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PubMed1987

Nebulization and selective deposition of LTD4 in human lungs.

The process of nebulization and deposition of LTD4 was studied in detail. The concentration of LTD4 in a saline solution decreased by approximately 90% after 2 min of nebulization in a DeVilbiss 35B ultrasonic nebulizer. This decrease was prevented by diluting LTD4 in a phosphate buffer, pH 7.4. Nebulization of tritiated LTD4 in this phosphate buffer did not cause any appreciable deterioration of the leukotriene, as demonstrated by an unchanged ratio between radioactivity and LTD4 concentration in the test solution before and after nebulization as well as in the condensed aerosol. The aerosol generated by the DeVilbiss 35B ultrasonic nebulizer was shown to generate particles with a mass median diameter of 1.3 microns (dry particle size). Interposition of a settling bag reduced the amount of large particles, reducing the mass median diameter to 0.84 microns (dry particle size). Nine healthy volunteers were challenged on separate days with 40 nmol LTD4 or 100 mumol histamine, and the changes in FEV1 and partial flow volume curves initiated at 50% of vital capacity (Vmax30) were measured. A relative diffuse deposition pattern was ensured by inhalation via a settling bag. These results were compared to challenges with a relatively central deposition pattern as ensured by inhalation directly from the nebulizer with brisk inhalation maneuvers. The diffuse deposition pattern caused minimal changes in FEV1 but pronounced effect in Vmax30. The effects of LTD4 and histamine on FEV1 and Vmax30 changed in parallel when the deposition of the mediators was changed to a more central pattern. This indicates that the two mediators do not differ with respect to any selective effects on different parts of the airways.

Adult↗

PubMed2006

Microbial colonization of nebulizers used by asthmatic children.

BACKGROUND: The aim of the present study was to determine the microbial colonization of nebulizers used at home by asthmatic children, and to investigate their parents' cleaning and maintenance routines. METHODS: The nebulizer equipment used at home by 39 asthmatic children was examined. Swabs taken from the inner surface of the reservoir cups, face masks and filters were cultured. Results were recorded as mean number of colony-forming units per cultured surface. Parents were interviewed regarding their cleaning and disinfection routines. RESULTS: Twenty-six reservoir cups (66.7%), 24 face masks (61.5%), and 18 filters (78.3%) were found to be contaminated. Pseudomonas aeruginosa was isolated from 17 reservoir cups (43.6%) and 12 face masks (30.8%), and Staphylococcus aureus from two face masks (5.1%). None of the parents knew that the nebulizer has a filter and that it requires periodic cleaning or changing; only eight of the parents (20.5%) received maintenance instructions from the medical staff, and only 19 (48.7%) cleaned the nebulizer equipment after use. CONCLUSION: Home nebulizers are frequently colonized with microorganisms. As recommended, nebulizers should be washed after each use and air-blown dry. Nebulizer maintenance should be emphasized in educational programs for managing asthma.

Asthma↗

PubMed1997

Ultrasonic nebulization for efficient delivery of surfactant in a model of acute lung injury. Impact on gas exchange.

We investigated the effect of ultrasonic nebulization versus instillation of exogenous surfactant on gas exchange abnormalities provoked by detergent inhalation in perfused rabbit lungs. Ventilation-perfusion (VA/Q) distribution was assessed by the multiple inert gas elimination technique. For nebulization of natural bovine surfactant (Alveofact), an ultrasonic device was placed in line with the inspiratory gas flow tubing, manufacturing particles with a mass median aerodynamic diameter of approximately 4.5 microM and high aerosol concentration. In vitro studies demonstrated biochemical and biophysical integrity of postnebulization surfactant. Lung aerosol deposition was monitored by a laser-photometric technique. In lungs with sham inhalation of saline, tracheal instillation of surfactant (approximately 11 mg/kg body weight, infused over 50 min) provoked substantial VA/Q mismatch and limited shunt flow, whereas lung surfactant deposition by ultrasonic nebulization (approximately 7 to 9 mg/kg body weight; nebulization time, 50 min) did not interfere with physiologic gas exchange. Tween 20 inhalation provoked severe VA/Q mismatch with predominant shunt-flow (approximately 21%). This was not reversed by "rescue" application of instilled surfactant, but largely reversed by nebulized surfactant (shunt reduced to 5.5%; p < 0.01). Analysis of postaerosol lavage fluid demonstrated partial reconstitution of surface activity by nebulized surfactant. We conclude that ultrasonic nebulization may be employed for efficient delivery of functionally intact natural surfactant to the distal bronchoalveolar space. This approach effects rapid improvement of gas exchange in a model of acute homogeneous lung injury.

