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PubMed1986

Size and concentration measurement of an industrial aerosol.

Several real-time particle sizing instruments were evaluated for measuring the size distribution and concentration of the aerosol produced during the high speed grinding of gray iron castings. Aerosol was sampled in the airstream entrained by the motion of a spinning grinding wheel in a pilot grinding operation. Measurement methods based on differing physical principles were selected for evaluation and compared: particle inertia (aerodynamic particle sizer and quartz crystal microbalance cascade impactor); light scattering (laser aerosol spectrometer); and projected-area microscopy (scanning electron microscope). Inferences of aerodynamic diameter based on measurements by the laser aerosol spectrometer consistently undersized that determined by the aerodynamic particle sizer by a factor of 1.5. Estimates of aerodynamic diameters from projected area diameters determined by scanning electron microscopy differed from those obtained by the aerodynamic particle sizer by a factor of 2. Differences appeared to be a non-linear function of particle diameter. Estimates of respirable mass determined from mass-weighted particle size spectra varied by a factor of 6 between the largest estimate (scanning electron microscope) and the smallest estimate (laser aerosol spectrometer).

Aerosols↗
PubMed1990

Endotoxin measurement: aerosol sampling and application of a new Limulus method.

A new Limulus test was designed specifically for measuring endotoxin in environmental aerosols. The new Limulus method has a detection limit for airborne endotoxin of 2.2 pg (NP-1 activity)/m3 and can precisely quantitate aerosols containing 14 or more pg/m3 from samples representing 6.5 m3 of air. Aerosols in the range 100 to 500 pg/m3 were measured with 95% confidence of +/- 32% and an aerosol of 10 pg/m3 with 95% confidence of +/- 50%. Qualitative information about airborne endotoxin was also obtained from the assay. A wide variety of filter media were found to inactivate lipopolysaccharide in solution. This implies that airborne endotoxin can be measured only relative to the conditions of a particular study and that comparison of endotoxin aerosol measurements made under different circumstances are invalid. The research and policy implications of this observation are discussed. The need for improved collection and extraction methods notwithstanding, it was proposed that a buffered, parallel-line Limulus assay method be adopted as the standard method for measuring environmental endotoxin. The kinetic-turbidimetric Limulus assay with resistant-parallel-line estimates (KLARE), rate response method, should be considered a prime candidate for the standard method because of its precision, sensitivity, resistance to interference by pH, internal validation of estimates, and ability to provide qualitative as well as quantitative information about airborne endotoxin.

Aerosols↗
PubMed1991

Collection efficiency of a personal sampler for microbiological aerosols.

A modified personal impinger (MPI) for sampling airborne microorganisms was tested for collection efficiency with the jet nozzle placed at various positions above and below the liquid surface. The sampler was operated with 10 mL of water and sampling rates between 1.08 and 3.4 L/min. The collection efficiencies for a polydisperse aerosol of diethylhexyl phthalate (DEHP) and monodisperse aerosols of polystyrene latex particles (ULP) were determined with an optical particle counter. The results show that a test aerosol generated from a suspension, such as ULP, gives test results that agree better with theoretical predictions than a polydisperse oil aerosol such as DEHP. The measured aerodynamic 50% cutoff diameters (D50) agreed with those predicted from impaction theory with the jet nozzle 4 mm from the flask bottom. For preservation of viability during sampling of microorganisms, it is common to use impingers with the jet nozzle above the liquid surface. These tests showed that if the MPI is operated with the jet nozzle above the liquid surface, D50 will be displaced toward larger particle sizes because the jet-to-plate distance/jet diameter ratio increases substantially when a soft impaction surface such as the liquid is used. The increased D50 could to some extent be compensated for by increasing the flow rate. An increased flow rate will, however, result in more losses because of aerosol regeneration.

Aerosols↗
PubMedDate not supplied

Photometer response determination based on aerosol physical characteristics.

