Treatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.).

Our findings suggest that ILC2s can promote the persistence of airway eosinophilia in patients with severe asthma through uncontrolled localized production of the type 2 cytokines IL-5 and IL-13, despite high-dose oral corticosteroid therapy.

Background Many subjects with asthma exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding interleukin-5 receptor alpha, inducing apoptosis via antibody-dependent cell-mediated cytotoxicity. Objectives To evaluate the safety of benralizumab in adults with eosinophilic asthma, and its effects on eosinophil counts in airway mucosal/submucosal biopsies, sputum, bone marrow, and peripheral blood. Methods In this multicenter, double-blind, placebo-controlled Phase I study, 13 subjects were randomized to single intravenous placebo or benralizumab 1 mg/kg (day 0) [Cohort 1], and 14 subjects were randomized to three monthly subcutaneous doses of placebo or benralizumab 100 or 200 mg (days 0, 28, and 56) [Cohort 2]. Cohorts 1 and 2 were consecutive. Results The incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. Cohort 1: intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophils (day 28; placebo: +19.6%; P = .28), 18.7% (day 21) in sputum and 100% (day 28) in blood. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n=4). Cohort 2: subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophils (day 84; placebo −46.7%; P = .06), 89.9% (day 28) in sputum and 100% (day 84) in blood. Conclusion Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum, and suppressed eosinophils in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess clinical benefit in asthma.

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC) causing a 20% fall in forced expiratory volume in 1 s (FEV)), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV (provocative dose (PD)). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test.