Physical properties of aerosols produced by several jet- and ultrasonic nebulizers

In order to estimate the administered dose of inhaled drugs from aqueous aerosols, we have examined the output characteristics of eleven jet- and nine ultrasonic nebulizers. Under various operating conditions we measured driving pressure, airflow, solution- and solute output of the nebulizers, particle concentration and size distribution in the aerosol. The particle size distributions were determined of the dry particles from evaporated droplets of aerosolized 9 mg X ml-1 NaCl solutions by using a mobility aerosols spectrometer. These physical properties of the aerosols were found to vary considerably between nebulizers (even among specimens of the same type). Solution output per litre of air from the ultrasonic devices was 2 to 10 times larger than that from the jets, being dependent on electric power and driving pressure respectively. The jet nebulizers showed the largest particle concentration per litre of air. The volume median aerodynamic diameter of the droplets generated by the jet nebulizers was about 1.5-4 microns. With the exception of the Siemens TV 6000 and the Bosch Halomed, this diameter ranged between 3 and 7 microns among the ultrasonic nebulizers, being dependent on the frequency of the ultrasonic vibrations. The output characteristics appeared also to be affected by extension tubes, air vents, solute concentration and airflow. Solute output varied nonproportionally with solution output, which confirms the comparative merit of output measurements by weighing. The results of the present study can be used to estimate the administered dose of therapeutic or provocative agents by nebulizer equipment. Actual drug output can only be quantified by careful calibration of each separate set-up.     

An in vitro analysis of the output of budesonide from different nebulizers

BACKGROUND: Inhaled corticosteroids are increasingly used in the treatment of asthma, and many different nebulizers are available to aerosolize steroid medications. There are few comparative data on their ability to do so. OBJECTIVE: Our purpose was to determine the particle size and mass output of budesonide nebulizer suspension from different nebulizers. METHODS: In vitro measurement of drug particle size and total drug output from 3 nebulizers (the Pari LC Plus, the Pari LC Star, and the Medicaid Ventstream) was performed under simulated breathing conditions. Nebulizers were charged with 2 mL (500 microg) of budesonide suspension. A sinus pump was used to draw aerosol from the nebulizers onto a filter during simulated inspiration at tidal volumes of 150 and 600 mL, mimicking pediatric and adult use. Aerosol particle size was determined separately by inertial impaction. RESULTS: The LC Plus nebulizer had the highest initial output rate and delivered the most budesonide at both breathing patterns. The maximal output rates of the Ventstream and LC Star nebulizers was half that of the LC Plus, but the LC Star nebulizer continued nebulization for longer and delivered twice as much budesonide as the Ventstream did. However, the Ventstream produced the smallest particles, mass median diameter 3.1 microm compared with 3.8 microm for the LC Star and 4.1 microm for the LC Plus. CONCLUSIONS: This study has identified differences among the nebulizers that would not have been apparent with current standards for nebulizer assessment. Incorporation of breathing simulation in the study imitates patient use and allows effective nebulization times to be predicted. The results suggest that the nebulizers studied would deliver different masses of budesonide to the lungs and to the upper airway. This may have important consequences in determining the efficacy and side effect profile of budesonide.     

Comparison of three commercial ultrasonic nebulizers.

