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PubMed1983

Comparison of nebulized salbutamol with nebulized ipratropium bromide in acute asthma.

Twelve patients admitted to hospital with an acute attack of bronchial asthma were studied. Six were treated initially with nebulized salbutamol solution by inhalation and 1 hour later by ipratropium bromide given in the same way; the other six were treated first with ipratropium bromide and 1 hour later by salbutamol. Ipratropium bromide was shown to be as effective as salbutamol when used as the initial bronchodilator but salbutamol produced significant further improvement when given 1 hour after ipratropium.

Acute Disease↗
PubMed1996

[Pulmonary deposition of colistin aerosols in cystic fibrosis. Comparison of an ultrasonic nebulizer and a pneumatic nebulizer].

The objective of this study was to quantify the deposition in the lung of a Colistine aerosol generated using a pneumatic nebuliser (Pari LL(R) equipped with a Pari Master, Pari, Germany) and to compare this with the results obtained with an ultrasonic nebuliser (DP100, DP Medical, France) in four subjects suffering from cystic fibrosis being colonised with Pseudomonas aeruginosa. To quantify the pulmonary deposition of the aerosols we have used an indirect isotopic method which consists in assimilating the kinetics of the molecules studied with a serum albumin tagged with Technetium 99m (Tc99mm) and added to a preparation of Colistine. We have previously verified that the addition of a radioactive tracer does not change the normal distribution or dynamics of the medication within the aerosol and the radioactive counter linked to the tracer reflects the mass of the medicament. The pulmonary deposition was expressed as a percentage of the nebuliser dose. A regional analysis of the deposition (central, peripheral, superior and inferior) was carried out and in central deposition compared to the periphery (C/P) and superior compared to inferior (S/I) were calculated. With the DP100 nebuliser the pulmonary deposition of the aerosol was very reproducible from one patient to another, varying only between 9.5 to 14 percent of the nebuliser dose. With the Pari LL the fraction deposited varied more from one patient to another from 5.6 to 27% of the nebuliser dose. In three of four patients, the pulmonary deposition was superior or equal to that obtained with the ultrasonic nebuliser. The patients whose pulmonary deposition was inferior, using the pneumatic nebuliser, was the youngest in the group and co-ordinately poorly the triggering of the nebuliser with the beginning of inspiration. With the two nebulisers, the pulmonary deposition of Colisitine was very heterogeneous throughout the pulmonary parenchyma. The mean of the ratio C/P and S/I obtained in all four patients was identical (1.35 an 0.86 respectively), indicating a deposition of the aerosol which was predominantly central and inferior but was distributed equally in the peripheral parts of the lung. Pneumatic nebulisers offer a reliable alternative notably for domiciliary treatment for Colistine aerosols in patients suffering from cystic fibrosis. In younger patients who have not yet acquired good motor co-ordination, nebulisers which function continuously or are triggered by inspiration seem to be the preferred choice.

Administration, Inhalation↗
PubMedDate not supplied

A comparison between nebulized terbutaline, nebulized corticosteroid and systemic corticosteroid for acute wheezing in children up to 18 months of age.

One hundred and twenty-three children, aged 1.5-18 months, participated in a randomized, double-blind, placebo-controlled multicentre study comparing different treatments for acute wheezing. The children were admitted to one of five participating paediatric departments. They were randomized into one of four treatment groups: (1) soluble prednisolone+placebo inhalation+terbutaline inhalation; (2) soluble placebo+budesonide inhalation+terbutaline inhalation; (3) soluble placebo+placebo inhalation+terbutaline inhalation; and (4) soluble placebo+placebo inhalation+normal saline inhalation. On admission, measurements of temperatures, respiratory rate and heart rate were made and once-a-day thereafter. Wheezing, accessory respiratory muscle use, prolonged expiration and general condition were scored on a scale ranging from 0 to 3. Significantly more treatment failures were recorded in the placebo group. Children from both steroid groups were discharged earlier than children from the terbutaline group. Compared with children from the placebo group, children from all three treatment groups had a greater improvement in symptom score, but this was significant for the budesonide group only.

Acute Disease↗
PubMed1997

The clinical efficacy of combination nebulized anticholinergic and adrenergic bronchodilators vs nebulized adrenergic bronchodilator alone in acute asthma. Canadian Combivent Study Group.

