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PubMed2005

Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children.

UNLABELLED: Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children. METHODS: Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50 or subcutaneous route (10(4.28) CCID50/0.5 mL); cellular and humoral immunity and adverse events were assessed. RESULTS: Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4+/-0.7 versus 6.9+/-1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Among infants who developed serologic responses, measles geometric mean titers (GMT; 95% CI) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06). CONCLUSIONS: The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the dose may enhance immunogenicity of primary aerosol measles vaccination in this age group.

Aerosols↗
PubMed1997

Chronic exposure of rats to ozone and sulfuric acid aerosol: biochemical and structural responses.

Groups of rats were exposed to either 0.12 or 0.20 ppm of ozone, 20, 100, or 150 ppm of sulfuric acid aerosol (0.4-0.8 microm diameter), or their mixtures in whole body exposure chambers for up to 90 days. Matched control animals were exposed to filtered air in comparable chambers. The rats were examined biochemically and morphometrically for centriacinar fibrosis or other indicators of pollutant-induced changes in the terminal bronchiole-alveolar duct junction region of the lung at the end of the exposures. By evaluating different markers of lung injury, we had previously demonstrated a synergistic interaction between ozone and sulfuric acid aerosol after acute exposures to these same concentrations of the pollutants. The present experiments were designed to answer the question of whether there was any interaction between ozone and respirable sized aerosols of sulfuric acid, synergistic or antagonistic, after chronic exposures. Exposure of rats to 0.12 or 0.20 ppm of ozone elicited tissue and cellular changes at the bronchiole-alveolar duct junction. Concurrent exposure to sulfuric acid aerosol did not affect the extent or magnitude of these changes. Intermittent exposure (12 h per day) to ozone, with or without the acid aerosol, elicited a greater response than did continuous exposure (24 h per day). No consistent effects of exposure to sulfuric acid aerosol alone were observed, either morphometrically or biochemically. The biochemical data were consistent with the morphometric analyses, showing trends towards or significantly increased lung 4-hydroxyproline content in the rats exposed to ozone, with or without sulfuric acid aerosol, in the intermittent exposure experiment, but not after continuous exposure. No interactive effects between ozone and sulfuric acid aerosol were observed with any of the biochemical parameters examined. We conclude that ozone and sulfuric acid aerosols do not exhibit synergistic interactions after chronic exposures (90 days) of rats to the concentrations tested in this study, which correspond to concentrations showing synergistic interactions in previously performed acute studies. We also observed that exposure of rats to ozone for 12 h per day elicited greater lung changes, which we interpret to indicate a mild fibrotic response, than did exposure of rats for 24 h per day, whether or not there was accompanying exposure to the acid aerosol.

Aerosols↗
PubMed2003

Particle growth by acid-catalyzed heterogeneous reactions of organic carbonyls on preexisting aerosols.

Aerosol growth by the heterogeneous reactions of different aliphatic and alpha,beta-unsaturated carbonyls in the presence/absence of acidified seed aerosols was studied in a 2 m long flow reactor (2.5 cm i.d.) and a 0.5-m3 Teflon film bag under darkness. For the flow reactor experiments, 2,4-hexadienal, 5-methyl-3-hexen-2-one, 2-cyclohexenone, 3-methyl-2-cyclopentenone, 3-methyl-2-cyclohexenone, and octanal were studied. The carbonyls were selected based on their reactivity for acid-catalyzed reactions, their proton affinity, and their similarity to the ring-opening products from the atmospheric oxidation of aromatics. To facilitate acid-catalyzed heterogeneous hemiacetal/acetal formation, glycerol was injected along with inorganic seed aerosols into the flow reactor system. Carbonyl heterogeneous reactions were accelerated in the presence of acid catalysts (H2SO4), leading to higher aerosol yields than in their absence. Aldehydes were more reactive than ketones for acid-catalyzed reactions. The conjugated functionality also resulted in higher organic aerosol yieldsthan saturated aliphatic carbonyls because conjugation with the olefinic bond increases the basicity of the carbonyl leading to increased stability of the protonated carbonyl. Aerosol population was measured from a series of sampling ports along the length of the flow reactor using a scanning mobility particle sizer. Fourier transform infrared spectrometry of either an impacted liquid aerosol layer or direct reaction of carbonyls as a thin liquid layer on a zinc selenide FTIR disk was employed to demonstrate the direct transformation of chemical functional groups via the acid-catalyzed reactions. These results strongly indicate that atmospheric multifunctional organic carbonyls, which are created by atmospheric photooxidation reactions, can contribute significantly to secondary organic aerosol formation through acid-catalyzed heterogeneous reactions. Exploratory studies in 25- and 190-m3 outdoor chambers were also implemented to demonstrate the formation of high molecular weight organic structures. The reaction of ozone with alpha-pinene to generate secondary organic aerosols (SOAs) was performed in the presence of background aerosol consisting of a mixture of wood soot and diesel soot. Results strongly suggest that indigenous sulfuric acid associated with the combustion of fossil fuels (e.g., diesel soot) can initiate acid-catalyzed heterogeneous reactions of SOAs on the particle phase.

