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[Comparison of the rapidity of action of dry-powder inhaler vs pressurized aerosol terbutaline].

The speed of bronchodilatation with terbutaline administered through the Turbuhaler system and the same drug administered through a pressurized liquid aerosol device was compared in 9 patients with reversible air flow obstruction. On 2 consecutive days, terbutaline 0.5 mg in aerosol or dry-powder form (Turbuhaler) was administered after baseline spirometric measurements were taken. Spirometry was repeated at 15, 45 and 90 s and at 3, 5, 10, 15, 30, 60 and 120 min after administration of the drug. Both forms of presentation produced approximately 50% of their maximum effect within the first 45 s; 80% of the patients in the dry-powder group reached the mean of maximum FEV1 increase at 10 min, while 83% in the pressurized-aerosol-device group did so. The maximum increase was reached at 52 (54) min with the Turbuhaler and at 69 (50) min for the aerosol. The difference in speed of effect for the two pharmaceutical forms were not statistically significant. The administration of terbutaline in powder form (Turbuhaler) was as fast and effective in achieving bronchodilatation as was the aerosol form.

Administration, Inhalation↗

Aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection.

Aerosol vaccination is used effectively to immunize poultry against Newcastle disease, but to the authors' knowledge, this vaccination procedure is not well studied in other species. The efficacy of IM and aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection was evaluated. Twenty-one pigs from a Mycoplasma-free herd were randomly allotted by litter and body weight into 3 groups. One group was given aerosolized phosphate-buffered saline solution (PBSS) by inhalation. The second group (AERO) was given aerosolized M hyopneumoniae vaccine by inhalation. The third group (IM) was given the same vaccine by IM injection. Vaccination by IM administration was repeated once, and aerosol vaccination was repeated twice at 2-week intervals. Two weeks after the last vaccination, all pigs were intratracheally challenge-exposed with 3 ml of broth culture containing 10(7) color-changing units (CCU) of a low-passage strain of virulent M hyopneumoniae. Pigs were observed daily for coughing. Four weeks after challenge exposure, all pigs were necropsied. Percentage of lung affected by gross pneumonia was measured, bronchioalveolar lavage fluid (BALF) cells were counted, and quantitative culture for mycoplasmas was performed on lung sections. Additionally, M hyopneumoniae-specific antibodies were measured in prevaccination, postvaccination, and postchallenge-exposure serum and BALF by use of indirect ELISA. Mean prevalence of persistent coughing in pigs of the AERO group (4.6 d/pig) was not different from that in pigs of the PBSS group (3.7 d/pig). Prevalence of coughing in IM vaccinated pigs (1.0 d/pig) was lower (P < 0.05) than that in pigs of the PBSS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Three-dimensional description of pulmonary deposition of inhaled aerosol using data from multimodality imaging.

UNLABELLED: Three-dimensional assessment of pulmonary deposition of inhaled aerosol may be performed using SPECT. The use of aligned anatomical images enables improved accuracy of quantification and anatomical localization of deposition. METHODS: Techniques of analyzing these data and their application to deposition studies of two nebulizer-generated aerosols (mass median diameter 1.5 and 6.5 microM respectively) in 12 normal subjects are described. The deposition data were transformed to a standard hemispherical shape and the mean distribution pattern for each aerosol evaluated. Deposition by airway generation was then calculated using a spatial model of airway morphology. The results were compared to those from planar image analysis. RESULTS: The hemispherical transform yielded considerably more qualitative information on deposition pattern. The central-to-peripheral concentration ratio between conducting and alveolated airways was 5.27 for the coarser aerosol and 2.43 for the fine. The two-dimensional spatial estimates of the ratio were 2.61 and 2.03 respectively. CONCLUSION: Analysis of multimodality imaging data considerably enhanced information on deposition compared to planar imaging. It provides new data on aerosol deposition which will be of value to physicians involved in drug inhalation therapy.

Aerosols↗

Clinical use of an aerosol-reduction device with an ultrasonic scaler.

