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PubMed2001

Analysis of aerosol distribution inside the object "shelter" at the Chernobyl nuclear reactor site.

Results of the aerosol sampling inside the Object Shelter at the Chornobyl nuclear reactor site are considered in the work. The results show a consistent and significant contribution of submicron fraction to the total aerosol activity. Different methods of interpretation of impactor data series are compared in order to indicate and detect in the most effective way the submicron fraction as a separate component of the distribution. The methods used are as follows-method of probabilistic-logarithmic scale, method of likelihood function, non-linear approximation by sum of several log-normal distributions, and restoration of the initial distribution using passage functions of impactor cascades. Practically all the collected data on aerosol distribution inside the Shelter show a distinct submicron component. The contribution of the submicron component into the total aerosol activity is about 35%. Influence of the actual aerosol distribution on the dose coefficients is analyzed.

Aerosols↗
PubMed1992

Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation.

Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0-3. Groups 4-7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/m3 with a mean particle size of 0.7 mu and estimated pulmonary depositions of CsA of 0.98-3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P less than 0.0002 and less than 0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.

Aerosols↗
PubMed1993

Characterization and administration of cyclosporine liposomes as a small-particle aerosol.

Systemically administered CsA has not consistently suppressed the pulmonary immunoreactivity that leads to rejection in lung transplant patients. Pulmonary T cells from patients given CsA systemically still retain their immunoreactivity, which can be suppressed with added CsA. Direct application of CsA by aerosol to the respiratory epithelium should achieve high lung concentrations with minimum systemic effects. In the present study, CsA was most efficiently incorporated into liposomes composed of egg yolk phosphatidylcholine at a molar ratio of CsA to egg yolk phosphatidylcholine of 1:20. These CsA liposomes retained their biological activity and were as effective as free CsA in the suppression of anti-CD3-stimulated [3H]thymidine incorporation by mouse spleen cells. The generation of a small-particle aerosol of CsA liposomes had no effect on this biological activity. CsA liposome aerosol particles have a mass median aerodynamic diameter of 2 microns, which allows for distribution of drug throughout the respiratory tract. Quantitation of CsA in the lungs and blood of mice exposed to CsA liposome aerosols for 4 days showed that as little as 15 min daily (0.11 mg/kg/day) was sufficient to achieve an estimated concentration of CsA in respiratory secretions of 6 micrograms/ml without detectable blood levels. Thus, CsA liposomes can be produced and aerosolized that achieve pulmonary concentrations with sufficient immunosuppressive activity to be effective in the treatment of lung diseases.

Aerosols↗
PubMed2004

Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury.

OBJECTIVES: To investigate whether aerosolized prostacyclin improves oxygenation in children with acute lung injury. DESIGN: Double-blind, randomized, and placebo-controlled trial. SETTING: Pediatric intensive care unit at a university hospital. PATIENTS: Fourteen children with acute lung injury defined by the criteria of an American-European Consensus Conference. INTERVENTIONS: Aerosolized prostacyclin (epoprostenol sodium) by stepwise increments of different doses (10, 20, 30, 40, and 50 ng x kg x min) vs. aerosolized normal saline (placebo). MEASUREMENTS AND MAIN RESULTS: Before the start of the study, and before and after each dose of prostacyclin/placebo, the following variables were measured: arterial blood gases, heart rate, mean arterial blood pressure, and ventilator settings required. Changes in oxygenation were measured by calculation of the oxygenation index (mean airway pressure x 100 x Pao2/Fio2). After treatment with aerosolized prostacyclin, there was a significant 26% (interquartile range, 3%, 35%) improvement in oxygenation index at 30 ng x kg x min compared with placebo (p =.001). The response to prostacyclin was not the same in all children. We saw an improvement of > or = 20% in eight of 14 children (i.e., responders), and the number needed to treat was 1.8 (95% confidence interval, 1.2-3.2). No adverse effects were observed. CONCLUSIONS: Aerosolized prostacyclin improves oxygenation in children with acute lung injury. Future trials should investigate whether this treatment will positively affect outcome.