Aerosols↗
PubMed2004

Aerosol optical and radiative properties observed at Anmyeon and Jeju, Korea in the spring of 2000 and 2001.

The radiative properties of atmospheric aerosols are determined by their masses, chemical characteristics, and optical properties, such as aerosol optical depth (AOD), Angström parameter (alpha) and single scattering albedo (SSA). In particular, the aerosol optical properties determine the surface temperature perturbation that may give some information in understanding regional atmospheric radiative forcing. To understand the radiative forcing and regional source of an aerosol, the present study focused on the analysis of the aerosol optical properties based on two different observations in the spring season, during the special Asian dust storm period. The Korean Global Atmosphere Watch Observatory (KGAWO), at Anmyeon Island, and the ACE-Asia super-site, at Gosan, Jeju Island, have measured radiations and aerosols since 2000. The sites are located in the mid-west and south of the Korean peninsula, which are strongly affected by the Asian dust coming from China every spring. The aerosol optical properties, measured by ground-based sun and sky radiometers, over both sites were analyzed to gain an understanding of the radiation and climate properties. The probability distributions of the aerosol optical depths were rather narrow, with a modal value of approximately 0.38 at both sites during 2001 and 2002. The Angström parameter frequency distributions showed two peaks at Anmyeon GAW, but only one peak at the Jeju ACE-Asia super site. One peak, around 0.63, characterizes the situation of a day having Asian dust, the second peak, around 1.13, corresponded to the relatively dust-free cases. The correlation between the aerosol optical depth and the Angström exponents resulted in a wide range of the Angström parameter, alpha, over a wide range of optical depths at Anmyeon, whereas a narrow range of alpha, with moderate to low values for the AOD at Jeju. Under dust free conditions the single scattering albedo (SSA) decreased with wavelength, while in the presence of Asian dust, the SSA either stayed neutral, or increased slightly with wavelength at Anmyeon, and showed higher value than Jeju. The change in the surface temperature was highly correlated with increases in the aerosol optical depth at Anmyeon to a greater extent than at Jeju.

Aerosols↗
PubMed2000

The effect of insecticide aerosols on lung function, airway responsiveness and symptoms in asthmatic subjects.

The object of this study was to compare the effect of standard and "low irritant" insecticide aerosols on lung function, airway hyperresponsiveness (AHR) and symptoms in asthmatic subjects. A double blind randomized, crossover study was conducted in 25 asthmatic subjects who reported sensitivity to insecticide aerosols. All subjects were exposed for 30 min, on separate occasions, to two standard insecticide formulations (A and B), one low irritant formulation (C) and a negative control aerosol. Spirometric function and chest, nose and eye symptoms were recorded during, and for 90 min after, the exposure. AHR to methacholine was measured 90 min after the exposure. Compared to the negative control, the maximum fall in forced expiratory volume in one second (FEV1) was slightly greater after standard insecticides (mean differences from control +/-95% confidence interval: aerosol A, 3.3+/-3.6%, p=0.08; aerosol B, 5.1+/-4.7%, p=0.04), AHR was significantly more severe (mean difference from control: aerosol A, 0.35+/-0.29 doubling doses, p=0.028; aerosol B, 0.52+/-0.43 doubling doses, p=0.028), and symptoms were more severe. The low irritant test aerosol (C) did not differ significantly from the negative control with respect to FEV1, AHR or symptoms. It is concluded that some insecticide aerosols trigger symptoms and falls in lung function in some people with asthma. Furthermore, these aerosols may also increase airway hyperresponsiveness, although the mechanism of this effect has not been determined. The low irritant formulation did not appear to have the same effects.