The traditional use of ultrasonic scalers has been to remove heavy deposits of calculus. Today, there is an increasing use of ultrasonic scalers in all areas of periodontal treatment, including periodontal maintenance and root planing. Coolant liquid must be used with an ultrasonic scaler because of heat buildup in the ultrasonic handpiece and scaler tip. The coolant liquid causes an infection control problem because of contaminated aerosols and a patient management problem because of water buildup in the patient's mouth. Data demonstrating the presence of blood in ultrasonic aerosols are presented. The clinical use of an aerosol reduction device that fits on an ultrasonic scaler is detailed. This device reduces the aerosol produced by more than 93%. Research that shows a reduction in water buildup in the patient's mouth of more than 76% (P < .01) is presented. The aerosol reduction device appears to greatly reduce many of the problems associated with the coolant liquid used during ultrasonic scaling.

Aerosols↗

[Modelling of influenza infection in mice inoculated by the aerosol method].

Modelling of experimental influenza infection was performed in an aerosol apparatus the main element of which was a glove box made of organic glass. Mice were infected by inhalation of a highly dispersed aerosol of influenza A2/Victoria/72 virus adapted to the mouse lungs. The aerosol was produced by means of a pneumatic atomizer. The fraction-dispersion composition of the aerosol, for the determination of which Andersen's cascade impactor was used, was characterized by virus-containing particles of 0.6 to 1.8 micrometer capable of penetrating to alveolar passages. A curve reflecting the dose--effect function was drawn on the basis of the relationship between the dilution of aerosolized virus suspension and mouse death rates. Virological, bacteriological, and histopathological examinations of the lungs of the infected mice revealed a correlation between the time of the animals' death, maximum influenza virus reproduction, multiplication of staphylococcal autoflora and the intensity of pathomorphological lesions.

Aerosols↗

Technetium-99m DTPA aerosol contamination in lung ventilation studies.

UNLABELLED: Contamination of working areas by 99mTc DTPA aerosol is of concern to nuclear medicine technologists. This study sought to determine the extent of 99mTc DTPA contamination to technologists, and to localize sources of aerosol leakage so that methods could be identified that would minimize contamination. METHODS: Fifty to eighty millicuries 99mTc DTPA, diluted to a volume of 4-5 ml with normal saline, were injected into the nebulizing chamber of two commercially available inhalation aerosol systems. The patient's nostrils were clamped and a damp washcloth was wrapped around the patient's mouth. An alcohol swab was placed in the exit port of the exhaust filter in each delivery system, and the technologist involved wore a face mask during the inhalation phase. The patient breathed DTPA-labeled aerosol by mouth until the counting rate in the lungs was four times greater than the counting rate from the pulmonary perfusion phase. Connecting joints of the delivery system were then wipe tested. Last, a Geiger-Mueller detector (pancake probe) was used to survey all device components. Readings above 0.05 mR/hr were considered contaminated. RESULTS: The patient was the greatest source of leakage as determined by the damp washcloth, followed by the joints of the tubes of the delivery system and, finally, the system's exhaust filter. Contamination readings from face masks worn by technical personnel during the lung ventilation studies were slightly greater than 0.05 mR/hr. CONCLUSION: The findings support trace levels of contamination to both the technologist and room while performing 99mTc DTPA aerosol ventilation studies. Comparative data using the two delivery systems revealed little difference in sources of leakage and little variation in contamination measurements.

Aerosols↗

Cytologic evaluation of bronchoalveolar lavage fluid from horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively.