Aerosol photometers often are calibrated against field measurements of total or respirable aerosol concentrations. However, the response of these instruments to a particular aerosol concentration level will change if there is a change in aerosol size distribution. To determine a predictable correction factor that relates photometer to gravimetric measurements of an aerosol, the authors performed an analysis of photometer response relative to particle size distribution, density, and refractive index. A series of trials was performed at different concentration levels using both Arizona road dust and ground corn dust. The correction factor was calculated from a knowledge of the instrument response pattern relative to particle size, as well as the ratios of actual dust density and refractive index relative to that of the dust used to calibrate the instruments. Results demonstrated that the calculated correction factors were within 10% of a correction factor predicted from the slope of a linear regression relating gravimetric measurements to the average of photometer readings taken during the sample period.

Aerosols↗
PubMed1994

Dichotomous sampling of vapor and aerosol of methylene-bis-(phenylisocyanate) [MDI] with an annular diffusional denuder.

A dichotomous sampler was developed for speciation of airborne methylene-bis-(phenylisocyanate) (MDI) into vapor and aerosol fractions. The sampler consisted of an impactor inlet and two sections of annular diffusional denuder, in series with a glass fiber filter. The denuders and filter were coated with N-4-nitrobenzyl-N-1-propylamine for collection and derivatization of MDI followed by high performance liquid chromatography analysis. The sampler was evaluated in the laboratory with test atmospheres of MDI over a range of 24 to 355 micrograms/m3 at an average temperature of 26 degrees C. The total amounts of MDI collected by the dichotomous sampler were not significantly different from a reference sampler over the entire range of MDI concentrations. The first denuder collected MDI vapor with an average efficiency of 91.6 +/- 5.2%, in comparison to a theoretical efficiency of 94.1%. MDI existed solely in the vapor state up to approximately 75 micrograms/m3 and was collected on the denuders. Above this, MDI partitioned into vapor and aerosol, and the device efficiently separated the sample into the vapor fraction, found on the denuders, and the aerosol fraction, which penetrated to the filter. While this work was done with condensation aerosol, appropriate modification of the sampler inlet should allow use of the device for sampling atmospheres containing larger aerosols.

Aerosols↗
PubMed1997

Evaluation of two inversion techniques for retrieving health-related aerosol fractions from personal cascade impactor measurements.

Personal cascade impactors are widely used in occupational aerosol exposure assessment. Appropriate algorithms must be used to determine the total particle size distribution from masses collected on the stages of the cascade impactor. Such algorithms should be regarded as integral components of the measurement system. When evaluating algorithms for reconstruction of size distributions from cascade impactor data, the eventual use of the size distribution must be considered. So, from an industrial hygiene perspective, an appropriate basis for comparison of given measurement systems is the accurate retrieval of the inhalable, thoracic, and respirable aerosol fractions as described by the new, internationally accepted, particle size-selective sampling conventions (which are expected to form the basis of future aerosol standards). This article compares two inversion routines in terms of their abilities to retrieve these aerosol mass fractions relative to the masses that would have been obtained using an ideal sampler that perfectly followed the sampling convention. The routines were used to invert measurements made with the Institute of Occupational Medicine personal inhalable dust spectrometer, a miniature cascade impactor that aspirates the inhalable aerosol fraction, and the results are presented graphically as contours of equal mass bias. The simplest algorithm, based on the a priori assumption of lognormality, appears to provide the best results.

Aerosols↗
PubMed2004

Elemental and ionic concentrations in the urban aerosol in Antwerp, Belgium.

The results of a study of the elemental and ionic composition of the ambient aerosol in and around Antwerp are presented. Four sampling campaigns were performed, covering all seasons. The samples were obtained by filtration and impaction methods. Subsequently, the filters were analyzed by X-ray fluorescence spectrometry for elements, and the impactor substrates were leached with water and analyzed by ion chromatography for ions. When comparing the results of the chemical analysis with the meteorological information, it was found that the concentration of certain elements and ions in aerosol samples was affected considerably by the location of the sampling site and by the meteorological conditions. In relatively less polluted places like small towns and rural regions around Antwerp, the concentrations of some elements and ions showed qualitatively a positive or negative correlation in their time variations with the amount of precipitation. Hence, we suppose that in the first case these elements and ions are contained mainly in the more hygroscopic fraction (the most apparent is the behavior of Na and Cl), and that in the second case, the elements are mainly present in the less hygroscopic fraction of the ambient aerosol. However, this behavior of the elements and ions may be different for various particle size ranges. In the highly urbanized and industrial sites close to the central and industrial parts of Antwerp, these correlations were not found. This could be connected with the high and variable local aerosol generation rate, when only heavy rains are able to provide a sufficient removal of the aerosols from the atmosphere.