Adult↗
PubMed2004

A novel method to aerosolize powder for short inhalation exposures at high concentrations: isolated rat lungs exposed to respirable diesel soot.

More efficient methods are needed to aerosolize dry powders for short-duration inhalation exposures at high concentrations. There is an increasing need to reach the peripheral lung with dry powder medications as well as with collected ambient aerosol particulates in environmental research projects. In a novel aerosol generator, a fixed volume of compressed air was used to create a short burst of a highly concentrated aerosol in a 300-ml holding chamber. Collected diesel soot was deagglomerated to a fine aerosol with a mass median aerodynamic diameter (MMAD) of 0.55 microm, not much larger than the 0.25 microm MMAD of diesel exhaust particles measured in air. A fine powder such as 3-microm silica particles was completely deagglomerated to an aerosol with a MMAD of 3.5 microm. Immediately after generation, the aerosol was available for exposure at a chosen flow rate by the use of an automated valve system. Tritium-labeled diesel soot was thus used to expose the isolated perfused rat lung at an air concentration of approximately 3 mg/L and a flow rate of 370 ml/min in a 1-min-long exposure. The lungs were ventilated at 75 breaths/min and a tidal volume of 1.13 +/- 0.11 ml (SD, n = 3). Results showed that 19.8 +/- 1.1 microg (SD, n = 3) soot was deposited in the lungs. This amount constitutes 9.5% of the amount inhaled and is close to literature data on deposition of similar sized particles in the rat lung. More than 97% of the deposited soot was located distal to the extrapulmonary bronchi, indicating that the system delivers a highly respirable aerosol. The aerosol system is particularly useful for peripheral lung delivery of collected ambient aerosols or dry powder pharmaceuticals following a minimal effort in formulation of the powder.

Administration, Inhalation↗
PubMed2006

Processes influencing secondary aerosol formation in the San Joaquin Valley during winter.

Air quality data collected in the California Regional PM10/ PM(2.5) Air Quality Study (CRPAQS) are analyzed to qualitatively assess the processes affecting secondary aerosol formation in the San Joaquin Valley (SJV). This region experiences some of the highest fine particulate matter (PM(2.5)) mass concentrations in California (< or = 188 microg/m3 24-hr average), and secondary aerosol components (as a group) frequently constitute over half of the fine aerosol mass in winter. The analyses are based on 15 days of high-frequency filter and canister measurements and several months of wintertime continuous gas and aerosol measurements. The phase-partitioning of nitrogen oxide (NO(x))-related nitrogen species and carbonaceous species shows that concentrations of gaseous precursor species are far more abundant than measured secondary aerosol nitrate or estimated secondary organic aerosols. Comparisons of ammonia and nitric acid concentrations indicate that ammonium nitrate formation is limited by the availability of nitric acid rather than ammonia. Time-resolved aerosol nitrate data collected at the surface and on a 90-m tower suggest that both the daytime and nighttime nitric acid formation pathways are active, and entrainment of aerosol nitrate formed aloft at night may explain the spatial homogeneity of nitrate in the SJV. NO(x) and volatile organic compound (VOC) emissions plus background O3 levels are expected to determine NO(x) oxidation and nitric acid production rates, which currently control the ammonium nitrate levels in the SJV. Secondary organic aerosol formation is significant in winter, especially in the Fresno urban area. Formation of secondary organic aerosol is more likely limited by the rate of VOC oxidation than the availability of VOC precursors in winter.