OBJECTIVE: To determine cytologic changes in horses with recurrent airway obstruction (heaves) after administration of aerosolized beclomethasone dipropionate and dexamethasone parenterally. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone, parenterally administered dexamethasone, aerosolized propellant), and pulmonary inflammation was evaluated by serial cytologic examination of bronchoalveolar lavage (BAL) fluid samples obtained on days 0, 7, 10, 14, and 21. Total and differential cell counting and phenotypic analysis of lymphocyte subpopulations in BAL fluid were performed. RESULTS: 7 days of natural challenge induced neutrophilic inflammation. Neutrophil counts in BAL fluid were reduced in beclomethasone- and dexamethasone-treated horses on days 10 and 14 but rebounded to pretreatment values on day 21. The proportion of proinflammatory lymphocyte subpopulations (CD4+ and B+) and MHC class-II antigen expression were increased on days 14 and 21 in propellant-treated horses, compared with beclomethasone- and dexamethasone-treated horses. CONCLUSIONS: Aerosolized beclomethasone attenuated neutrophilic pulmonary inflammation and prevented alteration in lymphocyte subpopulations in horses with heaves. Results were similar to the response associated with parenterally administered dexamethasone. Short-term administration of aerosolized beclomethasone without minimizing environmental allergen exposure is not expected to provide prolonged anti-inflammatory benefit for horses with heaves.

Administration, Inhalation↗

Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively.

OBJECTIVE: To determine changes in clinical signs of disease and response to pulmonary function testing in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure (challenge) to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone dipropionate, parenterally administered dexamethasone, aerosolized propellant [control]), and respiratory frequency and subjective assessment of respiratory effect were determined twice daily. Maximal change in pleural pressure (delta-Pplmax), pulmonary resistance (RL), and dynamic compliance (Cdyn) was determined on days 0, 7, 10, 14, and 21. RESULTS: The RL and delta Pplmax were increased, and Cdyn was decreased in all horses in response to natural challenge. Beclomethasone reduced RL on day 10, reduced delta Pplmax on days 14 and 21 and increased Cdyn on day 14. Dexamethasone reduced RL and delta Pplmax on days 10, 14, and 21 and increased Cdyn on days 10 and 14. Respiratory effort (subjective assessment) improved after 2 and 3 days of beclomethasone and dexamethasone administration but rebounded to pretreatment values 1 and 3 days after discontinuation of drugs. CONCLUSIONS: Pulmonary function testing responses and clinical signs of airway obstruction were improved by administration of beclomethasone. The magnitude of response to aerosolized beclomethasone generally was less marked than the response to parenterally administered dexamethasone. Higher or more frequent dosing of aerosolized beclomethasone may be necessary to achieve the anti-inflammatory response to parenterally administered dexamethasone.

Administration, Inhalation↗

[Aerosols: a re-emerging treatment].

Aerosol drug delivery is widely used by patients with asthma and chronic bronchial obstruction for beta-2 agonists and anticholinergic drugs. More recently, inhaled steroid sprays have also been introduced. The efficacy of easy to use aerosol sprays is well proven and has become an important administration route. Different models of metered dose inhalers with gas propellants or dry powder devices help improve patients compliance. Nebulizers can be used in particular situations. Aerosol administration is proposed for anti-infectious agents and for rhDNase in cystic fibrosis. Aerosol delivery of nucleotides and antiproteases are currently under evaluation. Gene therapy can also benefit from the aerosol route which may be proposed in the near future for many different types of systemic treatments. Possible drugs include cyclosporin for lung grafts, prostacyclin for primary pulmonary hypertension, insulin for diabetes or morphine in certain types of dyspnea.

Aerosols↗

Application of matrix-assisted laser desorption/ionization to on-line aerosol time-of-flight mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) mass spectra were obtained from single biological aerosol particles using an aerosol time-of-flight mass spectrometer (ATOFMS). The inlet to the ATOFMS was coupled with an evaporation/condensation flow cell that allowed the aerosol to be coated with matrix material as the sampled stream entered the spectrometer. Mass spectra were generated from aerosol composed either of gramicidin-S or erythromycin, two small biological molecules, or from aerosolised spores of Bacillus subtilis var niger. Three different matrices were used: 3-nitrobenzyl alcohol, picolinic acid and sinapinic acid. A spectrum of gramicidin-S was generated from approximately 250 attomoles of material using a molar ratio of 3-nitrobenzyl alcohol to analyte of approximately 20:1. A single peak, located at 1224 Da, was obtained from the bacterial spores. The washing liquid and extract solution from the spores were analyzed using electrospray mass spectrometry and subsequent MS/MS product ion experiments. This independent analysis suggests that the measured species represents part of the B. subtilis peptidoglycan. The on-line addition of matrix allows quasi-real-time chemical analysis of individual, aerodynamically sized particles, with an overall system residence time of less than 5 seconds. These results suggest that a MALDI-ATOFMS can provide nearly real-time identification of biological aerosols. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

