Bronchial Challenge Testing: Different Horses for Different Courses

A.J. Lexmond, G.W. Clarke, C.P. Page, B. Forbes

Bronchial challenge tests (inhaled delivery of provocation agents) are performed to measure bronchial hyperresponsiveness (BHR), a characteristic feature of asthma. Measuring BHR is useful in the diagnosis and assessment of asthma, both in a clinical setting and in the development of new asthma therapeutics. For the latter application, bronchial challenge testing has proven its value in studying active and variable airway inflammation and how treatment can alter this. The applications of bronchial challenge tests are diverse, but critically depend on selection of the challenge agent that best suits the study objective and on ensuring that this agent reaches its site of action in the airways reliably and reproducibly.
Despite the numerous challenges that have been performed over the last decennia, surprisingly little attention has been afforded to quantifying the delivery of challenge agents to the airways. The large variations in chemical composition of these challenges (sulphur, methacholine, adenosine, mannitol) and their dose requirements do not allow for a singular approach, which is what has mostly been used to date. Moreover, research groups tend to use their own, non-standardised challenge protocols, impeding comparison of study results across different groups. The diagnostic potential of bronchial challenge tests could greatly be enhanced by quantifying, optimising and standardising the delivery method for each challenge agent.
Bronchial challenge testing is a neglected field where it comes to drug delivery; its current limitations, potential and unmet needs warrant urgent consideration. By highlighting new applications, both existent and proposed, a future for bronchial challenge testing can be sketched in which there is an imperative opportunity for drug delivery scientists to contribute.

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