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Biomedical subjects

R B Schlesinger

Publications and source records attributed to R B Schlesinger.

At least 73 records · Page 4Linked to original sources

Effects of inhaled acids on respiratory tract defense mechanisms.

The respiratory tract is endowed with an interlocking array of nonspecific and specific defense mechanisms which protect it from the effects of inhaled microbes and toxicants, and reduce the risk of absorption of materials into the bloodstream, with subsequent systemic translocation. Ambient acids may compromise these defenses, perhaps providing a link between exposure and development of chronic and acute pulmonary disease. This paper reviews the effects of inhaled acids upon the nonspecific clearance system of the lungs.

Acids↗

Comparative irritant potency of inhaled sulfate aerosols--effects on bronchial mucociliary clearance.

The effect of 1-hr oral inhalation exposures to submicrometer aerosols of ammonium bisulfate (NH4HSO4), ammonium sulfate [NH4)2SO4), and sodium sulfate (Na2SO4) upon mucociliary clearance from the bronchial tree of rabbits was examined. Exposures to NH4HSO4 at concentrations of approximately 600-1700 micrograms/m3 produced a significant depression of clearance rate only at the highest exposure level. No significant effects were observed with the other sulfates at levels up to approximately 2000 micrograms/m3. When results were compared to those from another study in this laboratory using sulfuric acid (H2SO4) aerosol, the ranking of irritant potency was H2SO4 greater than NH4HSO4 greater than (NH4)2SO4, Na2SO4. Alteration in bronchial mucociliary clearance due to sulfate aerosols appears to be related to the deposition of [H+] on the mucus lining of conducting airways.

Aerosols↗

Measurement of respiratory tract ammonia in the rabbit and implications to sulfuric acid inhalation studies.

Ammonia (NH3) in the respiratory tract has the potential to neutralize inhaled acid vapors and aerosols. Levels of exhaled (nasal) NH3 were measured in rabbits at different times on the same day, on different days, and in rabbits in a normal fed state, or in a fasted or fed state in which the teeth were brushed and the mouth cleansed. The variability of NH3 levels within any individual rabbit was found to be of the same order as the variability found between different animals. In addition, rabbits which were fasted and had their teeth brushed exhaled significantly less NH3 than did fed animals. Levels in the former group ranged from 4 to 236 micrograms/m3, while those in the latter group ranged from 10 to 758 micrograms/m3. Although brushing the teeth of fed animals compressed the observable range of NH3 levels (22-404 micrograms/m3), this was not a significant reduction compared to fed, unbrushed animals. Thus, fasting likely minimized foodstuff in the mouth; the latter may contribute to NH3 formation through bacterial degradation, which appears to be a significant source of NH3 exhaled through the nose. The NH3 concentrations observed may produce variable degrees of neutralization of inhaled H2SO4 droplets before they deposit in the lungs.

Aerosols↗

Exposure-response relationship of bronchial mucociliary clearance in rabbits following acute inhalations of sulfuric acid mist.

Eight rabbits underwent 1 h oral inhalations of submicrometer sulfuric acid mist at concentrations ranging from approx. 100-1084 micrograms/m3, followed by measurement of the mucociliary clearance of a tracer aerosol from the bronchial tree. These data, plus those from a previous study, were used to construct an exposure concentration-response relationship for alterations in clearance produced by H2SO4. The response pattern is characterized by transient acceleration of clearance at low concentration exposures, and retardation at higher concentrations. In addition, comparison of these results with those from a similar study using human volunteers supports use of the rabbit as an appropriate model for studying mucociliary clearance alterations produced by inhaled irritants.

Aerosols↗

Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways.

Inhaled insoluble particles that deposit along normal healthy tracheobronchial airways of humans and other mammals are transported on the proximally moving mucous lining to the larynx, where they are swallowed. The transit time from the most distal ciliated airways varies from 0.1 to 1 d, with each individual having a relatively constant, characteristic time. The exact time course of clearance depends on the distributions of both particle deposition and mucus velocities along the airways. There are too few data on intrabronchial deposition and mucociliary transport rates for laboratory animals to permit a thorough intercomparison among species. However, enough is known about the relative lung sizes and anatomical differences among the various species to make some preliminary, but important, distinctions. As compared to commonly used experimental animals, humans have larger lungs and a more symmetric upper bronchial airway branching pattern. In addition, humans do considerable oral breathing, thus bypassing the effective air cleaning capability of the nasal airways. These differences contribute to a greater amount of upper bronchial airway particle deposition in humans, as well as to greater concentrations of deposition on localized surfaces near airway bifurcations. Airborne irritants that deposit in small ciliated airways may produce marked changes in mucociliary transport. Such materials include cigarette smoke, submicrometer-sized sulfuric acid mist, nitrogen dioxide, and ozone. For cigarette smoke and sulfuric acid, which have been studied for transient effects following single brief exposures in both humans and animals, the responses are similar. Upon repetitive exposures in animals, both of these irritants produce persistant alterations in clearance rates and airway morphometry. Studies of the effects of ozone on mucociliary clearance have, up to now, been limited to tests of the responses of rats to single exposures. The similarities between the known effects of various irritants suggests a nonspecific response.

Air Pollutants↗

Response of the bronchial mucociliary clearance system in rabbits to inhaled sulfite and sulfuric acid aerosols.

