utilizing a randomized double‐blind crossover design, enrolling participants likely to respond to ICS therapy, and carefully selecting treatment durations and washout periods to assess incremental improvement in airway hyperresponsiveness while reducing the likelihood of a carryover effect. [ABSTRACT FROM AUTHOR]