Effect of bronchoconstriction on airway cellular responses in asthma
Research type
Research Study
Full title
Effect of bronchoconstriction on airway cellular responses in asthma
IRAS ID
150264
Contact name
Peter Howarth
Contact email
Sponsor organisation
R&D Department, University Hospital Southampton NHS Foundation Trust
Research summary
Asthma is a common, complex immunological disorder with increasing prevalence. It is characterised by airways that contract too easily and too much causing symptoms of wheeze, chest tightness and shortness of breath. Many environmental agents and conditions precipitate asthma by causing contraction of airway smooth muscle and inflammatory cell activation, resulting in airway narrowing. Separate stimuli can preferentially influence different pathways that eventually lead to airway narrowing. For example allergen exposure leads to mast cell activation, lymphocyte activation and eosinophil airway recruitment while exposure to cold dry air causes smooth muscle contraction due to mast cell degranulation. However, the precise molecular changes occurring in the airways due to simply smooth muscle contraction are unknown.
Inhalation of methacholine acts directly on the airway smooth muscle causing contraction and induces airway narrowing without involving inflammatory cell activation. We thus wish to evaluate changes within the asthmatic airway after it has been exposed to repeated challenges with methacholine. Volunteers with mild asthma will be recruited into the study and methacholine inhalation is extremely safe in this group.
Fibreoptic bronchoscopy as a research tool in asthma was introduced in the 1980s and it enables sampling of the airway mucosa (by bronchial biopsy and brushing) and bronchial lumen (by bronchoalveolar lavage). Its use has facilitated great advances in our understanding of the inflammatory changes within the airways and allowed for the development of new treatments. This project thus aims to sample the asthmatic airway, using bronchoscopy, before and after research volunteers have been exposed to methacholine. Changes at the molecular level will be very closely examined using techniques including RNA-sequencing which will enable whole genome gene expression to be evaluated. Through this study we will obtain a much clearer understanding of the cellular processes that occur during airway narrowing, without the influence of inflammatory cell activation. Furthermore, how smooth muscle contraction, in isolation, affects responses to common asthma precipitants including virus and allergen will be evaluated.REC name
South Central - Oxford A Research Ethics Committee
REC reference
14/SC/0153
Date of REC Opinion
29 Apr 2014
REC opinion
Further Information Favourable Opinion