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PubMed2001

Multijet and multistage aerosol concentrator: design and performance analysis.

A multijet and multistage aerosol concentrator was designed and fabricated with two virtual impactors in a series. Collection efficiency, internal loss, and concentration factors were calculated at ambient conditions for each stage. The total inlet flow rate of the aerosol concentrator was set at 1000 L/min(-1), while the minor flow rate for the first stage was at 6.0% of the total inlet flow and the minor flow rate of the second stage was at 6.7% of the first stage minor flow. The aerosol concentrator was calibrated using polystyrene latex particles in aerodynamic sizes ranging from 0.5 to 10 microm. Several configurations of the multijet acceleration nozzles and multitube receptors were designed in this study. The effects of the different designs were subsequently evaluated through experimentation. It was found that a properly designed multijet and multistage aerosol concentrator can significantly improve aerosol concentration performance. Results showed that the concentration factor increases from 1 to 240 over the particle size range studied. Applications of the multijet and multistage aerosol concentrator with high-volume flow rate can vary widely, from detection of biological aerosols at low concentration, laboratory aerosol sampling, clean room monitoring, and ambient aerosol measurements.

Aerosols↗
PubMed2002

Carbon dioxide accumulation during small animal, whole body plethysmography: effects on ventilation, indices of airway function, and aerosol deposition.

Barometric (whole body) plethysmography is used to examine changes in ventilation and breathing pattern in unrestrained animals during exposure to therapeutic or toxic aerosols. Whole body plethysmographs (WBP) may be operated with a bias flow in order to maintain an adequate supply of oxygen and remove expired CO(2). However, some aerosol generation and delivery methods may require operation of the WBP without bias flow, which would artificially deplete aerosol concentration. Under these conditions, expired CO(2) accumulates in the plethysmograph and stimulates ventilation, increasing total aerosol deposition, shifting regional deposition, and significantly altering some airway function indices. We characterized these effects in guinea pigs using a commercially available 4.5-L WBP, with and without a 1 L/min bias flow. CO(2)-induced changes in breathing frequency (f), tidal volume (Vt), minute ventilation (Ve), and indices of airway function -- including enhanced pause (penh), flow derived parameter (FDP), and respiratory duty cycle -- were measured. Without bias flow, CO(2) in the plethysmograph increased steadily to 5.4% after 30 min compared to a steady state 0.9% with bias flow. This resulted in a moderate suppression of f, and significant increases in Vt and Ve by factors of 1.5 and 1.4, respectively. Changes in regional deposition were stimulated for 300 mg/m(3) polydisperse aerosols with mass median aerodynamic diameters of 0.3, 1, 3, or 7 microm and geometric standard deviations of 1.7. Percent increase in aerosol deposition from CO(2) inhalation ranged from 24% to 90%, by mass, depending on aerosol size distribution and respiratory tract region. In addition, fractional deposition shifted toward the pulmonary region. Empirical indices of airway constriction, penh and FDP, also were increased significantly to 1.7 and 1.3 times their respective baseline values. The study quantifies the effect of inadvertent coexposure to CO(2) on ventilation, aerosol deposition, and airway function in WBP evaluation of aerosol effects in airway function.

Administration, Inhalation↗
PubMed2002

Control of particle size by coagulation of novel condensation aerosols in reservoir chambers.

The coagulation growth behavior of capillary aerosol generator (CAG) condensation aerosols was investigated in a series of reservoir chambers. Aerosols consisted of a condensed system of 0.7% w/w benzil (model drug) in propylene glycol (vehicle). These were generated into 250-, 500-, 1,000-, and 2,000-mL reservoirs in both flowing air-stream and static air experiments. Changes in drug and total aerosol particle size were measured by a MOUDI cascade impactor. In both series of experiments the CAG aerosols grew in size. Growth in flowing air-stream experiments was attributed to the amount of accumulation aerosols experienced in reservoirs during sampling and increased with increasing reservoir volume. Mean (SD) MMAD's for the total mass distribution measured for the 250- and 2,000-mL reservoirs were 0.70 (0.02) and 0.87 (0.03) microm, respectively. For the benzil mass distribution, they were 0.64 (0.02) and 0.87 (0.06) microm, respectively. Growth in static air experiments was dependent on the volume aerosol boluses were restricted to and increased with decreasing reservoir volume. Mean (SD) initial MMAD's for the benzil mass distribution for the 250- and 2,000-mL reservoirs were 1.44 (0.03) and 1.24 (0.08) microm, respectively. Holding aerosols for up to 60 sec further increased their size. Mean (SD) MMAD's for benzil after holding for 60 sec in these reservoirs were 2.28 (0.04) and 1.67 (0.09) microm, respectively. The coagulation behavior and therefore particle size of CAG aerosols may be modified and controlled by reservoir chambers for drug targeting within the respiratory tract.