Real-time single particle mass spectrometry: a historical review of a quarter century of the chemical analysis of aerosols

Real-time single particle mass spectrometry, or continuous aerosol mass spectrometry, was originally developed in the 1970s for the purpose of identifying the chemical composition of airborne particulate matter in real-time. Although this technique has continued to evolve throughout the following decades, the fundamental characteristic of this method remains the same, involving the continuous introduction of solid particle or liquid droplets directly into the ion source region of a mass spectrometer. Continuous sample introduction allows for the chemical analysis of single airborne particles in real-time. A number of mass analyzers have been employed in real-time single particle mass spectrometry. The original real-time single particle mass spectrometer used a magnetic sector mass analyzer. Quadrupole, double-focusing, and ion trap mass spectrometers have also been utilized. The majority of the current real-time single particle mass spectrometry techniques use time-of-flight mass spectrometry. In the literature, a variety of general names have been applied to real-time single particle mass spectrometry methods. These names include direct-inlet mass spectrometry, on-line laser microprobe mass spectrometry, particle analysis by mass spectrometry, particle beam mass spectrometry, and rapid-single particle mass spectrometry. This review covers real-time single particle mass spectrometry techniques that were developed from 1973 through 1998, specifically for analyzing airborne particulate matter, including environmental aerosols, biological aerosols, and clean-room aerosols. Because the majority of the historical and current real-time single particle mass spectrometers have been employed for atmospheric aerosols, this topic is the primary focus of this review. This review does not include on-line mass spectrometry methods that are employed as a detector for other instrumental methods, such as liquid chromatography.

Journal Article↗

Comparison of oral and aerosol ribavirin regimens in the high risk elderly.

A comparison of different regiments of ribavirin (R), administered either orally or by aerosol, was performed in 16 elderly subjects (13 men, 3 women, mean age 63 +/- 8 years) considered to be in the "high-risk" category for complications from influenza as defined by the Centers for Disease Control. The subjects were divided into four groups. Group O-600 received 600 mg orally R every 8 hours for 48 hours followed by 200 mg every 8 hours for 72 hours for a total dose of 5.4 g (22.1 mmol). Group O-800 received 800 mg oral R every 8 hours for 24 hours followed by 400 mg every 12 hours for 96 hours for a total dose of 4.1 g (22.9 mMoles). Group A-40 received R (40 mg/ml) aerosolized through a small particle aerosol generator for 6 hours every 12 hours for 96 hours, yielding an average delivered dose of 6.2 g (25.4 mMoles) R. Group A-60 received aerosolized R (60 mg/mL) for 2 hours every 8 hours for 96 hours, yielding an average delivered dose of 4.6 g (18.8 mMoles) R. No hematologic or other laboratory abnormalities were associated with any of the regimens. Group O-800 and O-600 reached mean peak plasma R levels of 11.8 microM and 5.3 microM, respectively, after 18 hours of therapy. Subsequent administration of 20 mg R every 8 hours was sufficient to maintain a plasma R level greater than 7 microM. Among the aerosol groups, group A-40 approached steady state plasma R levels (8-10 microM) more quickly than group A-60.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Randomized controlled trial of three different doses of aerosol beclomethasone versus systemic dexamethasone to promote extubation in ventilated premature infants.

