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Copyright of Canadian Journal of Respiratory, Critical Care, & Sleep Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Background: Mannitol inhalation testing is specific for asthmatics with eosinophilic airway inflammation, a factor that has been negatively correlated with the development of deep inhalation bronchoprotection. Objective: To evaluate the effect of deep inhalations on responsiveness to inhaled mannitol in correlation with the degree of airway inflammation. Methods: Twenty participants with stable asthma completed this randomized, crossover study. A screening visit assessed responsiveness to methacholine and airway inflammation through fractional exhaled nitric oxide (FeNO) measures and sputum induction. Participants next completed two mannitol challenges, one with deep inhalations (standard method) and one with inhalations to half of total lung capacity, and two methacholine challenges, one with tidal breathing (standard method) and one with deep inhalations. Only the inhalation technique for dose administration differed between repeat mannitol or methacholine challenges. Results: Deep inhalations did not significantly influence the provocative dose of mannitol causing a 15% fall in forced expiratory volume in 1 second ((P =.73; n = 7) or the mannitol dose‐response slope (P =.26; n = 20). Deep inhalations produced significant bronchoprotection against methacholine (P =.03; n = 20). FeNO levels were significantly correlated to sputum eosinophilia (P =.02; n = 15), responsiveness to deep inhalation methacholine (P =.005; n = 20), the dose‐response slopes from deep inhalation mannitol (P =.01; n = 20), and the dose‐response slope from non–deep inhalation mannitol (P =.005; n = 20). Conclusions and Clinical Relevance: Deep inhalations did not produce significant bronchoprotection against inhaled mannitol. This result is in agreement with past findings linking airway inflammation with loss of deep inhalation bronchoprotection. Clinical Trial Registration: This study was prospectively registered on clinicaltrials.gov (NCT 03505489). [ABSTRACT FROM AUTHOR]

The article focuses on airway hyperresponsiveness (AHR) in asthma and explores its underlying mechanisms. Topics include the classification of stimuli that induce AHR, the distinction between persistent and variable AHR and their associated mechanisms, and the role of airway inflammation in driving AHR.

Background: New guidelines for methacholine challenge testing recommend reporting the test outcome as dose rather than concentration. Jet nebulizers have historically been used for methacholine challenge testing, but much of the weight loss, often (incorrectly) referred to as aerosol output, is actually evaporation. The Wright nebulizer is well characterized and still widely used, but its availability is unclear, and it is nondisposable. We developed a novel method using a vibrating mesh nebulizer (Solo). This method was compared with the standard 2-min tidal breathing method using the Wright nebulizer. Repeatability within and between nebulizers was also tested.Methods: Fifteen patients with mild asthma completed four methacholine challenges (two with the Solo vibrating mesh nebulizer and two with the Wright jet nebulizer). Challenges with the same nebulizer were 24 h apart, and challenges between nebulizers were separated by 1 week. Standard 2-min tidal breathing methods were used with the Wright nebulizer. For the Solo nebulizer, the tidal breathing method was modified by nebulizing to completion 0.5 mL of doubling concentrations of methacholine at 5-min intervals.Results: Geometric mean methacholine doses required to cause a 20% fall in FEV1 were similar (96 vs 110 μg; P > .05); methacholine concentrations that caused a 20% fall in FEV1 were significantly lower with the vibrating mesh nebulizer (0.48 vs 4.4 mg/mL; P < .001). Repeatability of methacholine doses required to cause a 20% fall in FEV1 within and between nebulizers was excellent (intraclass correlation coefficient > 0.92).Conclusions: We have developed a novel, simple, repeatable method for conducting methacholine challenges using new nebulizer technology. Importantly, the method meets recommendations set out in the new guidelines.Trial Registry: ClinicalTrials.gov; No.: 02965482; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]