Aerosols↗
PubMed1999

Reducing adverse effects of inhaled fenoterol through optimization of the aerosol formulation.

We compared the adverse effects of 160 micrograms of fenoterol in the form of a 2.8-micron monodisperse aerosol with those of 800 micrograms of fenoterol as a conventional metered dose inhaler (MDI) aerosol plus spacer. Previously, a monodisperse aerosol was shown to elicit equivalent degrees of bronchodilation at an 80% lower dose using a standard MDI. A total of 12 healthy volunteers (8 women and 4 men) participated in this study and inhaled in random order a placebo, the monodisperse aerosol, and the MDI aerosol. Changes in serum potassium level, finger tremor, blood pressure, heart rate, and specific airway conductance were measured before and 15 minutes after administration. Compared with placebo, the active aerosols elicited a significant improvement in airway conductance and adverse effects. Serum potassium level decreased by 0.27 mmol/L after the monodisperse aerosol, and the MDI lowered it by 0.67 mmol/L (P = 0.001). Finger tremor also increased less: 0.07 versus 0.29 V (P = 0.029). Changes in cardiovascular parameters were not significantly different from those elicited by the placebo. There were no significant specific airway conductance differences between the two active aerosols. By changing the formulation of MDI aerosols, the occurrence of adverse effects can be reduced.

Absorption↗
PubMed2001

Efficacy of aerosolized amphotericin B desoxycholate and liposomal amphotericin B in the treatment of invasive pulmonary aspergillosis in severely immunocompromised rats.

The effects of treatment with aerosolized amphotericin B desoxycholate and aerosolized liposomal amphotericin B were evaluated in severely immunosuppressed rats with invasive pulmonary aspergillosis. Aerosol treatment with amphotericin B desoxycholate consisted of a single dose (60 min) with amphotericin B concentrations in the nebulizer reservoir of 1, 2 and 4 mg/mL, respectively. For liposomal amphotericin B, aerosol treatment consisted of single, double or quadruple doses with a nebulizer reservoir concentration of 4 mg/mL of amphotericin B. Treatment, started at 30 h after inoculation, with aerosolized amphotericin B desoxycholate (nebulizer reservoir concentration 2 mg/mL) significantly prolonged survival of rats as compared with placebo-treated rats, whereas treatment with aerosolized amphotericin B desoxycholate with nebulizer reservoir concentration of 1 or 4 mg/mL did not have a significant effect on survival. Treatment with aerosolized liposomal amphotericin B significantly prolonged survival with all treatment regimens when compared with placebo-treated animals. Aerosol treatment did not prevent dissemination of the infection. The effects of amphotericin B desoxycholate and liposomal amphotericin B on pulmonary surfactant function were also evaluated in vitro. Amphotericin B desoxycholate inhibited surfactant function in a dose-dependent fashion. Liposomal amphotericin B had no detrimental effect on surface activity of surfactant. These results indicate that aerosol administration of amphotericin B, especially the liposomal formulation, could be an additional approach to optimizing treatment of invasive pulmonary aspergillosis.

Aerosols↗
PubMed1982

Leakage of aerosols from containment buildings.

Experimental data on the plugging of ducts by aerosols are reviewed and compared with a simple model. The model predicts that the mass of the aerosol entering the duct prior to plugging is proportional to the cube of the duct diameter. This relation has been used to correlate experimental data on a variety of aerosols over a range of duct diameters from 100 micrometers to 30 cm. The proportionality constant appears to be a function of the effective density of the aerosol deposit and of the location of the plug. In the process of plugging leak paths, aerosols attach to the walls or to previously deposited aerosols. Some of these agglomerates break off and are resuspended in the airstream so that the sizes of aerosols exiting from short length leaks are substantially increased. When all of these effects are considered, it appears that less than 1 mg of respirable aerosol can leak from a typical Reactor Containment Building operating at the design pressure and gas leak rate (0.1 vol% per day). This is a reduction of more than four orders of magnitude from the case where the aerosol is assumed to leak as a gas.