Aerosols↗
PubMed2004

Induction of cellular and humoral immunity after aerosol or subcutaneous administration of Edmonston-Zagreb measles vaccine as a primary dose to 12-month-old children.

Infants were immunized by aerosol (10(3.6) plaque-forming units [pfu]/dose) or subcutaneous (sc) (10(4.27) pfu/dose) administration of Edmonston-Zagreb measles vaccine. Measles-specific T cell proliferative responses with a stimulation index of > or =3 developed in 72% of children given aerosol-administered vaccine, compared with 87% given s.c.-administered vaccine (P =.06). Seroconversion rates were 90% after aerosol-administered vaccine and 100% after s.c.-administered vaccine (P=.01), and measles geometric mean titers were 237 milli-international units (mIU) (95% confidence interval [CI], 146-385 mIU) and 487 mIU (95% CI, 390-609 mIU) in each group, respectively (P=.01). Measles-specific T and B cell responses were weaker after aerosol than after sc vaccination, indicating a need to use a higher aerosol dose to achieve optimal immunogenicity.

Aerosols↗
PubMed2001

In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices.

Experiments were performed to determine the effect of different pharmaceutical aerosol inhalation devices on the deposition of monodisperse aerosols in an idealized mouth and throat geometry. The devices included two dry powder inhalers (Diskus and Turbuhaler), two nebulizers (Pari LC STAR and Hudson T-Updraft), and a metered dose inhaler with attached holding chamber (Aerochamber), in addition to a straight tube (1.7 cm inner diameter). Aerosol particles (DL-alpha tocopheryl acetate) of diameters of 2.5, 5, and 7 microm generated by a vibrating orifice generator were inhaled at steady air flow rates of Q = 5-90 L/min through the devices and into the mouth-throat. Deposition in the mouth-throat and after-filter were determined by ultraviolet (UV) spectrophotometric assay. The amount of deposition in the mouth and throat region was found to depend on the type of device that the aerosol entered through. Deposition in the extrathoracic region with the two types of jet nebulizers did not differ significantly (p > 0.1) from that of a straight tube or each other over their entire tested range of 590 > or = pd2Q > or = 11,375, where p is particle density (in g/cm3), d is particle diameter (in microm), and Q is flow rate (in cm3/s). The metered dose inhaler with attached holding chamber was found to differ from the straight tube only at two intermediate values of pd2Q = 5,145 and 16,033. The deposition occurring for the dry powder inhalers was found to be significantly greater than for the straight tube for all values of pd2Q > or = 10,954 for the Diskus and pd2Q > or = 9,435 for the Turbuhaler. Deposition with the dry powder inhalers was found to be up to 14 times greater than that with the straight tube. Thus, the inhaler geometry that the aerosol passes through prior to entering the mouth and throat region can greatly affect the deposition in the mouth-throat.

Aerosols↗
PubMed2001

Effects of unilateral bronchoconstriction on distribution of aerosols in ovine airways.

