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Characterization of marine aerosol for assessment of human exposure to brevetoxins.

Red tides in the Gulf of Mexico are commonly formed by the fish-killing dinoflagellate Karenia brevis, which produces nine potent polyether brevetoxins (PbTxs). Brevetoxins can be transferred from water to air in wind-powered white-capped waves. Inhalation exposure to marine aerosol containing brevetoxins causes respiratory symptoms. We describe detailed characterization of aerosols during an epidemiologic study of occupational exposure to Florida red tide aerosol in terms of its concentration, toxin profile, and particle size distribution. This information is essential in understanding its source, assessing exposure to people, and estimating dose of inhaled aerosols. Environmental sampling confirmed the presence of brevetoxins in water and air during a red tide exposure period (September 2001) and lack of significant toxin levels in the water and air during an unexposed period (May 2002). Water samples collected during a red tide bloom in 2001 showed moderate-to-high concentrations of K. brevis cells and PbTxs. The daily mean PbTx concentration in water samples ranged from 8 to 28 microg/L from 7 to 11 September 2001; the daily mean PbTx concentration in air samples ranged from 1.3 to 27 ng/m(3). The daily aerosol concentration on the beach can be related to PbTx concentration in water, wind speed, and wind direction. Personal samples confirmed human exposure to red tide aerosols. The particle size distribution showed a mean aerodynamic diameter in the size range of 6-12 microm, with deposits mainly in the upper airways. The deposition pattern correlated with the observed increase of upper airway symptoms in healthy lifeguards during the exposure periods.

Aerosols↗

Ambient sulfate aerosol deposition in man: modeling the influence of hygroscopicity.

Atmospheric sulfate aerosols [H2SO4, (NH4)2SO4, and NH4HSO4] are of international concern because of their global prevalence and potential irritant or toxic effects on humans. To assess hazards following inhalation exposure, the total dose delivered to the human respiratory tract and its regional distribution must be determined. The mass median aerodynamic diameter of the inhaled aerosol will influence the sites of deposition in the respiratory tract. Atmospheric sulfate aerosols are hygroscopic and will have changing particle sizes and densities as they absorb water vapor in the humid environment of the human respiratory tract. Experimental and theoretical data that describe particle size as a function of temperature and relative humidity were used in computer subroutines of an aerosol deposition model in order to calculate the dose dispersion of H2SO4, (NH4)2SO4, and NH4HSO4 aerosols in man. Different temperature and relative humidity environments that approximately correspond to nasal and oral breathing were studied. The predicted deposition patterns are very different from those of nonhygroscopic aerosols with identical inhaled mass median aerodynamic diameter values.

Aerosols↗

Global atmospheric change: potential health effects of acid aerosol and oxidant gas mixtures.

Inhalation toxicology experiments in whole animals have demonstrated a remarkable lack of toxicity of sulfuric acid in the form of respirable aerosols, especially in rats and nonhuman primates. Thus, much of the current experimental emphasis has shifted to the evaluation of the potential health effects of acid aerosols as components of mixtures. Rats have been concurrently exposed to mixtures of ozone or nitrogen dioxide with respirable-sized aerosols of sulfuric acid, ammonium sulfate, or sodium chloride, or to each pollutant individually. Their responses to such exposures have been evaluated by various quantitative biochemical analysis of lung tissue or wash fluids ("lavage fluid") or by quantitative morphological methods ("morphometry"). Such studies have mainly been performed in the acute time frame due to the inherent limitations of the most sensitive assays available and have generally involved exposures for 1 to 9 days, depending on the assays used. Good correlations were found between the most sensitive biochemical indicators of lung damage (protein content of lung lavage fluid or whole lung tissue and lung collagen synthesis rate) and the exposure concentration of oxidant gas present alone or in mixtures with acidic aerosols showing interactive effects. Synergistic interaction between ozone and sulfuric acid aerosol was demonstrated to occur at environmentally relevant concentrations of both pollutants by several of the analytical methods used in this study. Such interactions were demonstrated at concentrations of ozone as low as 0.12 ppm and of sulfuric acid aerosol at concentrations as low as 5 to 20 micrograms/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗

Sensitivity metric approach for retrieval of aerosol properties from multiangular and multispectral polarized radiances.