Accidents↗
PubMed2002

239,240Pu and inorganic substances in aerosols from the vicinity of a waste isolation pilot plant: the importance of resuspension.

Aerosol samples were collected and analyzed to characterize the spatial and temporal variations in the concentrations of plutonium and selected inorganic substances in the atmosphere around the Waste Isolation Pilot Plant (WIPP). High-volume aerosol sampling was conducted at three sites: (1) On Site, (2) Near Field, and (3) Cactus Flats. 239,240Pu was determined by alpha spectrometry following chemical separations; mass loadings were determined gravimetrically. A separate set of low-volume aerosol samples was analyzed for major ions using ion chromatography and for trace elements by inductively-coupled plasma emission spectrometry and mass spectrometry. The average 239,240Pu activity concentrations in total suspended particle (TSP) samples (12 to 16 nBq m(-3)) were consistent with those previously reported, but they varied strongly with season, with the highest values generally in spring. Further, the 239,240Pu activity concentrations were comparable among the three sites, and therefore there was no evidence for elevated 239,240Pu activities due to WIPP operations. The fraction of the 239,240Pu activity concentrations in the PM10, samples (particles less than 10 microm diameter) relative to TSP was lower than the corresponding PM10/TSP ratios of either high-volume mass or several inorganics (sulfate, aluminum or lead), indicating that 239,240Pu tends to be on large particles. Aerosol mass loadings (microg m(-3)) and 239,240Pu activity concentrations were correlated for all sets of samples, but at On Site, the TSP samples showed higher mass to 239,240Pu ratios than the other sites. Thus activities or processes occurring at or near the WIPP site evidently produced aerosols that contributed to the mass loadings but contained less 239,244Pu than ambient aerosols. About 63% of the variability in 239,240Pu activity concentrations was explained by wind travel, sampling location, length of the sampling interval, and aerosol mass. 239,240Pu activity concentrations also were correlated with aluminum (an indicator of mineral dust), further implicating the resuspension of soils as an important determinant of 239,240Pu in aerosols. The 239,240Pu/Al ratios for the aerosols were higher than in soils, and this could be explained by the preferential binding of 239,240Pu to small soil particles that have large surface area to mass ratios and also have higher aluminum contents than larger particles.

Aerosols↗
PubMed2006

Uncertainties in aerosol deposition within the respiratory tract using the icrp 66 model: a study in workers.

This study estimates uncertainties in aerosol deposition within the main regions of the human respiratory tract calculated using the ICRP 66 model. Uniform, triangular, normal, or lognormal distributions were assigned to the model parameters, which involve physical properties of aerosols, their inhalability, their thermo- and aerodynamic deposition efficiencies, and the anatomy, physiology, and exertion level of the individuals. Calculations were performed over a range of aerosol sizes from 0.01 to 50 mum. Monodispersed aerosols were characterized by their aerodynamic diameter (dae). Polydispersed aerosols were characterized by their activity median aerodynamic diameters (AMADs) and the geometric standard deviation (GSD) in diameter. Lognormal distributions of particle deposition were generally observed with low GSD (< 2). The highest uncertainties were observed within the deep lung for the smallest and the largest aerosol sizes, which were mainly due either to particle density or to aerodynamic deposition efficiencies and anatomical and physiological variability, respectively. In the case of diameters larger than 5 mum, uncertainties in the deep lung deposition were much more important for monodispersed than for polydispersed aerosols. This was explained both by the size distribution of the deposited aerosol, the median of which corresponded to a maximal dae value of about 7 and 5 in bronchioles and alveoli, respectively, and by the absence of deposition, which occurs for dae equal to or larger than 50 mum, depending on the exertion level. Thus, in the range of AMADs considered, for the four default workers proposed by ICRP 66, uncertainties in aerosol deposition remain low, with GSD smaller than 3.

Aerosols↗
PubMed2006

A study of the dispersion of expiratory aerosols in unidirectional downward and ceiling-return type airflows using a multiphase approach.

