Tracheobronchial clearance of inhaled 6mum Teflon particles (density 2 gm/cu cm) tagged with technetium 99m was studied in healthy subjects by external measurement of the radioactivity in the lungs for two hours. Clearance, salivary secretion, blood pressure, and heart rate were determined in eight subjects after double-blind, subcutaneous administration of 0.25 mg terbutaline sulfate, a beta-adrenoceptor stimulating compound and vehicle, respectively, in a crossover study. Terbutaline produced a marked increase in clearance and a slight increase in heart rate, but had no important effect on salivary secretion or blood pressure. The result indicates that the blood concentrations of catecholamines might be of importance for the regulation of the mucociliary transport rate.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Lung clearance of 4-micron particles coated with silver, carbon, or beryllium.

Lung clearance in rabbits during the first week after inhalation of 4-micron teflon particles tagged with chromium-51 and coated with silver, carbon, or beryllium was studied by external measurements of the radioactivity in the lungs. Ten rabbits were exposed to silver- and carbon-coated particles on two separate occasions within 3 weeks. Clearances of the two types of particles were quite similar. Clearance in eight other rabbits that had inhaled silver-coated particles was quite similar to clearance in eight rabbits that had inhaled beryllium-coated particles. The result is regarded as evidence that alveolar macrophages do not play an active role in removing intact particles from the lung the first week after inhalation.

Animals↗

PubMedDate not supplied

Human alveolar deposition of 4 micron teflon particles.

On two occasions ten healthy men inhaled with maximally deep inhalations at 0.5 1/sec a test aerosol of 4 micron teflon particles tagged with 111In. Radioactivity in the lungs was measured a few min, 24 hr, and 2, 3, and 4 days after inhalation. Retention decreased greatly between the measurements performed a few min and 24 hr after inhalation, but was similar in measurements 1 to 4 days after inhalation. Among individuals, retention varied considerably 1 to 4 days after inhalation (by a factor of 2), but the retention in each individual subject was uniform. Measuring the retention of a radioactively tagged test aerosol 1 day after inhalation, and regarding this retention as alveolar deposition, might be of value in preventive measures against certain toxic dusts.

Adult↗

PubMedDate not supplied

Human tracheobronchial deposition and effect of two cholinergic aerosols.

The effects of two methacholine aerosols with mass median diameters congruent to 7 and 3 microns were measured in 10 healthy subjects. The concentrations of the two aerosols were increased until forced expiratory volume in 1 s (FEV1) decreased with about 20%. Pulmonary fraction (FEV1, FVC, FEV25-75%, FEF75-85%, R(aw), and phase III of single breath O2 test) and deposition of 3.6-microns radiolabeled Teflon particles were studied before and after bronchial challenge with the two aerosols. Output from the nebulizers and size distribution were measured and from these data and from data on deposition of Teflon particles from this and seven earlier studies the doses of the two methacholine aerosols to the tracheobronchial region were calculated. The changes in all pulmonary function parameters and deposition of 3.6-microns particles were similar for the two aerosols. The calculated dose for the aerosol with the large particles was 3-4 times higher than that with the smaller particles. The results indicate greater effect of a certain dose to the tracheobronchial part of the lung if the mass is spread on many small particles than on fewer large ones.

Adult↗

PubMedDate not supplied

Human deposition and clearance of 6-micron particles inhaled with an extremely low flow rate.

In human experimental data, tracheobronchial deposition reaches its maximum for particles of about 6 microns inhaled at 0.5 L/s. The purpose of the present study was to investigate if tracheobronchial deposition of 6-microns particles could be increased, especially in the smaller bronchi, using an extremely slow inhalation rate. Six healthy nonsmokers inhaled monodisperse 6-microns (aerodynamic diameter) Teflon particles labeled with 111In at 0.04 L/s. Radioactivity in mouth and throat, lung, and stomach was measured immediately after inhalation by profile scanning and in the lung also after 24, 48, 72, and 96 h. There was a substantial clearance between 24 and 72 h; around 20% of the total clearance occurred between 24 and 72 h. This is in contrast to earlier studies in which only around 1% of 6-microns particles inhaled at 0.5 L/s cleared between 24 and 72 h. This indicates a markedly higher deposition in the smaller bronchi at 0.04 L/s than at 0.5 L/s. The total tracheobronchial deposition was 50%, compared to about 30% when particles were inhaled at 0.5 L/s. These findings could be therapeutic use. They also implicate the possibility of developing a diagnostic model that can separate between bronchial reactivity in large and small bronchi.

