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The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma.

It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (approximately 60 L/min) versus low (approximately 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, greater than 1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (+/- SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 +/- 0.51 and 1.84 +/- 0.30, respectively (p less than 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 +/- 0.35 and 3.86 +/- 1.25, respectively, compared to 0.74 +/- 0.36 and 2.64 +/- 0.77 after slow inhalation (p less than 0.01). Geometric mean PD20 methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Detection of the cytogenetic effect of inhaled aerosols by the micronucleus test.

The induction of micronuclei in mice exposed to aerosols of the following 6 genotoxic chemicals by inhalation was examined: cyclophosphamide (CP), methyl methanesulfonate (MMS), mitomycin C (MMC), dimethylnitrosamine (DMN), ethylcarbamate and colchicine. Exposure of mice to CP aerosols at a theoretical concentration of 2426 mg/m3 for 29, 81 and 139 min induced 0.6, 1.0 and 2.3% micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow 24 h after the termination of exposure. The other chemicals except for DMN showed a similar exposure-response relationship following in vivo exposures to their aerosols. The results obtained in this study suggest that the cytogenetic effect of inhaled aerosols can be detected by the micronucleus test, and the method described in the present report is useful as a rapid in vivo test for atmospheric aerosols.

Aerosols↗

Further studies with short duration ribavirin aerosol for the treatment of influenza virus infection in mice and respiratory syncytial virus infection in cotton rats.

Ribavirin aerosol administration has been shown to be effective in the treatment of respiratory syncytial virus (RSV) infections in infants and in influenza A and B virus infections in young adults. Long treatment schedules and potential for environmental contamination have stimulated the search for alternative dosing schedules. Thus, we attempted to determine the length of time of ribavirin aerosol necessary for effective treatment of influenza and RSV. In RSV-infected cotton rats, aerosolization for just 30 min with high-dose ribavirin (HDR:60 mg ribavirin/ml in reservoir), 3 times daily, reduced viral lung titers/gm of tissue by 1.1 log10. In influenza virus-infected mice, 15 min of aerosolized HDR, 3 times daily, was effective in reducing both mortality and pulmonary virus titers (1.1 log10 reduction). When the intervals between aerosol administration each day were equally divided (i.e., q.8 h), the treatments were most effective. Treatment for 45 min, once daily, was not as effective as divided doses. Calculations of ribavirin concentrations in respiratory secretions following 15 min treatment in mice with HDR indicated that drug levels dropped below the ED50 for influenza viruses after about 9 h. A daily dosage of ribavirin, estimated to be 8-15 mg/kg, was effective for the treatment of influenza and RSV infections.

Aerosols↗

Aprotinin aerosol treatment of influenza and paramyxovirus bronchopneumonia of mice.

The therapeutic efficacy of aerosolized aprotinin, a natural proteinase inhibitor, against influenza and paramyxovirus bronchopneumonia of mice is shown. Small-particle aerosol of aprotinin solution was generated by a Collison type nebulizer and infected mice were exposed to aerosol atmosphere by four 30-40 min incubations per day for 6 days. This regimen provided an inhalation aprotinin dosage of approx. 6 micrograms/mouse/day. With such treatment more than 50% of mice infected with lethal doses of either influenza virus or paramyxovirus were protected from death. A suppression of the development of fatal hemorrhagic bronchopneumonia and a normalization of the body weight gain were observed in infected mice treated with aerosolized aprotinin. These data suggest that low doses of aerosolized proteinase inhibitors could be successfully applied against respiratory influenza-like virus diseases.

Administration, Inhalation↗

Effects of RU 41740 aerosol treatment on mouse bronchoalveolar cells, and protection afforded against influenza virus infection.

RU 41740, an immunomodulating compound extracted from Klebsiella pneumoniae, was previously shown to enhance mice resistance to bacterial and viral lung infections. To explore lung defense mechanisms, we studied the influence of RU 41740 aerosol treatment on the bronchoalveolar cell populations. Five successive daily RU 41740 aerosol treatments induced a large accumulation of leukocytes in the lungs 4h after the last treatment. Polymorphonuclear leukocytes predominated. The numbers of lymphocytes and monocytes rose significantly. A single RU 41740 aerosol treatment significantly raised the number of polymorphonuclears only. A luminol-dependent chemiluminescence assay was used to test the effect of RU 41740 on the opsonized zymosan induced response of alveolar macrophages. In vitro, addition of RU 41740 enhanced this chemiluminescence. After a single RU 41740 aerosol treatment of mice, the chemiluminescence of purified alveolar macrophages from these mice increased significantly. The protective effect of five daily RU 41740 aerosol treatments against influenza virus infection was believed to be due to the great intensity of the cellular response and the polymorphonuclear influx. The alveolar macrophage activation observed might also explain the enhanced resistance of mice to influenza virus infection.

