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Biomedical subjects

R C Mannix

Publications and source records attributed to R C Mannix.

11 recordsLinked to original sources

Effects of breathing parameters on sidestream cigarette smoke deposition in a hollow tracheobronchial model.

The effects of variations in cyclic breathing parameters (i.e., tidal volume and breath frequency) have been the subject of few studies devoted to the deposition of submicrometer aerosols in the human respiratory tract. Therefore, a series of experiments was performed to investigate whether the deposition efficiency (DE) of sidestream cigarette smoke is altered by varying tidal volume and breath frequency in a child-size hollow tracheobronchial (TB) model while maintaining a fixed minute ventilation rate of 5 L/min. Under cyclic flow conditions with tidal volumes of 100 mL (50 breaths/min), 250 mL (20 breaths/min), 500 mL (10 breaths/min) and 750 mL (6.7 breaths/min), sidestream cigarette smoke was passed through replicas of an idealized hollow TB model. The smoke deposits were extracted and then quantitated spectrophotometrically. The experiments revealed a significant difference in DE between the 100-mL tidal volume (DE = 6.0%) and the 750-mL tidal volume (DE = 11.1%). Under equivalent steady flow conditions, the mean DE was 21.5%. A trend was evident in the data--DE increased as tidal volume increased (and breathing frequency decreased)--suggesting that the influence of diffusion and secondary flows on DE becomes greater as the air residence time increases and the degree of air turbulence decreases. The results provide evidence of the importance of breathing parameters when attempting to model in vivo deposition of environmental tobacco smoke and other similar-size respirable aerosols.

Adult

Deposition of monodisperse particles in hollow models representing adult and child-size tracheobronchial airways.

A series of experiments was performed to determine deposition efficiencies of four sizes of radiolabeled monodisperse particles in custom-made hollow tracheobronchial models. The particles had geometric diameters of about 1, 5, 10, and 15 microm. The tracheobronchial models, consisting of a trachea and two or more additional generations, had dimensions representative of a typical adult, a 7-y-old child, and a 4-y-old child; the child-size models were appropriately scaled-down replicas of the adult-size model. Each deposition experiment was conducted using a steady inspiratory airflow representative of low physical activity for the appropriate age of individual: 20 L min(-1) for the adult; 9 L min(-1) for the 7-y-old; 5.5 L min(-1) for the 4-y-old. The results indicate that deposition efficiency of the particles increased substantially (up to 35 times) in all three models as particle diameter increased from 1-15 microm, undoubtedly as a result of particle impaction and sedimentation-related phenomena. An analysis of variance demonstrated the occurrence of statistically-significant (p < 0.05) main effects of hollow model size and particle size; the interaction between the two parameters was also significant. In general, deposition efficiencies of the various sizes of particles were greater in the child-size models than in the adult-size model; this effect may have risk assessment implications. In addition, the results obtained experimentally agreed more closely with those predicted using a radiation-protection mathematical particle deposition formulation as the particle size increased for each of the sizes of models.

Adult

Physical characterization of incense aerosols.

Experiments were performed to study the physical characteristics of smoke aerosols generated by burning three types of stick incense in a 4 m3 clean room. Sidestream cigarette smoke was also examined under the same conditions to provide a comparison. Among the parameters measured were (a) masses of aerosol, carbon monoxide and nitrogen oxides generated by burning the incense or cigarettes, (b) rates of decay of the particles from the air, and (c) estimates of count median particle size during a 7 h period post-burning. There was variability among the types of incense studied with respect to many of the parameters. Also, as a general trend, the greater the initial particulate mass concentration, the more rapid the rate of decay of the smoke. In relation to the quantity of particulate generated, cigarette smoke was found to produce proportionally larger quantities of carbon monoxide and nitrogen oxides than did incense. Due to the fact that burning incense was found to generate large quantities of particulate (an average of greater than 45 mg/g burned, as opposed to about 10 mg/g burned for the cigarettes), it is likely, in cases in which incense is habitually burned in indoor settings, that such a practice would produce substantial airborne particulate concentrations.

Aerosols

Effects of nitrogen dioxide on respiratory tract clearance in the ferret.

