Search

Purpose: The purpose of this scoping review was to identify existing clinical and basic science knowledge surrounding the effect of muscarinic receptor antagonism on allergen-induced airway responses to inform future clinical research in this area. Methods: Multiple advanced searches were performed using the National Library of Medicine PubMed search engine. Each search began with two terms; for example, “atropine and asthma” or “tiotropium and airway inflammation”. Results were then further refined to include terms such as “allergen” or “ovalbumin (OVA)”. Abstracts of refined searches were reviewed for relevance to allergic asthma and allergen-induced airway responses including the early and late asthmatic responses, airway inflammation and tissue remodelling. There was no restriction regarding publication date. Reference lists of selected papers were also reviewed for relevant publications. Results: Nine human clinical trial publications and fourteen animal model publications were identified. In humans, single dose atropine (n=4), ipratropium (n=4) or oxitropium (n=1) administered pre-challenge produced equivocal effects on allergen-induced early asthmatic responses as reported but favored inhibition in eight of nine studies after re-analyses. Animal model investigations (n=14) showed mostly favorable results, especially with respect to airway inflammation and tissue remodelling, although two studies were negative, and one study showed a worsening in allergen induced airway inflammation following muscarinic receptor antagonism. Conclusion: Existing human and animal model data suggest muscarinic receptor antagonism may be beneficial in preventing allergen induced airway responses in those with allergic asthma. Additional human research utilizing current standardized methodologies is required.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review.