Aerosols↗
PubMed1990

Chemical distribution in high-solids paint overspray aerosols.

The chemical composition of high-solids basecoat paint overspray aerosols was determined as a function of particle size. Detailed information on the chemical composition of the overspray aerosols is important in health hazard evaluation since the composition and distribution within the airborne particles may differ significantly from the bulk paint material. This study was conducted in a typical down-draft paint booth equipped with air-atomized spray painting equipment. A fixed paint target was used to simulate typical overspray generation conditions and the aerosols were collected isokinetically with a seven-stage cascade impactor for size-fractionated analysis. The overspray aerosol from six paints consisted of organic paint binders with varying amounts of inorganic species as pigments or luster enhancers. These overspray aerosols had mass median aerodynamic diameters (MMAD) ranging from 2.9 to 9.7 microns. The size-fractionated paint samples collected on the impaction stages were analyzed by energy dispersive X-ray spectrometry on a scanning electron microscope (SEM-EDXRS) to identify the metallic elements. Atomic absorption spectrometry was used to determine the mass distribution of aluminum and iron as indicators of nonuniform distribution. Three of the aerosols containing aluminum were found to have bimodal distributions with most aluminum distributions having cumulative MMADs larger than the total aerosol. Iron in the aerosols was bimodal for three of the paints with all samples having an overall iron MMAD less than or equal to the overspray aerosol MMAD. Analysis using ultraviolet spectrometry revealed that the organic compounds present in the size-fractionated particulate samples consisted of a single, polydispersed mode with an MMAD similar to that of the total overspray aerosol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1996

Exposures to inhalable and "total" oil mist aerosol by metal machining shop workers.

Several recent studies have compared worker personal aerosol exposures as measured by the current method with those obtained by a new approach based on collecting the inhalable fraction, intended to represent all the particles that are capable of entering through the nose and/or mouth during breathing. The present study investigated this relationship for a metal machining facility where aerosols were generated from severely refined, nonaqueous ("straight") cutting oils used during the lathe working of metal rod stock. Workers (n = 23) wore two personal aerosol samplers simulataneously, one of the 37-mm type (for "total" aerosol exposure, E37) and the other of the Institute of Occupational Medicine (IOM) type (for inhalable aerosol exposure, EIOM). The data were analyzed by weighted least squares linear regression to determine the coefficient S in the relation EIOM = S.E37. It was found that S = 2.96 +/- 0.60. This ratio-in which exposure to inhalable aerosol was greater than to "total" aerosol-is consistent with previous observations in other industries. The relative coarsenss of the oil mist aerosol, as estimated by cascade impactor measurements, probably explains the difference between the sampling methods. The collection of large "splash" droplets, may also contribute. Future occupational aerosol standards for metalworking fluids will be based on the new, health-related criteria, and exposures will be assessed on the basis of the inhalable fraction. Results of studies like that described here will enable assessment of the impact on future workplace aerosol exposure assessments of introducing new standards.

Aerosols↗
PubMed2001

Preliminary study of the deposition of aerosol in the maxillary sinuses using a plastinated model.

In spite of the widespread use of aerosols in respiratory diseases, very few studies have been performed in the field of ear, nose, and throat (ENT) disorders. The conditions for penetration of aerosols inside the sinus cavities are thus still not understood fully. The aim of this study was to investigate the penetration of aerosols inside maxillary sinuses in vitro, using plastinated models. Three plastinated specimens of the nose and sinuses were made from three different corpses. These specimens were validated by CT scans and were used to study deposition of aerosol in the maxillary sinuses. We performed scintigraphic images of the models in above, face, and profile views using a technetium (99mTc)-labelled solution to show aerosol deposition. We also counted the radioactivity deposited on gauze compresses placed inside the maxillary sinuses. In addition, we constructed a measuring unit with miniature humidity sensors placed inside the sinuses. We recorded the changes in relative humidity observed during nebulization. Results from these studies showed that scintigraphic images of the specimen, whatever the incidence of the views, were not accurate enough to differentiate the aerosol deposition in the maxillary sinuses from that in the nasal cavity. Using indirect counting on gauze compresses made possible the quantification of local aerosol deposition, and we found that aerosols entered into the sinuses. This confirmed that aerosols could reach the middle meatus, which is the main area for sinusitis disorders. The increased activity compared to background varied from 17 to 127%. The humidity sensors recorded changes in relative humidity during the nebulization. These humidity changes fitted a nonlinear model represented by the equation: y = b0 (1 - e(-b1t)), where b0 is the plateau and b1 is the speed to reach the plateau. These techniques may be useful in the future for in vitro characterization of aerosol penetration into the maxillary sinuses.

