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Induction of protective immunity by aerosol or oral application of candidate vaccines in a dose-controlled pig aerosol infection model.

In order to outline basic concepts for the design of a bacterial aerosol infection model, the development of a pig model with Actinobacillus pleuropneumoniae is described. First, reproducibility of aerosol parameters should be maintained by optimizing generating and sampling conditions. Survival rates of the chosen strain must be predictable. Secondly, inhalation conditions for the recipients have to be standardized to enable the determination of deposition sites and the dose administered. Subsequently, dose-response relationship should be evaluated to find a suitable challenge dose. Furthermore, it seems necessary to establish methods to obtain local specimens for determination of the local immune responses. The present study demonstrates that after aerosol challenge pigs were completely protected after inhalation and partially protected after oral application of A. pleuropneumoniae vaccines and describes techniques to administer bacteria in a dose-dependent, viable way. Using the infection model several stages of the disease from acute pleuropneumonia to chronic infection can be induced for research purposes.

Actinobacillus Infections↗

Evaluation of 1047-nm photoacoustic instruments and photoelectric aerosol sensors in source-sampling of black carbon aerosol and particle-bound PAHs from gasoline and diesel powered vehicles.

A series of measurements have been performed at Hill Air Force Base to evaluate real-time instruments for measurements of black carbon aerosol and particle-bound PAHs emitted from spark and ignition compression vehicles. Vehicles were operated at idle or fast idle in one set of measurements and were placed under load on a dynamometer during the second series. Photoacoustic instruments were developed that operated at a wavelength of 1047 nm where gaseous interference is negligible, although sensitivity to black carbon is good. Compact, efficient, solid-state lasers with direct electronic modulation capabilities are used in these instruments. Black carbon measurements are compared with samples collected on quartz fiber filters that were evaluated using the thermal optical reflectance method. A measure of total particle-bound PAH was provided by photoelectric aerosol sensors (PAS) and is evaluated against a sum of PAH mass concentrations obtained with a filter-denuder combination. The PAS had to be operated with a dilution system held at approximately 150 degrees C for most of the source sampling to prevent spurious behavior, thus perhaps compromising detection of lighter PAHs. PA and PAS measurements were found to have a high degree of correlation, perhaps suggesting that the PAS can respond to the polycyclic nature of the black carbon aerosol. The PAS to PA ratio for ambient air in Fresno, CA is 3.7 times as large in winter than in summer months, suggesting that the PAS clearly does respond to compounds other than BC when the instrument is used without the heated inlet.

Acoustics↗

Fast determination of the relative elemental and organic carbon content of aerosol samples by on-line single-particle aerosol time-of-flight mass spectrometry.

Different particulate matter (PM) samples were investigated by on-line single-particle aerosol time-of-flight mass spectrometry (ATOFMS). The samples consist of soot particulates made by a diffusion flame soot generator (combustion aerosol standard, CAST), industrially produced soot material (printex), soot from a diesel passenger car as well as ambient particulates (urban dust (NIST) and road tunnel dust). Five different CAST soot particle samples were generated with different elemental carbon (EC) and organic carbon (OC) content. The samples were reaerosolized and on-line analyzed by ATOFMS, as well as precipitated on quartz filters for conventional EC/OC analysis. For each sample ca. 1000 ATOFMS single-particle mass spectra were recorded and averaged. A typical averaged soot ATOFMS mass spectrum shows characteristic carbon cluster peak progressions (Cn+) as well as hydrogen-poor carbon cluster peaks (CnH(1-3)+). These peaks are originated predominately from the elemental carbon (EC) content of the particles. Often additional peaks, which are not due to carbon clusters, are observed, which either are originated from organic compounds (OC-organic carbon), or from the non-carbonaceous inorganic content of the particles. By classification of the mass spectral peaks as elemental carbon (i.e., the carbon cluster progression peaks) or as peaks originated from organic compounds (i.e., molecular and fragment ions), the relative abundance of elemental (EC) and organic carbon (OC) can be determined. The dimensionless TC/EC values, i.e., the ratio of total carbon content (TC, TC = OC + EC) to elemental carbon (EC), were derived from the ATOFMS single-particle aerosol mass spectrometry data. The EC/TC values measured by ATOFMS were compared with the TC/EC values determined by the thermal standard techniques (thermooptical and thermocoulometric method). A good agreement between the EC/TC values obtained by on-line ATOFMS and the offline standard method was found.