Linearly polarized radiation is sensitive to the microphysical properties of aerosols, namely, to the particle-size distribution and refractive index. The discriminating power of polarized radiation increases strongly with the increasing range of scattering angles and the addition of multiple wavelengths. The polarization and directionality of the Earth's reflectances (POLDER) missions demonstrate that some aerosol properties can be successfully derived from spaceborne polarimetric, multiangular measurements at two visible wavelengths. We extend the concept to analyze the retrieval capabilities of a spaceborne instrument with six polarimetric channels at 412, 445, 555, 865, 1250, and 2250 nm, measuring approximately 100 scattering angles covering a range between 50 and 150 deg. Our focus is development of an analysis methodology that can help quantify the benefits of such multiangular and multispectral polarimetric measurements. To that goal we employ a sensitivity metric approach in a framework of the principal-component analysis. The radiances and noise used to construct the sensitivity metric are calculated with the realistic solar flux for representative orbital viewing geometries, accounting for surface reflection from the ground, and statistical and calibration errors of a notional instrument. Spherical aerosol particles covering a range of representative microphysical properties (effective radius, effective variance, real and imaginary parts of the refractive index, single-scattering albedo) are considered in the calculations. We find that there is a limiting threshold for the effective size (approximately 0.7 microm), below which the weak scattering intensity results in a decreased signal-to-noise ratio and minimal polarization sensitivity, precluding reliable aerosol retrievals. For such small particles, close to the Rayleigh scattering limit, the total intensity provides a much stronger aerosol signature than the linear polarization, inspiring retrieval when the combined signals of intensities and the polarization fraction are used. We also find a strong correlation between aerosol parameters, in particular between the effective size and the variance, which forces one to simultaneously retrieve at least these two parameters.

Aerosols↗

Rotational Raman lidar for obtaining aerosol scattering coefficients.

Two-channel lidar signals that are composed of total rotational scattering and elastic signals provide good information about aerosol scattering coefficients. We can calculate the aerosol backscattering coefficient and extinction coefficient directly, without making any assumption or calibration. Generally, a high-spectral-resolution lidar is used for aerosol monitoring, but we have designed a new low-spectral-resolution lidar system that contains both kinds of scattering information simultaneously, and we have retrieved the aerosol scattering coefficient. The results show that there is no need to assume any relation between aerosol backscattering and extinction or to consider any wavelength calibration to determine the aerosol scattering coefficient.

Aerosols↗

Dosing efficiency and particle-size characteristics of pressurized metered-dose inhaler aerosols in narrow catheters.

An experimental in vitro model was used to determine the effects of intraluminal catheter diameter and length on the delivered dose and particle-size characteristics of salbutamol (albuterol) aerosol delivered by metered dose inhaler (MDI) (Ventolin, 100 micrograms per puff). The dose of aerosolized drug that exited a 16-cm-long tracheal tube with an inner diameter (ID) of 6 mm was compared with that from 4 catheters of differing diameters and lengths that were inserted individually into the tracheal tube. The salbutamol MDI canister was actuated ten times into each delivery system, and the effluent aerosol was trapped onto a filter. The filtrate was dissolved in methanol, and the salbutamol concentration was determined using high-performance liquid chromatography. For the 3 22-cm-long catheters, the delivered dose (mean +/- SD) of salbutamol per actuation for the 22-standard wire gauge (SWG) catheter was 97.5 +/- 3.9 micrograms, which was similar to that for the 19-SWG catheter (102.3 +/- 2.5 micrograms) but was significantly less than that for the 14-SWG catheter (108.2 +/- 4.2 micrograms) (p < 0.05). These delivered doses exceeded those of the 6.0-mm-ID tracheal tube alone (2.33 +/- 0.76 micrograms) and the 13-cm-long 19-SWG catheter (2.17 +/- 0.29 micrograms) (p < 0.001). In a second experiment using a cascade impactor, the distribution of aerosol particle diameters that exited the 6-mm-ID tracheal tube was compared with that exiting a 13-cm-long 19-SWG catheter that extended halfway down the tracheal tube and with that exiting a 22-cm-long 19-SWG catheter inserted into the distal end of the 6-mm-ID tracheal tube. The mass median aerodynamic diameter (mean +/- SD) of the salbutamol aerosols delivered through both the 6.0-mm-ID tracheal tube (1.1 +/- 0.1 microns) and that of the 13-cm-long 19-SWG catheter (1.2 +/- 0.2 microns) were significantly less than that delivered through the 22-cm-long 19-SWG catheter (2.0 +/- 0.1 microns) (p < 0.05). The authors conclude that delivery of respirable aerosol can occur through narrow catheters that function as extended nozzles for MDIs. Optimal dosing will be obtained when the catheter extends the full length of the tracheal tube.