Aerosols↗
PubMed2002

Miniaturized nebulization catheters: a new approach for delivery of defined aerosol doses to the rat lung.

A nebulization catheter technique (AeroProbe) was adapted and evaluated as a new approach for pulmonary delivery of defined aerosol doses to the rat lung. The lung distribution profile was evaluated by dosing Evans blue and Nile blue dye, respectively, to isolated and perfused rat lungs (IPL) and to the lungs of anesthetized and tracheal-intubated rats. The intratracheal aerosol dosing was synchronized with the inspiration of the lungs. Immediately after dosing, the lungs were dissected into upper- and lower trachea, bronchi, and parenchyma. The dye was then extracted from the tissue samples to determine the regional distribution and the recovery of the aerosol dose in the lungs. The droplet-size distribution and the weight of the delivered aerosol dose were analyzed with laser diffraction and gravimetric analysis respectively. The recovery of the delivered dose was high, 99 +/- 12 and 105 +/- 1%, respectively, in the in vivo administrations and IPL-experiments. The lung distribution profile after aerosol dosing to anesthetized rats was mainly tracheobronchial. Only 12 +/- 4% of the dose was recovered in the lung parenchyma. However, after aerosol dosing to the IPL, 38 +/- 11% of the dose was distributed to the lung parenchyma. At the settings used, the nebulization catheter aerosolized 1-2 microL of liquid per puff using 1-1.5 mL of air. The droplet-size distribution of the generated aerosols was broad (2-8% <3 microm; 10% <4-7 microm; 50% <10-15 microm; and 90% <20-40 microm). The nebulization catheter technique provides a complement to existing methodology for pulmonary drug delivery in small animals. With this new technique, defined aerosol doses can be delivered into the lungs of rats with no need for aerosol dosimetry.

Administration, Inhalation↗
PubMed1996

Surfactant effects on aerosolized and instilled adenoviral-mediated gene transfer.

The effects of surfactant on aerosolization of adenovirus and the distribution of aerosolized and instilled adenovirus in rabbit lungs were measured. Using 99Tc sulfur colloid as a marker for the aerosol, 33P-adenovirus with and without 3H-surfactant, we found that the aerosol had the same particle size distribution independent of surfactant and the 33P-adenovirus distributed proportionately to the other radiolabels in the aerosol. Rabbits received aerosolized or instilled suspensions of adenovirus and 99Tc-sulfur colloid with or without 10 mg/ml surfactant. Rabbit lungs were separated into large airways (trachea, carina, and primary bronchi) and more distal lung parenchyma either immediately after treatment for measurement of 99Tc distribution or 3 days after treatment for luciferase transgene expression. More instillate (94 +/- 1%) than aerosol (68 +/- 2%) was recovered in the parenchyma immediately after treatment (p < 0.01). Transgene expression in the parenchyma as a percent of total lung expression was lower for both instillation (72 +/- 8%) and aerosolization (30 +/- 8%) than for the initial distributions (p < 0.01). Surfactant did not change the distributions of 99Tc sulfur colloid or transgene expression. The adenovirus was aerosolized successfully but the distribution of the aerosol did not favor transgene expression in the lung parenchyma.

Adenoviruses, Human↗
PubMed2000

Characterization of a microprocessor-controlled tubular multiple metered dose inhaler aerosol generator for inhalation exposures of pharmaceuticals.

