Pulmonary Clearance of Inhaled Particles 24 to 48 Hours Post Deposition: Effect of Beta-Adrenergic Stimulation

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Abstract
Recent studies have suggested considerable particle retention in the bronchial, ciliated airways 24 hours after depositing in the lung. A significant presence of particles in the ciliated airways at 24 hours post deposition may be indicated if beta-adrenergic treatment between 24 and 48 hours is shown to enhance particle clearance during this same period. We tested this hypothesis in ten young, normal subjects who inhaled Tc99m-iron oxide particles (5μm MMAD) on three separate occasions. Following the first aerosol exposure, each subject inhaled a dose of albuterol sufficient to decrease specific airway resistance by 63% (mean baseline sRaw = 3.47 +/−0.99(SD) cm H2O-sec, and post albuterol Raw = 1.27 +/− 0.28(SD) cm H2O-sec) and clearance was measured by gamma camera over a 3 hour period. For the subsequent two aerosol exposures, baseline mucociliary clearance was measured, again over the initial 3 hour period, and then retention of particles was monitored with a six crystal gamma detector between 24 and 48 hours. During this 24-48 hour period, each subject inhaled 2 doses of either albuterol (a similar dose to that described above) or saline (double-blinded design). We found that albuterol significantly enhanced clearance at one hour post deposition. Mean retention (as a fraction of initial deposition) at 1 hour (R1) with albuterol was R1 =.39 +/− 0.11 vs. control(A) R1 =.7 6 +/− 0.11 and control(S) R1 =.74 +/− 0.12, p <.001 by repeated measures analysis). On the other hand, albuterol did not significantly enhance clearance of particles between 24 and 48 hours, e.g. as a fraction of 24 hour retention mean saline R31 =.84 +/−.05 (SD) and mean albuterol R31 =.81 +/−.04, and similarly mean saline R48 =.68 +/−.15 and mean albuterol R48 =.65 +/−.12. These data do not support the hypothesis that a significant number of particles are present on the ciliated airways at 24 hours post deposition. There may be particles retained at this time but not readily accessible to clearance by the mucociliary system.