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Chemical breakdown of technetium-99m DTPA during nebulization.

Aerosols of 99mTc diethylenetriaminepentaacetic acid ([99mTc]DTPA) used for measuring lung permeability and lung ventilation require a radioaerosol delivery system to produce an aerosol with reproducible size and radiochemical purity. To test how well nebulizers meet this requirement, radiochemical purity of aerosols produced with a jet and an ultrasonic nebulizer was evaluated. The activity median aerodynamic diameter (AMAD) and geometric standard deviation (sigma g) of radioaerosols were 0.46 micron (sigma g = 1.6) for the jet nebulizer and 0.70 micron (sigma g = 1.7) for the ultrasonic nebulizer. Paper and liquid chromatographic assays were obtained on the [99mTc]DTPA aerosol solute produced with each nebulizer. The results of these tests showed major differences in radiochemical purity. Aerosols produced in the jet nebulizer consistently showed greater than 90% of the radioactivity bound to the DTPA ligand whereas aerosols produced in the ultrasonic nebulizer showed less than 10% of the radioactivity bound to DTPA. The results support the need to test radiochemical purity of aerosols before using an aerosol nebulizer for pulmonary imaging and clearance studies.

Aerosols↗

Protective effect of a nebulized beta2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs.

BACKGROUND: It seems inevitable that non-beating-heart donors will be utilized to resolve the shortage of donors for clinical lung transplantation. The control of warm ischemia-reperfusion injury is crucial in manipulating non-beating-heart donors. We hypothesized that nebulization of a beta2-adrenoreceptor agonist, salmeterol xinafoate (SLM), during warm ischemia would increase lung tissue cyclic adenosine monophosphate (cAMP) levels, resulting in lung protection. METHODS: Two studies were conducted. The first investigated the effect of SLM nebulization during ischemia on pulmonary ischemia-reperfusion injury, using an isolated rat lung-perfusion model. The heart-lung block was excised with cannulation of the pulmonary artery and vein, exposed to 55 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. Several parameters were measured during reperfusion. In the second study, to measure changes in lung tissue cAMP levels during warm ischemia with or without SLM nebulization, rat lungs were harvested and exposed to 60 minutes of warm ischemia with ventilation. RESULTS: Salmeterol xinafoate nebulization significantly decreased the pulmonary shunt fraction, airway resistance, and pulmonary vascular resistance. It also inhibited pulmonary edema throughout the reperfusion period. Lung tissue cAMP was effectively maintained by SLM nebulization at the end of reperfusion. Myeloperoxidase activity in the lungs was decreased significantly by SLM nebulization. Lung tissue cAMP levels decreased during the 60 minutes of warm ischemia, but increased with SLM nebulization (p < 0.01). CONCLUSIONS: Our results confirmed that SLM nebulization during warm ischemia maintained lung tissue cAMP levels, resulting in the alleviation of pulmonary warm ischemia-reperfusion injury.

Adenosine Triphosphate↗

Nebulized glucagon in the treatment of bronchospasm in asthmatic patients.

This study sought to determine if nebulized glucagon, a well-known smooth muscle relaxant, is effective in relieving asthmatic bronchospasm. Ten subjects, aged 12 to 26 years, with chronic stable asthma were studied in a pulmonary function laboratory under a randomized double-blind, placebo-controlled, crossover design. Bronchospasm was induced in each subject with progressive doses of nebulized methacholine until forced expiratory volume in 1 second (FEV1) had decreased at least 20% from baseline. Subjects then received either nebulized saline or 2 mg of nebulized glucagon. Spirometry was performed at 5, 15, and 30 minutes after treatment. Subjects then received 2.5 mg of nebulized albuterol and had spirometry 15 and 30 minutes thereafter. Each subject returned for testing with the alternative solution at least 1 week later. Treatment with nebulized glucagon resulted in a 58% +/- 15% improvement in FEV1 15 minutes after treatment compared with 36% +/- 7% after nebulized saline (P < .05). No adverse effects of glucagon treatment occurred. This study suggests that nebulized glucagon reduces methacholine-induced bronchospasm in asthmatic patients.

Administration, Inhalation↗

Spatial mapping of droplet velocity and size for direct and indirect nebulization in plasma spectrometry.