Aerosols↗

PubMed1992

Nebulizer function during mechanical ventilation.

In the setting of mechanical ventilation, recent studies have cast doubt on the ability of nebulizer systems to deliver adequate amounts of medication. We therefore studied ventilator-related and nebulizer-related factors that could potentially affect the amount of aerosol inhaled by an intubated subject. Utilizing two separate protocols, we used a bench model of a ventilator circuit, radiolabeled (technetium pertechnetate, 99mTc) saline droplets and a filter technique to measure the percentage of radioaerosol delivered. First, we compared four commercially available jet nebulizers and found that there were significant differences in rate of aerosol production between systems, ranging from 3 to 37%. Delivered aerosol was measured at different ventilator settings, and it was found that the duty cycle can potentially influence output by sevenfold. Some nebulizers were also sensitive to changes in the initial volume of solution placed in the nebulizer. The inclusion of a humidification device significantly reduced output by a mean of 41 +/- 3.5%, but it did not affect particle distribution. Endotracheal tube diameter was not an important variable. Then, with the effects of the above variables established, a separate series of experiments was performed to test whether the use of different radiolabeling compounds can confound the measurement of inhaled drugs. Two nebulizers (AeroTech II and Twin Jet) and pentamidine as the test drug were studied with fixed ventilator settings, treatment time, endotracheal tube size, and volume fill. No humidification was used. The nebulizer solution was labeled with 99mTc, which was bound to either human serum albumin (HSA) or sulfur colloid (SC).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

PubMed1993

Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation.

Ultrasonic nebulizers may be particularly suitable for the administration of therapeutic aerosols to patients undergoing mechanical ventilation, but the amount of aerosol that reaches the patients' respiratory tract during ultrasonic nebulization has not been adequately studied. The delivery through an endotracheal tube of nebulized aerosols labeled with 99mTechnetium human serum albumin was therefore measured for five commercially available ultrasonic nebulizers using an in vitro model representing mechanical ventilation of an adult patient. Delivery of aerosol through the endotracheal tube ranged from 3.1 +/- 0.3% for Samsonic to 10.1 +/- 2.0% for Portasonic using 3 ml nebulizer solution. Increasing the volume of nebulizer solution to 18 ml (not possible for the Portasonic) increased delivery to 11.5 +/- 2.0 for the DP 100, 8.7 +/- 3.1 for Ultraneb, and 15.9 +/- 1.8% for Samsonic. Addition of a 600 ml aerosol storage chamber to the ventilator circuit increased delivery for the Samsonic (18 ml solution) to 22.3 +/- 5.0%. Aerosol delivery was also increased by reducing the respiratory rate and minute volume and by increasing the inspiratory time settings on the ventilator. These results confirm the potential value of ultrasonic nebulizers during mechanical ventilation and indicate that clinical trials in ventilated patients are warranted.

Adult↗

PubMed1995

Actual pentamidine dose delivered by Respigard II nebulizer.

The Respigard II nebulizer system is the approved method to deliver pentamidine aerosols in the USA. Although continuous operation of the nebulizer until dryness is a designated regimen, the actual pentamidine dose delivered under the operating condition has not been thoroughly studied. Pentamidine solutions (300 mg in 6 mL water) were nebulized continuously with the Respigard II nebulizer system until dryness (40 min operation). Aerosols were delivered to the lower airways via an oropharyngeal model and sampled on a filter with a standard breathing mode of 20 breaths.min-1 frequency and 750 mL tidal volume. Intermediate samples were also obtained for the initial 20 min delivery. The pentamidine dose delivered to the mouth was 1.6% of the dose placed in the nebulizer. Of the dose delivered to the mouth, 92% was delivered during the initial 20 min period. Aerosol loss in the oropharyngeal model was 15% of the dose delivered to the mouth or 0.24% of the dose initially placed in the nebulizer. Pentamidine dose delivered to the lower airways was a very small fraction of the initial dose in the nebulizer. A partial delivery for the initial 20 min was nearly comparable to complete delivery.

