The review by Brusasco et al 1 demonstrates that a simple causal hypothesis is insufficient to explain airway hyperresponsiveness in asthma. We have also refuted this hypothesis by identifying that airway eosinophilia can occur without airway hyperresponsiveness,2 and that in asthma airway hyperresponsiveness can persist despite suppresssion of airway inflammation and pancytopenia induced by chemotherapy.3 However, airway inflammation and airway hyperresponsiveness are so intrinsically linked in asthma that an alternative hypothesis must be provided.

My hypothesis is that airway inflammation can modulate the level of intrinsic airway responsiveness such that an increase in airway inflammation from, for example, allergen exposure will lead to an increase in airway responsiveness, and a decrease in airway inflammation from, for example, corticosteroid therapy will lead to a reduction in airway responsiveness. The absolute level of airway responsiveness, and hence whether it is categorised as normal or increased, will depend upon two …