BACKGROUND: The clinical acceptance of the initial ultrasonic nebulizers was impeded by their production of significant quantities of droplets larger than the respirable range that could have resulted in poor pulmonary deposition of nebulized medications. Subsequent modifications in the design of ultrasonic nebulizers have occurred. Overall nebulizer performance characteristics of the newer ultrasonic devices have not been evaluated. OBJECTIVE: Three commercially available ultrasonic nebulizers (DeVilbiss-Pulmosonic, Omron-Microair, Rh?ne Poulenc-Rorer-Fisoneb) were studied to compare the aerosol output characteristics. METHODS: The parameters studied were total volume output (TVO), time to nebulize total output (TTO), percent of droplets with volume diameters in the respirable range (PDVRR, 1 to 5 microm), albuterol concentration during nebulization, and the total drug delivered. All nebulizers were filled with 2.5 mL of saline and 0.5 mL of albuterol nebulizer solution. Three units from each manufacturer, each from a different lot, were evaluated in duplicate. RESULTS: The nebulizer with the largest volume output was the Omron (mean 2.94 mL), which also demonstrated the longest nebulization time (mean 10.3 min). The DeVilbiss and Rh?ne Poulenc-Rorer units delivered smaller volumes (mean 2.5 mL, 2.4 mL, respectively) but nebulized more rapidly (mean 2.21 min, 3.54 min, respectively). The Omron nebulizer generated the highest PDVRR with a mean of 38%. The DeVilbiss had a mean PDVRR of 16% and the Rh?ne Poulenc-Rorer a mean PDVRR of 21%. The majority of droplets from all three machines had a volume diameter smaller than the respirable range, ie, in the 0.5 to 1.0 microm range (Omron-60%, DeVilbiss-83%, Rh?ne Poulenc-Rorer-79%). For all three nebulizers there appeared to be no concentrating or diluting effect during nebulization implying that equal quantities of albuterol and diluent were delivered. The Rh?ne Poulenc-Rorer units demonstrated the greatest unit-to-unit variability with respect to TVO while the Omron units demonstrated the greatest unit to unit variability with respect to TTO. CONCLUSION: We conclude that several improvements in the design of ultrasonic nebulizers have resulted in the reduction of the size of the droplets generated. Our evaluation of the three commercially available ultrasonic nebulizers revealed that the majority of droplets generated were within or below the respirable range. There was no concentrating or diluting effect during nebulization for all three nebulizers. The output characteristics of the three devices differ and this will effect the delivery time as well as amount of drug delivered to the lungs.     

The effects of particle size on measurement of airway hyperresponsiveness to methacholine

BackgroundThe effect of particle size on methacholine provocation concentration causing a decrease in forced expiratory volume of 1 second (FEV₁) of 20% (PC₂₀) is debatable.ObjectiveTo evaluate the functional effects of 3 different particle size nebulizers on methacholine PC₂₀.MethodsParticipants were randomly assigned to have 3 methacholine challenges on 3 separate days. Nebulizer mass median aerodynamic diameter (MMAD) was provided by manufacturers. The Wright nebulizer (MMAD, 1.0 μm), Aeroneb (MMAD, 3 μm), and Aeroneb (MMAD, 5 μm) were calibrated, and the nebulizer outputs were calculated to administer 0.26 mL of methacholine over 120, 112, and 83 seconds, respectively. After each inhalation, spirometry was performed and the test was terminated when the PC₂₀ was achieved.ResultsEight nonsmoking patients with mild asthma (4 male and 4 female) completed the study. The mean (SD) age was 25 (13.9) years, and the mean (SD) baseline FEV₁ was 88% (11.3%). Patients using the Aeroneb (MMAD, 5 μm) nebulizer had the lowest PC₂₀ (bronchoconstricted at lowest methacholine concentration), with a PC₂₀ geometric mean of 0.62 mg/mL compared with patients using the Aeroneb (MMAD, 3.0 μm), who had a PC₂₀ of 1.76 mg/mL, and patients using the Wright nebulizer (MMAD, 1.0 μm), who had a PC₂₀ of 6.32 mg/mL. There was a significant difference in PC₂₀ across all particle sizes (P < .001). The pairwise differences revealed a P < .001 between 3 μm and 1 μm and between 5 μm and 1 μm and a P = .008 between 5 μm and 3 μm.ConclusionOur results reveal a variability in methacholine PC₂₀ using 3 different nebulizers, despite adjusting the nebulizers' outputs. Our results are consistent with the previous reports, which recommended using larger particle size nebulizers in the assessment of airway hyperresponsiveness in asthma.Trial Registrationclinicaltrials.gov Identifier: NCT00529477     

Design characteristics for drug nebulizers.

