Airway hyperresponsiveness (AHR), inflammation and heterogeneity in airway constriction and ventilation within the airway tree are fundamental features of asthma.¹ Heterogeneity in ventilation is relevant not only because it affects gas exchange efficiency (ventilation/perfusion in asthma), but also because it can theoretically magnify the degree of mechanical obstruction² which could affect the degree of AHR. By thickening of airway walls, increasing airway secretions and releasing mediators, inflammation could also be linked to ventilation heterogeneity and AHR in asthma.^3,4 Indeed, the exhaled nitric oxide concentration (Fe_NO) is substantially increased by inflammation in asthma and has been proposed as a non-invasive biological marker to guide treatment.⁵

In this issue of Thorax, Downie and coworkers⁶ present convincing evidence that ventilation heterogeneity is strongly associated with AHR in patients with asthma, regardless of the level of inflammation (see page 684). In a group of subjects with a wide range of asthma severity, the authors measured, among other parameters, the heterogeneity of the conducting airways by multiple breath nitrogen washout (S_cond) and Fe_NO with AHR to methacholine. A subgroup of patients with poorly controlled symptoms was also studied after 3 months of …