The role of ipratropium bromide as adjunct therapy to beta-agonists in acute asthma is uncertain. We therefore decided to compare the use of 3 mg of salbutamol sulfate alone vs 3 mg salbutamol sulfate with 0.5 mg ipratropium bromide in patients with acute asthma. Patients presenting with acute asthma and an FEV1 less than 70% predicted were randomized to a single combination treatment vs salbutamol alone. All patients received supplemental oxygen and methylpred-nisolone, 125 mg, IV. Baseline measurements were repeated at 45 and 90 min and these included spirometry, oximetry, and vital signs. A total of 952 patients were screened of whom 342 patients were deemed eligible and were randomized in two groups of 171 patients. The mean (SE) age was 30 years (0.9) vs 29 years (0.7), women, 103 (60.2%) vs 110 (64%), 81 (47.4%) never-smoked vs 83 (48.5%), and duration of asthma in years 16.0 (0.8) vs 16.6 (0.8) were no different in the combination vs salbutamol alone group, respectively. Likewise, there was no significant difference in asthma therapy received in the 24 h prior to presentation; most notably, 151 (88.3%) vs 153 (89.5%) received inhaled beta-agonists in that period. Baseline FEV1 was 1.62 L (0.05 L) vs 1.53 L (0.03 L), and median time to treatment being received was no different between both groups. Both treatment arms improved significantly. The increase in FEV1 in the combination group was 0.6I L (0.04 L) and in the salbutamol alone group was 0.52 L (0.04 L) at 90 min. There was a trend toward greater bronchodilation in the combination group, but this did not reach statistical significance. Fewer hospitalizations, 5.9% vs 11.2%, occurred in the combination group, but this did not reach statistical significance. In conclusion, this large multicenter study failed to show a significantly better response to a combination of salbutamol and ipratropium bromide vs salbutamol alone.

Adrenergic beta-Agonists↗
PubMed2002

Design principles of liquid nebulization devices currently in use.

Liquid nebulization is a common method of medical aerosol generation. Nebulizers are of 2 types: jet (or pneumatic) small-volume nebulizer, and ultrasonic nebulizer. Jet nebulizers are based on the venturi principle, whereas ultrasonic nebulizers use the converse piezoelectric effect to convert alternating current to high-frequency acoustic energy. Important variables for both types of nebulizer are treatment time required, particle size produced, and aerosol drug output. There are several advantages to jet nebulization, including that effective use requires only simple, tidal breathing, and that dose modification and dose compounding are possible. Disadvantages include the length of treatment time and equipment size. Design modifications to the constant-output nebulizer have resulted in breath-enhanced, open-vent nebulizers such as the Pari LC Plus and the dosimetric AeroEclipse. Ultrasonic nebulizers generally have a higher output rate than jet nebulizers, but a larger average particle size. Ultrasonic nebulizers can also substantially increase reservoir solution temperature, the opposite of jet nebulizer cooling. Drug concentration in the reservoir does not increase with ultrasonic nebulization, as it does with jet nebulization. Ultrasonic nebulizers have the same advantages as jet nebulizers. Ultrasonic nebulizers are more expensive and fragile than jet nebulizers, may cause drug degradation, and do not nebulize suspensions well. Neither type of nebulizer meets the criteria for an ideal inhaler: efficient and quick dose delivery with reproducibility, cost-effectiveness, and no ambient contamination by lost aerosol.

Administration, Inhalation↗
PubMed2000

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, Rhône 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 Rhône 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 Rhône 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%, Rhône 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 Rhône 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.

Aerosols↗
PubMed2000

A review of the technical aspects of drug nebulization.

Nebulizers are widely used for the inhalation of drug solutions in a variety of respiratory diseases. The efficacy of nebulizer therapy is influenced by a great number of factors, including the design of the device and the characteristics of the drug solution. Incorrect cleaning, maintenance and disinfection procedures may change the nebulizer performance in time, whereas patient factors can influence the lung deposition of the generated aerosol. In this review the technical aspects of nebulization of drug solutions will be discussed. Two main parameters are generally used to evaluate the performance of nebulizers: the droplet size distribution of the aerosol and the drug output rate. The droplet size distribution and the drug output rate are basically determined by the design and user conditions of the nebulizer. A higher gas flow of the compressor in a jet nebulizer or a higher vibration frequency of the piezo electric crystal in an ultrasonic nebulizer, decreases the droplet size. The choice of the type of nebulizer for nebulization of a certain drug solution may initially be based on laboratory evaluation. The major part of the mass or volume distribution should preferably correspond with aerodynamic particle diameters in the range of 1 to 5 micrometer. The intended drug output must be realized within a reasonable nebulization time (less than 30 min). From the drug output only a minor fraction will be deposited in the lung. The relation between in vitro and in vivo deposition is only partly understood and to date it has not been possible to predict drug delivery only from in vitro studies on nebulizers. Therefore, studies in patients should be performed before a drug solution for nebulization can be recommended for clinical practice. The mechanical properties of nebulizers are likely to change during use. An average utilization time of nebulizers is not available. Therefore, the performance of nebulizers should be checked periodically. Patient compliance in nebulizer therapy is relatively low. This is partly due to the fact that, at present, drug solutions for nebulizers cannot be administered efficiently within a short period of time. More efficient systems should be developed. If possible, nebulizers should be substituted to more efficient systems, e.g. dry powder inhalers or metered dose inhalers.

