Bronchoprovocation tests continue to play a valuable role clinically. While the preferred tests for clinical diagnosis and monitoring of asthma are chosen based largely on experience and recommended guidelines, limited access to some agents in different parts of the world may limit the options.
Bronchoprovocation tests, both direct and indirect, also play a valuable role in research laboratories for investigating the pathobiology of asthma. These tests are also recognized for their unequivocal potential in assessing efficacy of asthma treatments. In addition to the tests described herein, other inhalation challenges are being validated as models for drug development. One such test uses lipopolysaccharide (Figure 10.2) (Janssen et al. 2013), a derivative of bacterial endotoxin, which activates TLR4 on epithelial cells and induces a distinct neutrophilic inflammatory response in the airways.
When employing bronchoprovocation tests in clinical trials to determine the efficacy and/or proof of activity of asthma therapies, care must be taken to select a challenge most suitable to test the drug under investigation. Direct airway challenges have been central for the determination of optimal doses and duration of action when evaluating bronchodilator therapies, while indirect challenges, such as allergen, are valuable for assessing the effects anti-inflammatory therapies on the late-phase airway responses and accumulation of inflammatory cells. One must also be certain to allow sufficient recovery between tests, particularly tests that induce refractoriness (such as exercise challenge, not described here) or those that induce airway inflammation, such as allergen challenges.
Research investigations into the pathogenesis of asthma will continue to identify new therapeutic targets. An improved understanding of the mechanisms by which indirect airway challenges induce bronchoconstriction will enable the most appropriate model to be selected for testing of drugs in the early clinical development.