Aerosols↗

Treating diabetes with aerosolized insulin.

Because of the pain, inconvenience, and disruption of lifestyle associated with the injection of insulin, many patients with diabetes are noncompliant in terms of treatment regimens that require daily multiple injections. To eliminate the pain and to improve treatment outcome, there has been increasing interest in the development of aerosolized insulin to replace subcutaneously (SC) delivered formulations. Recent studies in human volunteers have shown that when aerosolized insulin is effectively delivered to the alveolar region of the lung, absorption rates and decreases in glucose levels are similar to those achieved with SC-delivered insulin during the fasting state. Other human trials have shown that inhaled insulin also effectively controls postprandial glucose levels. Aerosolized insulin is well-tolerated, and there is no evidence of irritation, hypoglycemia, or changes in pulmonary function when administered over short periods. At present, limitations in the delivery device result in less efficient administration of insulin aerosol compared to SC dosing. However, new devices and different formulations of insulin, which are currently under development, should improve the efficiency. It is likely that the treatment of diabetes with aerosolized insulin will provide an effective alternative means for controlling plasma glucose levels in diabetic individuals. Aerosolized insulin also will serve as a developmental model for this route of administration for a number of other therapeutic peptides that are currently administered by injection only.

Aerosols↗

Aerosol, humidity and oxygenation.

Patients with artificial airways frequently need aerosol or humidity therapy. For this study, we used aerosols generated from a heated Puritan all-purpose nebulizer and humidity generated from a heated Bennett cascade humidifier to determine the effects of these therapies in spontaneously breathing neurosurgical patients with nasal endotracheal tubes and normal lungs. Crossover comparison of oxygenation status before and after aerosol or humidity therapy was done by analyzing P(A-a)O2 in these patients. We found that aerosols have a detrimental effect on the patient's oxygenation status, suggesting that humidity is preferable in maintaining adequate oxygenation in a patient with a normal lung plus artificial airway. The arterial pH and PaCO2 were not affected by aerosol therapy. Care should be exercised with regard to the adverse hypoxemic effect of bland aerosols when a large-reservoir jet nebulizer is used in an intubated patient who already has impaired cardiopulmonary function or borderline PaO2.

Aerosols↗

Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients.

STUDY OBJECTIVES: To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator-associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: University teaching hospital. PATIENTS: Forty critically ill trauma patients at high risk for VAP Intervention. Within 48 hours of admission to the intensive care unit (ICU), patients were randomly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo (normal saline) for up to 7 days. Bronchoalveolar concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were determined at baseline and the end of therapy (days 4-7). MEASUREMENTS AND MAIN RESULTS: The frequency of VAP in patients receiving aerosolized ceftazidime was 73% lower than that in patients receiving placebo at ICU day 14 (15% vs 55%, p = 0.021), and 54% lower for the entire ICU stay (30% vs 65%, p = 0.022). No clinically significant changes in bacterial culture and sensitivity patterns were observed. No adverse events from aerosolized ceftazidime were reported. Pulmonary TNF-alpha, IL-beta, and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p < 0.001, p = 0.02, and p = 0.003). The frequency of VAP was related directly to changes in TNF-alpha and IL-beta (p < 0.001, p = 0.02). CONCLUSIONS: Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients, without adversely affecting ICU flora. Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung.

Adult↗

An aerosolized fluorescent microsphere technique for evaluating particle deposition in the avian respiratory tract.

The objective of this study was to examine the feasibility of using aerosolized fluorescent microspheres to examine particle distribution in the respiratory tract of birds following aerosol exposure. Adult domestic pigeons (Columbia livia domestica; n = 5 birds per microsphere size) were exposed to aerosolized monodispersed populations of various sized carboxylate microspheres (0.5, 1.0, 2.0, 3.0, 6.0, and 10.0 microm) for 30 min. For aerosol-exposure purposes, the birds were anesthetized with injectable anesthetics, intubated, and placed on positive-pressure ventilation using a mechanical ventilator. Immediately following aerosol exposure, the birds were euthanatized, and carcasses were preserved via intravenous infusion of modified paraformaldehyde/gluteraldehyde fixative (pH = 7.2 and 340 mOsm). Initial evaluation of microsphere distribution in air sacs (cranial and caudal thoracic and abdominal) and at the level of the ostia was performed using a stereoscopic microscope with an epifluorescent module. More detailed examination of the distribution of microspheres within the respiratory tract was achieved using a confocal scanning laser microscope with a krypton argon laser and a scanning electron microscope. The results from this study revealed that positive-pressure ventilation resulted in distribution of smaller sized fluorescent microspheres (sizes 1.0, 2.0, and 3.0 microm) throughout the pigeon's respiratory tracts, and these microspheres were in highest concentration in the secondary bronchi and ostia for all of the examined air sacs. The larger sized beads (6.0 and 10.0) were confined to the upper airway (trachea and primary bronchi). The results from this study allow for a better understanding of particle deposition following positive-pressure ventilation and aerosol exposure in birds.