Humans↗

PubMed1999

Nebulization of sodium nitroprusside in lung-lavaged newborn piglets.

The aim of the present study was to test the hypothesis that nebulization of the nitric oxide donor sodium nitroprusside may selectively reduce pulmonary vascular resistance and improve oxygenation in lung-lavaged newborn piglets. Thirteen anesthetized piglets (1-3 d old) were subjected to repeated lung lavages and then randomly assigned to one of the following two groups: 1) an SNP group, which received SNP nebulization, and 2) a saline group, which received saline nebulization. Pulmonary arterial pressure and pulmonary vascular resistance increased significantly after lung lavage, whereas cardiac output decreased significantly in both groups. After SNP nebulization, pulmonary arterial pressure decreased from 32+/-1 to 17+/-1 mm Hg (p < 0.01) and PVR decreased from 255+/-20 to 172+/-15 mm Hg L(-1) min(-1) kg(-1) (p < 0.01). The arterial tension of oxygen concomitantly increased from 9.4+/-4.0 to 17.0+/-3.0 kPa (p < 0.01), and the arterial/alveolar ratio of oxygen tension increased from 0.11+/-0.01 to 0.22+/-0.03 (p < 0.01). Systemic hemodynamics were not modified significantly during nebulization of SNP. On the other hand, all variables were stable during nebulization of saline. These data suggest that SNP nebulization produces a selective pulmonary vasodilatation and improves oxygenation in lung-lavaged newborn piglets.

Acid-Base Equilibrium↗

PubMed2006

Microbial contamination of nebulization solution and its measures.

We evaluated the microbial contamination of nebulization solutions in medication cups from a total of 76 ultrasonic nebulizers in use in 10 hospitals. In addition, an interview survey was given to nurses to evaluate the disinfection methods of these ultrasonic nebulizers. Of a total of 76 nebulization solution samples, 11 (14.5%) were contaminated with 10-10(2) colony-forming units (CFU)/ml and 9 (11.8%) with 10(3)-10(5) CFU/ml. The major contaminants were glucose non-fermentative bacilli such as Burkholderia cepacia, CDC gr.IV C-2, and Sphingomonas paucimobilis. Comparison of microbial contamination between the frequencies of disinfection showed a significantly lower number of contaminated samples when the cups were disinfected once daily than when disinfected once at intervals of 2-7 d (p=0.00037). In addition, comparison between the presence and absence of preservatives contained in the nebulization solution showed a significantly lower number of contaminated samples in the presence, rather than in the absence, of preservatives (p=0.00001). These results show that disinfection of ultrasonic nebulizers at 24-h intervals is desirable. In particular, when nebulization solutions not containing preservatives are used, disinfection at 24-h intervals is indispensable.

Bacteria↗

PubMed2001

Nebulizer choice for inhaled colistin treatment in cystic fibrosis.