Drug nebulizers should be designed to produce an aerosol which efficiently targets drug to the respiratory tract. In this article we review the basic principles of aerosol generation from both jet and ultrasonic nebulizers, and the factors governing respiratory tract penetration and deposition. We review methods for accurate measurement of aerosol dose and size, with emphasis on evaporative effects and the implications to drug nebulizer design. We identify three forms of drug aerosol waste attributable to: generation of non-respirable aerosol, losses to the environment, and dead volume solution; and we consider how each may be minimized through good nebulizer design. Finally, we compare the relative merits of jet and ultrasonic nebulizers, and conclude by predicting a new trend in future drug nebulizer therapy.     

A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation

Airway inflammation can be demonstrated by the modem method of sputum induction using ultrasonic nebulizer and hypertonic saline. We studied whether compressed-air nebulizer and isotonic saline which are commonly available and cost less, are as effective in inducing sputum in normal adult subjects as the above mentioned tools. Sixteen subjects underwent weekly sputum induction in the following manner: ultrasonic nebulizer (Medix Sonix 2000, Clement Clarke, UK) using hypertonic saline, ultrasonic nebulizer using isotonic saline, compressed-air nebulizer (BestNeb, Taiwan) using hypertonic saline, and compressed-air nebulizer using isotonic saline. Overall, the use of an ultrasonic nebulizer and hypertonic saline yielded significantly higher total sputum cell counts and a higher percentage of cell viability than compressed-air nebulizers and isotonic saline. With the latter, there was a trend towards squamous cell contaminations. The proportion of various sputum cell types was not significantly different between the groups, and the reproducibility in sputum macrophages and neutrophils was high (Intraclass correlation coefficient, r [95%CI]: 0.65 [0.30-0.91] and 0.58 [0.22-0.89], p < 0.001). Overall changes in median FEV, were small and comparable between all groups. Induction using ultrasonic nebulizers together with hypertonic saline was generally less well tolerated than compressed-air nebulizers and isotonic saline. We conclude that in normal subjects, although both nebulizers and saline types can induce sputum with reproducible cellular profile, ultrasonic nebulizers and hypertonic saline are more effective but less well tolerated.     

The physical properties of a jet-nebulizer and their relevance for the histamine provocation test

We have examined the physical properties of eight specimens of a frequently used jet-nebulizer (Wiesbadener Doppelinhalator). For each nebulizer, under various conditions we measured driving pressure, solution output, solute output, particle concentration and size distribution in the aerosol, and the change of solute concentration in the storage vessel. Using histamine acid phosphate solutions in distilled water, there was considerable variability between the nebulizers in solute output (range about a factor 3). Solute output was strongly related to driving pressure (r2 = 0.89), to solution output (r2 = 0.96) and to particle concentration (r2 = 0.87). The particle size distributions of the eight nebulizers were very similar. The volume median aerodynamic diameter (VMAD) of the stable evaporated particles was on average 0.33 micrograms (geometric standard deviation of 1.78), which implies a VMAD of the primary droplets of about 3.2 micrograms. In fifteen subjects with bronchial hyperreactivity, a twofold increase of histamine output of the nebulizer without a change in particle size resulted on average in a twofold decrease of the histamine concentration that caused a 20 per cent fall (PC20) in FEV1. At constant histamine output the administration of dry particles instead of direct nebulization of (partly) saturated droplets into the mouth increased PC20 by a factor 2. This difference could not be explained by a changed deposition in the hypopharynx. There were large interindividual differences in the response to the altered aerosol characteristics. We conclude that the physical properties of the administered aerosols should be carefully controlled since they influence the biological response to inhaled histamine. The solute output of the investigated jet-nebulizer can satisfactorily be validated by weighing, for which an equation is given. In bronchial provocation testing, administration of dry particles is recommended.     

Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram-negative bacteria in patients with cystic fibrosis.

Inhalation of aerosols contaminated with gram-negative bacteria generated from home-use nebulizers used by cystic fibrosis (CF) patients may be a primary route for bacterial colonization of the lung. Burkholderia cepacia was isolated from 3 of [corrected] 35 home-use nebulizers, and Stenotrophomonas maltophilia was isolated from 4 of 35 home-use nebulizers. Sputum cultures for two patients whose nebulizers were contaminated with B. cepacia did not yield the organism. However, DNA macrorestriction analysis by pulsed-field gel electrophoresis confirmed that one of two strains of B. cepacia recovered from the nebulizer of a third patient was also present in the sputum of that patient. Although Pseudomonas aeruginosa was isolated from 34 patients, none of the nebulizers were positive for the organism. Sixty-nine percent of nebulizers were contaminated, and up to 16 different environmental colistin-resistant, gram-negative species were identified. The heaviest contamination was found beneath the chamber atomizer. A questionnaire survey showed that the majority of patients (28 of 34) were receiving nebulized colistin and/or gentamicin. Patients who followed recommended instructions for good nebulizer hygienic practice and paid particular attention to drying had minimal or no contamination of their nebulizers.     

Sputum induction: effect of nebulizer output and inhalation time on cell counts and fluid-phase measures

BACKGROUND: A knowledge of the factors that can affect induced sputum results is essential in order to standardize the procedure. OBJECTIVE: We investigated the influence of nebulizer output on sputum cell counts and fluid phase measurements at increasing times of sputum induction. METHODS: Eighteen adults with stable asthma inhaled an aerosol of 3% hypertonic saline to induce sputum after 7, 14 and 21 min on 2 days separated by 48 h. On one day, in random order, the ultrasonic nebulizer used had a relatively low output of 0.87 mL/min (particle size 5.58 microm mass median aerodynamic diameter, MMAD) and, on the other, a higher output of 1.90 mL/min (particle size 4.14 microm MMAD). The sputum was selected from each expectorate and examined blind to the induction procedures. RESULTS: With both nebulizers, the 14- and 21-min samples were lower in weight, neutrophils, eosinophils, eosinophil cationic protein (ECP) and interleukin (IL)-8 and higher in macrophages. The higher output nebulizer induced sputum with higher cell viability and lower ECP and IL-8. CONCLUSION: The results identify that the volume of hypertonic saline inhaled in sputum induction influences the fluid-phase measurements. The duration of induction does alter the cell counts and suggests that the later expectorated sputum samples originate from more peripheral airways. The results draw attention to the need to standardize the volume and time of nebulization to accurately interpret and compare results.     

The effect of particle size and amount of inhalation on the pulumonary function testsn in asthmatic children]

The effect of three nebulizers, Nisshou and LC plus, were compared by the particle size and amount of inhalation. The improvement of FEV1 at 15 minutes after the inhalation was significantly higher in LC plus than Nisshou (MMD: 7.43microm, 10.76microm). The amount of inhlation were compared between Nisshou with/without Y tube and LC plus nebulizer with/without LC valve system. Nisshou nebulizer with Y tube and LC plus nebulizer with LC valve systems were significantly better than that of LC plus nebulizer without LC valve system. Small loss of inhalation gave us better efficacy. The urinary excretion of disodium cromoglycate (DSCG) was highest in LC plus with LC valve system, Nisshou with Y tube and lowest in Nisshou without Y tube. The elecctric nebulizers produced better in MMD of 5microm and a smaller loss of inhalation. These results suggested that MMD less than 5microm and small loss from nebulizer are very important for inhalation therapy.     

Characterization of aerosol output from various nebulizer/compressor combinations.