Two novel laser-based imaging techniques centered on particle image velocimetry and optical patternation are used to map and contrast the size and velocity distributions for indirect and direct pneumatic nebulizations in plasma spectrometry. The flow field of droplets is illuminated by two pulses from a thin laser sheet with a known time difference. The scattering of the laser light from droplets is captured by a charge-coupled device (CCD), providing two instantaneous images of the particles. Pointwise cross-correlation of the corresponding images yields a two-dimensional velocity map of the aerosol velocity field. For droplet size distribution studies, the solution is doped with a fluorescent dye and both laser-induced florescence (LIF) and Mie scattering images are captured simultaneously by two CCDs with the same field of view. The ratio of the LIF/Mie images provides relative droplet size information, which is then scaled by a point calibration method via a phase Doppler particle analyzer. Two major findings are realized for three nebulization systems: (1) a direct injection high-efficiency nebulizer (DIHEN); (2) a large-bore DIHEN; and (3) a PFA microflow nebulizer with a PFA Scott-type spray chamber. First, the central region of the aerosol cone from the direct injection nebulizers and the nebulizer-spray chamber arrangement consists of fast (>13 and >8 m/s, respectively) and fine (<10 and <5 microm, respectively) droplets as compared to slow (<4 m/s) and large (>25 microm) droplets in the fringes. Second, the spray chamber acts as a momentum separator, rather than a droplet size selector, as it removes droplets having larger sizes or velocities. The concepts and results presented in this research may be used to develop smart-tunable nebulizers, for example, by using the measured momentum as a feedback control for adjusting the nebulizer, i.e., its operating conditions, its critical dimensions, or both.

Journal Article↗

Effects of nebulized diethylenetetraamine-NONOate in a mouse model of acute Pseudomonas aeruginosa pneumonia.

OBJECTIVE: Endogenous and exogenous nitric oxide (NO) may have important antibacterial effects in patients with pneumonia. NO administration has been limited to the continuous inhalation of gas-phase NO (ie, inhaled NO [iNO]). Intermittent nebulization of NONOates, novel NO donors, may permit the continuous intrapulmonary delivery of NO. Thus, we assessed the effects of nebulized diethylenetetraamine-NONOate (DETA-NO) in a model of acute Pseudomonas aeruginosa pneumonia. DESIGN: Randomized, controlled study. SUBJECTS: Male C57Bl/6 mice. INTERVENTIONS: Pneumonia was induced by intratracheal instillation of P aeruginosa (3 x 10(7) CFU in 50 microL). Pneumonia and sham mice were randomized to receive no treatment, nebulized DETA-NO (12.5 or 125 micromol) at 4 h and 12 h, or continuous iNO for 24 h (10 or 40 ppm) until they were killed at 24 h. MAIN RESULTS: The nebulization of DETA-NO was associated with a marked increase in mean (+/- SEM) exhaled NO levels (after nebulization, 484 +/- 34 parts per billion [ppb]; baseline, 13.4 +/- 0.4 ppb; p < 0.01) and plasma levels of nitrites/nitrates (after nebulization, 73 +/- 28 microM; at baseline, 14 +/- 3 microM; p < 0.05). Nebulized DETA-NO decreased the pulmonary bacterial load in mice with pneumonia by 65 +/- 19% (p < 0.05 vs untreated mice) but had no effect on pulmonary leukocyte infiltration. Although the growth of P aeruginosa colonies in vitro was impaired on exposure to DETA-NO, growth was similarly impaired by exposure to DETA nucleophile/backbone alone. CONCLUSIONS: The nebulization of DETA-NO provides a method for the prolonged intrapulmonary delivery of NO. The antibacterial effect of DETA-NO in vivo and in vitro is due, in large part, to the DETA nucleophile moiety and is independent of NO, suggesting a limited therapeutic role for exogenous NO in pneumonia.

Acute Disease↗

Comparison of the efficacy and safety of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in paediatric patients with moderate to severe exacerbation of asthma.