Aerosols↗

Heterogeneous uptake of ozone on reactive components of mineral dust aerosol: an environmental aerosol reaction chamber study.

We have undertaken a kinetic study of heterogeneous ozone decomposition on alpha-Fe2O3 (hematite) and alpha-Al2O3 (corundum) aerosols under ambient conditions of temperature, pressure, and relative humidity in order to better understand the role of mineral dust aerosol in ozone loss mechanisms in the atmosphere. The kinetic measurements are made in an environmental aerosol reaction chamber by use of infrared and ultraviolet spectroscopic probes. The apparent heterogeneous uptake coefficient, gamma, for ozone reaction with alpha-Fe2O3 and alpha-Al2O3 surfaces is determined as a function of relative humidity (RH). The uptake of ozone by the iron oxide surface is approximately an order of magnitude larger than that by the aluminum oxide sample, under dry conditions. At the pressures used, alpha-Fe2O3 shows clear evidence for catalytic decomposition of ozone while alpha-Al2O3 appears to saturate at a finite ozone coverage. The measured uptake for both minerals decreases markedly as the RH is increased. Comparison with other literature reports and the atmospheric implications of these results are discussed.

Aerosols↗

The Aerosol Research and Inhalation Epidemiology Study (ARIES): PM2.5 mass and aerosol component concentrations and sampler intercomparisons.

The Aerosol Research and Inhalation Epidemiology Study (ARIES) was designed to provide high-quality measurements of PM2.5, its components, and co-varying pollutants for an air pollution epidemiology study in Atlanta, GA. Air pollution epidemiology studies have typically relied on available data on particle mass often collected using filter-based methods. Filter-based PM2.5 sampling is susceptible to both positive and negative errors in the measurement of aerosol mass and particle-phase component concentrations in the undisturbed atmosphere. These biases are introduced by collection of gas-phase aerosol components on the filter media or by volatilization of particle phase components from collected particles. As part of the ARIES, we collected daily 24-hr PM2.5 mass and speciation samples and continuous PM2.5 data at a mixed residential-light industrial site in Atlanta. These data facilitate analysis of the effects of a wide variety of factors on sampler performance. We assess the relative importance of PM2.5 components and consider associations and potential mechanistic linkages of PM2.5 mass concentrations with several PM2.5 components. For the 12 months of validated data collected to date (August 1, 1998-July 31, 1999), the monthly average Federal Reference Method (FRM) PM2.5 mass always exceeded the proposed annual average standard (12-month average = 20.3 +/- 9.5 micrograms/m3). The particulate SO4(2-) fraction (as (NH4)2SO4) was largest in the summer and exceeded 50% of the FRM mass. The contribution of (NH4)2SO4 to FRM PM2.5 mass dropped to less than 30% in winter. Particulate NO3- collected on a denuded nylon filter averaged 1.1 +/- 0.9 micrograms/m3. Particle-phase organic compounds (as organic carbon x 1.4) measured on a denuded quartz filter sampler averaged 6.4 +/- 3.1 micrograms/m3 (32% of FRM PM2.5 mass) with less seasonal variability than SO4(2-).

Aerosols↗

"Worst case" aerosol testing parameters: I. Sodium chloride and dioctyl phthalate aerosol filter efficiency as a function of particle size and flow rate.

