Multisite Comparison of Mucociliary and Cough Clearance Measures Using Standardized Methods

Abstract

A standardized protocol for measuring mucociliary (MCC) and cough clearance (CC) was developed and tested at the University of North Carolina at Chapel Hill, NC (UNC), Johns Hopkins University (JHU), and the University of Pittsburgh (Pitt). A total of 50 healthy nonsmoking adults with normal lung function were studied at the three sites: 30 [21 males/9 females (21M/9F)] at UNC, 10 (6M/4F) at JHU, and 10 (4M/6F) at Pitt. Subjects inhaled an aerosol of (99m)technetium sulfur colloid in 0.9% saline (mass median aerodynamic diameter=5.4 μm) under controlled breathing conditions (500 mL/sec, 30 breaths/min) by following a metronome and flow signal from a commercial dosimeter. Following inhalation, subjects sat in front of a gamma camera as sequential lung images were acquired for 60 min. Subjects then coughed 60 times, and images were acquired after each set of 20 coughs, i.e., at 70, 80, and 90 min. Subjects returned to the laboratory approximately 24 hr later for a final image of residual lung activity. Initial aerosol distribution was measured as a central/peripheral (C/P) ratio of activity. MCC/CC was expressed as the area under the retention versus time curve over 90 min (AUC90). A multivariate analysis of clearance versus time with site and C/P as covariates showed no significant site-specific differences. Interestingly, MCC/CC was greater in females (n=19) versus males (n=31), with AUC90=0.84 ± 0.11 and 0.90±0.07, respectively (p=0.03), for the combined data set from all sites (not significant for any given site). There were no gender differences for either C/P ratio or 24-hr clearance. This standardized protocol may prove beneficial in multicenter trials for testing new therapies that are designed to improve MCC/CC.