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PubMed2005

A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols.

This research investigates a promising antiviral compound based on polyprenols from Siberian silver fir (Abies sibirica). The physico-chemical characteristics of a preparation developed in aerosol form and an estimation of its protective efficacy against aerosol challenge of laboratory animals are presented. It is shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of three formulations studied with about 70% of its mass accumulated in the size range below 1.8 microm; (2) 40-100% of aerosol particles contain preparation for different formulations; (3) after delivering under specified schedules, the preparations as developed can protect up to 100% of mice against 5 LD(50) of influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the preparation doses (which were 100 times lower than injection ones of the same efficacy) and did not exceed 10 microg/mouse. It was shown that the mode of action of this immunomodulating preparation was nonspecific stimulation of immune cells' various activities.

Abies↗
PubMed2006

Comparison of SPECT aerosol deposition data with twenty-four-hour clearance measurements.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. Information on regional distribution of deposited aerosol can also be obtained from 24-hour clearance measurements. In this study, a nebulizer was used to deliver a radiolabeled aerosol to nine human subjects. Single photon emission computed tomography (SPECT) has been used to assess the distribution of aerosol deposition per airway generation. The deposition pattern was also estimated using measurements of the aerosol remaining in the lung 24 h after inhalation. The error in the SPECT value was assessed by simulation and that in the 24-h clearance value by repeat analysis. The mean fraction of lung deposition in the conducting airway (CADF) from SPECT was 0.21. The corresponding 24-h clearance value was 0.23. These values were not significantly different. There was a weak but non-significant correlation between the SPECT and 24-h measurements (r = 0.49). The standard error of the difference was 0.11. The corresponding errors on the SPECT and 24-h clearance measurements were 0.04 and 0.05, respectively. There was no systematic difference between the values of conducting airways deposition obtained from 24-h measurements and SPECT. However, there were random differences on individual subjects, which were larger than the estimated measurement errors.

Administration, Inhalation↗
PubMed2006

Nebulized drug admixtures: effect on aerosol characteristics and albuterol output.

Although not recommended, co-administration of drugs separately prescribed for nebulization is done in real life. The impact of this practice on drug output and aerosol characteristics is poorly understood. We studied the effect of drug admixtures (DA) on aerosol characteristics and drug output of nebulized albuterol delivered by a continuous output (CONT) and a breath enhanced nebulizer (BEN). Albuterol was nebulized alone (ALB) and combined with cromolyn sodium (A+CRO), ipratropium bromide (A+IB), tobramycin (A+TOB), flunisolide (A+FLU), and n-acetylcysteine (A+NAC). A BEN (PARI LC Plus) and a CONT (Hudson T UP-DRAFT II) were tested at 8 liters per minute (Lpm) for 2 and 5 min, respectively. Albuterol output and aerosol characteristics were determined by impaction and chemical analysis. Mass median aerodynamic diameter (MMAD; microm) A+CRO reduced MMAD from 2.57 (ALB) to 1.29 with CONT. A+FLU increased MMAD from 2.71 (ALB) to 3.40 with BEN. Geometric standard deviation (GSD) A+CRO increased GSD from 2.66 (ALB) to 3.36 with CONT. GSD was 2.33 for ALB and was not changed by DA with BEN. BEN generated a smaller and less heterodisperse aerosol than CONT. Respirable fraction (RF%) was 74% for ALB and was not changed by DA with CON. A+TOB and A+FLU decreased RF% from 75%, to 70% and 67% (respectively) with BEN. Respirable mass (RM; microg) for ALB was 935 and was not changed by DA with CONT. A+IB and A+FLU increased RM from 917 (ALB) to 1172 and 1240, respectively, with BEN. Co-nebulization of albuterol with other drugs can affect its output and aerosol characteristics. In vivo data is needed to asses the clinical implications of our findings.

Adrenergic beta-Agonists↗
PubMed2002

Measuring the emission rate of an aerosol source placed in a ventilated room using a tracer gas: influence of particle wall deposition.