The efficiency of filter media is dependent on the characteristics of the challenge aerosol and the filter's construction. Challenge aerosol parameters, such as particle size, density, shape, electrical charge, and flow rate, are influential in determining the filter's efficiency. In this regard, a so-called "worst case" set of conditions has been proposed for testing respirator filter efficiency in order to ensure wearer protection. Data collected on various types of filters (dust and mist; dust, fume, and mist; paint, lacquer, and enamel mist; and high efficiency) challenged with a worst case-type sodium chloride (NaCl) and dioctyl phthalate (DOP) aerosol are presented. The particle size of maximum penetration varies as a function of filter type and was less than 0.25-micron count mean diameter (CMD) in all cases. The count efficiency for high efficiency filters was greater than 99.97% at worst case testing conditions, but the worst case count efficiencies for dust and mist; dust, fume and mist; and paint, lacquer and enamel mist filters were not nearly as efficient as existing test methods indicate. Also, as the test flow rate is increased, the count efficiency decreases. Thus, respirator filters were found to conform to the prediction of single-fiber filtration theory.

Aerosols↗

Gene therapy for cystic fibrosis with aerosolized adenovirus-CFTR: characterization of the aerosol and scintigraphic determination of lung deposition in baboons.

For cystic fibrosis (CF) gene therapy using an aerosolized adenovirus expressing the CFTR gene, optimization of the inhalation conditions is a prerequisite to obtain sufficient amount of CFTR protein expression in the target areas of the respiratory tract. For such a purpose, in vivo radioisotopic imaging of the radiolabeled virus is a unique strategy for a quantitative assessment of the actual deposition. In the present study, an adenovirus CFTR (AdCFTR) was labeled with 99m Technetium gamma emitting isotope in such conditions that its bioactivity was preserved. The 99mTc-AdCFTR aerosol was characterized using both laser diffraction and cascade impaction for sizing with further determination of nebulized and inhalable fractions. After administration to baboons, scintigraphic quantitation of the regional lung distribution was performed and the actual dose deposited in the target area was estimated and expressed as an equivalent viral titer. Since a virus scintigraphy is not realistic in a hospital setting, we have developed an approach using 99mTc-DTPA (diethylene triamino pentaacetic acid) that could be used to predict the virus deposition. Indeed, similarities observed between 99mTc-DTPA and 99mTc-adenovirus aerosol imaging patterns validates the use of the 99mTc-DTPA scintigraphy that we propose as a pretherapeutic test for each patient prior to gene transfer.

Adenoviridae↗

Use of an in-house-built ribavirin aerosol evacuation system to control incidental employee exposure to ribavirin aerosol.

Ongoing controversy regarding the hazards of exposure of healthcare workers to ribavirin aerosol led to the design and evaluation of a ribavirin aerosol evacuation system that scavenges the excess ribavirin. An oxyhood was placed within a croupette oxygen and cool mist tent. The tent was placed under negative pressure, using the hospital wall suction. Air samples were taken to determine ambient air concentrations and patient exposure concentrations and were compared to airborne ribavirin concentrations that occurred during administration of ribavirin without an evacuation system. The ribavirin evacuation system reduced ribavirin ambient air concentrations from 54 ug/m3 (mean) to 11 ug/m3 (mean) without reducing patient exposure concentrations. The results suggest that the system evaluated is an efficient and inexpensive means of reducing incidental employee exposure to ribavirin aerosol.

Aerosols↗

Noninvasive diagnosis of emphysema. Aerosol morphometry and aerosol bolus dispersion in comparison to HRCT.

