Abstract
Rationale: In asthma, airway inflammation, obstruction and reactivity may lead to ventilation heterogeneity; our understanding of this process is limited in asthmatic children. Objectives and Methods: The study’s objective was to measure ventilation heterogeneity, by the lung clearance index (LCI), in children with well controlled asthma and assess the association of LCI with airway reactivity through methacholine challenge tests. LCI and spirometry were measured in 24 children with asthma and 21 healthy controls between 4 and 10 years of age. Sixteen children with asthma and 11 healthy controls also performed methacholine challenge tests. Results: LCI was higher in children with asthma compared to healthy controls (7.58 vs 6.79, p=0.004); no differences in FEV1 or FEF25-75 were noted between groups. Ages were similar (p=0.54); however, the slope of LCI versus age differed between groups (p=0.001). The LCI slope increased with age in asthmatics. Further, higher LCI values were associated with decreasing PC20 (provocative concentration of methacholine to decrease baseline FEV1 by 20%) values in children with asthma (p=0.02), but not healthy controls (p=0.16). Conclusions: Ventilation heterogeneity is present from preschool age in children with well controlled asthma. The relationship between ventilation heterogeneity and airway reactivity suggests that normalizing ventilation heterogeneity may be an important therapeutic target for treating children with asthma.
Highlights
Asthma is characterized by recurrent episodes of airway obstruction, hyperreactivity, and inflammation, which may contribute to airway remodeling and progressive flow limitation [1,2]
lung clearance index (LCI) was higher in children with asthma compared to healthy controls (7.58 vs. 6.79, p = 0.004); no differences in Forced Expired (FEV1) or FEF25-75 were noted between groups
Higher LCI values were associated with decreasing PC20 values in children with asthma (p = 0.02), but not healthy controls (p = 0.16)
Summary
Asthma is characterized by recurrent episodes of airway obstruction, hyperreactivity, and inflammation, which may contribute to airway remodeling and progressive flow limitation [1,2]. The multiple breath inert gas washout technique (MBW) can assess ventilation heterogeneity within the lung by calculating the lung clearance index (LCI) [4]. This technique quantifies the washout of an inert gas during regular tidal breathing, making it suitable for all ages, young children who may not perform reproducible spirometry [5]. Studies have demonstrated that well-controlled adults with asthma may have normal spirometry, but an elevated LCI, reflecting greater ventilation heterogeneity [6,7]. Greater ventilation heterogeneity is associated with increased airway reactivity [8]. We hypothesized that pre-school and school age children with well-controlled asthma have evidence of ventilation heterogeneity and that school age children with well-controlled asthma have increasing ventilation heterogeneity associated with greater airway reactivity
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