Dispersion characteristics of expiratory aerosols were investigated in an enclosure with two different idealized airflow patterns: the ceiling-return and the unidirectional downward. A multiphase numerical model, which was able to capture the polydispersity and evaporation features of the aerosols, was adopted. Experiments employing optical techniques were conducted in a chamber with downward airflow pattern to measure the dispersion of aerosols. Some of the numerical results were compared with the chamber measurement results. Reasonable agreement was found. Small aerosols (initial size <or=45 microm) had settling times of below 20 s in downward flow but increased to 32-80 s in ceiling-return flow. Lateral dispersion was limited to around 0.3 m in downward flow, in which only turbulent dispersion was significant. It increased to over 2 m in ceiling-return flow, which had a combination of both turbulant dispersion and bulk flow transport mechanisms. The significance of aerosol transport by bulk flow was about an order of magnitude stronger than that by turbulent dispersion. However, results also show that aerosols could be dispersed for considerable distances solely by turbulence if they were suspended longer. Large aerosols settled within very short time due to heavy gravitational effects. The results provided new insights in designing proper bed spacing in hospital ward environments. This study shows that transport by bulk airflow stream was the major dispersion mechanism of expiratory aerosols in ventilated indoor environments. Dispersion by turbulence was about an order of magnitude less than that by bulk flow transport but considerable distance could be achieved by turbulent dispersion with long enough settling time. It was demonstrated that the dispersion of expiratory aerosol could be controlled by manipulating the ventilation airflow patterns in indoor environments.

Aerosols↗
PubMed2006

Recirculatory pharmacokinetic model of the uptake, distribution, and bioavailability of prochlorperazine administered as a thermally generated aerosol in a single breath to dogs.

A thermal aerosol generation process is capable of delivering pure drug reliably to the alveoli where it is absorbed systemically. Although deep lung absorption of drugs administered as an aerosol has been shown to be rapid, detailed characterization of their absorption and distribution has not been reported. The present study describes the pharmacokinetics of prochlorperazine from the moment of administration as either a rapid intravenous infusion or a thermally generated aerosol and determines the bioavailability of the aerosol by two independent methods. Prochlorperazine disposition was determined in four anesthetized dogs after a 5-s intravenous infusion and after thermally generated aerosol administration in one breath. Venous blood samples were collected frequently from the time of drug administration to 24 h and left ventricular blood samples were drawn more often until 10 min after drug administration. Prochlorperazine disposition after intravenous and aerosol administration was characterized by fitting a recirculatory model to left ventricular and venous drug concentration data simultaneously. Prochlorperazine aerosol administration produced plasma drug concentrations similar to those after rapid intravenous administration of the same nominal dose, with peak left ventricular concentrations achieved in less than 30 s. Plasma concentration profiles of prochlorperazine administered by both routes were well described by the recirculatory model. Bioavailability of the thermally generated aerosol was consistent and averaged more than 80% of emitted dose. Pulmonary administration of a thermally generated drug aerosol in one breath may be a viable alternative to rapid intravenous administration of drugs requiring rapid and predictable production of effective plasma concentrations.

Aerosols↗
PubMed2003

Pilot intervention: aerosolized adrenomedullin reduces pulmonary hypertension.

In pulmonary hypertension, systemic infusion of adrenomedullin (ADM), a potent vasodilator peptide, leads to pulmonary vasodilatation. However, systemic blood pressure declines alike. The present study investigated the effect of aerosolized ADM on pulmonary arterial pressure in surfactant-depleted newborn piglets with pulmonary hypertension. Animals randomly received aerosolized ADM (ADM, n = 6), aerosolized ADM combined with intravenous application of NG-nitro-l-arginine methylester to inhibit nitric-oxide (NO) synthases (ADM + l-NAME, n = 5), or aerosolized normal saline solution (control, n = 6). Aerosol therapy was performed in 30-min intervals for 5 h. After a total experimental period of 8 h, mRNA expression of endothelial and inducible NO synthase and endothelin-1 (ET-1) in lung tissue was quantified using TaqMan real-time polymerase chain reaction. Aerosolized ADM reduced mean pulmonary artery pressure (MPAP) compared with control (p < 0.001; at the end of the study, Delta-MPAP -13.5 +/- 1.4 versus -6.2 +/- 2.4 mm Hg). PaO2 significantly increased in the ADM (DeltaPaO2 243.3 mm Hg) and the ADM + l-NAME group (DeltaPaO2 217.4 mm Hg) compared with the control group (DeltaPaO2 82.9 mm Hg; p < 0.001). Aerosolized ADM did not influence mean systemic arterial pressure (baseline 63.2 +/- 2.7 versus end of the study 66.3 +/- 6.5 mm Hg; not significant). NO synthases gene expressions were 20 to 30% lower with ADM compared with control. ET-1 gene expression was significantly reduced (>50%) after ADM aerosol therapy (p < 0.001). Aerosolized adrenomedullin significantly reduced MPAP without lowering the systemic arterial pressure and improved profoundly the arterial oxygen tension. This effect seems to be mediated at least in part by the reduction of ET-1.

