Ventilation heterogeneity in children with well controlled asthma with normal spirometry indicates residual airways disease

Background: In adults with asthma, ventilation heterogeneity, independent of inflammation, has been hypothesised to be associated with airway remodelling. Bronchial biopsy in preschool children with wheeze demonstrates early structural changes. Ventilation heterogeneity is sensitive to airway disease in other paediatric respiratory conditions such as cystic fibrosis, so may be sensitive to early airway disease in asthma. An observational study was performed in which it was hypothesised that ventilation heterogeneity (lung clearance index (LCI) and phase III slope indices (S-cond and S-acin)) were more sensitive than conventional measurements (forced expiratory volume in 1 s (FEV1) and exhaled nitric oxide (FeNO)) for detecting residual airways disease in children with well controlled asthma. Methods: In 31 children with asthma of mean age 10.6 years (range 5-15), FEV1, LCI, Scond and Sacin were measured at two separate visits, before and after blinded salbutamol or placebo, with FeNO measured once. 29 healthy volunteers of mean age 11.2 years (range 5-16) completed measurements at one visit only. Results: Baseline mean (SD) LCI was significantly higher in children with asthma than in controls (6.69 (0.91) vs 6.24 (0.47), p = 0.02). There were no significant differences in FEV1 or median FeNO. Following salbutamol there was a small significant change in mean (SD) FEV1 (from -1.26 (1.25) to -0.93 (0.23), p = 0.03) but not in LCI, Scond or Sacin. Importantly, LCI remained significantly higher after bronchodilator in children with asthma than in controls (6.64 (0.69), p = 0.01). Conclusion: This study identifies the presence of residual ventilation heterogeneity in children with well controlled asthma and normal FEV1. The role of LCI in measuring early airway disease in children with asthma requires further exploration, possibly as a surrogate of structural remodelling.