STUDY OBJECTIVES: To develop practical ways of nebulizing colistin by determining the rate of drug output, total drug output, and particle-size distribution of two commercially available jet nebulizers, the disposable Hudson 1730 Updraft II (Hudson Respiratory Care; Temecula, CA) and the reusable Pari LC Star breath-enhanced nebulizer (Pari Respiratory Equipment; Midlothian, VA). METHODS: The nebulizers contained colistin, 75 mg, in 4 mL of isotonic solution. Particle-size distribution was measured by helium-neon laser diffraction, allowing calculation of the respirable fraction (RF), the mass of aerosol comprised of droplets < 5 microm. RESULTS: The mean (95% confidence interval [CI]) total rate of output of the Updraft II was 2.6 mg/min (2.0, 3.1; n = 4) with 1.3 mg/min (1.0, 1.5) mg/min within the RF. The rate of output of the LC Star increased in a quadratic relationship to the inspiratory flow, delivering 1.8 mg/min (0.7, 2.0; n = 4) with 1.4 mg/min (1.3, 1.6) within the RF, and 6.2 mg/min (5.6, 6.8) with 5.3 mg/min (4.8, 5.7) within the RF, at 0 L/min and 20 L/min inspiratory flows, respectively. Efficiency, as the rate of expected pulmonary deposition divided by rate of total output, was then calculated. The LC Star estimated 56% (51, 61) efficiency, with pulmonary delivery of 29% (26, 32) of the charge of the nebulizer, compared to the Updraft II at 22% (22, 23) efficiency and expected pulmonary deposition of 10% (10, 10) of the dose. CONCLUSIONS: Colistin can be successfully nebulized with both nebulizers tested. This study provides an estimate of in vivo efficiency and expected pulmonary deposition that may be used in future trials.

Adolescent↗

PubMed1988

Comparison of beta-adrenergic agents delivered by nebulizer vs metered dose inhaler with InspirEase in hospitalized asthmatic patients.

The present study was undertaken to determine if beta-agonists delivered by nebulizer provide better clinical responses than MDI therapy in status asthmaticus. We divided 28 hospitalized asthmatic patients into three groups. Group 1 received albuterol by MDI with InspirEase. Group 2 received nebulized albuterol. Group 3 received nebulized metaproterenol. Both nebulizer regimens resulted in significant improvements in both FVC and FEV1 by 30 min after initial hospital beta-agonist treatment. No significant improvement was noted in initial spirometry in the MDI with InspirEase group. In spite of the superiority of nebulizer therapy in the initial phase of hospitalization, the daily rates of spirometric improvement and duration of hospitalization were not significantly different among the three groups. Our results indicate that nebulizer therapy provides superior spirometric improvement in the initial phase of status asthmaticus. However, both MDI and nebulizer regimens provided similar rates of spirometric improvement and duration of hospitalization.

Adult↗

PubMed1989

Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma. Efficacy and pulmonary deposition.

Bronchodilator responses to both nebulized albuterol (salbutamol) and ipratropium bromide and aerosol delivery to the tracheobronchial tree have been assessed in eight patients with chronic stable asthma (mean baseline FEV1, 50 percent; reversibility greater than 20 percent). Two commercially available nebulizer systems were used, namely, a Turret nebulizer operated at a compressed gas flow rate of 12 L/min (droplet MMD, 3.3 mu) and an Inspiron nebulizer driven at 6 L/min (MMD, 7.7 mu). Albuterol was given as doses of 250 micrograms, 250 micrograms, 500 micrograms, and 1,000 micrograms (cumulative dose, 2 mg) and ipratropium bromide as doses of 50 micrograms, 50 micrograms, 100 micrograms, and 200 micrograms (cumulative dose, 400 micrograms) at intervals of 35 minutes. For albuterol, bronchodilatation was significantly (p less than 0.05) greater at all dosage levels with the Turret. For ipratropium, bronchodilatation was similar for both nebulizers. Measurements of aerosol deposition using 99mTc-labelled pentetic acid (diethylenetriamine pentaacetic acid; DTPA) showed that 9.1 +/- 1.1 percent and 2.7 +/- 0.2 percent of the dose reached the lungs during nebulization to dryness for Turret and Inspiron, respectively (p less than 0.01); distribution within the lungs was similar for the two aerosols. Selection of nebulizer apparatus can influence delivery of aerosol and subsequent bronchodilator response to albuterol in patients with chronic stable asthma but is less important for aerosol delivery of ipratropium bromide in these patients.

Adult↗

PubMed2002

Nebulized morphine as a treatment for dyspnea in a child with cystic fibrosis.