Aerosols↗

Blood contamination of the aerosols produced by in vivo use of ultrasonic scalers.

Disease transmission and barrier techniques during dental treatment have been areas of recent concern in dentistry. Ultrasonic scalers are known to produce aerosols, and these aerosols are often produced from areas of significant disease activity, including bleeding. This study was performed to determine if these aerosols contain blood from the gingival sulcus. Forty areas consisting of two contiguous periodontally involved teeth (probing depth of at least 5 mm on one site of each tooth) were scaled subgingivally with an ultrasonic scaler for 30 seconds. A high volume evacuator (HVE) tip was positioned 3 to 5 cm away from the operating site and utilized to capture the aerosols produced. The water remaining in and on the HVE tube was tested for occult blood by the guiac resin method. Gingival index, mean probing depth, presence of bleeding with scaling, and presence of visible blood in the HVE tip were recorded. All 40 test sites showed a positive result for blood in the captured aerosols despite the wide variation in the measured parameters. It may be concluded that subgingival scaling on periodontally involved teeth with ultrasonic scalers would be expected to produce aerosols containing blood.

Aerosols↗

Equivalent diameter of standard quartz dust used as a test aerosol for the dust respirator.

In the standard of the approval test for dust respirator certification, test aerosols are defined as air containing quartz particles of 2 microns or smaller1. However, it is well-known that the filtration efficiency of air filters depends on the size of the test aerosol particles. Alternative test aerosols containing submicron size particles will be studied for use in future approval test of dust respirators. Before searching for alternatives, characterization of currently-used quartz dust, e.g. information about size and electrostatic charge of the aerosol particles, should be determined. The currently-used approval test measures filtration efficiencies with a light scattering photometer. The photometer gives overall aerosol concentration, while Aerodynamic Particle Sizer (APS-33B, TSI Inc., St. Paul, U.S.A.) is able to give the number concentration for each particle size based on the aerodynamic diameter ranging from 0.9 to 2.0 microns. In this study, equivalent diameter was defined as the diameter at which penetration has the same value when measured by APS-33B and by light scattering photometer. The equivalent diameter for the ten filter samples for dust respirator was around 1 microns, irrespective of neutralization of the test aerosol.

Aerosols↗

Deposition and dispersion of aerosols in the airways of the human respiratory tract: the effect of particle size.

Small volumes of aerosols (boluses) were inspired predominantly into the conducting airways of human lungs with a fast operating valve system, injecting preselected aerosol volumes near the end of a clean air inhalation. Particle recovery and bolus dispersion in the exhaled air after various periods of breathholding were investigated by measuring aerosol number concentration directly in front of the mouth with a laser photometer. Inspired and expired flow rates were measured with a pneumotachograph. The effect of particle size on these measurements has been investigated using aerosol particles with aerodynamic diameters (dae) between 0.9 and 5 microns. For aerosol particles smaller than 2 microns, bolus dispersion increases with increasing periods of breathholding (tb). After reaching a maximum, dispersion decreases with even longer tb. An increase in particle size yields a smaller increase in dispersion during the first seconds of breathholding while it is not changed significantly without breathhold. Particle losses during inhalation and exhalation increases with particle size. However, with increasing periods of breathholding, the losses of the smaller particles (less than 1.5 microns) were found to be much higher than expected theoretically, implying particle losses by sedimentation in the same airway structures. The small aerosol particles are deposited in smaller airways than bigger particles. These observations can be explained by cardiogenic mixing during periods of breathholding by pulsatile flow oscillations and confirm measurements with enhanced heart rate as described in an earlier paper. Small particles with restricted settling velocities remained longer in an airborne state in the airways and this leads to a more efficient cardiogenic mixing.

Administration, Inhalation↗

Human tracheobronchial deposition and effect of two cholinergic aerosols.

