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Biomedical subjects

R F Phalen

Publications and source records attributed to R F Phalen.

At least 19 recordsLinked to original sources
PubMed1994

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↗
PubMed1992

Low-cost wind tunnel for aerosol inhalation studies.

A low-cost wind tunnel for aerosol studies has been designed, constructed, and evaluated for aerosol uniformity with 2- and 0.46-micron particles. A commercial nebulizer was used to produce the suspended test particles, and a custom-made, four-hole injector was used to introduce the aerosol into the wind tunnel. A commercially available optical particle counter measured the particle concentration. Performance tests of the velocity profile and particle concentration distribution at two flow rates showed that the system performs well for small particles.

Aerosols↗
PubMed1991

Inflated, dried whole lung specimens.

A method is described for preparing fully-inflated whole lung specimens that are suitable for instruction or research purposes. Undamaged lungs are removed from the body and then tracheally cannulated and lavaged with tap water more than 250 times. The treatment also includes rinsing blood from vessels with water. A final filling of the lung with alcohol is optional. The multiply rinsed lung is drained and inflated to 30 cm of H2O pressure with dehumidified air and held at that pressure until the tissue is completely dry. The resulting specimens are light in color and appear to be permanent if stored properly.

Humans↗
PubMed1990

Growth of the ferret tracheobronchial tree.

Because the ferret is being used increasingly in inhalation toxicology and lung physiology studies, it is necessary to better understand the airway structure of its tracheobronchial tree. Previously published information does not include dimensions of bronchi and bronchioles in either adult or growing ferrets. The airway structure of interest for calculating inhaled particle deposition patterns includes airway lengths, diameters and branching angles in each generation. Measurements of these dimensions were obtained for several selected airway paths on replica casts. Casts were made in-situ in four male litter mates age 14 hours, 9.5 days, 16.5 days and 56 days. These data demonstrate, that as with human lung growth, body length at a given age is a good predictor of airway lengths and diameters. Airway branch angles do not appear to change significantly during growth. Sufficient measurements were made to provide dimensions of a typical tracheobronchial pathway for this species. This pathway begins with the trachea and ends at the terminal bronchiole. The morphometric data were not sufficient to determine whether or not the number of tracheobronchial generations increase or decrease postnatally.

Animals↗
PubMed1989

Aerosol deposition in the nose as a function of body size.

The effect of body size on nasal doses from inhaled aerosols has not been measured directly in people. Two basic types of computational models are used to calculate inhaled particle deposition in adults. One type uses an impaction parameter that incorporates particle aerodynamic diameter and the average airflow rate. The second type uses the nasal pressure drop and particle aerodynamic diameter. Although both types of models have been adjusted to give reasonably accurate deposition efficiencies for adults, they predict very different deposition efficiencies when they are applied to young children. This is not surprising because the airflow-type model has no body-size-dependent parameters, unlike the pressure-drop-type model. The objective of our studies was to test these two types of computational models using idealized hollow nasal models of two sizes, representing the adult and young child. The results indicate that a pressure-drop relationship fits the aerosol deposition data very well. When the properly scaled physiological air flows and minute ventilations are used in a nasal dose calculation, the young child is seen to have potentially larger nasal doses than those of an adult.

Adult↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

Effects of exercise exposure on toxic interactions between inhaled oxidant and aldehyde air pollutants.

Respiratory tract injury resulting from inhalation of mixtures of ozone (O3) and nitrogen dioxide (NO2) and of O3 and formaldehyde (HCHO) was studied in Sprague-Dawley rats under exposure conditions of rest and exercise. Focal inflammatory injury induced in lung parenchyma by O3 exposure was measured morphometrically and HCHO injury to the nasal respiratory epithelium was measured by cell turnover using tritium-labeled thymidine. Mixtures of O3 (0.35 or 0.6 ppm) with NO2 (respectively 0.6 or 2.5 ppm) doubled the level of lung injury produced by O3 alone in resting exposures to the higher concentrations and in exercising exposures to the lower concentrations. Formaldehyde (10 ppm) mixed with O3 (0.6 ppm) resulted in reduced lung injury compared to O3 alone in resting exposures, but exercise exposure to the mixture did not show an antagonistic interaction. Nasal epithelial injury from HCHO exposure was enhanced when O3 was present in a mixture. Mixtures of O3 and NO2 at high and low concentrations formed respectively 0.73 and 0.02 ppm nitric acid (HNO3) vapor. Chemical interactions among the oxidants, HNO3, and other reaction products (N2O5 and nitrate radical) and lung tissue may be the basis for the O3-NO2 synergism. Increased dose and dose rate associated with exercise exposure may explain the presence of synergistic interaction at lower concentrations than observed in resting exposure. No oxidation products were detected in O3-HCHO mixtures, and the antagonistic interaction observed in lung tissue during resting exposure may result from irritant breathing pattern interactions.

Air Pollutants↗
PubMed1987

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↗
PubMed1986

Effect of ozone on mean linear intercept in the lung of young beagles.

