Lung clearance index is elevated in young children with symptom-controlled asthma

Abstract

Background: Pulmonary function testing has been recommended as an adjunct to symptom monitoring for assessment of asthma control. Lung clearance index (LCI) measures ventilation inhomogeneity and is thought to represent changes in the small airways. It has been proposed as a useful early marker of airway disease in asthmatic subjects, and determining it is feasible in preschool children. This study aims to assess whether LCI remains elevated in symptomatically controlled asthmatic children with a history of severe asthma, compared with healthy controls. A secondary aim was to determine whether the results were consistent across the preschool and school-aged populations. Methods: Using a case-control design, we compared 33 children with currently well-controlled symptoms who had a history of severe asthma, to 45 healthy controls (age 3-15 years) matched by age, height, and sex. We performed multiple breath washout tests using sulfur hexafluoride as a tracer gas, to determine their LCI and Scond values. Results: In the overall study, LCI z-score values were on average 0.86 units (95% confidence interval: 0.24-1.47, P = 0.01, t-test) higher in children with a history of severe asthma with current well-controlled symptoms compared with healthy controls. In addition, within the subgroup of preschool children (age ≤ 6), the asthmatic had significantly higher LCI z-score values than their healthy controls peers (mean (SD), 0.57 (2.18) vs −1.10 (1.00), P = 0.03, t-test). Twenty-seven percent (27%; 9/33) of subjects had an LCI value greater than the upper limit of our healthy controls despite being symptom controlled. Amongst preschool children, 5 (42%; 5/12) of the asthmatic children had abnormal LCI at the individual level. Conclusions: LCI is elevated in children with asthma, which may be driven by differences in the preschool population. LCI may be useful in defining preschool asthma endotypes with persistent ventilation inhomogeneity despite symptomatic control.