OBJECTIVES: Different commercially available nebulizers and compressors are available. However, the optimal combination for drug delivery is unknown. METHODS: Flow rates of five different compressors (n = 3/compressor) tested alone and in combination with five different commercial nebulizers (n = 9 of each brand of nebulizer) were evaluated. Thereafter, the performances of the different nebulizers were evaluated using 2.5 mg albuterol solution (0.5 mL) added to 2.5 mL saline at flow rates of 2, 3, 4, and 5 L/minute using a laser particle analyzer. Volume median diameter and percentage of particles in the respirable range (1-5 microm) were calculated from this data. Time for nebulization (in seconds) and residual volume (in milliliters) were also recorded. RESULTS: The mean flow rates for the compressors evaluated without a nebulizer attached ranged from 6.6 L/minute (LifeCare Freedom-neb; LifeCare International, Lafayette, CO) to 12.2 L/minute (DeVilbiss Pulmo-Aide; DeVilbiss Health Care, Somerset, PA). Flow rates for the nebulizer/compressor combinations ranged from 2.08 L/minute (Pari LC Jet Proneb; Pari Respiratory Equipment, Richmond, VA) to 5.42 L/minute (Puritan Bennett Raindrop; Puritan Bennett, Lenexa, KS/Omron Compare; Omron, Health Care,Vernon Hills, IL). Using the repeated measure ANOVA model, the interaction between flow rate and device was significant (P < 0.001) for both percentage of particles in the respirable range and log volume median diameter. It was observed that the percentage of particles in the respirable range for the Pari LC Jet did not increase across flow rates in contrast to the other 4 nebulizers. All comparisons to the Pari LC Jet at 2 L/minute were significant. CONCLUSIONS: Marked variability exists in the flow rates among different commercially available compressors used for home nebulization of inhaled pulmonary medications. Different nebulizer/compressor combinations have markedly different performance characteristics which could result in different efficacy and safety profiles of the medications being administered via these devices. We recommend that this type of information be used as a starting point for selecting different nebulizer/compressor combinations. Further clinical evaluation is warranted.     

Immunological and physical properties of allergen solutions

Lyophilised birch pollen allergen extracts, reconstituted with different diluents (H₂O, saline, Albumin diluent® (AD)) were investigated to determine whether the allergen activity and quality of the extracts deteriorated by nebulization with different nebulizers (Pari, Wright, and Samdoz). Allergen activity was measured by IgG₄ RAST inhibition technique and allergen quality was analysed by crossed immunoelectrophoresis (CIE). The distribution of particle sizes of aerosols different allergen solutions was determined by a TSI Aerodynamic Particle Sizer. A significant difference (P < 0.05) in allergen activity was found between the AD and H₂O diluents before and after using a Sandoz nebulizer and a Wright nebulizer equipped with a small chamber. This suggested greater allergen activity in AD-diluted solutions, and the pattern was repeated with the other two nebulizers, but was not statistically significant. The samples diluted with saline showed no significant differences in quality after nebulization except for the impacted aerosol in which one of the precipitates was slightly diminished. In the AD-diluted sample one of the precipitates disappeared from the impacted aerosol and from the nebulization chamber after 2 min nebulization. To CIE with rabbit anti-human albumin in an intermediate gel. By this procedure one precipitate was transformed to a precipitate in the intermediate gel, indicating that one or more proteins in the extracts may associate with albumin. No significant difference in output was observed between the nebulizers. The particle size distribution curves for each diluent (saline, AD) were identical for the Wright nebulizer with 99% of the dry particles distributed within 0.5–2.0 μm. Although allergen solutions reconstituted with different diluents were not deteriorated in different nebulizers, it may be that the addition of human albumin to an allergen solution may induce one or more proteins in the extracts to associate with it. This could reduce allergen adsorption over periods longer than this study. The use of different diluents did not change the distribution of particle size generated by the nebulizer tested.     

