Effects of inhaled iron oxide particles on alveolar epithelial permeability in normal subjects.
Pulmonary inflammation secondary to oxidant generation catalyzed by transition metals associated with inhaled particles is one factor postulated to underlie the acute health effects of particulate air pollution. We postulated that inhaled iron oxide particles with associated amounts of soluble iron should induce mild pulmonary inflammation and lead to altered alveolar epithelial integrity and altered gas exchange. To test this hypothesis we examined the effects of inhaled iron oxide particles on alveolar epithelial permeability. Sixteen healthy subjects inhaled aerosols of iron oxide particles (1.5 microm mass median aerodynamic diameter) having either high or low water-soluble iron content [3.26 +/- 0.25 (SE) and 0.14 +/- 0.04 microg soluble iron/mg of particles, respectively] for 30 min at an average mass concentration of 12.7 mg/m(3). Alveolar epithelial permeability was assessed by measuring the pulmonary clearance of an inhaled radiolabeled tracer molecule ((99m)Tc-DTPA, diethylene triamine pentaacetic acid) using a gamma camera at 1/2 h and 24 h post particle exposure. Carbon monoxide lung diffusing capacity (DL(CO)) and spirometry were also performed before and after breathing the iron oxide. As a control, on a separate day, the procedures were duplicated except that the subject breathed particle-free air. For those subjects breathing aerosols with high soluble iron, we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at 1/2 h (97.4 +/- 15.4 vs. 116.1 +/- 15.5 min, respectively) or 24 h postinhalation (105.1 +/- 13.8 vs. 106.9 +/- 12.9 min, respectively). Likewise, for those subjects breathing aerosols with low soluble iron content we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at 1/2 h (108.6 +/- 31.9 vs. 95.6 +/- 10.8 min, respectively) or 24 h postinhalation (130.0 +/- 18.0 vs. 105.8 +/- 13.7 min, respectively). We found no significant differences in DL(CO) between particle exposures and air exposures. Minor differences in spirometric measurements were noted but were not statistically significant. We conclude that inhalation of iron oxide particles did not cause an appreciable alteration of alveolar epithelial permeability, lung diffusing capacity, or pulmonary function in healthy subjects under the studied conditions.
Lay
J C
JC
Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, CB# 7310, EPA Human Studies Facility, 104 Mason Farm Road, Chapel Hill, NC 27599, USA. JCL@med.unc.edu
Zeman
K L
KL
Ghio
A J
AJ
Bennett
W D
WD
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002463:Cell Membrane Permeability / Q000187:drug effects*; D018592:Cross-Over Studies; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism
D005290:Ferric Compounds; D007502:Iron Chelating Agents; C000499:ferric oxide; D004369:Pentetic Acid