Short-term control of asthma is often lacking even though forced expiratory volume in 1 s (FEV1) remains above normal value. Small airways are a potential key site of persistent inflammation and structural modification. Noninvasive assessment of small airways was found to be difficult, but the computerized single breath nitrogen washout test (SBNT) has been recently successfully reintroduced with this aim. Twenty-four asthmatics (13 females) of various severity but with normal FEV1 were compared with 24 healthy volunteers (13 females) and studied at steady-state after bronchodilatation (400 microg salbutamol). Spirometric values, plethysmographic data, phase III (slope of phase III of the SBNT, dN2) and IV [closing volume (CV), with closing capacity (CC) = CV + residual volume (RV)] of the SBNT were checked. Asthma severity, recent control, exacerbation rate, and therapy requirements were assessed on the basis of validated questionnaires (ACQ) and international guidelines. Patients were prospectively pooled into two equal groups according to their exacerbation rate. The reproducibility of the measurements obtained on 2 following days was assessed. All plethysmographic values, except total lung capacity (TLC), differentiated asthmatic patients from controls. The CC/TLC [124 (117-148) vs 117 (112-123), P = 0.04] and dN2 [110 (99-190) vs 94 (75-111), P = 0.02] were increased in asthma. The dN2 was significantly increased in patients with frequent exacerbations [100 (83-105) vs 195 (141-212), P = 0.0005]. A correlation was obtained between dN2 and recent asthma control (rho: 0.62; P = 0.003), number of exacerbations (rho: 0.71, P = 0.0008), and RV/TLC (rho: 0.49, P = 0.026). This study demonstrated that ventilation inequalities assessed by dN2 represent an important indicator of poor asthma control and high exacerbation rate in high symptom perceivers. New therapies focused on small airways should now be developed.