Although photochemical air pollutants are believed to be associated with respiratory illness, there is also a need to consider their possible effects on postnatal lung maturation. The purpose of this study was to determine whether the maturation of lungs of young beagle dogs might be altered by an inhalation exposure to ozone that represents a severe 5-d episode of photochemical oxidant air pollution. Exposures were at 6 wk of age to purified air, 1 or 2 ppm ozone for 4 h/d on 5 consecutive days. After holding for 6 wk in clean air, lungs were removed and weighed, and the left lung was fixed both by inflation at 30 cm pressure and immersion using buffered formalin. Histologic sections were used for morphometric measurements. Statistical analysis showed that the mean linear intercept (inversely related to lung surface area) was greater than controls (up to about 5%) in the 1 ppm ozone-exposed group. This effect was not seen at 2 ppm ozone, apparently due to large variations in mean linear intercept. No significant differences were seen in body weight, chest girth, lung weight, or volumes of the fixed, inflated lungs. It is concluded that if anatomic maturation of the lung was retarded by this brief regimen of ozone exposure, the effect was small and not likely to have major health consequences.

Animals↗
PubMed1985

Postnatal enlargement of human tracheobronchial airways and implications for particle deposition.

In support of predictions for inhaled particle deposition, morphometric measurements were taken on 20 replica airway casts of people aged 11 days to 21 years. Measurements of right upper lobe airway lengths, diameters, and branching angles were made such that a growth model suitable as input to predictive equations for particle deposition efficiency was obtained. The tracheobronchial airways growth was describable by linear regressions on body length. The length-to-diameter ratio of growing airways did not change in any simple way as a function of airway generation. Airflow rates for a given state of physical activity for various ages were found from previously published data to be describable by linear regressions on body mass. Three states of physical exertion-low activity, light exertion, and heavy exertion-were used for modeling purposes. The computed particle deposition efficiencies indicate that under most circumstances smaller (younger) people will have greater tracheobronchial deposition efficiencies than larger (older) people. For example, tracheobronchial dose on a per kilogram body mass basis for 5-micron-diameter particles may be more than 6 times higher in the resting newborn than in the resting adult assuming equivalent deposition efficiencies above the larynx.

Adolescent↗
PubMed1985

Enhancement of ozone-induced lung injury by exercise.

Rats were exposed for up to 3.75 h to 0.20-0.80 ppm O3 under conditions of rest and treadmill exercise up to 30 m/min, 20% grade, to assess the importance of exposure duration, O3 concentration, and exercise on lung tissue injury. Focal lung parenchymal lesions increased in abundance and severity in response to the three variables; however, exercise was the most important. Lesion response to exercise was greater than that predicted by a simple proportion to estimated effective dose of O3. The results emphasize the importance of including exercise in assessment of possible adverse health effects of exposure to airborne pollutants.

Animals↗
PubMed1985

A rodent treadmill for inhalation toxicological studies and respirometry.

A 10-runway treadmill was enclosed for inhalation toxicological studies of rodents under exercise exposure to environmental pollutants. The exposure system was lined with sheet stainless steel to minimize scrubbing of charged particles and reactive gases. Average metabolic gas exchange of exercising animals was derived from measurements of inlet or outlet airflow and data from an O2 analyzer in conjunction with either a CO2 or N2 analyzer. An airflow rate of 400 l X min-1 ensured a response time of 1 min to reach 95% of a step change in metabolic rate and held scrubbing losses of an O3 test atmosphere to less than 2% of treadmill inlet concentration. Gas exchange averaged for 10 rats during incremental exercise up to their highest collective performance was similar to published data for rats tested individually.

Air Pollutants↗
PubMed1984

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↗
PubMed1983

Tracheobronchial airway structure as revealed by casting techniques.

Research quality tracheobronchial airway casts, prepared in the intact thorax, have proved to be useful in comparative mammalian anatomic studies. Grossly, casts trimmed free of alveoli are quite different in appearance for different species. Overall organ shape, tracheal length/diameter ratio, presence or absence of a tracheal bronchus, and degree of branching symmetry constitute the major gross characteristics. Detailed morphometric measurements performed on such casts reveal important species differences in branch shape, number of divisions in the tree, and variations in such structure as a function of airway generation number. Of the mammalian tracheobronchial casts examined to date, those of humans have several distinctive characteristics. Their overall shape is the most nearly spherical; most other mammals have lungs that are significantly longer along the tracheal axis in relation to their width or thickness. Human branches are typically relatively symmetric with respect to both daughter tube diameter ratio and daughter branch angle ratio. In short, of all of the studied mammalian lungs those of humans appear to be the least heterogeneous.

Animals↗
PubMed1982

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↗
PubMed1982

An airway perfusion apparatus for whole lung fixation.

An apparatus was designed and built for the constant pressure fixation of up to 48 small to medium sized animal lungs by tracheal perfusion. The system hae a 40-liter fixative capacity, automatically maintained selectable fixative fluid levels in all reservoirs, and filtered and recirculated fixation fluid for periods up to several days.

Animals↗