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (ABD) test are altered in patients with emphysema. We examined the diagnostic power of these aerosol methods in comparison with the noninvasive "gold-standard" HRCT in 50 consecutive patients with various lung diseases. The severity of airflow limitation was mild to moderate in the group of patients without emphysema and moderate to severe in the group of patients with HRCT-confirmed emphysema (FEV(1), 78 +/- 23% pred versus 53 +/- 33% pred; p < 0. 001). Among all lung function parameters under consideration ADAM showed the highest sensitivity and specificity for separating patients with emphysema from those without emphysema (area under the operating characteristics curve: p(ROC), 0.92), followed by ABD (p(ROC), 0.90), a marker for ventilation inhomogeneities. In patients with HRCT-confirmed macroscopic emphysema, peripheral air-space dimensions (EAD) at a relative volumetric lung depth V(pr) of 0.20 measured by ADAM were 155% larger, and bolus dispersion (ABD) at a lung depth of V(p) 600 ml was 53% larger than those observed in patients with other lung diseases (EAD = 0.84 +/- 0.53 mm versus 0.33 +/- 0.10 mm, p < 0.0001; ABD = 706 +/- 154 cm(3) versus 462 +/- 109 cm(3); p < 0.0001). EAD showed a significant correlation with the HRCT visual score (r = 0.78, p = 0.01). ABD showed weak significant correlations with all HRCT parameters under consideration (visual score, pixel density, mean lung density) (r = 0.45 to 0.66; p < 0.05). ADAM and ABD are powerful tools for the noninvasive diagnosis of macroscopic emphysema.

Aerosols↗

Aerosol-derived airway morphometry and aerosol bolus dispersion in patients with lung fibrosis and lung emphysema.

OBJECTIVE: Patients with lung emphysema show increased aerosol-derived dimensions of peripheral airspaces and increased aerosol bolus dispersion (AD). To apply these tests in epidemiologic studies, the objective of this pilot study was to investigate whether morphometric changes caused by lung fibrosis can be distinguished from those caused by emphysema. DESIGN: This study was designed as a cross-sectional study in which airspace dimensions and AD in patients with emphysema and in patients with fibrosis were compared. Forty patients participated in the study: 20 patients had high-resolution CT (HRCT)-proved lung emphysema and 20 patients had HRCT-proved lung fibrosis. All patients underwent conventional lung function tests, aerosol-derived airway morphometry (ADAM), and AD measurements. RESULTS: Patients with lung emphysema showed normal dimensions of small airways but enlarged airspace dimensions in the lung periphery. Patients with fibrosis showed in all lung depths increased airspace dimensions. AD was increased in patients with emphysema but was normal in patients with fibrosis. CONCLUSIONS: These results show that when using ADAM and AD, morphometric changes caused by emphysema can be distinguished from those caused by fibrosis with high sensitivity and specificity.

Adult↗

Beclomethasone dipropionate aerosol in the treatment of steroid-dependent asthma. A 12-week double-blind study comparing beclomethasone dipropionate and a vehicle aerosol.

In a randomized double-blind 12-week trial of steroid-dependent patients with chronic asthma, ten (59 percent) out of 17 patients receiving beclomethasone dipropionate aerosol in a total daily dose of 400mug were able to discontinue systemic corticosteroid therapy successfully, compared to two (13 percent) out of 15 patients in the placebo group (P=0.002). At the end of the trial, the average 8 am plasma cortisol level in the group receiving beclomethasone was more than twice the pretherapy value, whereas the level in the placebo group showed no significant change. There was no significant difference between the beclomethasone group and the placebo group in the overall incidence of side effects related to the aerosol and the effects of systemic corticosteroid withdrawal. Oral candidiasis was not found in any patient receiving beclomethasone dipropionate aerosol. Allergic nasal symptoms were disabling in many patients when the oral dosage of corticosteroids was tapered.

Administration, Oral↗

Use of two different acidic aerosol samplers to measure acidic aerosols in Hsinchu, Taiwan.

