[Mechanisms of non-specific airway hyperresponsiveness: Methacholine-induced alterations in airway architecture]

Multiple mechanisms drive non-specific airway hyperresponsiveness in asthma. At the organ level, methacholine inhalation induces a complex bronchomotor response involving both bronchoconstriction and, to some extent, paradoxical bronchodilatation. This response is heterogeneous both serially, along a single bronchial axis, and in parallel, among lung regions. The bronchomotor response to methacholine induces contraction of distal airways as well as focal airway closure in select lung territories, leading to anatomically defined ventilation defects and decreased vital capacity. In addition, loss of the bronchoprotector and bronchodilator effects of deep inspirations is a key contributor to airway hyperresponsiveness in asthma.