A method to measure the emission rate of an airborne pollutant source using a tracer gas was tested in the case of an aerosol source. The influence of particle deposition on the walls of a test room of 72 m3 was studied. The deposition rate of an aerosol of MgCl2 was determined by means of two methods: one based on measuring the aerosol concentration decay inside the ventilated room, the other based on calculation of the material mass balance. The concentration decay was monitored by optical counting and the aerosol mass concentration determined by means of sampling on a filter and analysis of the mass deposited by atomic absorption spectrometry. Four series of measurements were carried out. The curve giving the deposition rate according to the particle aerodynamic diameter (d(ae)) was established and shows deposition rates higher than those predicted using the model of Corner. The decay method gives the best results. The study carried out has shown that the phenomenon of deposition has little effect on the measurement of the aerosol source emission rate using a tracer gas for particles of aerodynamic diameter < 5 microm (underestimation < 25%). For particles of a greater diameter, wall deposition is an extremely limiting factor for the method, the influence of which can, however, be limited by using a test booth of small volume and keeping the sampling duration as short as possible.

Aerosols↗
PubMed2006

Large organic aerosols in a dynamic and continuous whole-body exposure chamber tested on humans and on a heated mannequin.

Exposure to large airborne organic aerosols may cause respiratory and skin symptoms. The use of human exposure chambers permits safe mechanistic studies of the effect of inhalation or dermal deposition of such particles. The performance of a dynamic and continuous whole-body human exposure chamber using turbulent air mixing during exposure to these organic aerosols of humans and of a new heated mannequin was evaluated. Variability of temporal and spatial distribution of the airborne particle concentration, and aerodynamic aerosol size distribution of the inhalable fraction, were evaluated. The temporal and spatial distribution of these aerosols close to the breathing zone during an exposure session was typically < or = 10%, which is low for airborne particles of this size. In a larger section around a human, only slightly higher spatial variation was found. Variability between exposure sessions was also low (< 10%). Only limited effect of relative humidity for the organic aerosols was observed. The aerodynamic particle size distribution curves differed slightly, but some were comparable to those in occupational environments. The outcome of the performance tests as measured with the heated mannequin was almost the same as with humans, indicating that the mannequin could be used in preparatory tests in this type of chamber.

Aerosols↗
PubMed1976

Small-particle aerosols of antiviral compounds in treatment of type A influenza pneumonia in mice.

Three chemotherapeutic drugs active against type A influenza virus (amantadine, rimantadine, and ribavirin) were tested as therapeutic agents against established infections with influenza virus in mice. The drugs were administered intraperitoneally or as aerosols either from 6 hr to four days or from three to seven days after infection. Small-particle aerosols were administered continuously 24 hr per day. Continuous dissemination of aerosols was superior to intraperitoneal administration, as evidenced by higher survival rates at 21 days. Rimantadine, amantadine, and ribavirin were effective when treatment was delayed for three days. Ribavirin was the most efficacious if therapy was initiated as an aerosol 6 hr after infection. In contrast to amantadine, ribavirin given in samll-particle aerosols at 6 hr prevented the development of pneumonia and decreased titers of virus in lung.

Administration, Intranasal↗
PubMed1980

Therapeutic effects of aerosolized amantadine in naturally acquired infection due to influenza A virus.

The effect of small-particle aerosol therapy with amantadine was assessed in a randomized, double-blind study of 20 patients with naturally acquired influenza A virus infection. Aerosol treatments of 20 min with either distilled water or with amantadine hydrochloride (1.0 g/100 ml of distilled water) were given three times a day for four days. The amantadine-treated patients experienced a significantly more rapid resolution of clinical signs and symptoms when compared with placebo-treated patients. The resolution of fever was similar for both groups. Aerosol delivery of amantadine did not affect the frequency of viral isolation from upper respiratory tract secretions but was associated with a trend toward reduced quantity of viral shedding. Serial pulmonary function tests found no important differences between the groups. Amantadine-treated patients experienced a greater frequency of mild local side effects (rhinorrhea, nasal irritation) during aerosol exposures, but aerosol treatments did not cause any apparent decline in pulmonary function.

Adult↗
PubMed1987

Aerosol transmission of rhinovirus colds.

Rhinovirus infections may spread by aerosol, direct contact, or indirect contact involving environmental objects. We examined aerosol and indirect contact in transmission of rhinovirus type 16 colds between laboratory-infected men (donors) and susceptible men (recipients) who played cards together for 12 hr. In three experiments the infection rate of restrained recipients (10 [56%] of 18), who could not touch their faces and could only have been infected by aerosols, and that of unrestrained recipients (12[67%] of 18), who could have been infected by aerosol, by direct contact, or by indirect fomite contact, was not significantly different (chi 2 = 0.468, P = .494). In a fourth experiment, transmission via fomites heavily used for 12 hr by eight donors was the only possible route of spread, and no transmissions occurred among 12 recipients (P less than .001 by two-tailed Fisher's exact test). These results suggest that contrary to current opinion, rhinovirus transmission, at least in adults, occurs chiefly by the aerosol route.