Acidic aerosol concentrations measured by an annular denuder system (ADS) and a honeycomb denuder system (HDS) in Hsinchu, Taiwan, were compared. Aerosols were also sampled by a MOUDI (micro-orifice uniform deposit impactor) and analyzed by an ion chromatograph to determine the size distributions of different species. Using the measured aerosol size distribution, theoretical analysis showed that positive HNO3 artifact due to volatilization of NH4NO3 is generally negligible for both samplers. Comparing two different denuder samplers, the average concentration of HNO3 measured by the ADS was found to be lower than that measured by the HDS, while the difference between the two samplers for the average concentration of other species was found to be within +/- 15%. A possible cause of the difference in HNO3 concentrations is due to a greater loss of HNO3 in the cyclone used by the ADS than in the impactor used by the HDS. The study also showed incomplete absorption of the evaporated HCl and HNO3 from the particles on the Teflon filter by the first nylon filter in the filter pack of the ADS. Collection efficiency and capacity of HCl and HNO3 by the nylon filters need further investigation.

Aerosols↗

[Aerosol generators and the determination of their aerosol size distribution].

To determine aerosol size distribution of several particle generators for the inhalation therapy we employed a laser scattering method and QCM cascade impactor method. The particle size distribution measured by the latter method showed MDI less than Diskhaler less than Jet nebulizer, the smaller in order. Our model analysis also suggests that an usage of a spacer (especially the size of around 150 ml) enable to increase the total amount of aerosol inhalation into the lungs, when MDI is applied as an aerosol generator.

Aerosols↗

Bitolterol mesylate aerosol in adults with steroid-dependent asthma: a comparison with isoproterenol hydrochloride aerosol.

A double-blind randomized study of 29 patients was conducted to evaluate the efficacy, safety, and possible subsensitivity of bitolterol mesylate aerosol and isoproterenol hydrochloride aerosol in the treatment of patients with moderate to severe steroid-dependent asthma. Patients received two sprays, three times a day, of either bitolterol or isoproterenol for 3 months. There were four 8-hour office visits at approximately 30-day intervals to assess pulmonary function. On days when pulmonary functions were evaluated, electrocardiogram and laboratory analysis were performed to help assess safety. Both medications gave bronchodilatation within five minutes. Bitolterol had a maximum effect within 60 minutes while isoproterenol was within 15 minutes. The magnitude of peak effect was consistently greater for bitolterol, but not statistically different from isoproterenol. The mean FEV1 (forced expiratory volume in one second) remained at least 15% or greater above baseline for four to eight hours postmedication for bitolterol on the four monthly pulmonary function test days, compared with one to two hours postmedication for isoproterenol. Both medications were well tolerated, with no significant changes in pulse rate, blood pressure, or respiratory rate. Adverse reactions were mild to moderate in nature and were typical sympathomimetic effects. There were no clinically significant laboratory changes or electrocardiographic findings. During the 3-month study, there was no evidence of subsensitivity. Bitolterol mesylate aerosol was shown to be an effective bronchodilator with a prolonged duration of action in steroid-dependent asthma.

Adolescent↗

Aerosol-, but not intradermal-immunization with the live vaccine strain of Francisella tularensis protects mice against subsequent aerosol challenge with a highly virulent type A strain of the pathogen by an alphabeta T cell- and interferon gamma- dependent mechanism.

Francisella tularensis is an extremely virulent facultative intracellular bacterial pathogen of many mammalian species including mice and humans in which it causes a spectrum of disease collectively called tularemia. In humans, intradermal or inhaled inocula of 10cfu or less of the most virulent strains of the pathogen are sufficient to cause severe infection and possible death; in mice similar inocula are routinely lethal. An attenuated live vaccine strain, F. tularensis LVS, was developed almost 50 years ago, and remains the sole prophylactic against virulent strains of the pathogen. Using F. tularensis LVS as a model vaccine, we recently showed that it was possible to systemically immunize various mouse strains and protect them against subsequent massive (2000 cfu) intradermal (i.d.) challenge, but not against low dose (approximately 10 cfu) aerosol challenge, with virulent strains of the pathogen. This is troubling because the latter route is considered an important means of deliberately disseminating F. tularensis in a bioterrorist attack. Others have previously shown that administering LVS to humans, guinea pigs and monkeys as an aerosol enhanced protection against subsequent aerosol challenge with virulent F. tularensis. In the present study, we show the same phenomenon in BALB/c and C3H/HeN mice. In this model, interferon gamma (IFNgamma) and CD4+ and CD8+ T cells are essential for the expression of anti-Francisella immunity in the lungs. Combined this immune response operates by limiting dissemination of the pathogen to susceptible internal organs. Further, understanding of how inhaled LVS elicits local cell-mediated protective immunity will be critical for devising improved vaccines against pulmonary tularemia.

