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Biomedical subjects

P Camner

Publications and source records attributed to P Camner.

171 records · Page 10Linked to original sources

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↗

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↗

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↗

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↗

Human bronchiolar deposition and retention of 6-, 8- and 10-micrograms particles.

Three groups, each consisting of 6 healthy subjects, inhaled, respectively, 6-micrograms (aerodynamic diameter), 8-micrograms, and 10-micrograms Teflon particles, labeled with indium-111. The particles were inhaled at an extremely low flow rate, 0.05 L/s. Lung retention was measured after 0, 24, 48, and 72 h. Two models were used to calculate particle deposition in the lungs in the various generations: the Karolinska Institute model (KI model) and the University of Southampton model (US model). From the experimental clearance data and the theoretical deposition data, it was calculated that the average retention after 24 h was around 100% for particles deposited in generations 13-16 (ciliated bronchioles) and around 20% in generations 0-12 (both large and small ciliated airways). In these calculations, it was assumed that the retained fractions were independent of particle size. The depositions in the bronchial region (generations 0-8), bronchiolar region (generations 9-15 or 9-16), and the alveolar region were calculated using the two models and compared with the recent ICRP model. On the whole, the three models agreed fairly well.

Administration, Inhalation↗

Effect of adrenergic stimulation on clearance from small ciliated airways in healthy subjects.

Mucociliary transport is an important clearance mechanism of larger airways, but in the smallest ciliated airways (bronchioles) it may be less effective. The present study aimed at investigating whether clearance from the bronchioles in subjects with healthy airways was stimulated by an adrenergic agonist (terbutaline sulphate). Tracheobronchial clearance was studied twice in 10 healthy subjects after inhalation of 6-micron (aerodynamic diameter) monodisperse Teflon particles labeled with 111In. At one exposure, oral treatment with terbutaline sulphate, known to stimulate clearance in large airways, began immediately after inhalation of the particles. The other exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 L/s, which gave deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48, and 72 h. Clearance was significant every 24 h for both exposures (p < .05, two-tailed paired t-test), with similar fractions of retained particles at all time points. During treatment with terbutaline sulphate, the subjects' pulse rates tended to be higher, but clearance rates did not increase. We found, as expected, no significant correlation between lung retention and lung function in either exposure. This study shows that an adrenergic agonist does not significantly influence overall clearance from the bronchiolar region in healthy subjects. This suggests that mucociliary transport does not significantly contribute to clearance from the smallest ciliated airways. Other mechanisms may be more important for the transportation of mucus from these airways.

Administration, Inhalation↗

Influence of bethanechol on retained particles deposited on the first bifurcation of rabbits.

Retention of 4 micron 51Cr labelled Teflon particles administered to nine male rabbits via trachea was measured externally. About 5 microliter of a suspension with a particle concentration of 40 mg X ml-1 was deposited on the first bifurcation through a fiberoptic bronchoscope under urethane anesthesia. Over a period of two weeks, the rabbits were exposed twice, under the influence of the cholinergic drug bethanechol chloride and in a control examination. The time period during which 90% of deposited particles had cleared was significantly shorter in the presence of bethanechol (16 h) than in the control experiment (70 h). The magnitude of the fraction which cleared within the first hour did not differ significantly for drug administration and control, being 39.0% and 36.8%, respectively. The fraction which did not clear within the first hour tended (p = 0.1) to clear faster, half-time 10.4 h, when bethanechol chloride was given than it did in the controls, half-time 31.3 h. A reasonable interpretation of the results is that the cholinergic compound, bethanechol, increases bronchial secretion, which results in a reversed movement of the particles that previously penetrated the mucous layer, back to the mucous layer.

Animals↗

Retention of particles on the first bifurcation and the trachea of rabbits.

Retention of 6 micron, intratracheally-administered radioactively-tagged, teflon particles on the lower trachea and the first bifurcation of rabbits was measured externally for 2-3 days. Clearance occurred in a fast and a slow phase. The fast phase was finished after 1-2 h. The slow phase differed markedly between the lower trachea and the first bifurcation. The mean half-times were 19 and 39 h i trachea and first bifurcation, respectively. On average, 39% of the particles on the trachea and 71% on the first bifurcation cleared with the slow phase. Thus the bifurcation is more exposed to pollutants not only from deposition of more particles caused by impaction but also because of less efficient clearance.

Animals↗

Interaction between Cryptococcus neoformans and alveolar macrophages.

Phagocytosis, oxidative metabolism and phagolysosomal pH of rat alveolar macrophages (AM) were studied at different points of time after challenge with Cryptococcus neoformans. Phagocytosis was evaluated using a fluorescent quenching technique which distinguishes between attached and ingested organisms. The nitroblue tetrazolium (NBT) test was used as an indirect measurement of the oxidative metabolism of the phagocytes. The pH of the phagolysosomes was measured using a cytofluorometric technique. Both the attachment and ingestion of serum opsonized C. neoformans by AM were slow during the first hours of incubation, but were considerable after 24 h. The oxidative metabolism of Am challenged with the yeast was insignificant during the first hour, but reached high levels after 24 h. Most phagolysosomes in AM with ingested cryptococci had a pH < 5.5. Our results indicate that these AM defence mechanisms, although poor during the first hours after exposure to the yeast, are of significance after 24 h. Thus, in the immunocompetent host the AM should prevent the dissemination of C. neoformans from the lungs.

Animals↗