The pulmonary deposition and retention of indium-111 labeled ultrafine carbon particles in healthy individuals.

CONTEXT: Particulate air pollution, for example, from ultrafine (UF) particles, has negative health effects. However, there is still limited knowledge regarding the fate of inhaled particles in the human body. OBJECTIVES: To describe the normal lung deposition and 1 week particle retention of indium-111 labeled UF carbon particles in healthy subjects. Additionally, the possibility to extend the follow-up period to 4 weeks was also investigated for one of the subjects. RESULTS: The cumulative pulmonary particle clearance 1 week post-administration, corrected for activity leaching and mucocilliary transport of activity deposited in the central airways, was 4.3 ± 8.5% (average ± standard deviation at group level), with marginal translocation of particles from lungs to blood, 0.3%. There was no observable elimination of particles from the body via urine. Seven days after exposure, the cumulated activity leaching was 3% (group level), which indicates a stable bonding between the particles and Indium-111. The volunteer followed for a total of 4 weeks, showed a cumulative decrease of activity retention in the lungs of 10.5%. After correction for activity leaching and clearance from central airway deposition, the estimated particle clearance was about 2%. CONCLUSIONS: No evidence for particle translocation from the lungs could be proven 7 days after exposure. It is possible to follow-up Indium-111 labeled UF carbon particles at least 1 month post-administration without increasing the administered activity.

No significant translocation of inhaled 35-nm carbon particles to the circulation in humans.

Human pulmonary retention of 35 nm 99mTc-labeled carbonaceous particles, produced with a modified Technegas generator, was followed for 24 h using a gamma camera imaging technique. Nine healthy subjects and four asthmatics inhaled the test particles. Particle labeling stability was tested in vitro during 48 h. We also measured in vivo leaching in blood and in urine for 24 h. One additional subject was exposed to particles with unstable labeling. There were no significant differences between healthy and asthmatic subjects in any of the parameters studied. Particle retention after 24 h was 102% (SD +/- 4.7). Cumulative in vitro leaching of 99mTc activity from the particles was 1.7% (+/-1.1) after 24 h. In blood samples, 80 min after exposure, 1.1% (+/- 0.4) of initially deposited activity was detected and 91% of the activity was not bound to particles. In urine sampled during the first 24 h after exposure, 3.6% (+/- 0.9) of lung deposited activity was detected. Lung retention was 30% after 1 h in the subject exposed to the leaching aerosol (n = 1). Thirty-one percent of the deposited activity was detected in the blood after 80 min and 80% was not bound to particles. Fifty percent of the activity was excreted with urine within 24 h. On gamma camera images the activity visibly translocated from lungs to thyroid and gastrointestinal tract. In conclusion, over a 24-h period there was no significant translocation of inhaled 35-nm particles to the systemic circulation.

Long-term clearance from small airways in subjects with ciliary dysfunction.

The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD) inhaled 111 Indium labelled Teflon particles of 4.2 microm geometric and 6.2 microm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24) was higher (p < 0.001) in the PCD subjects, 79 % (95% Confidence Interval, 67.6;90.6), compared to 49% (42.3;55.5) in the healthy controls. There was a significant clearance after 24 h both in the PCD subjects and in the healthy controls with equivalent clearance. The mean Ret24 with slow inhalation flow was 73.9 +/- 1.9% compared to 68.9 +/- 7.5% with normal inhalation flow in the three PCD subjects exposed twice. During day 7-21 the three PCD subjects exposed twice cleared 9% with normal flow, probably representing predominantly alveolar clearance, compared to 19% with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.

Residential radon and lung cancer--detailed results of a collaborative analysis of individual data on 7148 persons with lung cancer and 14,208 persons without lung cancer from 13 epidemiologic studies in Europe.