Administration, Inhalation↗

Real-time measurement of oligomeric species in secondary organic aerosol with the aerosol time-of-flight mass spectrometer.

Real-time detection of oligomers in secondary organic aerosols has been carried out with an aerosol time-of-flight mass spectrometer sampling particles generated in a smog chamber. The photooxidation products of 1,3,5-trimethylbenzene and NOx were studied over a range of initial 1,3,5-trimethylbenzene concentrations (137-1180 ppb), while keeping the 1,3,5-trimethylbenzene to NOx ratio nearly constant. The photooxidation products of a mixture of alpha-pinene (initial concentration 191 ppb), 1,3,5-trimethylbenzene (60 ppb), and NOx were also investigated. In both systems, ions were observed in the single-particle mass spectra up to 750 Da; the species observed differed in the two systems. These high-mass ions occur with characteristic spacing of 14 and 16 Da, indicative of oligomeric species. The results obtained agree well with off-line (matrix-assisted) laser desorption/ionization mass spectrometry results. The real-time capabilities of the aerosol time-of-flight mass spectrometer make it possible to investigate the temporal development of the oligomers with 5-min time resolution and also demonstrate that there are certain ions within the oligomer population that occur in nearly all of the particles and with relatively high signal intensity, suggesting that these ions have higher stability or that the species are formed preferentially.

Journal Article↗

A strategy for characterizing the mixing state of immiscible aerosol components and the formation of multiphase aerosol particles through coagulation.

We demonstrate that the coagulation of two aerosol droplets of different chemical composition can be studied directly through the unique combination of optical tweezers and Raman spectroscopy. Multiple optical traps can be established, allowing the manipulation of multiple aerosol droplets. Spontaneous Raman scattering allows the characterization of droplet composition and mixing state, permitting the phase segregation of immiscible components in multiphase aerosol to be investigated with spatial resolution. Stimulated Raman scattering allows the integrity of the droplet and uniformity of refractive index to be probed. The combination of these spectroscopic probes with optical tweezers is shown to yield unprecedented detail in studies of the coagulation of decane and water droplets.

Letter↗

Aerosol lidar intercomparison in the framework of the EARLINET project. 2. Aerosol backscatter algorithms.

An intercomparison of aerosol backscatter lidar algorithms was performed in 2001 within the framework of the European Aerosol Research Lidar Network to Establish an Aerosol Climatology (EARLINET). The objective of this research was to test the correctness of the algorithms and the influence of the lidar ratio used by the various lidar teams involved in the EARLINET for calculation of backscatter-coefficient profiles from the lidar signals. The exercise consisted of processing synthetic lidar signals of various degrees of difficulty. One of these profiles contained height-dependent lidar ratios to test the vertical influence of those profiles on the various retrieval algorithms. Furthermore, a realistic incomplete overlap of laser beam and receiver field of view was introduced to remind the teams to take great care in the nearest range to the lidar. The intercomparison was performed in three stages with increasing knowledge on the input parameters. First, only the lidar signals were distributed; this is the most realistic stage. Afterward the lidar ratio profiles and the reference values at calibration height were provided. The unknown height-dependent lidar ratio had the largest influence on the retrieval, whereas the unknown reference value was of minor importance. These results show the necessity of making additional independent measurements, which can provide us with a suitable approximation of the lidar ratio. The final stage proves in general, that the data evaluation schemes of the different groups of lidar systems work well.

Journal Article↗