Adult↗
PubMed1992

Immunotherapy of respiratory syncytial virus infection in cotton rats (Sigmodon fulviventer) using IgG in a small-particle aerosol.

To determine whether aerosolized IgG can be used effectively in the treatment of respiratory syncytial virus (RSV) infections, cotton rats were infected intranasally with RSV and treated 3 days later with human IgG containing anti-RSV antibodies delivered in a small-particle aerosol. Pulmonary histology and virus titers were determined 24 h after IgG treatment. A single 15-min exposure to aerosolized IgG did not exacerbate pulmonary pathology and effected a 50-fold reduction in pulmonary virus titer (2.95 vs. 4.67 log10 geometric mean pfu/g for untreated controls, P < .001), which was comparable to that effected by intranasally instilled IgG (50 mg/kg) (3.24 vs. 4.67 log10 geometric mean pfu/g for controls, P < .001). A 15-min exposure to aerosolized ribavirin (20 mg/mL) was not effective in reducing pulmonary virus. This study suggests that aerosolized IgG could be useful in the treatment of RSV lower respiratory tract infections and that it compares favorably with ribavirin.

Administration, Intranasal↗
PubMed1989

Culicidae (Diptera) mortality resulting from insecticide aerosols compared with mortality from droplets on sentinel cages.

The mortality of female Aedes aegypti exposed to an ultralow-volume (ULV) aerosol for 15 min and then transferred to clean cages was compared to the mortality of females exposed to the contaminated sentinel exposure cages. ULV aerosol sprays of fenitrothion (50% AI) were dispersed at 180 and 205 ml/min, and ULV aerosol sprays of bendiocarb (18.87% AI) were dispersed at 90 and 120 ml/min in an open field. At 24 h after exposure, the mean percentage of mortality of Ae. aegypti in cages previously exposed to insecticides was 87% at 46 m and 71.8% at 91 m downwind of aerosol generation for the four flow rates. The mean percentage of mortality of Ae. aegypti exposed to the aerosol and then transferred to clean cages was 74.5% at 46 m and 68% at 91 m. Insecticide droplets deposited on exposed cages caused significant mortality to Ae. aegypti. Data show that sentinel mosquitoes used in insecticide bioassays should be transferred into clean holding containers as soon as possible after exposure to prevent biasing of results from insect contact with insecticide deposited on cage walls and screens.

Aerosols↗
PubMed1990

Metered dose inhaler aerosol characteristics are affected by the endotracheal tube actuator/adapter used.

The authors studied the particle size of aerosols of metaproterenol produced by three different actuators designed for use in patients with endotracheal tubes in place. These were compared with the metaproterenol aerosol produced by the actuator (provided by Boehringer-Ingelheim [BI]) that was supplied by the manufacturer for use in patients whose tracheas are not intubated. The volume of particles in the respiratory size range (1.0-5.1 microns) delivered to the end of the endotracheal tube were measured using adapters designed by Intec (IT), Instrumentation Industries (II), and Monaghan (MAIS). Particle numbers were measured using a CSAS 100 scattering-aerosol laser spectrometer, and volumes were calculated by assuming the particles were spheres. The authors found that the volume of particles in the respiratory range with the IT, II, and MAIS adapters plus endotracheal tube were 11, 31, and 66%, respectively, of the volume produced in the respiratory range by the BI. When particles likely to impact before reaching the lower airways (greater than 5 microns) were measured, almost none was produced by the adapters plus endotracheal tube, whereas the majority of drug volume in the BI aerosol was in the greater than 5 microns range. It was concluded that the aerosol produced by different actuators differ from each other, that all three produced less drug in the respiratory range than was produced by the manufacturer-supplied actuator, and that large particles are effectively removed by the adapter plus endotracheal tube.

Administration, Inhalation↗
PubMed1994

Aerosolized pentamidine as primary prophylaxis for Pneumocystis carinii pneumonia: efficacy, mortality and morbidity.