The effects of two methacholine aerosols with mass median diameters congruent to 7 and 3 microns were measured in 10 healthy subjects. The concentrations of the two aerosols were increased until forced expiratory volume in 1 s (FEV1) decreased with about 20%. Pulmonary fraction (FEV1, FVC, FEV25-75%, FEF75-85%, R(aw), and phase III of single breath O2 test) and deposition of 3.6-microns radiolabeled Teflon particles were studied before and after bronchial challenge with the two aerosols. Output from the nebulizers and size distribution were measured and from these data and from data on deposition of Teflon particles from this and seven earlier studies the doses of the two methacholine aerosols to the tracheobronchial region were calculated. The changes in all pulmonary function parameters and deposition of 3.6-microns particles were similar for the two aerosols. The calculated dose for the aerosol with the large particles was 3-4 times higher than that with the smaller particles. The results indicate greater effect of a certain dose to the tracheobronchial part of the lung if the mass is spread on many small particles than on fewer large ones.

Adult↗

Pulmonary effects of chronic exposure to liposome aerosols in mice.

Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage-directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991).

Administration, Intranasal↗

Characteristics of biological aerosols in dairy processing plants.

The viable aerosol in dairy processing plant environments was characterized by using an Andersen six-stage sieve sampler and a Reuter centrifugal sampler. Artificially introduced Serratia marcescens were detected in the air during drain flooding and after rinsing the floor with a pressured water hose, thus illustrating the ability of a specific microorganism to be disseminated from drains and wet surfaces via physical disruption activities often observed in food plants. Once a high concentration of wet viable aerosol was generated, it took 40 or more min to return to the background level in the absence of forced ventilation or other activity. The greatest reduction in viable particles occurred during the first 10 min. Estimated mean aerosol particle sizes were decreased from approximately 4.6 to 3.2 mu with time lapse. The estimated mean aerosol particle sizes from actual dairy processing plant environments ranged from approximately 4.3 to 5.3 mu. In addition, a more heavily contaminated dairy processing environment contained larger aerosol particles. These results indicate that the RCS sampler will often overestimate the true aerosol concentration in highly contaminated air, because mean particle sizes are over 4 mu in diameter.

Aerosols↗

Aerosolized hyaluronic acid decreases alveolar injury induced by human neutrophil elastase.

This laboratory has previously shown that an intratracheally instilled solution of hyaluronic acid (HA) protects the lung from elastase-induced airspace enlargement. In those studies, fluorescein-labeled HA was found to bind preferentially to lung elastic fibers, suggesting a mechanism for the protective effect. The current investigation extends these findings by examining the capacity of an aerosol preparation of HA to similarly inhibit elastase-induced lung injury. Syrian hamsters were exposed to aerosolized bovine tracheal HA (0.1% solution in water) for either 25 or 50 min, then immediately instilled intratracheally with 80 units of human neutrophil elastase. One week later the lungs were examined for airspace enlargement, using the mean linear intercept method. Animals exposed to HA for 50 min showed a significant decrease in airspace enlargement compared to controls exposed to aerosolized water alone (68.2 microm vs 85.9 microm; P < 0.05). The 25-min exposure to the HA aerosol also reduced the mean linear intercept compared to controls (73.7 microm vs 85.9 microm), but this decrease was not statistically significant. With regard to possible inflammatory effects of HA, there was no difference in the percentage of lavaged neutrophils between HA-treated and control lungs at 24 hr (1.4% vs 1.8%, respectively). As with earlier experiments using intratracheally instilled HA, aerosolized fluorescein-labeled HA was found to bind to lung elastic fibers. These results suggest that aerosolized HA may prevent elastase-mediated injury in pulmonary emphysema.

Administration, Inhalation↗

Wearing a noseclip improves nebulised aerosol delivery.

OBJECTIVE: The efficiency of nebulised aerosol delivery is limited due to drug retained within the nebuliser, and due to a poor ratio between inspiratory drug delivery and expiratory drug loss. Several technical approaches have improved the ratio between inspiratory aerosol delivery and expiratory aerosol loss. In our pilot study we aimed to investigate if wearing a noseclip during inhalation therapy improves the inspiratory versus expiratory ratio and hence, improves nebulised aerosol delivery. METHODS: Drug delivery was measured in thirteen subjects (7 males; age range 23-36 years) inhaling in random order nebulised aerosol through a mouthpiece once while wearing a noseclip and once without. RESULTS: Wearing a noseclip leads to an increase of 113% (SEM 23.5) in drug delivery and improves the inspiratory versus expiratory ratio (ratio 2.07 versus 0.75). CONCLUSIONS: We have shown that aerosol delivery is increased due to an improved inspiratory versus expiratory ratio when wearing a noseclip.

Administration, Inhalation↗