Nebulization simplifies the administration of effective inhaled medications to young asthmatics who experience hand-to-lung co-ordination problems and inspiratory difficulties associated with metered-dose and dry-powder inhalers, respectively. The objective of this double-blind, double-dummy multicentre, randomized, parallel-group study was to compare the efficacy and safety of corticosteroids given by nebulization or metered-dose inhalation in paediatric patients with exacerbation of asthma. Following a 24-h run-in period, 151 patients, aged 6-16years, with moderate to severe exacerbation of asthma were randomized to one of two treatment groups for 4 weeks: beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. given via a nebulizer (n = 75), or BDP spray 800 microg day(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 76). Superimposable and statistically significant improvements over baseline were noted at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, asthma symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was the morning pulmonary expiratory flow rate (PEFR). In the BDP nebulization group, mean morning PEFR increased statistically significantly from 233.2 +/- 86.31 min(-1) to 322.0 +/- 101.81 min(-1), while in the BDP MDI group the increase was from 222.9 +/- 87.31 min(-1) to 314.9 +/- 96.61 min(-1). Moreover, an additional 4-week treatment period at half doses, completed by 26 patients, demonstrated that improvements were maintained or further enhanced. The two treatments were equally well tolerated. A total of 25 and 26 patients in the BDP nebulization and BDP MDI groups, respectively reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 1,600 microg day(-1) given via a nebulizer and BDP spray 800 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in paediatric patients with moderate to severe asthma exacerbation.

Administration, Inhalation↗

Effectiveness of oral or nebulized dexamethasone for children with mild croup.

OBJECTIVE: To assess the efficacy of oral dexamethasone or nebulized dexamethasone sodium phosphate in children with mild croup. METHODS: Double-blind, placebo-controlled study of 264 children between 6 months and 6 years of age with symptoms of croup for fewer than 48 hours. Patients were excluded if they received racemic epinephrine or corticosteroid treatment. Other exclusion criteria included corticosteroid treatment during the 14 days prior to enrollment or complicating medical condition. Subjects randomly received oral dexamethasone (0.6 mg/kg), nebulized dexamethasone sodium phosphate (160 microg), or placebo. Telephone follow-up was obtained on days 1, 2, 3, 4, and 7. MAIN OUTCOME MEASURES: The primary outcome measure was treatment failure, defined as receiving corticosteroid or racemic epinephrine treatment during the 7 days after enrollment in the study. Secondary outcome measures included seeking additional care and the parental assessments of the patients' condition obtained during follow-up (worse, same, better, or gone). RESULTS: Eighty-five patients received oral dexamethasone, 91 received nebulized dexamethasone, and 88 received placebo. There were 3 treatment failures in the oral dexamethasone-treated group, 12 in the nebulized dexamethasone-treated group, and 10 in the placebo-treated group (P =.05). Ten children in the oral dexamethasone-treated group sought additional care compared with 27 and 29 in the nebulized dexamethasone-treated and placebo-treated groups, respectively (P =.002). Parents of children in the oral dexamethasone-treated group reported greater improvement on day 1 (P<.001) compared with the nebulized dexamethasone-treated and placebo-treated groups. CONCLUSIONS: Children with mild croup who receive oral dexamethasone treatment are less likely to seek subsequent medical care and demonstrate more rapid symptom resolution compared with children who receive nebulized dexamethasone or placebo treatment.

Administration, Inhalation↗

Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department.

OBJECTIVE: To determine if administration of albuterol by a metered-dose inhaler with a spacer device is as efficacious as administration of albuterol by nebulizer to treat wheezing in children aged 2 years and younger. DESIGN: Double-blind, randomized, placebo-controlled clinical trial. SETTING: Pediatric emergency department. PATIENTS: From a convenience sample of wheezing children aged 2 to 24 months, 85 patients were enrolled in the nebulizer group and 83 in the spacer group. INTERVENTIONS: The nebulizer group received a placebo metered-dose inhaler with a spacer followed by nebulized albuterol. The spacer group received albuterol by a metered-dose inhaler with a spacer followed by nebulized isotonic sodium chloride solution. Treatments were given every 20 minutes by a single investigator blinded to group assignment. MAIN OUTCOME MEASURES: The primary outcome was admission rate. Pulmonary Index score and oxygen saturation were measured initially and 10 minutes after each treatment. RESULTS: The nebulizer group had a significantly higher mean (SD) initial Pulmonary Index score compared with the spacer group (7.6 [2.5] vs 6.6 [2.0]; P =.002). With the initial Pulmonary Index score controlled, children in the spacer group were admitted less (5% vs 20%; P =.05). Analyses also revealed an interaction between group and initial Pulmonary Index score; lower admission rates in the spacer group were found primarily in children having a more severe asthma exacerbation. CONCLUSION: Our data suggest that metered-dose inhalers with spacers may be as efficacious as nebulizers for the emergency department treatment of wheezing in children aged 2 years or younger.