Calibration of an x-ray cabinet unit for radiobiology use

A Faxitron sealed x-ray cabinet, operated at 100 kV, was modified to irradiate monkey testicles, to a uniform, accurately calibrated dose, for work aimed at investigating spermatogenesis in children undergoing radiotherapy. An aluminium filter was added to increase the beam quality and a lead collimating system manufactured to reduce the beam size to between 1 and 4 cm diameter. Percentage depth doses and profiles were analysed and relative in-air outputs measured with a selection of small (0.2 cc, 0.015 cc) ion chambers. The absolute calibration of the unit was carried out in a 10 x 10 cm2 beam with a 0.6 cc chamber. Backscatter factors were based on standard tables, but then modified according to experimental results with thermoluminescent dosimeters (TLD) in a phantom to account for reduced scatter in the irradiation situations. A suitable irradiation set-up was devised for the monkeys, to ensure accuracy of delivered dose to the target volume and minimize the dose to the surrounding healthy tissue. The homogeneity throughout the testes was calculated to be well within +/-5%, using a parallel-opposed irradiation technique. The TLD measured doses to the testes on three monkeys were lower than the calculated doses by 3 to 6%. Following modifications to the standard percentage depth doses to account for changes in scatter conditions, these differences became +/-3%. The uncertainties on both calculated and measured dose were estimated to be approximately +/-3.2% at 1 SD.     

The effect of inspiratory flow rate regulation on nebulizer output and on human airway response to methacholine aerosol

Increased inspiratory flow rate has been demonstrated to decrease pulmonary deposition of inhaled aerosols. To study the effect of inspiratory flow rate regulation on the physiologic response to an active substance administered by aerosol, we compared the effect of high unregulated flow rate (66 to 212 L/min) with regulated low flow rate (20 to 35 L/min) on nebulizer output and on the pulmonary response to methacholine in patients with asthma. Four No. 646 DeVilbiss nebulizers were used in sequence with a nebulization dosimeter to deliver tenfold incremental concentrations of methacholine aerosol (mass median aerodynamic diameter = 1.52 micron; geometric standard deviation = 1.96) ranging from 0.025 to 25 mg/ml. When flow was unregulated, nebulizer output was not greater than when flow was regulated, but coefficients of variation of output were significantly greater (p less than 0.01). The PD20 on the two unregulated days was significantly different (p = 0.01), whereas the PD20 on the two flow regulated days was not significantly different (p greater than 0.05). We conclude that regulation of inspiratory flow rate at rates within the range of tidal breathing significantly decreases variability in nebulizer output and variation of pulmonary responses to methacholine challenge.     

Contamination of nebulizers with environmental allergens.

BACKGROUND: A previous article described cockroach allergen in the nebulizer reservoir of an asthmatic patient who experienced a life-threatening exacerbation after nebulizer use. OBJECTIVE: To determine whether indoor allergens can be measured in home nebulizers. METHODS: As part of a large study examining nebulizer use in underserved asthmatic children, visiting nurses replaced nebulizer sets in patients' homes. Twenty used sets were randomly selected for analysis, without linkage to clinical or home environmental data. Nebulizer reservoirs and negative controls (buffer and albuterol) were extracted overnight with 2 mL of buffer. For positive controls, nebulizer sets were placed in homes with cats and dogs, and other reservoirs were intentionally contaminated with cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1 and Bla g 2), and mouse (Mus m 1) skin test solutions. Extracts were tested for allergens in a masked manner using enzyme-linked immunosorbent assay. RESULTS: Of 17 reservoirs with adequate specimens for allergen detection, 5 (29%) had measurable levels for at least 1 of 5 allergens tested. One reservoir had measurable Can f 1, 2 had Bla g, 3 had Mus m 1, and none had Fel d 1 allergen. Two of 3 homes with cats where nebulizer setups were placed had measurable Fel d 1 in the reservoir, and 1 of 2 homes with dogs had measurable Can f 1. Reservoirs kept in sealed plastic bags had no detectable allergen. CONCLUSIONS: Indoor allergens can be found in the nebulizer equipment of children with asthma, with the potential for adverse consequences. Storing nebulizer sets in sealed plastic bags may prevent contamination.     