A microprocessor-controlled tubular multiple metered dose inhaler (MDI) aerosol generator was constructed for the delivery of pharmaceutical aerosols to inhalation chambers. The MDIs were mounted in four cassettes containing one to four MDIs on a stepped end plate. The MDIs in each cassette were pneumatically activated at intervals that were controlled by the microprocessor. The cassettes permitted easy replacement of each set of MDIs with a fresh set of MDIs whenever necessary. Aerosol concentration was controlled by varying the number of active MDIs in each cassette and the frequency of activations per minute of each row. Aerosol from the MDIs flowed along the long axis of the tube, which provided a path length sufficient to diminish impaction losses. Using a light-scattering device to monitor the aerosol concentration, the pulsatile output from the MDIs in the cassettes was demonstrated to be adequately damped out provided that the dilution/mixing/aging chamber exceeded 3 ft in length. The tube diameter selected was the minimum compatible with mounting the required number of MDIs so that the linear velocity of the aerosol was adequate to efficiently transport the aerosol out of the dilution chamber. Aerosol concentration and particle size data were recorded for a nose-only rodent exposure chamber. Reproducible aerosol concentrations ranging from 0.03 to 0.6 mg/L were generated. Particle sizes ranged from 2- to 3-microm mass median aerodynamic diameter. Thus, the aerosol generated was within the size range suitable for inhalation exposures.

Aerosols↗
PubMed2006

Aerosol sampling methods in workplace and ambient environments.

Aerosols are emitted into the workplace atmosphere and the ambient environment through a variety of processes. Aerosol particles are known to have significant effects on both human health and the ambient environment. For this reason, monitoring aerosol concentrations in the atmosphere by aerosol sampling is undertaken in workplace and ambient environments. A wide range of aerosol sampling methods using different collection mechanisms has been used for collecting representative aerosol samples using either a collecting or sensing medium. This paper shows the existing and commonly used aerosol sampling methods based on aerosol collection and real-time measurements. The method of choice for aerosol sampling will ultimately depend on a variety of factors, such as purpose of sampling, type of aerosol, analysis requirements, and available budget.

Aerosols↗
PubMed1996

Prevention of lidocaine aerosol-induced bronchoconstriction with intravenous lidocaine.

BACKGROUND: Lidocaine applied topically provokes bronchoconstriction in persons with hyperreactive airway disease. The authors questioned whether intravenous lidocaine would prevent lidocaine-aerosol induced bronchoconstriction. They compared the effects of lidocaine administered intravenously and by the aerosol route on baseline airway tone, and on the prevention of histamine-induced bronchoconstriction in five Basenji-Greyhound dogs. METHODS: Dogs were pretreated with either intravenous or aerosol lidocaine followed by histamine aerosol challenge. On separate days, dogs were pretreated with intravenous lidocaine, followed by aerosol lidocaine administration at similar doses. Airway caliber was assessed using high-resolution computed tomography. Data were analyzed by two-way analysis of variance. Serum lidocaine concentrations were obtained. RESULTS: Histamine alone decreased the airway area by 32 +/- 3%. Lidocaine administered intravenously or by the aerosol route significantly inhibited histamine-induced bronchoconstriction. There was no significant difference between the two routes in preventing histamine-induced bronchoconstriction. At the dose that inhibited histamine-induced bronchoconstriction, lidocaine administered by the aerosol route decreased baseline airway area by 27 +/- 3% (P < 0.01), whereas intravenous lidocaine had no effect. Intravenous lidocaine prevented lidocaine aerosol-induced bronchoconstriction, and the combination of intravenous and aerosol lidocaine significantly dilated the airways by 20 +/- 5% (P < 0.01 compared with control). CONCLUSIONS: An intravenous bolus of lidocaine prevents the initial bronchoconstriction induced by lidocaine when administered as an aerosol.

Aerosols↗
PubMed1997

Perfluorocarbon compound aerosols for delivery to the lung as potential 19F magnetic resonance reporters of regional pulmonary pO2.