Adrenomedullin↗
PubMed1982

Comparison of coliphage and bacterial aerosols at a wastewater spray irrigation site.

Microbiological aerosols were measured on a spray irrigation site at Fort Huachuca, Ariz. Indigenous bacteria and tracer bacteriophage were sampled from sprays of chlorinated and unchlorinated secondary-treatment wastewaters during day and night periods. Aerosol dispersal and downwind migration were determined. Bacterial and coliphage f2 aerosols were sampled by using Andersen viable type stacked-sieve and high-volume electrostatic precipitator samplers. Bacterial standard plate counts averaged 2.4 x 10(5) colony-forming units per ml in unchlorinated effluents. Bacterial aerosols reached 500 bacteria per m3 at 152 m downwind and 10,500 bacteria per m3 at 46m. Seeded coliphage f2 averaged 4.0 x 10(5) plaque-forming units per ml in the effluent and were detected 563 m downwind. Downwind microbial aerosol levels were somewhat enhanced by nighttime conditions. The median aerodynamic particle size of the microbial aerosols was approximately 5.0 micrometer. Chlorination reduced wastewater bacterial levels 99.97% and reduced aerosol concentrations to near background levels; coliphage f2 was reduced only 95.4% in the chlorinated effluent and was readily measured 137 m downwind. Microbiological source strength an meteorological data were used in conjunction with a dispersion model to generate mathematical predictions of aerosol strength at various sampler locations. The mean calculated survival of aerosolized bacteria (standard plate count) in the range 46 to 76 m downwind was 5.2%, and that of coliphage f2 was 4.3 %.

Aerosols↗
PubMed1973

Interaction of some factors in the mechanism of inactivation of bacteriophage MS2 in aerosols.

The mechanisms involving inactivation of bacteriophage MS2 in aerosols and the effect of protective substances in the spray-medium were studied after spraying from various NaCl solutions. Results with aerosols generated from the salt solutions showed that with higher salt concentration in the spray-medium higher concentrations of protective substances were needed to protect phage MS2 against aerosol inactivation. Phenylalanine, which has a protective action at low concentration, produced less protection in aerosol droplets that were supersaturated solutions of this substance or in which crystals of phenylalanine can be expected to form. Our results suggested that protection by peptone and phenylalanine was related to the concentration in the aerosol droplet after evaporation to equilibrium, whereas protection by the surface active agent OED (a commercial mixture of oxyethylene docosylether and oxyethelene octadecylether) was related to the concentration at which a monolayer is formed around the aerosol particle. Inactivation of phage MS2 was maximal in the aerosol particle in fluid phase and became less at lower relative humidity where aerosol particles are expected to be in the solid state. It is suggested that inactivation of bacteriophage MS2 in aerosols could be explained by surface inactivation at the air-water interface.

Aerosols↗
PubMed1995

Occupational exposure to inhalable and total aerosol in the primary nickel production industry.

OBJECTIVES: This paper describes a study that was carried out in the primary nickel production industry to investigate the levels of personal exposure to aerosols containing nickel and the impact on exposure assessment of introducing new personal sampling techniques with performance consistent with the latest particle size-selective criteria. METHODS: Experiments were carried out at workplaces in mining, milling, smelting, and refining works to investigate the effect of changing from the current method of total aerosol (with the widely used 37 mm filter holder) to the new method of measuring inhalable aerosol (with the Institute of Occupational Medicine (IOM) inhalable aerosol sampler). RESULTS: The results show that inhalable aerosol exposure concentrations--for both overall aerosol and for total nickel--were consistently and significantly higher than the corresponding total aerosol concentrations. Weighted least squares linear regression yielded IOM/37 mm factors ranging from about 1.2 to 4.0. The exposure data for each company process were found to be log-normally distributed. CONCLUSIONS: The results suggest the possibility of generating a single pragmatic factor for each company process for converting current total aerosol exposures to new exposures based on the inhalability concept contained in the latest particle size-selective criteria for aerosol exposure assessment. Such data may be important in determining new occupational exposure limits for nickel.

Aerosols↗
PubMed1986

Effect of aerosol particle size on bronchodilatation with nebulised terbutaline in asthmatic subjects.