OBJECTIVE: To shed light on nebulized morphine, a new treatment for dyspnea in children with terminal lung disease. METHODS: A clinical case study was conducted on a patient in a tertiary care medical center. RESULTS: Nebulized morphine was administered in incremental doses ranging from 2.5 mg to 12.5 mg in a 10-year-old, 20-kg boy with end-stage cystic fibrosis. Before the nebulized morphine treatments were started, a dose of nebulized lidocaine failed to provide the patient with any relief. After each dose of morphine, the following parameters were recorded: visual analog "dyspnea" scores, vital signs, venous blood gases, and blood levels of morphine. The nebulized morphine was found to have a modest effect on the patient's dyspnea, with no significant differences found between the varying doses. Venous carbon dioxide tension levels increased <4 mm Hg for all doses except 12.5 mg, for which there was a 9-mm Hg increase. Systemic blood levels of morphine were <10 ng/mL at all doses. The nebulized morphine did not cause any significant changes in blood pressure or heart rate for doses <12.5 mg. CONCLUSIONS: Inhaled morphine was associated with a mild, beneficial effect on dyspnea, with minimal differences found between the lowest and highest doses. This "ceiling" effect may be the result of saturation of opioid receptors in the lung, the variable bioavailability of inhaled morphine, or a placebo response. More studies are needed to determine what, if any, the optimum dose of nebulized morphine is for children.

Administration, Inhalation↗

PubMed2002

Standardization issues: in vitro assessment of nebulizer performance.

The delivery of nebulized drugs is poorly controlled and the choice of the most appropriate delivery device is poorly understood, particularly because of off-license prescriptions and a lack of evidence-based medicine. Standardized in vitro methods for measuring nebulizer performance have been adopted in Europe, by the 2001 publication of a European Standard, prEN13544-1. These standardized methods were subsequently incorporated within the European Respiratory Society nebulizer guidelines, which will provide clinicians with useful information to improve nebulizer therapies. Standards for measuring nebulizer performance should be considered in North America and elsewhere. Careful consideration should be given to either adopting the methods embodied in the European Standard or developing the basis for developing that standard further through the International Standards Organization. Either way, confusion among clinicians would be reduced and nebulizer safety and aerosol delivery efficiency increased by standardizing in vitro methods of nebulizer performance assessment.

Administration, Inhalation↗

PubMedDate not supplied

Farnesol for aerosol inhalation: nebulization and activity against human lung cancer cells.

PURPOSE: A nebulized aerosol formulation of the anti-cancer agent farnesol is developed and shown to induce cell death of human lung cancer cells in vitro. METHODS: A nebulized farnesol formulation containing polysorbate 80 (Tween 80) is developed. The measurements of the aerosol properties during nebulization were used as input for a mathematical model of airway surface liquid in the lung of an average adult, to estimate the airway surface liquid drug concentration of the deposited farnesol. Cytotoxicity of the formulations was measured in vitro on non-small cell lung cancer cells (H460 and A549). RESULTS: As much as 100% of lung cancer cytotoxicity can be achieved by using Pari LC Star and LC Plus nebulizers. The estimated airway surface liquid concentrations of the deposited farnesol reveal that the IC50 of the nebulized farnesol can be achieved over the entire tracheobronchial region, using the above Pari nebulizers with a volume fill of 5 ml. CONCLUSIONS: Drug concentrations higher than IC50 in the airway surface liquid are predicted with our methods, suggesting in vivo trials of a formulation may be warranted with these particular nebulizers.

Administration, Inhalation↗

PubMed1986

A standard method of intermittent inhaled therapy via a jet nebulizer.

Current methods of inhaled therapy using gas-propelled nebulizers lack standardization. The frequent use of nebulized therapy in a continuous flow may be the major reason for the inconsistency of the actual fraction of nebulized drug delivered to the patient. In an effort to achieve consistency in the amount of drug delivered to the patient, we evaluated an intermittent system of nebulized therapy, using a fingertip controlled nebulizer, in 18 adolescent asthmatics. This mode of delivery was found to be highly efficient, providing a nebulized fraction of more than 70% of the initial volumes used (0.75 to 2.6 mL). Initial volumes of 0.9 mL and above were equally efficacious, indicating no further benefit of using higher volumes. Nebulized fractions were found to be highly consistent from one patient to another (+/- 1 SD of 14.1%). We conclude that control of the actual dose delivered to the patient can be best achieved through an intermittent mode of delivery.

