Abstract
Rationale: Lung clearance index (LCI) has good intravisit repeatability with better sensitivity in detecting lung disease on computed tomography scan compared with forced expiratory volume in 1 second (FEV(1)) in adults with bronchiectasis. Alternative multiple-breath washout parameters have not been systematically studied in bronchiectasis. Objectives: To determine the validity, repeatability, sensitivity, specificity, and feasibility of standard LCI (LCI(2.5)), shortened LCI (LCI(5.0)), ventilation heterogeneity arising within proximal conducting airways (S(cond)VT), and ventilation heterogeneity arising within the acinar airways (S(acin)VT) in a cross-sectional observational cohort of adults with bronchiectasis. Methods: Cross-sectional multiple-breath nitrogen washout data (Exhalyzer D; Eco Medics AG) from 132 patients with bronchiectasis across five United Kingdom centers (BronchUK Clinimetrics study) and 88 healthy control subjects were analyzed. Results: Within-test repeatability (mean coefficient of variation) was <5% for both LCI(2.5) and LCI(5.0) in patients with bronchiectasis, and there was no difference in mean coefficient of variation for LCI(2.5) and LCI(5.0) in patients with bronchiectasis compared with healthy volunteers. Moderate-strength correlations were seen between FEV(1) and LCI(2.5) (r = -0.54), LCI(5.0) (r = -0.53), S(cond)VT (r = -0.35), and S(acin)VT (r = -0.38) z-scores. The proportion of subjects with abnormal multiple-breath washout (z-score > 2) but in normal FEV(1) (z-score < -2) was 42% (LCI(2.5)) and 36% (LCI(5.0)). Overall results from the receiver operating characteristic curve analysis indicated that LCI(2.5) had the greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI(5.0), FEV(1), and S(cond)VT z-scores. There was a 57% time saving with LCI(5.0). Conclusions: LCI(2.5) and LCI(5.0) had good within-test repeatability and superior sensitivity compared with spirometry measures in differentiating between health and bronchiectasis disease. LCI(5.0) is quicker and more feasible than LCI(2.5). Clinical trial registered with www.clinicaltrials.gov (NCT02468271).