HUMAN ALVEOLAR LONG-TERM CLEARANCE OF FERROMAGNETIC IRON OXIDE MICROPARTICLES IN HEALTHY AND DISEASED SUBJECTS

Abstract

Monodisperse ferrimagnetic microparticles (Fe 3 O 4) with 1.3 μ m geometric diameter were inhaled to study alveolar long-term clearance in healthy and diseased human subjects. Nineteen younger (age 20 to 39 years) and 20 older (age 40 to 65 years) healthy volunteers participated in the study as well as 15 patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis (IPF), and 15 patients with chronic obstructive bronchitis (COB). In each group the subjects were divided into never smokers (NS) and active smokers (S). Clearance was measured by magnetopneumography (MPG)for 300 days after inhalation. In COB, 50% of the deposited particles were removed from the lungs after 2 days, indicating high bronchial deposits due to bronchial obstructions. In healthy NS, only 10% of the particles were removed after 2 days and cigarette smoking enhanced the fraction of fast-cleared particles. In subjects who smoked, slow clearance was significantly impaired (P <;. 02). Clearance half-lives (in days) for younger, healthy, NS were 124 ± 66 (mean ± SD) compared to 220 ± 74 for S. Similarly for older subjects, the times were 162 ± 120 for NS and 459 ± 334 for S. The impairment of alveolar clearance due to cigarette smoking increases by 5.7 ± 1.3 days/pack-year (P <; 01). Alveolar clearance was impaired in SAR and in IPF; half-lives were 275 ± 109 days (P <;. 05) and 756 ± 345 days (P <. 02), respectively, compared to healthy NS. Most COB patients were ex-smokers, their long-term clearance was 240 ± 74 days, which is more than healthy NS (P <; 01), but less than healthy S and might indicate a recovery of alveolar clearance. In view of studies using totally inert particles like Teflon, we conclude that the lung clearance measured with iron oxide tracer particles primarily reflects clearance by intraphagosomal particle dissolution within alveolar macrophages, which is impaired by cigarette smoke consumption and in patients.