The purpose of the study was to assess the effect of unilateral bronchoconstriction on the deposition patterns of aerosolized particles in a sheep model. Unilateral bronchoconstriction was induced in intubated conscious sheep by placing a protective, obstructing balloon catheter in either main bronchus, prior to administration of aerosolized carbachol at a dose that increased pulmonary resistance by 200-400% above baseline. The catheter was then removed and the animals were positioned under a gamma camera. An equilibrium image was obtained with xenon (133Xe), to determine a lung outline that was used to calculate the proportion of counts in each lung. Aerosols, labeled with technetium (99mTc) and generated by two jet nebulizers, were inhaled tidally by the sheep in serial experiments. (For nebulizer A, mass median aerodynamic diameter [MMAD] = 0.39 microm; for nebulizer B, MMAD = 1.1 microm.) For nebulizer A, percentage deposition in the treated and untreated lungs was not significantly different (50.8% versus 49.2%, respectively), while for nebulizer B, the median deposition in the carbachol treated lung was significantly greater than in the untreated lung (55.8% versus 44.2% respectively; p = 0.005). There was a more central pattern of deposition in the treated lung than in the untreated lung for both nebulizers, but the degree of central deposition was significantly greater with nebulizer B. The findings of the present study suggest that regional obstruction does not preclude the delivery of therapeutic aerosols to the airways in such a region, and may, depending on the size of the aerosol, result in enhanced airway deposition relative to less obstructed regions.

Aerosols↗
PubMed2003

A comparison of planar scintigraphy and SPECT measurement of total lung deposition of inhaled aerosol.

Planar gamma camera imaging of inhaled aerosol deposition is extensively used to assess the total deposition in the lung. However, validation of the measurements is not straightforward, as gold standard measurements of lung activity against which to compare are not readily available. Quantitative SPECT imaging provides an alternative method for comparison. Four different methods for planar image quantification are compared. Two attenuation correction techniques, thickness measurement and transmission measurement, have been combined with two scatter correction techniques, reduced attenuation coefficient and line-source scatter function convolution subtraction. Each technique has been applied to 10 studies of aerosol deposition of a fine aerosol (mass median aerodynamic diameter 1.8 microm) and 10 studies using a coarse aerosol (mass median aerodynamic diameter 6.5 microm). The total activity in the right lung for each measurement has been compared to the value determined from SPECT imaging on the same subjects. When the thickness measurement and transmission techniques were applied with scatter compensation using a reduced attenuation coefficient, activity was systematically overestimated by 5% in both cases. The corresponding random errors (coefficient of variation) were 8.6% and 6.6%. Separate scatter correction reduced these systemic errors significantly to -1.5% and 2.7%, respectively. The random errors were not affected. All techniques provided assessment of total lung activity with an accuracy and precision that differed by less than 10% compared to the SPECT values. Planar gamma camera imaging provides a good method of assessing total lung deposition of inhaled aerosol.

Adult↗
PubMed1998

Aerosolization of cationic lipid:pDNA complexes--in vitro optimization of nebulizer parameters for human clinical studies.

Previously, we have described the optimization of the aerosol delivery of a nonviral gene therapy vector to the lungs of rodents (Eastman et al., 1997b). Although aerosolizing cationic lipid:pDNA complexes into a whole-body exposure chamber resulted in high levels of reporter gene expression in the lungs of BALB/c mice, the conditions employed were not optimal for the delivery of lipid:pDNA complexes to the lungs of human patients. That is, the consumption rate of the material in the nebulizer, and thus the delivery time, were very slow and the aerosol was delivered in a continuous flow. Here we describe in vitro experiments used to develop a cationic lipid:pDNA aerosol with characteristics more suitable for delivery to the lungs of humans, as a necessary prerequisite for conducting a clinical study with human cystic fibrosis patients. Using cascade impactors and all-glass impingers, we have screened several commercially available nebulizers for their ability to deliver intact, respirable, active lipid:pDNA complexes in the shortest time possible, and have identified the Pari LC Jet Plus nebulizer as the optimal nebulizer that meets these criteria. Using this nebulizer in an intermittent mode to mimic breath actuation, consumption rates of approximately 0.6 ml/min of the cationic lipid:pDNA complexes (6 mM cationic lipid:8 mM pDNA) were obtained. The plasmid DNA remained intact and the complexes were shown to maintain activity throughout the nebulization run. Based on measurements of the nebulized dose and the mass median aerodynamic diameter, we calculate a delivered dose of approximately 22 micromol (7.2 mg) of pDNA for each 8 ml of cationic lipid:pDNA complex aerosolized to the lungs of a human patient. This dose should be sufficient to test the clinical efficacy of cationic lipid-mediated gene delivery for the treatment of cystic fibrosis.