During growth and development, young children are periodically exposed to relatively high concentrations of various air contaminants, including tobacco smoke and environmental pollutants generated by fossil fuel use. The effects of these exposures on respiratory function and lung development are difficult to determine because of interindividual variation and lack of accurate dosimetry. To provide information on the effects of chronic exposure to a common indoor and outdoor pollutant during lung development, a study was performed to assess the effects of exposure to two concentrations of nitrogen dioxide (NO2; 0.5 or 10 ppm) on tracer particle clearance from the airways of ferrets exposed during postnatal respiratory tract development. Separate groups of ferrets were exposed nose-only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15 wk. Those animals exposed for 8 wk were subsequently housed in a filtered air environment until the particle clearance measurements commenced at 3 wk prior to the end of the 15-wk exposure protocol. Radiolabeled (51Cr) tracer particles were deposited in the respiratory tract of all animals by inhalation, and the clearance rates from the head and thoracic regions were separately monitored for 18 d. No significant effects of the NO2 exposure on head airways clearance were seen. In contrast, the rates of particle clearance from the thorax of both the 8- and 15-wk groups exposed to 10 ppm NO2 were significantly reduced, and did not differ from each other. Thoracic clearance was also reduced in animals exposed to 0.5 ppm, but the rate was not significantly different from that of the clean air exposed controls. These results show that NO2 at moderate concentrations caused highly significant changes in the deep lung of the juvenile ferret, and suggest that impairment of the clearance function may be only slowly recovered after chronic exposure.

Animals

Health effects of acid aerosols formed by atmospheric mixtures.

Under ambient conditions, sulfur and nitrogen oxides can react with photochemical products and airborne particles to form acidic vapors and aerosols. Inhalation toxicological studies were conducted, exposing laboratory animals, at rest and during exercise, to multicomponent atmospheric mixtures under conditions favorable to the formation of acidic reaction products. Effects of acid and ozone mixtures on early and late clearance of insoluble radioactive particles in the lungs of rats appeared to be dominated by the oxidant component (i.e., the mixture did cause effects that were significantly different from those of ozone alone). Histopathological evaluations showed that sulfuric acid particles alone did not cause inflammatory responses in centriacinar units of rat lung parenchyma (expressed in terms of percent lesion area) but did cause significant damage (cell killing followed by a wave of cell replication) in nasal respiratory epithelium, as measured by uptake of tritiated thymidine in the DNA of replicating cells. Mixtures of ozone and nitrogen dioxide, which form nitric acid, caused significant inflammatory responses in lung parenchyma (in excess of effects seen in rats exposed to ozone alone), but did not damage nasal epithelium. Mixtures containing acidic sulfate particles, ozone, and nitrogen dioxide damaged both lung parenchyma and nasal epithelia. In rats exposed at rest, the response of the lung appeared to be dominated by the oxidant gas-phase components, while responses in the nose were dominated by the acidic particles. In rats exposed at exercise, however, mixtures of ozone and sulfuric acid particles significantly (2.5-fold) elevated the degree of lung lesion formation over that seen in rats exposed to ozone alone under an identical exercise protocol.

Acid Rain

Effects of pollutant atmospheres on surface receptors of pulmonary macrophages.

The effects of two multicomponent pollutant atmospheres on the surface receptors (FcR) and phagocytic activity of rat pulmonary alveolar macrophages have been studied. FcR are crucial for the macrophages to become cytotoxic against target cells. The atmospheres were composed of pollutants that are prevalent in the South Coast Air Basin of southern California. Rats were exposed nose-only to a 7-component oxidant-and sulfate-containing atmosphere for 4 h/d for either 7 or 21 consecutive days. In another experiment rats were exposed 5 h/d for 5 consecutive days to another pollutant combination--acid droplets plus carbon-containing dilute diesel engine exhaust. In both experiments matched rats were exposed nose-only to purified air to be used as controls. Each of the atmospheres studied significantly reduced FcR activity for at least 3 d following the exposure, with the group of rats exposed to the 7-component atmosphere for 21 d exhibiting the most pronounced effect. Macrophages from rats exposed to the diesel exhaust plus acid atmosphere and the 7-component atmosphere for 7 d had significantly reduced phagocytic activity for at least 3 d postexposure, while the macrophages from rats exposed to the latter atmosphere for 21 d had phagocytic activity near control values. The decrease in phagocytosis and inhibition of FcR of macrophages suggests an impairment of macrophage function that probably renders the host vulnerable to bacterial and/or viral infections.

Air Pollutants

Tracheal and bronchoalveolar permeability changes in rats inhaling oxidant atmospheres during rest or exercise.

