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A letter to the editor is presented in response to the article "At Least Three FEV1 Blows Are Required at Each Time Point During the Assessment of Bronchial Hyperresponsiveness" published in the previous issue.

Background: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma., Methods: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed., Results: 46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively., Conclusion: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction., Competing Interests: Conflict of interest: G.M. Gauvreau reports support for the present manuscript from AstraZeneca, grants from AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, and receipt of equipment, materials, drugs, medical writing, gifts or other services from AstraZeneca. R. Sehmi reports support for the present study from AstraZeneca. R. Leigh reports support for the present study from AstraZeneca, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca. D.W. Cockcroft reports support for the present manuscript from AstraZeneca, and grants from SHRF, Biohaven, AllerGen, University of Saskatchewan College of Medicine and CIHR. I. Mayers reports grants from AstraZeneca Canada and Boehringer Ingelheim, consultancy fees from Sanofi Canada and AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, and payment for expert testimony from Alberta Justice. L-P. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron, royalties or licences from UptoDate and Taylor & Francis, consultancy fees from AstraZeneca, Novartis, GlaxoSmithKline, Merck and Sanofi-Regeneron, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Novartis, Merck and Sanofi, and leadership role as Past-Chair of the Global Initiative for Asthma (GINA) Board of Directors, Past President of the Global Asthma Organisation (Interasma), Past Member of the Canadian Thoracic Society Respiratory Guidelines Committee and Past Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. T. Ho reports grants from Fisher & Paykel, consultancy fees from Valeo and AstraZeneca, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and GlaxoSmithKline. I. Satia reports grants from Merck, GlaxoSmithKline and Bellus, consultancy fees from Merck, Genentech, Respiplus and GlaxoSmithKline/Bellus, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Merck, GlaxoSmithKline, AstraZeneca and Sanofi. P.D. Mitchell reports grants from Teva, consultancy fees from Pfizer and GlaxoSmithKline, and support for attending meetings from AstraZeneca. I.P. Magee reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline. C. Bergeron reports support for the present study from AstraZeneca, grants from AstraZeneca, Sanofi and Regeneron, consultancy fees from ValeoPharma, Sanofi, AstraZeneca and GlaxoSmithKline, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, ValeoPharma, Sanofi and Grifols. M. Bhutani reports grants from CIHR, GlaxoSmithKline, AstraZeneca and Sanofi, consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Sanofi, Covis and Valeo, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Sanofi and Covis. V. Werkström was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. T. Durżyński was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. K. Shoemaker was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. R.K. Katial was an employee of AstraZeneca at the time of the study and reports personal fees from AstraZeneca. M. Jison was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. C. McCrae was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. P.M. O'Byrne reports support for the present study from AstraZeneca, grants from AstraZeneca, Merck and Biohaven, consultancy fees from AstraZeneca, GlaxoSmithKline, Sage, Teva and Affibody, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi, GlaxoSmithKline and Covis. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: Omalizumab is an established anti-IgE therapy for the treatment of allergic diseases that prevents IgE from binding to its receptor. QGE031 is an investigational anti-IgE antibody that binds IgE with higher affinity than omalizumab., Objective: This study compared the effects of QGE031 with those of omalizumab on clinical efficacy, IgE levels, and FcεRI expression in a clinical model of allergic asthma., Methods: Thirty-seven patients with mild allergic asthma were randomized to subcutaneous omalizumab, placebo, or QGE031 at 24, 72, or 240 mg every 2 weeks for 10 weeks in a double-blind, parallel-group multicenter study. Inhaled allergen challenges and skin tests were conducted before dosing and at weeks 6, 12, and 18, and blood was collected until 24 weeks after the first dose., Results: QGE031 elicited a concentration- and time-dependent change in the provocative concentration of allergen causing a 15% decrease in FEV 1 (allergen PC 15 ) that was maximal and approximately 3-fold greater than that of omalizumab (P = .10) and 16-fold greater than that of placebo (P = .0001) at week 12 in the 240-mg cohort. Skin responses reached 85% suppression at week 12 in the 240-mg cohort and were maximal at week 18. The top doses of QGE031 consistently suppressed skin test responses among subjects but had a variable effect on