Comparison of Multiple Breath Washout and Spirometry in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis and Healthy Controls.

RATIONALE In cystic fibrosis (CF), the lung clearance index (LCI) derived from multiple breath washout (MBW) is more sensitive in detecting early lung disease than FEV1; MBW has been less thoroughly evaluated in young patients with PCD. OBJECTIVES To evaluate (1) sensitivity of MBW and spirometry for detection of mild lung disease in young children with PCD and CF compared to healthy controls (HC), and (2) compare patterns of airway obstruction between disease populations. METHODS Multicenter, single visit, observational study in children with PCD and CF with an FEV1 >60% predicted and HC, ages 3-12 years. Nitrogen MBW and spirometry were performed and over-read for acceptability. Chi-square and Kruskall-Wallis tests compared demographic and lung function measures between groups, linear regression evaluated the effect of disease state and Spearman's rank correlation coefficient was used to compare LCI and spirometric measurements. RESULTS 25 children with PCD, 49 with CF, and 80 HC were enrolled, among whom 17 PCD (68%), 36 CF (73%), and 53 (66%) HC performed both acceptable spirometry and MBW and comprised the analytic cohort. Median age was 9.0 years (IQR 6.8-11.1). LCI was abnormal (>7.8) in 10/17 (59%) PCD patients and 21/36 (58%) CF patients, whereas FEV1 was abnormal in 3/17 (18%) PCD patients and 6/36 (17%) CF patients. LCI was significantly elevated in PCD and CF compared to HC (ratio of geometric mean vs. HC: PCD 1.27 (95% CI: 1.15-1.39) and CF 1.24 (95% CI: 1.15-1.33)). Children with PCD had lower FEF25-75 percent predicted compared to children with CF (62% (IQR: 50-78%) versus 85% (IQR: 68-99%), p=0.05). LCI did not correlate with FEV1. CONCLUSIONS LCI is more sensitive than FEV1 in detecting lung disease in young PCD patients, similar to CF. LCI holds promise as a sensitive endpoint for assessment of early PCD lung disease.