ERS technical standard on bronchial challenge testing: pathophysiology and methodology of indirect airway challenge testing

Abstract

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a “direct” airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

Airway epithelium–shifted mast cell infiltration regulates asthmatic inflammation via IL-33 signaling

“…The expression of these mast cell genes was also assessed by copy number analysis of RNA isolated from epithelial brushings obtained at the time of research bronchoscopy. We found that the T2GM in induced sputum was associated with the number of copies of TPSAB1 (r 2 Figure 3F). In accordance with our results showing a relationship between the T2GM and the severity of indirect AHR, we found that the severity of EIB measured by the AUC30 was also associated with TPSAB1 (r 2 = 0.22, P = 0.006; Supplemental Figure 3D) and CPA3 (r 2 = 0.31, P = 0.0007; Supplemental Figure 3E) in induced sputum cells and not with CMA1 (r 2 = 0.00, P = 0.82; Supplemental Figure 3F).…”

“…Asthma is a heterogeneous disorder with features of airway inflammation, reversible airflow obstruction, and airway hyperresponsiveness (AHR). Indirect AHR is a particularly important pathophysiologic finding because it is a highly specific feature of asthma not seen in other diseases (1,2), and because it is associated with the persistence of asthma (3). In contrast to direct AHR, in which an exogenous stimulus for bronchoconstriction is administered, indirect AHR is the result of the endogenous release of mediators from the airways.…”

“…Despite the specificity of indirect AHR, the basis of this fundamental aspect of asthma is incompletely understood. Indirect AHR can be measured by tests such as the dry air exercise challenge test to assess exercise-induced bronchoconstriction (EIB), as well as osmotic challenge tests (2). Indirect AHR occurs across all levels of asthma severity, and is not related to baseline lung function (5).…”

Association of air humidity with incidence of exercise‐induced bronchoconstriction in children

“…Asthma is one of the most prevalent chronic diseases in children worldwide . Exercise‐induced bronchoconstriction (EIB) is a common feature in asthma, but its mechanisms are not fully understood . There are two major hypotheses explaining the link between exercise and bronchial smooth muscle contraction, the thermal and the osmotic hypotheses.…”

“…feature in asthma, but its mechanisms are not fully understood. 2 There are two major hypotheses explaining the link between exercise and bronchial smooth muscle contraction, the thermal and the osmotic hypotheses. Exercise can cause cooling of the airways due to elevated ventilation, which is followed by rewarming at rest.…”