OBJECTIVE: Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with HIV infection has been recommended by the Centers for Disease Control and Prevention. We evaluated alternatives to routine primary PCP prophylaxis with aerosolized pentamidine. METHODS: A total of 121 HIV-infected patients with CD4+ cell counts < or = 200 x 10(6)/l or an AIDS diagnosis were enrolled in a controlled study of aerosolized pentamidine as primary PCP prophylaxis. Patients were randomly assigned to treatment (n = 61) with aerosolized pentamidine once every month or to no treatment (n = 60). Patients were evaluated for PCP, mortality, morbidity and progression of HIV disease. Morbidity was estimated from the number of days patients were unable to work due to illness, number of days hospitalized and AIDS events. RESULTS: Baseline characteristics were similar in the treatment and control groups and mean CD4+ cell counts were 116 and 107 x 10(6)/l, respectively. Eight incidents of PCP and 19 deaths were observed in the treatment group during a median follow-up of 16.4 months (range, 2.3-32.4 months). Nineteen incidents of PCP and 13 deaths, of which one was related to an acute episode of PCP, were noted in the control group. Median follow-up of controls was 18.5 months (range, 3.1-32.9 months). Patients in the treatment group were unable to work 19% of the observation time and were hospitalized for 4.3% of that time. Corresponding figures were 20 and 3.0%, respectively, in the control group. CONCLUSIONS: Aerosolized pentamidine had significant prophylactic efficacy, but we could not detect any major effect on mortality and morbidity. The overall mortality and morbidity were not markedly influenced by PCP. Clinical check-ups and treatment of acute PCP could be a justifiable alternative to drug prophylaxis with aerosolized pentamidine in selected patients.

AIDS-Related Opportunistic Infections↗
PubMed1987

Clinical experience with technetium-99m DTPA aerosol with perfusion scintigraphy in suspected pulmonary embolism.

To evaluate the clinical value of radioaerosol imaging, 156 patients with suspected pulmonary embolism (PE) were studied. In 25 patients, a preperfusion xenon-133 (Xe-133) study was compared with a postperfusion study using Tc-99m DTPA aerosol. It was found that they were of equal value most of the time (56%), but that the aerosol study was more often helpful. Because of this, and the technical ease of using six standard views with radioaerosol, the series was completed using perfusion scintigraphy followed by radioaerosol images. In 19 patients the perfusion scintigraphy with Tc-99 macroaggregated albumin (Tc-99m MAA) was normal or nearly normal and no aerosol study was required. Tc-99m DTPA aerosol images were satisfactory when the count rate was at least twice and preferably three times that of the previous perfusion study. There were 17 studies (11%) classified as intermediate. There were 26 patients classified as high probability for PE, and angiographic or autopsy correlation was available in 14. All of the 14 proved to have PE. In the 113 patients classified as low probability, there were ten with angiographic or autopsy correlation. In the ten, there was one patient with a small pulmonary embolus found at autopsy. Clinical follow-up for over two months confirmed the absence of PE in the remainder of this group. Aerosol studies have proven technically easier to perform and a satisfactory substitute for xenon imaging in suspected PE.

Adult↗
PubMed1990

Utility of Tc-99m DTPA aerosol inhalation scans following perfusion lung scans in the diagnosis of pulmonary embolism.

The authors report their experience with the use of Tc-99m DTPA aerosol following a perfusion lung scan. The study includes 422 consecutive patients with suspected pulmonary embolism. The final diagnosis was determined by (a) clinical follow-up for 2 months or more, (b) pulmonary angiography, or (c) autopsy. There were 79 patients (19%) who had a normal or near-normal perfusion study and in whom no aerosol study was required. Interpretation groups were classified and divided as follows: Normal or low probability 281 (66.5%) High probability 75 (18.0%) Intermediate 60 (14.0%) Technically inadequate 6 (1.5%) There was autopsy or angiographic confirmation of 72 patient studies with confirmation of the scan diagnosis in 29 of 31 classified as normal or low probability and 24 of 25 classified as high probability. The background perfusion albumin activity was not computer-subtracted from the combined aerosol-perfusion image. Technical improvements included the use of eight standard views for both the perfusion and the subsequent aerosol scan, and the use of 75 mCi (2,775 MBq) of Tc-99m DTPA in the radioaerosol nebulizer. This allowed for easy accumulation of more than three times the count rate in a posterior aerosol image when compared with the previous posterior perfusion image. The authors' experience shows that the perfusion lung scan followed by this radioaerosol technique is a reliable means to evaluate suspected pulmonary embolism.

Administration, Inhalation↗
PubMed1995

Supine lung clearance of Tc-99m DTPA and HMPAO aerosols.