Administration, Inhalation↗
PubMed2000

In vitro comparison of the circulaire and AeroTee to a traditional nebulizer T-piece with corrugated tubing.

BACKGROUND: Nebulizers are a popular means of delivering aerosolized medication, primarily albuterol, to the bronchial airways of patients, and there has been extensive research done on numerous nebulizers used with nebulizer T-pieces and corrugated tubing. Very little research has been performed on other types of nebulizer delivery systems and there is no substantial information on how effective various nebulizer delivery systems are in terms of the quantity and particle size of aerosolized medication delivered to the patient. In this study the Circulaire and the AeroTee, two devices that rely on bags to store aerosol during patient exhalation, are evaluated and compared to the conventional nebulizer T-piece with corrugated tubing. METHODS: Three each of the nebulizer T-piece with corrugated tubing, the Circulaire, and the AeroTee were sampled using 3 Vixone nebulizers. Each one of the 3 nebulizer delivery systems used the same 3 Vixone nebulizers. Each nebulizer delivery system was evaluated by connecting a constant-flow vacuum and compressed gas source cycled to simulate patient breathing at a respiratory rate of 14 breaths/min and an inspiration-expiration ratio of 1:2. Medication delivered was determined by sampling a portion of the simulated patient's flow onto a membrane filter and calculating the total medication received by the patient. Particle size was determined by sampling with a cascade impactor under ambient conditions. RESULTS: The Circulaire delivered significantly less medication than the nebulizer T-piece with corrugated tubing (p < 0.001), whereas the AeroTee delivered substantially more medication than the nebulizer T-piece with corrugated tubing (p < 0.001). The particle size delivered by the Circulaire was significantly smaller than that of the nebulizer T-piece with corrugated tubing (p < 0.001), whereas the AeroTee delivered particle size equivalent to a nebulizer T-piece with corrugated tubing (p = 0.82). CONCLUSION: There are clinically important differences between nebulizer delivery systems. When evaluating the optimum means for delivering aerosolized medication, equal consideration should be given to both the brand of nebulizer and the nebulizer delivery system.

Administration, Inhalation↗
PubMed2006

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↗
PubMed2006

Formulations generated from ethanol-based proliposomes for delivery via medical nebulizers.

Multilamellar and oligolamellar liposomes were produced from ethanol-based soya phosphatidyl-choline proliposome formulations by addition of isotonic sodium chloride or sucrose solutions. The resultant liposomes entrapped up to 62% of available salbutamol sulfate compared with only 1.23% entrapped by conventionally prepared liposomes. Formulations were aerosolized using an air-jet nebulizer (Pari LC Plus) or a vibrating-mesh nebulizer (Aeroneb Pro small mesh, Aeroneb Pro large mesh, or Omron NE U22). All vibrating-mesh nebulizers produced aerosol droplets having larger volume median diameter (VMD) and narrower size distribution than the air-jet nebulizer. The choice of liposome dispersion medium had little effect on the performance of the Pari nebulizer. However, for the Aeroneb Pro small mesh and Omron NE U22, the use of sucrose solution tended to increase droplet VMD, and reduce aerosol mass and phospholipid outputs from the nebulizers. For the Aeroneb Pro large mesh, sucrose solution increased the VMD of nebulized droplets, increased phospholipid output and produced no effect on aerosol mass output. The Omron NE U22 nebulizer produced the highest mass output (approx. 100%) regardless of formulation, and the delivery rates were much higher for the NaCl-dispersed liposomes compared with sucrose-dispersed formulation. Nebulization produced considerable loss of entrapped drug from liposomes and this was accompanied by vesicle size reduction. Drug loss tended to be less for the vibrating-mesh nebulizers than the jet nebulizer. The large aperture size mesh (8 mum) Aeroneb Pro nebulizer increased the proportion of entrapped drug delivered to the lower stage of a twin impinger. This study has demonstrated that liposomes generated from proliposome formulations can be aerosolized in small droplets using air-jet or vibrating-mesh nebulizers. In contrast to the jet nebulizer, the performance of the vibrating-mesh nebulizers was greatly dependent on formulation. The high phospholipid output produced by the nebulizers employed suggests that both air-jet and vibrating-mesh nebulization may provide the potential of delivering liposome-entrapped or solubilized hydrophobic drugs to the airways.

Aerosols↗