Aerosols↗
PubMed1991

Aerosolized drug delivery: fractional deposition of inhaled particles.

Delivery of drugs by aerosol is increasingly used as a means of providing therapy to both the lungs and to the rest of the body through absorption into the pulmonary circulation. The techniques, definitions, and terminology for aerosol delivery are not standardized or necessarily understood by the increasing number of clinicians and clinical investigators involved in these studies. This paper attempts to establish some definitions and guidelines for defining and characterizing deposition of aerosols in the respiratory tract. Some of the parameters that affect deposition are discussed (e.g., particle size, breathing pattern, airway caliber). It is suggested that these parameters be controlled or measured when characterizing new aerosol delivery systems for clinical investigations. These recommendations were discussed and agreed upon during an expert meeting on definitions and standards related to aerosols in medicine at the 8th Congress of ISAM.

Administration, Inhalation↗
PubMed1994

A nebulizer system for highly reproducible aerosol delivery.

The output characteristics of current nebulizer systems are influenced by factors such as inspiratory flow, temperature and relative humidity of the ambient air as well as surface tension of the nebulizing solutions. Due to the resulting alteration of droplet characteristics the delivery of aerosolized drugs is variable. A nebulizer system, the PARI IS-2, has been designed for the delivery of aerosolized potent drugs. It is characterized by a highly consistent aerosol output and a high proportion of droplet mass in the respirable range. Laboratory testing was performed with a Malvern Particle Sizer and by measurement of total and effective output rates. Preconditioned air was supplied to the system in order to simulate different inspiratory flows (steady state) at varying ambient conditions. There was only a small effect on droplet sizes (MMD 3.0 to 3.6 microns) over the investigated range of inspiratory flow, ambient conditions and drug solutions. Total and effective output rates of the nebulizer were found to be linearly proportional between 5 and 20 l/min inspiratory flow thereby compensating for the dilution of aerosol by entrained air. Total output, at a relative humidity between 20% and 80% and at fixed inspiratory flow, varied only by +/- 6% with respect to 50% relative humidity (r.h.). The proportion of the dose delivered from the system ranged from 28% to 67% for an initial fill volume between 0.5 and 3 ml, respectively. Thus, for standardized breathing and by using the manual interrupter for on-command therapy, a highly effective delivery and deposition of therapeutic aerosols in the lungs may be achieved with the PARI IS-2 nebulizer system.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1996

Aerosol transport and deposition in the rhythmically expanding pulmonary acinus.

Little is known about factors controlling the dynamics of aerosol dispersion and deposition in the lung periphery, though this knowledge becomes increasingly important in many fields such as environmental and occupational exposure, diagnostic applications, and therapeutic deliver of drugs via aerosols. For the last several years, we have been studying aerosol behavior in the pulmonary acinus, where the airway structure and the associated fluid mechanics are distinctly different from those in the conducting airways. Our major research efforts have been focused on the basic physics underlying acinar fluid mechanics and particle dynamics, which are likely to be conditioned by the two key geometric factors of acinar airways: structural alveolation and rhythmic expansion and contraction of the alveolar walls. A combination of computational and experimental analyses revealed that due to these unique geometric features acinar flow can be extremely complex despite the low Reynolds number, and can have substantial effects on particle dynamics. In particular, chaotic mixing can occur in the lung periphery. In the course of such a mixing process, the inhaled aerosol particles quickly mix with the residual alveolar gas in a manner that is radically different from the previously considered classical diffusion process. The objective of this paper is to briefly review our current understanding of these processes, to discuss existing deposition models, and to describe our ongoing research efforts toward a basic understanding of aerosol behavior in the pulmonary acinus.

Administration, Inhalation↗
PubMed1996

The pulmonary deposition of two aerosol preparations of nedocromil sodium delivered by MDI assessed by single photon emission computed tomography.