The speed of Tc-99m DTPA/HMPAO radioaerosol clearance from the lungs that is represented as a slope from lungs to blood was measured in 23 male normal controls using commercial lung radioaerosol delivery units in the supine position in order to avoid the influences of gravity. The right lung was selected and three regions of interest were created for equal subdivisions of the upper, middle, and lower third. The results show that the clearance of Tc-99m DTPA/HMPAO aerosols in the upper lung is slowest. The differences between upper and lower lungs for Tc-99m DTPA/HMPAO aerosol clearances are significant. The clearance of Tc-99m DTPA aerosols was significantly faster than those of Tc-99m HMPAO in any region. The authors conclude that, although the effect of gravity disappears in the supine position in our study, the differences of aerosol clearance in different regions are still significant. Lipophilic Tc-99m HMPAO aerosols were slower than those of hydrophilic Tc-99m DTPA, which suggests there are at least two different mechanisms.

Aerosols↗
PubMed1985

Aerosol delivery in intubated, mechanically ventilated patients.

To study the effects of respiratory failure and mechanical ventilation on aerosol delivery to the lungs, we performed nuclear scans after aerosolization of 5 to 9 mCi of Tc-99m diethylenetriamine pentaacetic acid in seven stable, intubated, and mechanically ventilated patients. The radioactivity reaching the lungs was 2.9 +/- .7% (mean +/- SD) of the administered dose, an amount significantly less than that in three healthy nonintubated subjects and also less than what would be expected in nonintubated subjects from other published reports. We then performed a subsequent study in 15 additional mechanically ventilated patients who were receiving aerosolized bronchodilators through their endotracheal tube. In these patients, heart rate and lung mechanical function values before and after treatment were not significantly different. We conclude from these studies that aerosol delivery in mechanically ventilated patients is significantly reduced and that this is probably due to a combination of suboptimal breathing pattern, intrinsic airway disease, and the endotracheal tube functioning as both a site for aerosol deposition through impaction as well as a barrier to gastrointestinal absorption.

Aerosols↗
PubMed1994

Aerosolized ribavirin in mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease: a prospective, double-blind, randomized trial.

OBJECTIVE: To study the effect of ribavirin aerosol therapy on the immediate clinical course of mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Pediatric intensive care unit (ICU) of a university teaching hospital. PATIENTS: Forty-one children requiring mechanical ventilation for respiratory syncytial virus lower respiratory tract disease. INTERVENTIONS: Patients were stratified by the presence or absence of and underlying disease and then randomized to receive aerosolized ribavirin (20 mg/mL) or saline for 18 hrs/day for 5 days or until endotracheal extubation, whichever came first. MEASUREMENTS AND MAIN RESULTS: Dependent variables included the time course of the illness and the change in FIO2, ventilatory rate, PaO2/FIO2 ratio, and ventilatory-efficiency index of patients while they received aerosol therapy. Ribavirin- and placebo-treated patient groups were not significantly different in the number of ventilator days (6.4 +/- 6.9 vs. 8.2 +/- 10.1; p = .5), oxygen days (10.8 +/- 7.7 vs. 12.2 +/- 11.8; p = .9), ICU days (7.9 +/- 7.0 vs. 10.3 +/- 11.0; p = .7), or hospital days (12.9 +/- 9.7 vs. 16.2 +/- 14.0; p = .6) after the initiation of aerosol therapy. The change in FIO2, ventilatory rate, PaO2/FIO2 ratio, or ventilatory-efficiency index did not differ between the two groups. No ventilator malfunction was observed. There were six deaths caused by intractable hypoxemia in patients with underlying cardiopulmonary disease. Four of these deaths were in the placebo group and two in the ribavirin group (p = .5). CONCLUSIONS: Ribavirin aerosol therapy can be safely administered to mechanically ventilated children with severe respiratory syncytial virus lower respiratory tract disease. However, this therapy does not appear to affect immediate clinical outcome in such patients.

Aerosols↗
PubMed1984

Predicted deposition rates of uranium yellowcake aerosols sampled in uranium mills.

Uranium aerosols generated during normal yellowcake packaging operations were sampled at four uranium mills. Samplers located in the packaging area were operated before, during and after drums of yellowcake were filled and sealed. Median aerosol concentrations in the packaging areas ranged from 0.04 micrograms U/1 to 0.34 micrograms U/1. The aerosols were heterogeneous and included a broad range of particle sizes such that 14% to 76% (by weight) of the airborne uranium was in particles with aerodynamic diameters greater than 12 micron. Air concentrations and particle-size distributions varied with time as larger particles settled or more aerosols were suspended. Aerosol characteristics could often be related to individual packaging steps. The results show that appreciable amounts of airborne uranium would be expected to deposit in the nasopharyngeal compartment of the respiratory tract if inhaled by a worker not wearing respiratory protection.

Aerosols↗