Albuterol↗

Randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer vs. jet nebulizer in young children with wheezing.

The jet nebulizer is a common device used for administering aerosol medication in young children. However, compared to a metered dose inhaler-spacer (MDI-spacer), it takes more time and personnel. This study aimed to compare the efficacy of salbutamol aerosol therapy given via these two devices in young wheezing children. A prospective randomized, double-blind, placebo-controlled trial was performed in children up to 5 years old who had acute wheezing and were admitted to the Department of Pediatrics, King Chulalongkorn Memorial Hospital. Patients were randomly divided into two groups. The first group received 2 puffs of placebo via MDI-spacer, followed by 0.15 mg/kg salbutamol respiratory solution via jet nebulizer. The second group received 2 puffs (100 microg/puff) of salbutamol via MDI-spacer, followed by placebo via jet nebulizer. Clinical scores and tidal breathing pulmonary function test were evaluated before and after treatment. Pulmonary function parameters included those derived from flow volume loops (volume to peak tidal expiratory flow over total expiratory volume, V(PTEF)/V(E); time to peak tidal expiratory flow over total expiratory time, T(PTEF)/T(E); and ratio of tidal expiratory flow at 25% remaining expiration to peak expiratory flow, 25/PF), compliance (Crs), and resistance (Rrs) of the respiratory system. The efficacy of both methods was compared by using analysis of covariance. Forty-seven wheezing children were studied (24 received salbutamol via MDI-spacer, and 23 received it via jet nebulizer). There was no statistical difference between the two groups regarding clinical scores and all pulmonary function parameters. However, heart rate was significantly increased after treatment in the jet nebulizer group when compared to those in the MDI-spacer group (P = 0.004). In conclusion, the efficacy of salbutamol aerosol therapy via MDI-spacer compared to jet nebulizer in young wheezing children was not different in terms of clinical score and postbronchodilator pulmonary function parameters. However, salbutamol aerosol therapy via jet nebulizer significantly increased the heart rate when compared to the MDI-spacer.

Aerosols↗

Nebulized therapies for childhood pulmonary hypertension: an in vitro model.

OBJECTIVES: Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol. DESIGN: Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium-neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical-breathing model. RESULTS: Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with (1/4) of particles < or = 5 microm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model. CONCLUSIONS: All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug.

Adolescent↗

Effects of nebulizing and drying gas flow on capillary electrophoresis/mass spectrometry.

This study was focused on examining the influence of gas flow parameters on capillary electrophoresis/mass spectrometry (CE /MS) performance using sheath-liquid CE /MS interfaces. The effects of nebulizing and drying gas velocity and drying gas temperature on CE separation and MS detection sensitivity were systematically determined. Nebulizing gas velocity was observed to be a critical parameter in the optimization of CE /MS method, since it affected both MS detection sensitivity, and also CE separation efficiency for one interface design tested. Better detection sensitivity was obtained when the nebulizing gas velocity was increased. However, high velocity of the nebulizing gas flow can cause a hydrodynamic bulk flow inside the CE capillary, thus clearly increasing the apparent mobility and decreasing the resolution obtained for the compounds studied. Increasing the drying gas velocity or temperature did not affect the apparent mobility or the separation efficiency and the temperature could be increased to achieve the optimal detection sensitivity in the CE /MS analysis. For comparison, the effects of nebulizing gas flow were studied using a different design of the coaxial sheath-liquid CE /MS interface, and in this case better detection sensitivity but no effect on CE separation efficiency was observed with increased nebulizing gas velocity. These different effects of nebulizing gas flow on the CE bulk flow were concluded to result from pressure differences at the tip of the CE capillaries for the different CE /MS interface arrangements. It is therefore recommended that the cross-sectional dimensions of the fused-silica and steel capillaries, and the gas streamlines, should be optimized when CE /MS interfaces are built. Moreover, the effect of gas flow on CE separation should be studied when optimizing the CE /MS operation parameters.