The pulmonary deposition and pharmacokinetics of fine and coarse radioactive aerosols of nedocromil sodium, of mass median aerodynamic diameters 16 microns and 24 microns respectively, delivered by metered dose inhaler (MDI) have been investigated. The corresponding geometric standard deviations of the particle size distributions were 5.32 and 3.93. Pulmonary deposition was assessed by both planar radionuclide scintigraphy and multi-modality three dimensional imaging using single photon emission computed tomography (SPECT) and x-ray computed tomography (CT). The three dimensional data were analysed by transformation to a hemispherical shape based on the fractional radial distance of each point in the lung from the centre to the corresponding extrapolated point on the periphery. This enabled parameters on the variation of both concentration of deposition and total amount deposited with penetration distance to be calculated. For both planar and SPECT data the central to peripheral concentration ratio (C/P ratio) was calculated. The three dimensional C/P ratio showed a median value (3.21) which was significantly higher than for the planar imaging (2.03) (p < 0.001). The parameter used to express the variation of total amount deposited was the median dose position. This showed that for both aerosols 50% of the dose was deposited at sites with a percentage central to peripheral distance of greater than 68%. There was a trend for total percentage of the fine aerosol in the lungs to be higher than for the coarse and for its deposition to be more peripheral. In addition the mean concentrations in blood were measured to be greater for the fine aerosol. However these differences were relatively small and none were individually statistically significant. The technique of combined SPECT and CT imaging was shown to be valuable in obtaining more accurate information on pulmonary distribution of inhaled aerosol deposition. The merits, limitations and potential applications of the technique are discussed.

Administration, Inhalation↗
PubMed1999

Time-of-flight aerodynamic particle size analyzers: their use and limitations for the evaluation of medical aerosols.

Time-of-flight (TOF) aerosol analyzers are a class of instruments that measure the aerodynamic diameter of individual particles following a controlled acceleration in a well-defined flow field. Two instruments have been used to analyze the size of medical aerosols: Aerosizer particle size analyzer (TSI Particle Instruments/Amherst, Amherst, MA), Aerodynamic Particle Sizer (APS) aerosol spectrometer (TSI) Both instruments are capable of sizing several thousand particles a second, making it possible to obtain aerodynamic particle size distributions in a few seconds compared with up to 1 hour per measurement using compendial methods that are based on either the multistage liquid impinger or cascade impactor. This rapidity makes TOF analysis attractive for product development, as many different variables can potentially be investigated during a short period of time. The data thus obtained should be used with caution, however. Several issues, most notably the lack of a direct relationship with the mass of drug substance present and the vulnerability of the measurements to coincidence effects when sampling concentrated aerosols, may severely limit the value of data from many aerosol delivery systems, especially pressurized metered dose inhalers (pMDIs). A review of the literature illustrating the issues that are involved and providing guidance on the most appropriate uses of these analyzers is presented.

Aerosols↗
PubMed2005

Dose delivery late in the breath can increase dry powder aerosol penetration into the lungs.

In addition to aerosol particle size and mode of inhalation, the time-point of dose delivery during inhalation may be an important factor governing the intrapulmonary distribution of aerosolized drug. To generate different intrapulmonary deposition patterns of a drug model aerosol, a device with the capability of delivering small amounts of technetium-99m-labeled lactose dry powder at pre-set time-points during inhalation was developed. A single dose of the radioaerosol was delivered after inhalation of 20% (A) or 70% (B) of the vital capacity inhaled through the device. Twelve healthy subjects were studied in a randomized crossover fashion. Planar gamma scintigraphy was carried out, and the penetration index, PI, defined as the ratio of peripheral to central lung zone deposition of radioactivity, was estimated. A significant increase in PI from 3.0 (A) to 3.7 (B) was observed with the change from early to late delivery of the dose (p < 0.01). No difference in the total amount of radioactivity within the lungs could be detected. In conclusion, independent of total pulmonary deposition, deeper dry powder aerosol penetration into the lungs was found for the dose delivered at near end instead of at the beginning of inhalation. By computational modeling of the aerosol transport and deposition, that finding was mechanistically explained by differences in airway caliber as a consequence of the level of lung inflation at the time-point of dose delivery.

Administration, Inhalation↗