Retention of particles inhaled in boli with and without induced bronchoconstriction

Large lung retentions (up to 50%) of particles < or = 4 microns inhaled with a bolus technique at a penetration depth less than dead space have been reported to occur after 24 h. This retention may be due to retarded clearance of particles deposited in the airways of the tracheobronchial tract; an alternative explanation could be that particles are deposited in the alveolar region. The purpose of the present study was to confirm the occurrence of retained fractions and to study the influence of a cholinergic drug, which is assumed to give a more central particle deposition, on these retentions in human lungs after shallow aerosol bolus inhalation. Twelve healthy subjects inhaled, with a bolus technique, monodisperse Teflon particles (2.4 microns geometric diameter, 3.5 microns aerodynamic diameter), labeled with 111In. The volumetric lung depth of the inspired bolus was around 60 mL and flow rate was about 300 mL/s. Six subjects inhaled the test particles after a provocation with a cholinergic aerosol, which induced a threefold increase in airway resistance. The other six subjects inhaled a cholinergic aerosol after inhalation of the test particles or inhaled no cholinergic aerosol at all. Radioactivity in the body was measured after 0.5, 24, 48, and 72 h with a whole-body scanner with three 127 x 101-mm Nal detectors. The investigation confirmed results obtained earlier by a group in Frankfurt claiming that great retentions occur after 24 h. The retentions tended to be lower in the group receiving a bronchoconstricting drug before the bolus inhalations. There was a significant lung clearance of particles between 24 and 72 h, in contrast to the findings in earlier studies in healthy subjects and asthmatics who inhaled Teflon particles in large volumes. On the other hand, the clearance agreed well with the clearance in healthy subjects with extensive deposition of Teflon particles in the small ciliated airways, obtained by means of an extremely low inhalation flow rate. The results suggest that a considerable fraction of the particles in the bolus inhalation have been deposited in small ciliated airways in which the mucociliary transport is less efficient or in the alveolar region.