Adult↗

PubMedDate not supplied

Retention of particles inhaled in boli with and without induced bronchoconstriction.

Large lung retentions (up to 50%) of particles < or = 4 microns inhaled with a bolus technique at a penetration depth less than dead space have been reported to occur after 24 h. This retention may be due to retarded clearance of particles deposited in the airways of the tracheobronchial tract; an alternative explanation could be that particles are deposited in the alveolar region. The purpose of the present study was to confirm the occurrence of retained fractions and to study the influence of a cholinergic drug, which is assumed to give a more central particle deposition, on these retentions in human lungs after shallow aerosol bolus inhalation. Twelve healthy subjects inhaled, with a bolus technique, monodisperse Teflon particles (2.4 microns geometric diameter, 3.5 microns aerodynamic diameter), labeled with 111In. The volumetric lung depth of the inspired bolus was around 60 mL and flow rate was about 300 mL/s. Six subjects inhaled the test particles after a provocation with a cholinergic aerosol, which induced a threefold increase in airway resistance. The other six subjects inhaled a cholinergic aerosol after inhalation of the test particles or inhaled no cholinergic aerosol at all. Radioactivity in the body was measured after 0.5, 24, 48, and 72 h with a whole-body scanner with three 127 x 101-mm Nal detectors. The investigation confirmed results obtained earlier by a group in Frankfurt claiming that great retentions occur after 24 h. The retentions tended to be lower in the group receiving a bronchoconstricting drug before the bolus inhalations. There was a significant lung clearance of particles between 24 and 72 h, in contrast to the findings in earlier studies in healthy subjects and asthmatics who inhaled Teflon particles in large volumes. On the other hand, the clearance agreed well with the clearance in healthy subjects with extensive deposition of Teflon particles in the small ciliated airways, obtained by means of an extremely low inhalation flow rate. The results suggest that a considerable fraction of the particles in the bolus inhalation have been deposited in small ciliated airways in which the mucociliary transport is less efficient or in the alveolar region.

Administration, Inhalation↗

PubMedDate not supplied

Clearance in smaller airways of inhaled 6-microm particles in subjects with immotile-cilia syndrome.

In subjects with an inherited lack of mucociliary transport, so called immotile-cilia syndrome (ICS), coughing effectively clears particles deposited in larger airways of the tracheobronchial region. The present study investigated clearance in smaller airways of 111In-labeled 6-microm (aerodynamic diameter) monodisperse Teflon particles in six subjects with ICS. The particles were inhaled at an extremely slow flow, 0.05 L/s. Theoretical calculations and experimental data in healthy subjects using this slow flow support particle deposition mainly in smaller ciliated airways, i.e., in bronchioli (generations 12-16). This contrasts with the more centrally deposited pattern obtained using a normal inhalation flow, 0.5 L/s. Lung retention was measured at 0, 24, 48,72 and 96 h. Clearance was significant every 24 h measured over the first 72 h, whereupon it slowed down. The fractions of retained particles were significantly (p < .01) larger than those found for healthy subjects using the slow inhalation flow and those found for ICS subjects using a normal inhalation flow. The results indicate that clearance of particles in smaller airways is incomplete and that cough cannot fully compensate for the lack of mucociliary transport in this region.

Adult↗

PubMedDate not supplied

Deposition and clearance in large and small airways in chronic bronchitis.