allergen PC 15 (2-fold to 500-fold change). QGE031 was well tolerated., Conclusion: QGE031 has greater efficacy than omalizumab on inhaled and skin allergen responses in patients with mild allergic asthma. These data support the clinical development of QGE031 as a treatment of asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The duration of bronchoprotection against methacholine-induced bronchoconstriction by long-acting muscarinic antagonists (LAMA's) in asthmatics and whether these drugs differ in their pharmacodynamic properties remain to be determined. The most recent published guidelines for methacholine challenge testing (MCT) suggest that LAMA's should be abstained from for 48 h prior to testing, perhaps one week in the case of tiotropium. The objectives were to determine and compare the duration of protection of a single dose of two different LAMA's, tiotropium and glycopyrronium, against methacholine-induced bronchoconstriction. Thirteen mild-to-moderate asthmatics [with a forced expiratory volume in 1 s (FEV1) > 65% of predicted and a baseline methacholine provocation concentration causing a 20% reduction in FEV1 (PC20) ≤ 8 mg/mL] completed this double-blind, double-dummy, crossover study. Methacholine challenges were performed before treatment (5 μg tiotropium or 50 μg glycopyrronium) and at 1, 24, 48, 72, 96 and 168 h post-treatment. The minimum duration between treatment administration was 11 days. Both drugs provided significant bronchoprotection, each producing greater than a 16-fold increase in mean PC20 by 1 h. Tiotropium still provided statistically significant protection at 7 days (p = 0.0282) while glycopyrronium provided bronchoprotection until day 7 (p = 0.0590). Tiotropium provided statistically superior bronchoprotection at 24 and 72 h compared to glycopyrronium. To minimize the occurrence of false negatives, MCT guidelines should be updated to recommend a minimum one-week abstinence period from all LAMA's. MCT was also able to statistically differentiate between tiotropium and glycopyrronium with respect to the degree and duration of bronchoprotection provided by each., Clinical Trial Registration Number: NCT02622243., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Exposure to the bronchoconstricting agent methacholine is a potential hazard to technical staff during methacholine challenge testing, which remains a useful and frequently performed test. There are several methods of performing the test. One of the 2 methods listed in the American Thoracic Society's guidelines is the 2-min tidal-breathing method. The methacholine can be inhaled using one of several methods. The loosely-fitting-mask method is likely to produce more contamination of the local environment than a filtered exhalation system., Methods: We tested 2 variations of the tidal-breathing method of measuring the methacholine provocational concentration (PC(20), the dose that produces a 20% decrease in forced expiratory volume in the first second). One involved use of the open-mask technique and the other a T-piece-and-filter system that precluded the release of methacholine-containing droplets into the environment. We performed duplicate methacholine challenge tests with 10 subjects who had a wide range of PC(20). The tests were done in random order, and each subject performed one test using the mask and one using the T-piece/filter system., Results: With the mask system the geometric mean PC(20) was 4.7 mg/mL, versus 5.1 mg/mL with the T-piece-filter system (p = 0.36). These values are very close and would not be substantially different clinically., Conclusion: The 2 methods are equivalent, and the low cost of the products used in the T-piece/filter method makes it suitable for reducing technician exposure to methacholine, using potentially completely disposable components.

Background: It is currently recommended that leukotriene modifiers (receptor antagonists and synthesis inhibitors) be withheld for a minimum of 24 h before direct bronchoprovocation testing, but there is little evidence to support this recommendation., Objective: To examine the effect of a single oral dose of montelukast sodium 10 mg on airway response to methacholine chloride-induced bronchoconstriction., Methods: A double-blind, placebo-controlled, randomized crossover trial was performed in 12 subjects with asthma whose methacholine chloride concentration causing a 20% decrease in the forced expiratory volume during the first second of exhalation (PC20) was 8 mg/mL or lower and a baseline forced expiratory volume during the first second of exhalation of 70% predicted or greater. Two-minute tidal breathing methacholine chloride inhalation challenges were performed 1 h and 25 h after both 10 mg montelukast sodium and identical-appearing placebo., Results: There were no significant differences in the methacholine chloride PC20 between active treatment and placebo at 1 h post-10 mg montelukast sodium (1.0 mg/mL versus 1.3 mg/mL; n=12; P=0.17, respectively) or at 25 h post-10 mg montelukast sodium (1.4 mg/mL versus 1.9 mg/mL; n=11; P=0.15, respectively)., Conclusion: A single dose of montelukast sodium did not affect methacholine chloride-induced bronchoconstriction measured after 1 h and 25 h.