Mediator Release During Exercise-induced Bronchoconstriction

This study will compare the inflammatory response in induced vs inhibited exercise induced bronchoconstriction (EIB) in patients with a medical diagnosis of asthma/EIB. Urinary and plasma samples will be analysed to compare the mediator release in each condition, alongside changes in lung function.

Exercise induced-bronchoconstriction (EIB) is a transient narrowing of the airways that occurs during or shortly after strenuous exercise. The prevalence of EIB in asthmatic patients is estimated around 30-50%, but EIB can also occur in individuals without asthma (especially children, army recruit forces, and elite athletes). Controversy remains about the causative mediators in the bronchoconstrictive response. Technological advancement in mass spectrometry has opened new avenues in the quantitative measurement of small endogenous metabolites in biological fluids (including urine and blood), which may provide insights into the pathophysiology of EIB and direct future therapeutic targets.

Utilising novel techniques in the analysis of inflammatory mediators in urine and blood, this study aims to conduct the most comprehensive analysis of mediator release during EIB to date.

Participants will attend a screening visit during which they will complete an exercise challenge (to determine the presence of EIB). A skin prick test will also be conducted to establish the atopic status of the participants. Following the screening visit, patients with EIB will be invited to complete a randomised cross-over study, where they will perform two further exercise challenges on separate days: one while inhaling temperate dry air, and one while inhaling hot humid air (the latter is known to inhibit EIB). Lung function and breathing discomfort will be recorded, and urine and blood samples will be collected, before and at various time points after exercise. As a control condition, participants will also attend one visit during which no exercise will be performed.

Participants aged 18-50yr, with diagnosed asthma and/or EIB, will be included in the study. 12 participants will complete 4 visits (lasting between 90 min and 4.5h). The study will take place on Brunel University London campus, Uxbridge. Urine and blood samples will be sent to the Karolinska Institutet, Stockholm, Sweden for analysis.

Eligibility Criteria:
Inclusion Criteria:

* Able to understand the study instructions
* Willing and able to give informed consent
* Aged 18-50yr
* Physician-diagnosed asthma and/or EIB
* Participants that demonstrate EIB at the screening visit (i.e., those who have a fall in FEV1 20% to 50%) will be eligible for the full study.

Exclusion Criteria:

* Any chronic medical condition other than asthma or EIB
* Baseline FEV1 \<70% predicted
* Exacerbation of asthma or respiratory infection within the last 4 wk
* Individuals who have varied their inhaled corticosteroid medication within the last 4 wk
* History of anaphylaxis
* Current smokers
* Pregnancy
* History of cardiovascular disease
* Injury that would prevent exercise on a cycle ergometer
* Medical contraindication to perform strenuous exercise
* Required oral corticosteroids in the past 3 months
* Any blood borne disease