Administration, Inhalation↗
PubMed2004

Quantitative lung perfusion scan as a predictor of aerosol distribution heterogeneity and disease severity in children with cystic fibrosis.

BACKGROUND: The assessment of lung ventilation by radionuclide imaging has proved useful for the optimization of aerosol therapy in children with cystic fibrosis. Further analysis of lung perfusion may provide additional information. METHODS: Quantitative analysis of regional lung aerosol distribution (Tc phytates) and perfusion (Tc macroaggregates) homogeneity was performed in 18 children with cystic fibrosis, using the third and fourth spatial moments (skew and Kurtosis) of count distribution. Patients were chosen from a prospective study whose goal was to compare the efficacy of two nebulization methods of a radiolabelled aerosol: one session involved a nebulizer activated by patient inspiratory flow (control session), whereas the other involved a nebulizer powered by a pressure support device (PS session). RESULTS: Quantitative regional distribution of perfusion was similar to aerosol distribution, although skew and Kurtosis were lower, indicating better homogeneity. Perfusion skew was inversely correlated with pulmonary volumes and Shwachman score, even more significantly than ventilation skew. Using receiver operating characteristic curve analysis, a perfusion skew threshold of 0.67 was predictive of disease severity (FEV1 > or =60% or FEV1 <60%) with 86% sensitivity and 91% specificity. Furthermore, same skew threshold allowed the identification of patients who were 'PS responders' (greater amount of radioactivity deposited after the PS session) or 'PS non-responders' with 80% sensitivity and 77% specificity. CONCLUSION: Quantification of regional lung perfusion is easy to perform and heterogeneity of the distribution is closely correlated to disease severity. Moreover, perfusion skew can identify patients who are likely to benefit from pressure support (to optimize aerosol therapy) and may be helpful for orienting potential non-responders towards alternative therapies.

Adolescent↗
PubMed2006

Microbial aerosol generation during laboratory accidents and subsequent risk assessment.

AIM: To quantify microbial aerosols generated by a series of laboratory accidents and to use these data in risk assessment. METHODS AND RESULTS: A series of laboratory accident scenarios have been devised and the microbial aerosol generated by them has been measured using a range of microbial air samplers. The accident scenarios generating the highest aerosol concentrations were, dropping a fungal plate, dropping a large bottle, centrifuge rotor leaks and a blocked syringe filter. Many of these accidents generated low particle size aerosols, which would be inhaled into the lungs of any exposed laboratory staff. Spray factors (SFs) have been calculated using the results of these experiments as an indicator of the potential for accidents to generate microbial aerosols. Model risk assessments have been described using the SF data. CONCLUSIONS: Quantitative risk assessment of laboratory accidents can provide data that can aid the design of containment laboratories and the response to laboratory accidents. SIGNIFICANCE AND IMPACT OF THE STUDY: A methodology has been described and supporting data provided to allow microbiological safety officers to carry out quantitative risk assessment of laboratory accidents.

Accidents, Occupational↗
PubMed1988

Effects of screen materials on droplet size frequency distribution of aerosols entering sentinel mosquito exposure tubes.

Aerosol filtration effects of three types of mesh screen used for mosquito cages were evaluated with aerosolized water, mineral oil and chlorpyrifos. The screen materials were two nylon tulles (3 x 4 and 8 x 11 repeats per cm2) and corrosion-resistant steel (7 x 7 repeats per cm2). Open areas of these three mesh materials were, respectively, 94%, 79% and 88%. Aerosol droplet size frequency distributions were altered when passed through test screens of these materials fitted to standard tubes from World Health Organization test-kits for exposure of adult mosquitoes. The alterations included reductions in total droplets and volume median diameter (VmD). Nylon screen with fewer repeats of the mesh altered droplet VmD and frequency distribution the least, allowing the greatest number of droplets to enter sentinel mosquito cages for bioassays of mortality-rates. The greater filtration effect of screens with less open area, giving rise to selective deposition of particular droplet sizes on the screen material, could result in anomalous exposures of test mosquitoes to contact with insecticide filtrate on the screen substrate. This might help to explain the poor correlation often observed between insecticide aerosol impact on wild target mosquito populations as compared with sentinel caged mosquitoes. In addition to other standard test procedures, the need for standardization of materials used for construction of sentinel cages employed for aerosol bioassays is emphasized.