Our objective was to determine the safety and efficacy of aerosol beclomethasone vs. systemic dexamethasone for extubation in premature infants at high risk for chronic lung disease (CLD). Intubated preterm infants who were identified as being at high risk for moderate-severe CLD on day 14 of life were randomized to one of four groups. The control group received systemic dexamethasone and aerosol placebo, while the other three groups received either high (2.40-3.69 microg/kg/day delivered to lungs), medium (1.0-1.85 microg/kg/day), or low (0.48-0.74 microg/kg/day) dose aerosol beclomethasone and systemic placebo. Those receiving aerosol steroids who remained ventilator-dependent after 7 days were switched to standard 42-day tapering doses of systemic dexamethasone. The primary outcome was extubation within 1 week of starting steroids, using predefined criteria. Secondary variables included changes in lung function, rates of side effects, and tracheal aspirate white blood cell counts. Sixty-one infants with birth weights of 761 +/- 18 g (mean +/- SEM) and gestational ages of 25.7 +/- 0.2 weeks were randomized to one of the four groups. Seven of 15 infants in the control systemic dexamethasone group were successfully extubated compared with 3/16 in the high-dose beclomethasone group, 1/15 in the medium-dose group, and 2/15 in the low-dose group (P < 0.01). Only dexamethasone subjects demonstrated improvements in lung function over the study period. These infants also had significant increases in blood pressure and blood glucose levels, as well as a decline in their tracheal aspirate white blood cell count. In conclusion, aerosol beclomethasone at the very low doses used in this study did not facilitate extubation in intubated premature infants at high risk for moderate-severe CLD.

Administration, Inhalation↗

Delivery of aerosolized medication to intubated babies.

We studied the delivery of aerosolized cromolyn sodium to intubated babies, and evaluated the effect of changes in delivery techniques. In addition, we compared these results with an in vitro model of aerosol delivery. Cromolyn sodium was used as a marker because once the drug is absorbed, it is excreted unchanged, approximately 50% in urine and 50% in bile. We demonstrated that, in vitro, a conventional, jet-type nebulizer aerosolized 20.5% of a test dose of cromolyn, and only 5.5% of the dose was recovered after passage through 60 cm of ventilator tubing and an endotracheal tube adapter. This increased to 44.5% nebulized and 19% recovered when the volume nebulized was increased from 2 mL to 5 mL. A submicronic nebulizer aerosolized 40% and delivered 33.5% of the test dose. A 20 mg dose of nebulized cromolyn sodium was used as a test dose in infants, after which urine was collected for 4 hours. Forty-three urine samples were collected, after the delivery of cromolyn test doses, from nine babies (16-128 days old) intubated for bronchopulmonary dysplasia. Both the jet and submicronic nebulizers were tested in two positions: 1) in place of the ventilator humidifier, and 2) at the endotracheal tube adapter. There were no statistically significant differences in cromolyn delivery for any system configuration. In all situations, means of less than 0.1% of the test dose were recovered in the urine. We estimated that in all cases, less than 1% of the test dose (approximately 50-100 micrograms of cromolyn) had been deposited in the lung. These results show that although the submicronic nebulizer aerosolized cromolyn more efficiently, no additional cromolyn could be detected in infants. We speculate that a significant portion of the smaller particles are exhaled.

Administration, Inhalation↗

Simultaneous In-Situ Measurement of Local Particle Size, Particle Concentration, and Velocity of Aerosols.

Photon correlation spectroscopy has been applied to the characterization of (quasi-)monodisperse aerosols. The experiments were carried out with an experimental standard pin hole setup on laminar flowing aerosols of the submicrometer particle size range. It is shown that beside local mean particle size and local aerosol velocity simultaneously the local particle number concentration may be obtained from a single measured autocorrelation function. The proposed procedure does not require calibration. It is pointed out that measurement conditions can be adapted to the properties of the aerosol to be characterized, thus allowing characterization of aerosols over a wide parameter range, e.g., it is not restricted to the case of low particle concentration. The experimental results are compared to data from literature, data from reference measurements and data from a theoretical model, respectively. The method can also be usefull for characterization of other fluid-particle systems as hydrosols. Copyright 1999 Academic Press.

