Multiple-breath inert gas washout to detect inhomogeneity of ventilation distribution in preschool children with cystic fibrosis
Measurement of lung function in preschool children (those aged two to five years) is notoriously difficult. The aims of this thesis were to determine whether multiple- breath inert gas washout (MBW) could be performed successfully in preschool children, and whether MBW indices were more sensitive for detecting cystic fibrosis (CF) lung disease in preschool children than spirometry indices. First, quality control criteria for data collection and interpretation in children with and without CF were examined. 75% of preschool children successfully performed spirometry at first attempt, but adult criteria for start and end of test and reproducibility were inappropriate. Similarly, 79% of preschool children completed MBW at first attempt. The primary outcome measure from MBW (Lung Clearance Index LCI ) was independent of subject characteristics in healthy preschool and school-age children. Analysis of the progression of the phase III slope through MBW allowed derivation of indices representing conducting zone (Scond) and acinar zone (Sacin) inhomogeneity. Volume correction of these indices facilitated comparison between groups. MBW and spirometry results were compared in 55 school-age and 60 preschool children. Whilst group differences were seen for both tests, 11/22 (50%) of school- age children with CF had normal spirometry, whilst only one (5%) had normal LCI. 26/30 (87%) of preschool children with CF had normal spirometry, whilst only eight (27%) had normal LCI. Virtually all children with CF had raised Scond, with no age relationship seen. Sacin was normal in most younger children with CF, and raised in most aged 10 years and older. MBW detected lung disease in preschool children with CF more frequently than spirometry. Most young children with CF had evidence of conducting airway disease, whilst acinar zone involvement was predominantly seen in older school-age children. These findings support the hypothesis that MBW will have value as a clinical measure in this patient group.