OBJECTIVES: Studies seeking direct estimates of the lung cancer risk associated with residential radon exposure lasting several decades have been conducted in many European countries. Individually these studies have not been large enough to assess moderate risks reliably. Therefore data from all 13 European studies of residential radon and lung cancer satisfying certain prespecified criteria have been brought together and analyzed. METHODS: Data were available for 7148 persons with lung cancer and 14,208 controls, all with individual smoking histories and residential radon histories determined by long-term radon gas measurements. RESULTS: The excess relative risk of lung cancer per 100 Bq/m3 increase in the observed radon concentration was 0.08 [95% confidence interval (95% CI) 0.03-0.16; P=0.0007] after control for confounding. The dose-response relationship was linear with no evidence of a threshold, and it remained significant when only persons with observed radon concentrations of <200 Bq/m3 were included. There was no evidence that the excess relative risk varied with age, sex, or smoking history. Removing the bias induced by random uncertainties related to radon exposure assessment increased the excess relative risk of lung cancer to 0.16 (95% CI 0.05-0.31) per 100 Bq/m3. With this correction, estimated risks at 0, 100, and 400 Bq/m3, relative to lifelong nonsmokers with no radon exposure, were 1.0, 1.2, and 1.6 for lifelong nonsmokers and 25.8, 29.9, and 42.3 for continuing smokers of 15-24 cigarettes/day. CONCLUSIONS: These data provide firm evidence that residential radon acts as a cause of lung cancer in the general population. They provide a solid basis for the formulation of policies with which to manage risk from radon and reduce deaths from the most common fatal cancer in Europe.

Long-term clearance from small airways in patients with chronic bronchitis: experimental and theoretical data.

Long-term clearance (21 days) from small airways was studied in 9 patients with chronic bronchitis (CB), 65 +/- 10 (mean +/- SD) years, and was compared to 15 age-matched healthy subjects of 67 +/- 7 (mean +/- SD) years. Six of the CB patients were studied twice. All subjects inhaled monodisperse 6 microm Teflon particles labelled with 111In with an extremely slow inhalation flow, 0.05 L/s. With this inhalation technique, particles are deposited mainly in the small conducting airways. Lung retention was measured at 0 and 24 hours, and at 7, 14, and 21 days after inhalation. Lung retention at 24 hours (% of deposition) was highly reproducible for the CB patients, studied twice, but it was not significantly different from that found for healthy subjects and, furthermore, not related to airway resistance (Raw), nor FEV1% predicted. Both healthy subjects and CB patients showed significant clearance in the period between 24 hours and day 21. The mean retention were higher (P<.001) in CB patients, 90%, 89%, 87% of 24 hours retention at 7, 14, and 21 days, compared to 80%, 76%, 71% of 24 hours retention at 7, 14, and 21 days measurements for healthy subjects. Clearance after 24 hours (retention at 21 days) was significantly related to FEV1% predicted, but not Raw. Reduced FEV1% predicted values was associated with slower clearance rates. Model calculations were performed to estimate intrapulmonary deposition patterns. A limited effect was shown for airway dimension and uneven ventilation. The differences between healthy and CB patients were, however, limited. It is not possible to conclude whether the difference in clearance after 24 hours is an effect of change in regional deposition, or slower small airway clearance in diseased airways. This technique to target the smallest ciliated airways, using an extremely slow inhalation flow, provides new possibilities to investigate smallest airway function and drug delivery that merits further investigations.

Glass-based radon-exposure assessment and lung cancer risk.

Lung cancer risk estimation in relation to residential radon exposure remains uncertain, partly as a result of imprecision in air-based retrospective radon-exposure assessment in epidemiological studies. A recently developed methodology provides estimates for past radon concentrations and involves measurement of the surface activity of a glass object that has been in a subject's dwellings through the period for exposure assessment. Such glass measurements were performed for 110 lung cancer subjects, diagnosed 1985 to 1995, and for 231 control subjects, recruited in a case-control study of residential radon and lung cancer among never-smokers in Sweden. The relative risks (with 95% confidence intervals) of lung cancer in relation to categories of surface-based average domestic radon concentration during three decades, delimited by cutpoints at 50, 80, and 140 Bq m(-3), were 1.60 (0.8 to 3.4), 1.96 (0.9 to 4.2), and 2.20 (0.9 to 5.6), respectively, with average radon concentrations below 50 Bq m(-3) used as reference category, and with adjustment for other risk factors. These relative risks, and the excess relative risk (ERR) of 75% (-4% to 430%) per 100 Bq m(-3) obtained when using a continuous variable for surface-based average radon concentration estimates, were about twice the size of the corresponding relative risks obtained among these subjects when using air-based average radon concentration estimates. This suggests that surface-based estimates may provide a more relevant exposure proxy than air-based estimates for relating past radon exposure to lung cancer risk.