Aerosols↗
PubMed1994

Effects of aerosol administration of a thromboxane receptor antagonist (S-1452) on experimental asthma in guinea pigs.

The importance of thromboxane A2 (TXA2), one of the arachidonate metabolites, in the pathogenesis of bronchial asthma has been emphasized recently. Because aerosolized administration of antiasthmatic drugs is effective and safe, this study examined the effect of aerosolized TXA2 receptor antagonist (S-1452) on allergic bronchoconstriction in passively sensitized and mechanically ventilated guinea pigs. Under the cover of antihistamine, antigen-induced bronchoconstriction was markedly inhibited by pretreatment with aerosolized S-1452 inhalation in a dose-dependent manner. Although aerosolized S-1452 itself provoked weak bronchoconstriction for its partial agonist effect, bronchial responsiveness to inhaled histamine did not change 10 min after S-1452 inhalation. These results indicate that aerosolized S-1452 may be useful in treating bronchial asthma.

Aerosols↗
PubMed1983

Sodium cromoglycate as a pressurised aerosol (vicrom) in exercise-induced asthma.

We investigated the effect of sodium cromoglycate (SCG), delivered as a pressurised aerosol, in a dose of 2 or 4 mg in 15 patients known to have exercise-induced asthma (EIA). All patients had a fall in peak expiratory flow rate (PEFR) greater than 20% of the pre-exercise level following placebo (Range 21.1 to 74.7%). When an identical exercise test was performed after 2 mg of SCG aerosol, nine of the 15 patients had falls in PEFR less than 50% of the value observed on placebo. Of the remaining six patients, four had greater than 50% protection afforded by 4 mg of SCG. Of the 15 patients, 12 had falls in PEFR less than 11% after either 2 or 4 mg of SCG aerosol. The dose of aerosol SCG required to inhibit EIA is only 10 to 20% of that delivered by conventional spinhaler. The apparent superiority of the pressurised aerosol may be due to its site of deposition in the airways.

Adolescent↗
PubMed2005

Aerosolization as novel sanitizer delivery system to reduce food-borne pathogens.

AIMS: As a preliminary experiment on new sanitizer delivery tools, the efficacy of aerosolized sanitizer on food-borne pathogens was investigated in larger model chamber system. METHODS: Peroxyacetic acid and hydrogen peroxide were aerosolized in a model system against artificially inoculated target micro-organisms on laboratory media. Cultures of four different food-borne pathogens were inoculated and affixed onto three different heights (bottom, wall and ceiling), and three different orientations (face-down, vertical and face-down) inside a commercial semi-trailer cabinet (14.6 x 2.6 x 2.8 m). Sanitizer was aerosolized into 2 microm droplet size fog and treated for 1 h at ambient temperature. RESULTS: Populations of Bacillus cereus, Listeria innocua, Staphylococcus aureus, and Salmonella typhimurium were reduced by an average of 3.09, 7.69, 6.93 and 8.18 log units per plate respectively. Interestingly, L. innocua, Staph. aureus, and Salm. typhimurium showed statistically not different (P >/= 0.05) reduction patterns relative to height and orientation that were never expected in a spraying system. CONCLUSIONS: Aerosolized sanitizers diffuse like gaseous sanitizers. SIGNIFICANCE AND IMPACT OF THE STUDY: Aerosolization has great potential for use in commercial applications.

Aerosols↗
PubMed2005

Evaluation of ionic air purifiers for reducing aerosol exposure in confined indoor spaces.