Adolescent↗

PubMedDate not supplied

Effects of nebulized terbutaline on oxygen saturation in acute asthmatic children.

To evaluate the paradoxical effect of oxygen desaturation following beta-2 bronchodilator nebulization treatment in acute asthmatic children, a total of 47 patients, aged between 1.8 and 14 years, 27 males and 20 females, were studied. Twenty ml of nebulized normal saline (NS), followed by 10 mg (4 ml) of terbutaline sulphate solution (TSS) in 20 ml NS, were delivered by an ultrasonic nebulizer in 10 min to each patient through a connecting air tube placed in front of the nose and mouth. Oxygen saturation (SaO2) and pulse rate were monitored, using a pulse oximeter, before study and every two minutes until the end of the study. The clinical severity score and peak expiratory flow rate (PEFR) were checked before the study, at the end of inhalation of NS, and at the end of inhalation of TSS. SaO2 was increased both after nebulized NS and TSS when compared with the pre-study data (p < 0.05 and p < 0.0001, respectively). Twenty two cases (47%) during NS and 12 cases (25%) during TSS nebulization had SaO2 below the pre-study level. The mean decrease of SaO2 for the former was 1.62 +/- 0.95% (range: 1.00% to 4.26%), and 1.64 +/- 0.83% (range: 1.02% to 3.13%) for the latter (p > 0.9). No SaO2 decrease after nebulized TSS was observed in any of the seven severe asthmatic children with a prestudy SaO2 < or = 90%. The clinical severity score and PEFR were also significantly improved both after nebulized NS and TSS (p < 0.0001 and p < 0.001, respectively for NS, and both p < 0.0001 for TSS).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1994

Light and electron microscopic radioautographic study on the incorporation of 3H-thymidine into the lung by means of a new nebulizer.

The aim of this study was to investigate whether the water particles produced by a nebulizer can reach the alveoli of the lung when they are inhaled with the air. For the purpose of demonstrating water particle incorporation into the lung, light and electron microscopic radioautography with tritiated thymidine was employed. Tritiated thymidine was dissolved in distilled water and nebulized to fine water particles with a new type nebulizer named Shinki, then inhaled by mice. The lungs were taken out and processed by either rapid-freezing and freeze-substitution for dry-mounting radioautography or conventional chemical fixation for wet-mounting radioautography. By wet-mounting radioautography, silver grains were observed in the nuclei of a few alveolar type 2 cells and interstitial cells, demonstrating DNA synthesis. By dry-mounting radioautography numerous silver grains were located diffusely in all the epithelial and interstitial cells, demonstrating diffuse localization of soluble radioisotope-labeled compounds. These results show that water particles produced by the Shinki nebulizer can directly reach the alveoli and thus, better therapeutic effect can be acquired with the Shinki nebulizer than with the usual nebulizer. Further, the nebulizer can be used for the radioautographic studies of the lung in demonstrating incorporation of some drugs into alveolar tissues.

Animals↗

PubMed1986

Changes in salbutamol concentration in the reservoir solution of a jet nebulizer.

An increase in concentration of salt in the reservoir solution of jet nebulizers driven by dry compressed gas has been observed but changes in salbutamol concentration have not been investigated; therefore: Concentration changes were observed following 10 minutes nebulization for two driving sources and starting volumes. Using an electric compressor, the time courses of changes in drug concentration and output were observed for a 5 mg dose of salbutamol in 2 and 4 ml starting volumes. Changes in drug concentration were smaller for a 4 ml starting volume and for compressor driven nebulizers. Salbutamol concentration increased with the length of nebulization and the rate of increase was inversely related to starting volume. There was poor agreement between fluid and drug output for the 2 ml starting volume and drug output did not increase significantly when nebulization exceeded 4 minutes. For the 4 ml fill there was closer agreement between fluid and drug output and drug output exceeded that for the 2 ml fill after 10 minutes. In conclusion, fluid output alone is an inadequate measure of drug output and changes in drug concentration cannot be overlooked when assessing nebulizers for nebulizer therapy.

Aerosols↗