Adjuvants, Immunologic↗

Aerosol penetration and leakage characteristics of masks used in the health care industry.

BACKGROUND: Historically, surgical masks have been worn to protect patients from being infected by large, pathogen-containing aerosol droplets emitted by health care personnel. Today, emphasis has shifted from solely protecting the patient to protecting the health care worker as well. As a result of new procedures used in operating rooms and clinical areas, aerosolized hazardous agents in the submicrometer size range are being produced, posing a potential threat to health care workers. METHODS: Eight surgical masks were tested for aerosol particle penetration through their filter media and through induced face-seal leaks. RESULTS: The percentage of filter penetration ranged from 20% to nearly 100% for submicrometer-sized particles. In comparison, a dust-mist-fume respirator used in industrial settings had significantly less penetration through its filter medium. When the surgical masks had artificially induced face-seal leaks, the concentration of submicrometer-sized particles inside the mask increased slightly; in contrast, the more protective dust-mist-fume respirator showed a fourfold increase in aerosol penetration into the mask with an artificial leak 4 mm in diameter. CONCLUSION: We conclude that the protection provided by surgical masks may be insufficient in environments containing potentially hazardous submicrometer-sized aerosols.

Aerosols↗

Inhalation chamber with size discriminator for liquid aerosols.

To minimize data variation in inhalation toxicity testing and to evaluate human and animal hazards of inhaled chemicals, a practical inhalation chamber with a size discriminator for mists was developed to provide high concentration liquid aerosols of defined particle sizes. Liquid aerosols generated with an atomizer were separated by an impinging separator which was composed of aerosol jets directed upward against a flat plate. The principle of the separator eliminates particles larger than a calculated cutoff size in micrometer and submicrometer ranges by changing the orifice diameter of the jet nozzle under constant air flow. The mists thus separated are introduced into the space between two concentric cylinders just above the impaction plate. Ten rats can be positioned around the periphery of the chamber wall equidistant from the impaction plate, with their snouts thrust into the inhalation space. Preliminary testing with olive oil and water aerosols using particle cutoff sizes of 1, 3, and 3.3 micron showed that the obtained separation of particles was very clear, although the cutoff point seemed to shift somewhat to smaller values than calculated; the shift was especially evident with water aerosols. The concentrations obtained were more than 1 mg/liter when the cutoff point was selected at 1 micron. The mist at the inhalation space attained a steady concentration and particle size distribution within 2 min of the onset of mist injection, remained over a 4-hr period, and was cleared within 2 min of the cessation of mist generation.

Aerosols↗

A novel ultrasonic aerosol generator.

An ultrasonic aerosol generator constructed from a domestic humidifier is described which has been used to produce liquid aerosols for physiological investigations. The instrument was constructed from a Pifco domestic humidifier modified to include an energy guide to direct the oscillations of the transducer through the coupling water, which would normally be aerosolized, onto a small membrane based sample chamber containing the liquid to be aerosolized. The size distribution of the aerosol produced was found to be between 2 and 6 mm, optimum for diffuse intrapulmonary deposition. Up to 4 ml/min of aqueous liquid was used; however the sample chamber could be made small enough to contain economic amounts of expensive material to administer by inhalation. The instrument has proved to be reliable over a period of three years.

Aerosols↗

Determination of sterols, estrogens and inorganic ions in waste water and size-segregated aerosol particles emitted from waste water treatment.

Concentrations of steroids and inorganic ions were measured in waste water of an aerated sand trap as well as in aerosol particles emitted from this tank at the waste water treatment plant (WWTP) of Bayreuth, Germany, in January and February 2003. The investigations comprised seven sterols, two estrogens, and several inorganic ions. Since an appropriate method for the determination of sterols in waste water was not available, a new method based on solid phase extraction was developed. The concentrations of the sterols coprostanol and cholesterol amounted to 30-180 microg l(-1) in waste water and to 400-5000 pg m(-3) in aerosol particles. All other sterols were present in markedly lower concentrations. The mean concentrations of the two estrogens estrone and 17beta-estradiol were about 165 pg m(-3) in aerosol particles. The steroid concentrations in both waste water and aerosol particles varied greatly over time, however with the exception of coprostanol, no clear correlation was detected between concentrations in waste water and aerosol particles.

Aerosols↗

Characterization of aerosols and its radiative impacts over urban and rural environments--a case study from Hyderabad and Srisailam.

In the troposphere anthropogenic aerosol emissions are increasing in recent decades, which can influence the earth's climate. The present study addresses the characterization of aerosols and their radiative impacts over urban (Hyderabad) and rural (Srisailam) environments by using aerosol optical depth (AOD) measurements from MICROTOPS-II sunphotometer. AOD measurements over the urban site showed high values compared to the rural site. Over the urban environment aerosol forcing at the surface is as high as -42 W m(-2) and at the top of the atmosphere (TOA) is +10 W m(-2) whereas at the rural environment aerosol forcing at the surface has been observed to be -11 W m(-2) and at TOA it is observed to be +5.7 W m(-2). The difference between TOA and the surface forcing over the urban environment is +32 W m(-2) and over the rural environment is +5.3 W m(-2), which shows the absorption capacity of the respective atmospheres.