UNLABELLED: Numerous techniques have been developed over the years for reducing aerosol exposure in indoor air environments. Among indoor air purifiers of different types, ionic emitters have gained increasing attention and are presently used for removing dust particles, aeroallergens and airborne microorganisms from indoor air. In this study, five ionic air purifiers (two wearable and three stationary) that produce unipolar air ions were evaluated with respect to their ability to reduce aerosol exposure in confined indoor spaces. The concentration decay of respirable particles of different properties was monitored in real time inside the breathing zone of a human manikin, which was placed in a relatively small (2.6 m3) walk-in chamber during the operation of an ionic air purifier in calm air and under mixing air condition. The particle removal efficiency as a function of particle size was determined using the data collected with a size-selective optical particle counter. The removal efficiency of the more powerful of the two wearable ionic purifiers reached about 50% after 15 min and almost 100% after 1.5 h of continuous operation in the chamber under calm air conditions. In the absence of external ventilation, air mixing, especially vigorous one (900 CFM), enhanced the air cleaning effect. Similar results were obtained when the manikin was placed inside a partial enclosure that simulated an aircraft seating configuration. All three stationary ionic air purifiers tested in this study were found capable of reducing the aerosol concentration in a confined indoor space. The most powerful stationary unit demonstrated an extremely high particle removal efficiency that increased sharply to almost 90% within 5-6 min, reaching about 100% within 10-12 min for all particle sizes (0.3-3 microm) tested in the chamber. For the units of the same emission rate, the data suggest that the ion polarity per se (negative vs. positive) does not affect the performance but the ion emission rate does. The effects of particle size (within the tested range) and properties (NaCl, PSL, Pseudomonas fluorescens bacteria) as well as the effects of the manikin's body temperature and its breathing on the ionic purifier performance were either small or insignificant. The data suggest that the unipolar ionic air purifiers are particularly efficient in reducing aerosol exposure in the breathing zone when used inside confined spaces with a relatively high surface-to-volume ratio. PRACTICAL IMPLICATIONS: Ionic air purifiers have become increasingly popular for removing dust particles, aeroallergens and airborne microorganisms from indoor air in various settings. While the indoor air cleaning effect, resulting from unipolar and bipolar ion emission, has been tested by several investigators, there are still controversial claims (favorable and unfavorable) about the performance of commercially available ionic air purifiers. Among the five tested ionic air purifiers (two wearable and three stationary) producing unipolar air ions, the units with a higher ion emission rate provided higher particle removal efficiency. The ion polarity (negative vs. positive), the particle size (0.3-3 microm) and properties (NaCl, PSL, Pseudomonas fluorescens bacteria), as well as the body temperature and breathing did not considerable affected the ionization-driven particle removal. The data suggest that the unipolar ionic air purifiers are particularly efficient in reducing aerosol exposure in the breathing zone when they are used inside confined spaces with a relatively high surface-to-volume ratio (such as automobile cabins, aircraft seating areas, bathrooms, cellular offices, small residential rooms, and animal confinements). Based on our experiments, we proposed that purifiers with a very high ion emission rate be operated in an intermittent mode if used indoors for extended time periods. As the particles migrate to and deposit on indoor surfaces during the operation of ionic air purifiers, some excessive surface contamination may occur, which introduces the need of periodic cleaning these surfaces.

Aerosols↗
PubMed1976

Size analysis of suspension inhalation aerosols by inertial separation methods.

The particle size distribution of beclomethasone dipropionate (BDP) aerosols delivered from pressurized metered dose suspension inhalers has been measured with three cascaded inertial separation instruments, the Casella Cascade Impactor, Multistage Liquid Impinger and Cascade Centripeter. Various methods for collecting the emitted aerosol before measurement have been examined. A bent glass tubular 'throat', used as a simulated oro-pharynx, collects 35-60% of the emitted dose by impingement of the wet spray cone in the throat. The aerosol passing through the throat has a similar but somewhat finer size distribution to that collected by firing directly into a large flask. The three cascaded instruments give similar results which in the Multistage Liquid Impinger also resemble those given by a salbutamol inhaler. The mass fraction (35-60%) emitted from the oral adaptor which is of a size capable of deep lung penetration ( less than 4 mum) is much higher than the fraction (10-16%) found in the lungs of dogs after inhalation of aerosol. The size distributions resemble those determined by microscopy and are expressed as aerodynamic sizes, thus showing that the particles approximate to unit density spheres. The performance of two simpler devices, Kirk's apparatus and the Harwell size selective air sampler are also assessed, the latter shows some promise for the simple evaluation of the respirable fraction of inhalation aerosols.