A group of eight rabbits was exposed (orally) for 1 hr to a distilled water aerosol (sham control) or to submicrometer aerosols of either a transition metal sulfite complex (Fe(III)-S(IV], sodium sulfite (Na2SO3), or sulfuric acid (H2SO4). Mucociliary clearance was evaluated by external retention measurements of radioactively tagged tracer particles from the bronchial tree. Fe(III)-S(IV) in the range of 238 to 1227 micrograms/m3 (as SO2-3) produced no significant change from sham control in the mean residence time (MRT) of the tracer, indicating no effect upon mucociliary clearance rate. On the other hand, Na2SO3 at levels greater than or equal to 1200 micrograms/m3 (as SO2-3) resulted in clearance acceleration; the lack of effect of Fe(III)-S(IV) is possibly due to its stability. H2SO4 at 260 to 2155 micrograms/m3 produced a significant dose-related response, indicating clearance acceleration at low concentrations and a depression at higher levels.

Aerosols↗

Comparative morphometry of the upper bronchial tree in six mammalian species.

The length, diameter, and angle of branching of all airways through the sixth level of branching below the trachea were measured on corrosion casts prepared from the lungs of two animals whose bronchial geometry has not previously been studied, namely the donkey and the rabbit. These measurements and morphometric data for the rat, hamster, dog, and human obtained from other sources were analyzed and compared. The case prepared from human lungs exhibited an airway geometry that was clearly distinct from that shown by the nonhuman species. The human upper bronchial tree was the most symmetrical with respect to airway diameter and angle of branching. In all species studied, airway length was the most irregular parameter. The reasons for differences in branching geometry are not clearly understood. However, when attempting to determine whether a particular species may be used as a model for man in inhalation toxicology, and in the subsequent interpretation of animal data, an appreciation of differences in airway morphometry is essential.

Animals↗

The effects of irritant aerosols on mucus clearance from large and small conductive airways.

The effects of one hour exposures of healthy nonsmoking human volunteers to submicrometer H2SO4 droplets via nasal mask on tracheobronchial mucociliary particle clearance were studied using two different sized monodisperse gamma-tagged Fe2O3 test aerosols. The larger sized Fe2O3 aerosol, 7.5 micrometers AMAD, was deposited primarily in the larger bronchial airways, while the smaller 4 micrometers AMAD aerosol had a much greater fraction deposited in the smaller and more distal conductive airways. Thoracic retention of the Fe2O3 aerosols as a function of time after a brief inhalation was measured with external collimated radiation detectors. At the highest H2SO4 exposure, 1,000 micrograms/m3, there was a pronounced transient slowing of bronchial mucociliary clearance of both the 7.5 and 4 micrometers Fe2O3. On the other hand, at the lowest H2SO4 concentration, 100 micrograms/m3, there was a marked acceleration of the clearance of the 7.5 micrometers Fe2O3, but a slowing of the clearance of the 4 micrometers Fe2O3. Thus, submicrometer H2SO4, which deposits primarily in the distal airways, can slow mucociliary clearance in those airways. In the larger airways, where its deposition is minimal, the H2SO4 can, at the same time, accelerate mucus transport.

Adult↗

Remanent magnetic fields for measuring particle retention and distribution in the lungs.

A relatively inexpensive method for the noninvasive in vivo detection of ferrimagnetic particles within the lungs of a large laboratory animal, viz., the donkey, is described. The particles were neutron activated prior to inhalation, which permitted a comparison of two different retention measurements for the same particles, i.e., a well-characterized radiological-detection method concurrent with the newer magnetic-field technique. The long-term clearance of the particles from the lung was monitored in terms of the reduction in initial remanent field following magnetization, and the reduction in gamma-ray flux reaching the collimated scintillation detectors. Comparison of the measurements confirmed that the reduction of the initial remanent-field values with time was due to particle clearance rather than a change of the iron state to a nonmagnetic form. This validates previous reports that particle clearance studies can be performed using remanent magnetic-field measurement techniques. However, remanent magnetic-field measurements require careful design and interpretation, since they are highly sensitive to the distribution of the particles within the effective viewing field.

Aerosols↗

Effects of sulfuric acid aerosol inhalations.

Submicrometer H2SO4 droplets can affect pulmonary functions in humans. The lowest concentration which has been reported to produce a statistically significant effect on pulmonary mechanics is 1 mg/m3. Effects on tracheobronchial mucociliary clearance of inert particles were observed in our laboratory at much lower concentrations. For ten nonsmoking humans exposed for one hour via nasal mask to 0.1 mg/m3 of H2SO4, the mean bronchial clearance half-time was reduced by 38% (p less than 0.02) while for 1 mg/m3, it was increased by 48% (p less than 0.03). Four donkeys exposed for 1 hour daily to 0.1 mg/m3 for six months developed clearance abnormalities which persisted for at least three months after the last exposure. The patterns of mucociliary clearance responses to H2SO4 are similar to those seen previously in humans and donkeys following exposure to cigarette smoke, a known causal factor for chronic bronchitis.

Aerosols↗

A variable-opening mechanical larynx for use in aerosol deposition studies.

The realistic study of article deposition in model systems of the tracheobronchial tree requires that respiratory patterns and airflow profiles mimic those occurring in vivo. This paper describes a variable-opening mechanical larynx which was designed for use in deposition studies performed under cyclic flow conditions.

Aerosols↗

Aerosol generation from a limited liquid medium.

A modified method for nebulization was developed for use with relatively small (20 mL) amounts of feed liquid, in this case, a suspension of radioactively tagged polystyrene (CMD = 2.87 micron, sigma g = 1.25). The method may be easily adapted for use in producing other aerosols where only this quantity of suspension material is available.

Aerosols↗

An interrupter method for measurement of airway resistance in small animals.

An interrupter technique for the measurement of airway resistance in spontaneously breathing, unanesthetized small experimental animals is described. The method makes use of an automatic 35-mm camera body to provide the necessary speed for interruption in these rapidly breathing animals and an analog computer to monitor breathing. The system was designed as a screening technique for assessing the irritancy of air pollutants. Initial results using rabbits is presented.

Airway Resistance↗