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

Abstract

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 (cystic fibrosis), so may be sensitive to early airway disease in asthma.

Objective: In this observational study we hypothesised that ventilation heterogeneity (Lung Clearance Index (LCI) and Phase III slope indices (S_cond and S_acin)) were more sensitive than conventional measurements (FEV₁ and exhaled nitric oxide (FeNO)) at detecting residual airways disease in children with well-controlled asthma.

Methods: In 31 asthmatic children (mean age 10.6, range 5-15), FEV₁, LCI, S_cond and S_acin were measured at two separate visits, before and after blinded salbutamol or placebo, with FeNO measured once. 29 healthy volunteers (mean age 11.2, range 5-16) completed measurements at one visit only.

Results: Baseline mean (SD) LCI was significantly higher in asthmatics vs. controls (6.69 (0.91) vs. 6.24 (0.47), p=0.02). There were no significant differences in FEV₁(p=0.16) or median FeNO (p=0.63). Following Salbutamol there was small significant change in mean (SD) FEV₁ (-1.26(1.25) to -0.93(0.23), p=0.03) but not LCI, S_cond or S_acin (p>0.05). Importantly, LCI post bronchodilator remained significantly higher than controls (6.64(0.69), p=0.01).

Conclusion: This study identifies the presence of residual ventilation heterogeneity in well controlled children with 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 remodeling.