Mucociliary and long-term particle clearance in the airways of healthy nonsmoker subjects

Abstract

Spherical monodisperse ferromagnetic iron oxide particles of 1.9-μm geometric and 4.2-μm aerodynamic diameter were inhaled by 13 healthy nonsmoking subjects using the shallow bolus technique. The bolus width was 100 ml, and the penetration front depth was 150 ± 27 ml. The mean flow rate during inhalation and exhalation was 250 ml/s. The Fowler dead space and the phase 1 dead space of the airways were 282 ± 49 and 164 ± 34 ml, respectively. Deposition was below 20% without breath holding and 51 ± 8% after an 8-s breath-holding time. We attempted to confine the bolus deposition to the bronchial airways by limiting the bolus front depth to the phase 1 dead space volume. Particle retention was measured by the magnetopneumographic method over a period of 9 mo. Particle clearance from the airways showed a fast and a slow phase; 49 ± 9% followed the fast phase with a mean half-time of 3.0 ± 1.6 h and characterized the mucociliary clearance. The remaining fraction was cleared slowly with a half-time of 109 ± 78 days. The slow clearance phase was comparable to clearance measurements from the lung periphery of healthy nonsmokers, which allowed macrophage-dependent clearance mechanisms of the slow cleared fraction to be taken into account. Despite the fact that part of the slowly cleared particles may originate from peripheral deposition, the data demonstrate that mucociliary clearance does not remove all particles deposited in the airways and that a significant fraction undergoes long-term retention mechanisms, the origin of which is still under discussion.