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1 Clinical Research Group Institute for Inhalation Biology, GSF - National Research Centre for Environment and Health, Gauting, Germany
2 Asklepios Clinic for Respiratory Medicine, Gauting, Germany
3 Institute of Physics and Biophysics, University of Salzburg, Salzburg, Austria
4 Inamed GmbH, Intelligent Aerosol Medicine, Gauting, Germany
* To whom correspondence should be addressed. E-mail: moeller{at}gsf.de.
Spherical monodisperse ferromagnetic iron oxide particles of 1.9 µm geometric and 4.2 µm aerodynamic diameter were inhaled by 13 healthy non-smokers 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 phase1 dead space of the airways was 282+/-49 ml and 164+/-34 ml, respectively. Deposition was below 20 % without breath holding and 51+/-8 % after 8 s breath holding time. We attempted to confine the bolus deposition to the bronchial airways by limiting the bolus front depth to the phase1 dead space volume. Particle retention was measured by the magnetopneumographic method over a period of 9 months. 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 hours 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 non-smokers, 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 being deposited in the airways and that a significant fraction undergoes long-term retention mechanisms, the origin of which is still under discussion.
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