Tracheobronchial clearance was studied twice in 16 patients with chronic obstructive bronchitis after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labeled with 111In. At one exposure the particles were inhaled at an extremely slow flow, 0.05 L/s; at the other they were inhaled at a normal flow, 0.5 L/s. Theoretical calculations and experimental data in healthy subjects indicate particle deposition mainly in the smallest ciliated airways using 0.05 L/s, i.e., in the bronchiolar region, and an enhanced deposition in larger airways using 0.5 L/s. Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significantly every 24 h for both exposures (p < .05). The fractions of retained particles were significantly larger for particles inhaled at 0.05 L/s compared to 0.5 L/s at all points of time (p < .001). Compared to healthy subjects, the retained fractions of deposited particles were larger in patients with bronchitis breathing at 0.05 L/s, but smaller with breathing at 0.5 L/s (p < .01). Significant relationships were found between lung retentions and airway resistance (Raw) at 0.5 L/s, r = -.68 (p < .01), but not at 0.05 L/s, and between lung retention at 24 h and weight of expectorated sputum at 0.05 L/s, r = -.50 (p < .05). There was, furthermore, an almost significant relationship between sputum volume and rate of tracheobronchial clearance between 0 and 24 h (in percentage of the total amount cleared during 72 h) at 0.05 L/s, r = .42 (p = .05). The results indicate that in patients with chronic bronchitis overall clearance of particles in small airways is incomplete, as compared to larger airways. An increased amount of mucus, however, seemed to improve clearance of peripherally deposited particles, possibly by making cough more effective in small airways.

Adult↗

PubMedDate not supplied

Long-term lung clearance of 195Au-labeled teflon particles in humans.

Ten healthy males inhaled monodisperse Teflon particles (geometric diameter 3.6 microns, aerodynamic diameter 5.3 microns) labeled with 195Au (half-life 183 days). The leakage of 195Au from the particles in vitro in water was less than 0.2% per year. Retention over the thorax was followed for about 900 days using two separate detector systems. One system consisted of four Ge detectors placed close to the front of the chest over the upper and lower regions of the lungs. The other system consisted of three NaI crystals placed in a ring around the thorax at some distance from the chest wall. Activities of 195Au in feces (24- or 48-h samples) could be measured as long as activities in the thorax could be measured. For the period 7-250 days, the half-times were similar for the two detectors, on the average 740 days for the NaI detectors and 680 days for the Ge detectors. The average half-times estimated from measurements from about 250 days to about 900 days were 1750 days with the NaI detectors and 880 days with the Ge detectors. Clearance curves constructed from measurements from feces agreed very well with clearance measured with the NaI detectors. The excretion via feces was well described by a power function with days after exposure as base. This total clearance from the thoracic region was slower than in earlier studies. No activity could be measured in the urine. The measurements with the two detector systems show that a translocation within the thoracic region occurred. This might be explained by transportation of particles from the lung parenchyma to the regional lymph nodes. The accumulation of particles in the regional lymph nodes was tentatively calculated on the basis of that assumption.

Administration, Inhalation↗

PubMedDate not supplied

Clearance of particles from small ciliated airways.

In recent years, there has been a debate on whether a considerable fraction of particles is retained after 24 h in the tracheobronchial region. In the present study, 8 healthy subjects inhaled 6.2-microns monodisperse Teflon particles labeled with 111 In twice, at flow rates of 0.45 and 0.045 L/s. According to theoretical calculations, the particles inhaled at 0.45 L/s should deposit mainly in large bronchi and in the alveolar region, whereas the particles inhaled at 0.045 L/s should be deposited mainly in small ciliated airways. Twenty-four hours after inhalation, about half of the particles inhaled with both modes of inhalation had cleared. Clearance during the period from 1 to about 30 days after inhalation, could, for both modes of inhalation, be described by the sum of two exponential functions. For the inhalation rate of 0.45 L/s, 15% cleared with a half-time of 3.4 days and 85% with a half-time of 190 days. For the inhalation of 0.045 L/s, 20% cleared with a half-time of 2.0 days and 80% with a half-time of 50 days. The results strongly indicate (1) that a considerable fraction of particles deposited in small ciliated airways had not cleared within 24 h, and (2) that these particles cleared differently from particles deposited in the alveolar region. The experimental data agree quite well with the IRTM predictions made using its default slow clearance fractions.

Administration, Inhalation↗