Aerosols↗

Physical stability and aerosol properties of liposomes delivered using an air-jet nebulizer and a novel micropump device with large mesh apertures.

The aerosol properties of liposomes and their physical stability to aerosolization were evaluated using an air-jet nebulizer (Pari LC Plus) and a customized large aperture vibrating-mesh nebulizer (Aeroneb Pro-8microm). Soya phosphatidylcholine: cholesterol (1:1 mole ratio) multilamellar liposomes (MLVs) entrapping salbutamol sulfate were nebulized directly, or after being reduced in size by extrusion through 1 or 0.4microm polycarbonate membrane filters. MLVs were very unstable to jet nebulization and stability was not markedly enhanced when vesicles were extruded before nebulization, such that drug losses from delivered liposomes using the Pari nebulizer were up to 88% (i.e. only 12% retained in liposomes). The Aeroneb Pro-8microm nebulizer was less disruptive to liposomes, completed nebulization in a much shorter time, and produced greater mass output rate than the Pari nebulizer. However, aerosol droplets were larger, total drug and mass outputs were lower and aerosolization performance was dependent on formulation. Vibrating-mesh nebulization was less disruptive to liposomes extruded through the 1microm membranes compared with the non-extruded MLVs, so that the retained entrapment of the drug in the nebulized vesicles was 56% and 37%, respectively. However, extrusion of liposomes to 0.4microm resulted in reduced stability of liposomes to vibrating-mesh nebulization (retained entrapment=41%) which was attributed to the reduced liposome lamellarity and subsequent reduced resistance to nebulization-induced shearing. This study has shown that vibrating-mesh nebulization using the customized large aperture mesh nebulizer (Aeroneb Pro-8microm) had a less disruptive effect on liposomes and produced a higher output rate compared with the Pari LC Plus air-jet nebulizer. On the other hand, the air-jet nebulizer produced higher total mass and drug outputs and smaller aerosol droplets.

Administration, Inhalation↗

Toward understanding the ionization of biomarkers from micrometer particles by bio-aerosol mass spectrometry.

The appearance of informative signals in the mass spectra of laser-ablated bio-aerosol particles depends on the effective ionization probabilities (EIP) of individual components during the laser ionization process. This study investigates how bio-aerosol chemical composition governs the EIP values of specific components and the overall features of the spectra from the bio-aerosol mass spectrometry (BAMS). EIP values were determined for a series of amino acid, dipicolinic acid, and peptide aerosol particles to determine what chemical features aid in ionization. The spectra of individual amino acids and dipicolinic acid, as well as mixtures, were examined for extent of fragmentation and the presence of molecular ion dimers, which are indicative of ionization conditions. Standard mixtures yielded information with respect to the significance of secondary ion plume reactions on observed spectra. A greater understanding of how these parameters affect EIP and spectra characteristics of bio-aerosols will aid in the intelligent selection of viable future biomarkers for the identification of bio-terrorism agents.

Aerosols↗

Use of a neuro-variational inversion for retrieving oceanic and atmospheric constituents from satellite ocean colour sensor: application to absorbing aerosols.

This paper presents a new development of the NeuroVaria method. NeuroVaria computes relevant atmospheric and oceanic parameters by minimizing the difference between the observed satellite reflectances and those computed from radiative transfer simulations modelled by artificial neural networks. Aerosol optical properties are computed using the Junge size distribution allowing taking into account highly absorbing aerosols. The major improvement to the method has been to implement an iterative cost function formulation that makes the minimization more efficient. This implementation of NeuroVaria has been applied to sea-viewing wide field-of-view sensor (SeaWiFS) imagery. A comparison with in situ measurements and the standard SeaWiFS results for cases without absorbing aerosols shows that this version of NeuroVaria remains consistent with the former. Finally, the processing of SeaWiFS images of a plume of absorbing aerosols off the US East coast demonstrate the ability of this improved version of NeuroVaria to deal with absorbing aerosols.

Aerosols↗

Aerosol therapy: the special needs of young children.

