Ability of the lung clearance index to monitor progression of early lung disease in children with cystic fibrosis

Abstract

Introduction: The lung clearance index (LCI) is a marker of ventilation inhomogeneity derived from the multiple breath washout test. Cross-sectional studies show that LCI is sensitive to detect the presence and extent of structural lung disease, inflammation and infection in infants and children with cystic fibrosis (CF). We aimed to determine if changes in LCI can identify the progression of structural lung disease on chest computed tomography (CT) and extent of pulmonary infection and inflammation. Methods: Repeated LCI measurements, bronchoalveolar lavage fluid (BAL) and chest CT were obtained from 26 children with CF (aged 3 to 9 years) over 12 months. Structural lung disease was assessed using the PRAGMA quantitative outcome measure. Neutrophil elastase (NE) and interleukin 8 (IL8) in BAL were quantified by ELISA. Changes in LCI and CT, infection and inflammation outcomes between repeated visits were assessed using mixed effects model. Results: Increased LCI was significantly associated with progression of bronchiectasis (p=0.005), air trapping (p=0.044) and bronchial wall thickening (p=0.012). There were no significant associations between change in LCI and the extent of NE and IL8. However, LCI was greater in children that had NE present in BAL at their second visit but not at their first visit, compared with children who had NE present at both visits. Similarly, increased LCI was associated with the development of a respiratory infection not present in the previous visit. Conclusion: LCI may be sensitive to monitor the progression of structural lung disease and the development of lower respiratory tract inflammation and infection in young children with CF.