Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis

Abstract

Rationale: The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. Objectives: We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Methods: Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3–6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Results: Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. Conclusions: These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.