Journal Article↗

Inhibition of experimental lung metastasis by aerosol delivery of PEI-p53 complexes.

Mutations in the p53 tumor suppressor gene and the pathways mediated by the p53 protein are common in many human cancers. Replacement of functional p53 by gene therapy is a potential way of combating these cancers and the associated drug resistance and tumor growth. Aerosol delivery of genes is a noninvasive way of targeting genes to the lung for gene therapy. Here we demonstrate, using a murine melanoma lung metastasis model, that aerosol delivery of polyethyleneimine-p53 (PEI-p53) complexes inhibits the growth of lung metastasis. A significantly reduced number of visible foci were observed in C57BL/6 mice injected with B16-F10 melanoma and treated with PEI-p53 complexes by aerosol for 3 weeks at twice a week. Fifty percent of the mice in the PEI-p53-treated group exhibited no visible tumor foci. There was a significant reduction in the lung weights of p53-treated mice (P < 0.01) compared to control groups. The tumor burden was also significantly lower (P < 0.001) in mice treated with PEI-p53 complexes. No extrapulmonary metastasis was observed in the groups treated with PEI-p53 complexes compared to 50% of the mice in control groups, which showed metastasis to lymph nodes in the neck or abdomen. Treatment with PEI-p53 aerosol also led to about a 50% increase in the mean length of survival of the mice injected with B16-F10 cells. These data suggest that delivery of the p53 gene by aerosol using PEI as the gene delivery vector can inhibit the growth of lung metastasis.

Administration, Inhalation↗

Tracers for aerosol ventilation scintigraphy: Tc-99m versus In-113m.

113mIn has been proposed as a suitable tracer for aerosol ventilation scintigraphy in combination with 99mTc pulmonary perfusion scintigraphy. The high energy (393 keV) of 113mIn allows it to be detected in the presence of 99mTc, but degrades the spatial resolution which can be achieved. We have compared the resolution obtained with 99mTc and 113mIn in phantom experiments and in aerosol ventilation scans in 14 patients with airways disease. The resolution at the distances from the collimator encountered in lung scintigraphy was 10-20 mm for 99mTc and 15-40 mm for 113mIn. Aerosol ventilation images were abnormal in all patients. The 99mTc images showed peripheral defects and frequently central hot spots reflecting increased local aerosol deposition. In the 113mIn images, the lower resolution had a smoothing effect, the central hot spots were less striking, and the distribution of activity appeared more uniform, some detail was lost in the periphery. It is suggested that 113mIn is useful for ventilation scintigraphy in the diagnosis of pulmonary embolism, but that 99mTc is the tracer of choice if aerosol ventilation scintigraphy is used to study airways disease.

Female↗

Remote sensing of atmospheric aerosol in the nocturnal boundary layer using lidar.

This paper presents the results of the lidar experiments that have been performed during January 1989 through August 1990 to study the aerosol vertical distributions in the nocturnal atmosphere and their comparison with near-simultaneous aerological soundings for environmental monitoring. During the study period, the aerosol distributions showed significant stratified aerosol layer structures in the lower atmosphere throughout the south-west monsoon season (June-September), while these structures appear to be either erratic or absent during remaining months of the year. In addition, the aerosols present in the lowest air layers up to 200 m are found to contribute significantly (about 40%) to the aerosol loading in the nocturnal boundary layer at the lidar site. The pre-monsoon to winter ratio of mixing depth and ventilation coefficient were found to be 1.11 and 1.62, respectively. Thus the height of the mixed layer (around 350 m) and the associated ventilation coefficients suggest that early winter evenings tend to have higher pollution potential at the experimental site. The results indicate that the lidar technique has the potential to yield good information on the structure of the nocturnal atmosphere which is found to be influenced by the atmospheric stability conditions as revealed by aerological observations.

Journal Article↗