RATIONALE AND OBJECTIVES: Perfluorocarbon (PFC) aerosols present the opportunity for simultaneous analysis of lung structure and pulmonary oxygenation patterns. The authors investigated techniques to nebulize neat liquid PFCs for inhalation as a new method of PFC administration and tested the hypothesis that PFC aerosols may be developed for efficient delivery to the lung in an experimental rat model allowing the potential for sequential monitoring of pulmonary status via quantitative fluorine-19 (19F) magnetic resonance (MR) partial pressure of oxygen (pO2) imaging. METHODS: Pneumatic aerosol generators were configured to produce a neat liquid PFC perfluorotributylamine (FC-43) aerosol. Perfluorocarbon inhalation breathing protocols for the rat model included: spontaneous direct breathing from an aerosol chamber, and use of a tracheotomy tube to bypass nasal breathing. The PFC aerosol delivery into the rat lung was documented through 19F MR imaging in correlation with high-resolution anatomic proton MR images. Theoretical model calculations for PFC mass deposition were compared with experimental results. RESULTS: The pneumatic generator produced a PFC aerosol droplet within the theoretically targeted range (geometric mean particle diameter of 1.2 microns; concentration of approximately 4 x 10(7) droplets per cm3). No measurable aerosol reached the lungs during spontaneous breathing because of the efficient filtering capabilities of the turbinated nasal passages. With tracheotomy, aerosol depositions within the lung were achieved in mass quantities consistent with theoretical expectations; however, the distribution patterns were nonuniform and unpredictable. Oxygen-enhanced 19F imaging was demonstrated. CONCLUSIONS: Perfluorocarbon aerosols of controlled size distribution can be produced at sufficient concentration with pneumatic generators for distribution to the terminal pulmonary architecture and visualization using 19F MR imaging. The potential exists for in vivo oxygen-sensitive imaging in the pulmonary system and development of sophisticated experimental animal models of systemic oxygen transport as a function of pulmonary status.

Administration, Inhalation↗
PubMed2000

9-Nitrocamptothecin liposome aerosol treatment of human cancer subcutaneous xenografts and pulmonary cancer metastases in mice.

The purpose of this study was to test the anticancer properties of the water-insoluble derivative of camptothecin, 9-nitrocamptothecin (9NC), administered in a liposome formulation (L-9NC) in aerosol to mice with subcutaneous xenografts of three human cancers and in mice with murine melanoma and human osteosarcoma pulmonary metastases. The drug was formulated with dilauroylphosphatidylcholine and nebulized in particle sizes of 1.2-1.6 microns mass median aerodynamic diameter and a geometric standard deviation of 2.0. The aerosol was generated with the nebulizer flowing at 10 l/min and delivered to mice in sealed plastic cages or in a nose-only exposure chamber. Aerosol was administered for 15 min to 2 hr daily, delivering deposited doses in the respiratory tract of 8.1-306.7 micrograms of 9NC/kg. With subcutaneous tumors, growth was greatly inhibited or tumors were undetectable after several weeks of treatment. We also showed that oral dosage with L-9NC had no detectable effect on cancer growth, and thus the benefit from aerosol treatment was due to pulmonary deposition and not the larger fraction of drug deposited in the nose of mice during aerosol treatment which is promptly swallowed. Intramuscular L-9NC in slightly larger doses than given in the aerosol had detectable anticancer activity, but it was significantly less than in mice receiving the drug by aerosol. With metastatic pulmonary cancers, treated animals showed highly significantly less cancer growth than control animals. L-9NC aerosol showed a major therapeutic benefit in the treatment of subcutaneous human cancer xenografts in nude mice, suggesting that cancers at systemic sites might be responsive to this treatment. In addition, the strong anticancer effect of L-9NC aerosol on pulmonary metastases offers a therapeutic approach for treatment of pulmonary cancers. Thus, L-9NC aerosol may have applicability in the treatment of cancers throughout the body.

Aerosols↗
PubMed1990

Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output.

Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly.

Aerosols↗