Efficient aerosol therapy in young children is a challenge. The aerosol administration method requires special features, because young children can not perform an inhalation manoeuvre, breath usually through the nose and may be distressed during the administration. The prescribing clinician should be aware of the advantages and disadvantages of the different inhalation devices available, in order to select the proper device for each individual patient. For maintenance asthma therapy in young children the pressurized metered dose inhaler (pMDI) combined with spacer is the first choice for delivering aerosols. A facemask can be attached if a child is unable to breath through the mouth. A small leak of the facemask can reduce the dose delivered dramatically, therefore a good seal is crucial. Lung deposition can be improved by using a pMDI with extra-fine particles. However, even if the most optimal device is chosen, cooperation during administration remains the most important determinant for efficient drug delivery. During crying the dose to the lungs is minimal. Optimal aerosol delivery to the lungs of young children can be achieved with a good facemask seal, good cooperation of the child, with quiet breathing and an aerosol with small particles.

Administration, Inhalation↗

The adequacy of inhalation of aerosol from canister nebulizers.

Thirty patients hospitalized with asthma who had been taking aerosol bronchodilators from canister nebulizers were evaluated for their aerosol inhalation technique. Fourteen patients (47 percent) used an incorrect technique. The most frequent mistake was to inhale first, then to actuate the canister and breathhold. These patients were taught the correct technique. Some learned it easily but others had difficulty. With a teaching aid, incorporating a horn which is actuated by inspiration, all 14 patients learned to inhale the aerosol correctly. When retested five of the 10 patients had reverted to the old incorrect technique and required another lesson. Physicians who prescribe aerosol medication from a canister nebulizer should evaluate each patient for the aerosol inhalation technique. Those who inhale incorrectly should be taught repeatedly until they learn the correct technique and retain it. The teaching aid, utilizing an audio signal, is helpful in this training.

Aerosols↗

Pharmacokinetics of liposomal aerosolized cyclosporine A for pulmonary immunosuppression.

BACKGROUND: The results of pulmonary transplantation are compromised by acute and chronic rejection. We hypothesized that a liposomal form of aerosolized cyclosporine A (CsA) would be selectively deposited and concentrated in the lungs. The theoretical advantage of this therapy is selective pulmonary immunosuppression with prolonged utilization. METHODS: Eighteen dogs were endotracheally intubated; aerosolized liposomal CsA was administered for 15 min. CsA levels were measured in whole blood, lung, trachea, heart, kidney, liver, and spleen at various times after treatment. RESULTS: The lung rapidly absorbs aerosolized liposomal CsA; other organs have much lower concentrations. The retention of pulmonary CsA delivered by liposome aerosol is approximately 120 min in this model. CONCLUSIONS: Aerosolized liposomal CsA is selectively deposited and concentrated in the lungs; other organs absorb less CsA.

Aerosols↗

Aerosolized perfluorocarbon reduces adhesion molecule gene expression and neutrophil sequestration in acute respiratory distress.

In acute respiratory distress syndrome, neutrophil migration into the lung plays a key role in the development of lung injury. To study the effect of different modes of ventilation with perfluorocarbon (FC77), intrapulmonary neutrophil accumulation and mRNA expression of E-selectin, P-selectin and intercellular adhesion molecule-1 (ICAM-1), mediating leukocyte sequestration, were measured in surfactant depleted piglets. After bronchoalveolar lavage, 20 animals either received aerosolized perfluorocarbon (Aerosol-PFC), partial liquid ventilation (PLV) with perfluorocarbon at functional residual capacity filling volume (FRC-PLV) or at low volume (LV-PLV) or intermittent mandatory ventilation (control). After 2 h of perfluorocarbon application, intermittent mandatory ventilation was continued for 6 h. In the Aerosol-PFC group, all measured adhesion molecules showed a significantly reduced gene expression compared to controls. FRC-PFC treatment was effective in significantly diminishing P-selectin and ICAM-1 mRNA expression. Relative lung tissue neutrophil counts were significantly reduced in the Aerosol-PFC and the FRC-PLV group. Treatment with aerosolized perfluorocarbon is at least as effective as partial liquid ventilation at FRC volume in reducing pulmonary adhesion molecule expression and neutrophil accumulation in acute respiratory distress syndrome.

Acute Disease↗

Aerosolization of an anionic surfactant (LAS) and dissolved organic carbon (DOC) under laboratory conditions.

Aerosolization of natural salt and brackish waters under laboratory conditions is responsible for the transfer of synthetic surfactants such as linear alkylbenzene sulphonate (LAS) from water to the atmosphere. Excluded the lagoon sample which stands apart, on the average ca. 45% of the LAS present at concentrations between 0.1 and 4.1 microg l(-1) in the tested coastal and offshore marine and lagoon waters was transferred to the aerosol extract. The distribution of the individual LAS homologs in the aerosol is very similar to that in water, which indicates no preferential removal from the bulk water of any LAS homolog. The fraction of dissolved organic carbon (DOC) undergoing aerosolization under the same conditions for each tested sample was on an average ca. 3.3%, corresponding to ca. 5.6 mg l(-1). On the average, the enrichment factor of the sea samples, resulting from the changing of the LAS/DOC ratio before and after aerosolization, was ca. 20.

Aerosols↗