Standardization of inhalation provocation tests: Influence of nebulizer output,particle size,and method of inhalation

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 μm aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 μm AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV₁) by 20% (PC₂₀). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC₂₀. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.     

Measurement of PC20 histamine with the use of two different nebulizers and measurement of FEV1 and PEF

Histamine challenge was performed in 19 patients using two nebulizers (PARI and Wright) and FEV1 and PEF were measured to determine PC20 histamine. FEV1 and PEF gave identical PC20 histamine values. The PARI nebulizer gave PC20 histamine values that were 2.5 doubling concentrations lower than the Wright nebulizer. The reproducibility of histamine challenge with the PARI nebulizer was studied in 15 patients and the results suggested that the challenge was reproducible within one doubling concentration of histamine.     

The influence of cooling rate on the accuracy of normoxic polymer gel dosimeters

Polymer gel dosimeters offer a wide range of applications in the three-dimensional verification of complex radiation dose distributions such as in intensity-modulated radiotherapy (IMRT). With the release of polymer gel dosimeters that can be fabricated in normal atmospheric ('normoxic') conditions, the gel manufacturing process has been significantly simplified. Gel dosimeters are calibrated by use of a series of calibration vials irradiated with known doses or by use of a calibration phantom with a known dose distribution. The overall accuracy of the polymer gel dosimeters is determined by different dosimetric properties. In this study, we show the influence of the temperature history during storage of the gel dosimeter on the dose response curve for two gel dosimeters using the monomers acrylamide/N,N'-methylene-bis-acrylamide (nPAG) and methacrylic acid (nMAG) respectively and bis[tetrakis(hydroxymethyl)phosphonium]sulphate (THP) as antioxidant in both gel dosimeters. This study reveals that differences in temperature history after fabrication of normoxic polymer gel dosimeters may compromise the dosimetric accuracy. It was found that the acrylamide based gel dosimeter (nPAG) is less dependent on the post-manufacture temperature history than the methacrylic acid based gel dosimeter (nMAG). The importance of an equal temperature history for the gel dosimeter and calibration vials is emphasized by this study. A reproducibility study has also been performed on the nPAG gel dosimeter when additional efforts are made to control the temperature changes upon cooling.     

Bronchial challenge: a small reservoir for the Wright jet nebulizer

A small reservoir for the Wright jet nebulizer was constructed and tested with regard to output and particle size characteristics. The Wright nebulizer has found widespread use for bronchial challenge testing. The new small reservoir delivers an aerosol with a size distribution comparable to that delivered from the standard reservoir. Comparable results were obtained when bronchial challenge with either the small or the standard reservoir was performed in 11 patients. The cost for bronchoconstrictor can be reduced by 50-80% by reducing the volume necessary for challenge. It is documented that calibration of the actual set-up is necessary to control the output from a nebulizer, since the output is, not linearly correlated to the flow.     

Time course of drug concentrations in nebulizers and nebulized solutions]

The drug concentrations in nebulizers and nebulized solutions generated by the ultrasonic nebulizer OMRON NE-U10B and the jet nebulizer INSPIRON NEBULIZER 002305 were examined. With the ultrasonic nebulizer, increases in the concentrations of saline, DSCG and isoproterenol in the nebulizer were observed; the concentrations of those in the nebulized solutions also increased. The increase was most dramatic just before the solution was emptied. No degradations of DSCG or isoproterenol were detected in the nebulized solutions, indicating that these drugs are stable against ultrasonic nebulization. An increase in the drug concentrations in the jet nebulizer was also observed. The concentrations of the nebulized solutions also increased, but the concentrations in the nebulized solution were lower than those in the nebulizer at any time. On inhalation therapy, it is important to give consideration to these concentration changes. The nebulizer should not, for example, be refilled with a new drug solution.