Aerosols↗
PubMed1997

Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution.

Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes. The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium (99mTc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1.98 microns and 2.02, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2: lipid:HSA) demonstrated a close correlation of size distributions (r = 0.9445; P < 0.001). The entrapment of interleukin 2 in liposomes was 93 +/- 4.3% before nebulization and 90 +/- 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean +/- s.d. central lung-to-peripheral lung deposition was 1.12 +/- 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen. The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers.

Aerosols↗
PubMed2006

High natural aerosol loading over boreal forests.

Aerosols play a key role in the radiation balance of the atmosphere. Here, we present evidence that the European boreal region is a substantial source of both aerosol mass and aerosol number. The investigation supplies a straightforward relation between emissions of monoterpenes and gas-to-particle formation over regions substantially lacking in anthropogenic aerosol sources. Our results show that the forest provides an aerosol population of 1000 to 2000 particles of climatically active sizes per cubic centimeter during the late spring to early fall period. This has important implications for radiation budget estimates and relevancy for the evaluation of feedback loops believed to determine our future climate.

Aerosols↗
PubMed1970

Smog aerosol: infrared spectra.

Infrared spectra of smog aerosol are similar to those of sulfuric acid aerosol, but they do not show the prominent CH and carbonyl bands of organic aerosols from terpenes. Some features of the smog aerosol spectra are not present in the spectra from either type of synthetic aerosol.

Aerosols↗
PubMed1992

Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability.

Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations.

Adult↗
PubMed1999

Efficacy of RD3-0028 aerosol treatment against respiratory syncytial virus infection in immunosuppressed mice.

RD3-0028, a benzodithiin compound, has antiviral activity against respiratory syncytial virus (RSV) in cell culture. We used a mouse model of RSV infection to determine the in vivo effect of RD3-0028. Cyclophosphamide (CYP)-treated, immunosuppressed mice were inoculated intranasally. The lungs of the mice were removed on day 4. The virus titers of the lungs of RD3-0028-treated mice were compared to the virus titers of the lungs of virus-inoculated, untreated control mice. In an effort to increase the therapeutic effectiveness of this compound, RD3-0028 was administered by aerosol to RSV-infected mice by using a head-exposure system. Aerosols generated from reservoirs containing RD3-0028 (7 mg/ml) administered for 2 h twice daily for 3 days significantly reduced the pulmonary titer of RSV-infected mice. It is clear that the minimal effective dose of RD3-0028 for RSV-infected mice is significantly less than that of ribavirin, the only compound currently available for use against RSV disease. Furthermore, the RD3-0028 aerosol administration appeared to protect the lungs of infected, CYP-treated mice against tissue damage, as evidenced by the preservation of the lung architecture and a reduction in pulmonary inflammatory infiltrates. RD3-0028 aerosol was not toxic for mice at the therapeutic dose. The present study demonstrates the effectiveness of aerosol administration of RD3-0028 for RSV-infected mice.

Aerosols↗
PubMed1982

Aerosol stability of infectious and potentially infectious reovirus particles.

The aerosol stability of two particle forms, infectious and potentially infectious, of reovirus were examined under static conditions for a range of relative humidities at 21 and 24 degrees C. Virus aerosolization efficiency was determined for two methods of dissemination: Collison nebulizer and Chicago atomizer. Suspensions of Bacillus subtilis var. niger spores were added to reovirus preparations that included both particle forms and disseminated into a dynamic aerosol toroid to estimate the physical decay of the aerosols. At 90 to 100% relative humidity, both reovirus particle forms showed less than 10-fold loss of infectivity after 12 h of aging. At lower relative humidities the aerosol decay curve showed rapid initial decay followed by a markedly lower decay rate. Our findings reveal that reovirus particles are relatively stable in the airborne state.

Aerosols↗