The bronchodilatation achieved by the beta 2 agonist terbutaline sulphate given as nebulised aerosol from different devices has been measured in seven patients with mild asthma (mean FEV1 76% predicted) over two hours after inhalation. The subjects were studied on four occasions. On three visits they received 2.5 mg terbutaline delivered from three different types of nebuliser, selected on the basis of the size distribution of the aerosols generated; and on a fourth (control) visit no aerosol was given. The size distributions of the aerosols expressed in terms of their mass median diameter (MMD) were: A: MMD 1.8 microns; B: 4.6 microns; C: 10.3 microns. The aerosols were given under controlled conditions of respiratory rate and tidal volume to minimise intertreatment variation. Bronchodilator response was assessed by changes in FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), and maximal flow after expiration of 50% and 75% FVC (Vmax50, Vmax25) from baseline (before aerosol) and control run values. For each pulmonary function index all three aerosols gave significantly better improvement over baseline than was seen in the control (p less than 0.05) and had an equipotent effect on FEV1, FVC, and PEF. Aerosol A (MMD 1.8 microns) produced significantly greater improvements in Vmax50 and Vmax25 than did B or C (p less than 0.05). These results suggest that for beta 2 agonists small aerosols (MMD less than 2 microns) might be advantageous in the treatment of asthma.

Adult↗
PubMed1996

On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs.

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a "particle growth factor" derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.

Aerosols↗
PubMed2003

Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols.

Aerosol particle size influences airway drug deposition. Current inhaler devices are inefficient, delivering a heterodisperse distribution of drug particle sizes where, at best, 20% reaches the lungs. Monodisperse aerosols are the appropriate research tools to investigate basic aerosol science concepts within the human airways. We hypothesized that engineering such aerosols of albuterol would identify the ideal bronchodilator particle size, thereby optimizing inhaled therapeutic drug delivery. Eighteen stable mildly to moderately asthmatic patients [mean forced expiratory volume in 1 s (FEV1) 74.3% of predicted] participated in a randomized, double-blind, crossover study design. A spinning-top aerosol generator was used to produce monodisperse albuterol aerosols that were 1.5, 3, and 6 microm in size, and also a placebo, which were inhaled at cumulative doses of 10, 20, 40, and 100 microg. Lung function changes and tolerability effects were determined. The larger particles, 6 and 3 microm, were significantly more potent bronchodilators than the 1.5-microm and placebo aerosols for FEV1 and for the forced expiratory flow between exhalation of 25 and 75% of forced vital capacity. A 20-microg dose of the 6- and 3-microm aerosols produced FEV1 bronchodilation comparable to that produced by 200 microg from a metered-dose inhaler. No adverse effects were observed in heart rate and plasma potassium. The data suggest that in mildly to moderately asthmatic patients there is more than one optimal beta2-agonist bronchodilator particle size and that these are larger particles in the higher part of the respirable range. Aerosols delivered in monodisperse form can enable large reductions of the inhaled dose without loss of clinical efficacy.

Administration, Inhalation↗
PubMed1986

Aerosol therapy of asthma: principles and applications.

Aerosols are the mainstay of therapy of reversible airflow obstruction. Currently available aerosols include bronchodilators such as beta-adrenoceptor agonists and anticholinergic agents which may be used alone or together with prophylactic, anti-inflammatory medications such as sodium cromoglycate and steroids. These agents are characterized by primarily topical activity and thus result in minimal systemic effects. By combining these medications in optimum doses, most patients can be readily managed. In patients with severe airway hyperreactivity, aerosols may need to be combined with oral sustained-release theophylline compounds and/or systemic steroids, the latter being used in minimum doses and if possible on alternate days to minimize adrenal suppression and steroid-related systemic complications. In recent years, an improved understanding of aerosol physics, pharmacology and airway physiology has led to greatly improved aerosol therapy with increasing emphasis on metered dose inhalers as the delivery system of choice while nebulizers are used less frequently except in hospital and pediatric applications. The use of intermittent positive-pressure devices for aerosol delivery has decreased considerably as physicians recognize that simpler delivery methods work equally well at much lower cost. While aerosol therapy techniques are now well worked out, research is continuing on methods of improving the efficiency of aerosol delivery and in the development of newer pharmacological agents such as longer-acting adrenoceptor agonists, calcium channel blockers, antagonists of mediators derived from arachidonic acid as well as higher dose aerosolized steroids.

Aerosols↗