Permeability of tracheal and bronchoalveolar airways of rats was measured and used to examine the effects of inhaled oxidant-containing atmospheres. The atmospheres studied were (a) ozone (O3) at 0.6 ppm (1.2 mg/m3) or 0.8 ppm (1.6 mg/m3); (b) nitrogen dioxide (NO2) at 6 ppm (11.3 mg/m3) or 12 ppm (22.6 mg/m3); (c) O3 + NO2 at 0.6 ppm (1.2 mg/m3) and 2.5 ppm (4.7 mg/m3), respectively; and (d) a 7-component particle and gas mixture (complex atmosphere) representing urban air pollution in a photochemical environment. The rats were exposed for 2 h. The effects of exercise during exposure were evaluated by exposing additional groups in an enclosed treadmill. Exposure of resting rats to 0.8 ppm O3 increased tracheal permeability to DTPA and bronchoalveolar permeability to diethylenetriamine pentaacetate (DTPA) and bovine serum albumin (BSA) at 1 h after the exposure. Bronchoalveolar, but not tracheal, permeability remained elevated at 24 h after the exposure. Exercise during exposure to O3 increased permeability to both tracers in the tracheal and the bronchoalveolar zones, and prolonged the duration of increased permeability in the tracheal zone from 1 h to 24 h, and in the bronchoalveolar zone from 24 h to 48 h. Permeability in the tracheal and bronchoalveolar zones of rats exposed at rest to 6 or 12 ppm NO2 did not differ from controls. However, rats exposed during exercise to 12 ppm NO2 for 2 h developed a significant increase in tracheal and bronchoalveolar permeability to DTPA and BSA at 1 h, but not at 24 or 48 h, after exposure. Exposure at rest to 0.6 ppm O3 plus 2.5 ppm NO2 significantly increased bronchoalveolar permeability at 1 and 24 h after exposure, although exposure at rest to 0.6 ppm O3 alone increased bronchoalveolar permeability only at 1 h after exposure. Exposure to O3 + NO2 during exercise led to significantly greater permeability to DTPA than did exercising exposure to O3 alone. Resting rats exposed to a complex gas/aerosol atmosphere composed of the above O3 and NO2 concentrations, plus 5 ppm (13.1 mg/m3) sulfur dioxide (SO2) and an aerosol of insoluble colloidal Fe2O3 with an aerosol of manganese, ferric, and ammonium salts, demonstrated increased permeability at 1 and 24 h after exposure. Nitric acid vapor was formed in both the O3 + NO2 atmosphere and the complex gas/aerosol atmosphere.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation

Relative permeability of nasal, tracheal, and bronchoalveolar mucosa to macromolecules in rats exposed to ozone.

Nasal, tracheal and bronchoalveolar injuries resulting from acute ozone exposure of rats were investigated by permeability changes. 99mTc-labeled diethylenetriaminepentaacetate (DPTA) and 125I-labeled bovine serum albumin (BSA) were selectively instilled into localized airway regions of anesthetized rats exposed to 0.8 ppm 03 or clean air for 2 h. Transmucosal transfer of the radiolabeled tracers was detected by counting the radioactivity in blood samples collected at short postinstillation time intervals. Permeability measurements were made on d 0, 1, and 2 after O3 exposure to analyze the extent and persistence of tissue injury in the nasal, tracheal, and bronchoalveolar regions. Normal mucosal permeability was low in nose, intermediate in bronchoalveolar zone, and high in trachea. The O3-related injury, reflected by elevated permeability, was substantial in the trachea and bronchoalveolar zone but was minimal in the nose immediately after the exposure. Abnormal permeability persisted for less than 24 h in the trachea but for more than 24 h in the bronchoalveolar zone. The results are consistent with the properties of O3 of causing greater injury in the smaller airways and the alveolar zone than in the trachea.

Animals

Inhalation exposure methodology.

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.).

Air Pollutants

Effect of sulfur dioxide-sulfate exposure on rat respiratory tract clearance.

The effects of a 4 hour exposure to a model sulfur pollutant atmosphere on the clearance of inhaled insoluble tracer particles from the lungs of rats has been studied. The pollutant combination consisted of 5 ppm of sulfur dioxide gas and 1.5 mg/m3 of sulfate aerosol at 80-85% relative humidity. The exposure atmosphere was aged for 30 minutes upstream of the exposure chamber in an aging line in order to provide for gas/ particle interactions such as those occurring in industrial and environmental atmosphere. Results indicate that the sulfur pollutant atmosphere did not produce a statistically significant alteration in early (nasopharyngeal and tracheobronchial) or late (parenchymal) clearance rates such as those which have been identified in this laboratory following exposure to ozone-containing atmospheres.

Aerosols

Effects of sulfur dioxide and formaldehyde on particle clearance in the rat.

The effects of exposures to sulfur dioxide and formaldehyde atmospheres on the clearance of inhaled, insoluble tracer particles from the lungs of rats have been studied. The tracer particles employed were polystyrene latex microspheres radio-labeled with 51Cr. Following the deposition of the 1.9-micron activity median aerodynamic diameter (AMAD) particles, the rats were divided into 3 groups for a single 4-h exposure to purified air, 20 ppm sulfur dioxide, or 20 ppm formaldehyde. Early, presumably upper-respiratory-tract, clearance was monitored by analysis of radioactivity excreted in feces, while late, presumably deep-lung, clearance was followed by thoracic counting of the animals. Both the sulfur dioxide and formaldehyde atmospheres did significantly delay early clearance (p less than 0.1, two-tailed t-test). However, the late clearance rates of the two pollutant-exposed groups of rats were not significantly different from that of the purified air-exposed group of rats. Although sulfur dioxide had numerically greater effects than formaldehyde, the differences were not statistically significant at the p less than 0.1 level.

Air Pollutants