Buprenorphine↗

A National Guard outbreak of Burkholderia cepacia infection and colonization secondary to intrinsic contamination of albuterol nebulization solution.

BACKGROUND: Burkholderia cepacia, a gram-negative pathogen, has been a known cause of hospital outbreaks because of a contaminated common source such as multidose medications. We describe an outbreak with Burkholderia cepacia infection in 2 major hospitals affiliated to the National Guard, related to an intrinsic contamination of a locally manufactured, multidose Albuterol nebulization solution (Tabouk Pharmaceutical Company, Tabouk, Saudi Arabia) and we report the interventions taken to interrupt this outbreak. METHODS: During the outbreak period between May 2003 and March 2004, a combined prospective surveillance and a retrospective chart and microbiologic data review were conducted in 4 major hospitals affiliated to the National Guard. Microbiologic cultures were also performed on environmental objects of concern, as well as certain medications. In addition, a questionnaire was distributed to the respiratory therapy staff to evaluate the process of administering respiratory medications and their adherence to sound infection control practices. RESULTS: An intrinsic contamination of a locally manufactured brand of multidose Albuterol nebulization with B cepacia was identified. Two of the 4 hospitals were found to be involved: hospital A a 700-bed tertiary care center and Hospital B a 150-bed hospital. A total of 2121 patients were exposed to Albuterol nebulization as inpatients at hospital A and 318 as outpatients. For hospital B, a total of 283 inpatients and 34 outpatients were exposed to the Albuterol nebulization. Forty and 12 patients, from hospital A and hospital B, respectively, were found to have at least 1 positive culture for B cepacia. From hospital A, most samples were respiratory, and, from hospital B, most were from blood. Molecular typing of 34 available isolates showed that 23 cases were of a single strain of B cepacia that matched the strain isolated from the 3 different batches of multidose Albuterol nebulization. Three culture-positive patients never received Albuterol nebulization of that brand but were in the same room of a patient who had been receiving the medication. CONCLUSIONS: We identified a large outbreak of B cepacia in 2 major hospitals affiliated with the National Guard, linked to an intrinsic contamination of a multidose Albuterol nebulization solution. During the period of prospective surveillance, only a few cases were identified as a result of nosocomial transmission. Immediate notification of the Ministry of Health and withdrawal of the medication and revisiting the respiratory therapy practices were necessary to halt this outbreak.

Adolescent↗

Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization.

Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising non-viral delivery systems for pulmonary inhalation gene therapy and thus require sufficient stability during nebulization. The structure and stability of four different PEI-DNA polyplexes, namely branched (bPEI), linear (linPEI), poly(ethylene glycol)-grafted PEI (PEGPEI), biodegradable (bioPEI) PEI with DNA, were investigated. Using atomic force microscopy, the morphology of DNA and polyplexes before and after both air-jet and ultrasonic nebulization was characterized. The influence of nebulization on physico-chemical properties, particle size and zeta potential, was studied. Efficient DNA condensation to spherical particles was achieved with bPEI (90 nm) and PEGPEI (110 nm). By contrast, incomplete DNA condensations, seen as flower structures, were observed with linPEI (110 nm) and bioPEI (105 nm). Air-jet nebulization altered the polyplex structure to a greater extent than ultrasonic nebulization and resulted mainly in smaller and non-spherical particles (30-200 nm). Ultrasonic nebulization did not change the spherical structure or particle size of the polyplexes. In particular, the shape and size of the PEGPEI polyplexes did not change. We conclude that ultrasonic nebulization is a milder aerosolization method for gene delivery systems based on PEI. Additionally, PEGPEI-DNA polyplexes seem to be more stable than their counterparts, which may be advantageous in pulmonary inhalation gene therapy.

Aerosols↗

Outbreak of severe Pseudomonas aeruginosa respiratory infections due to contaminated nebulizers.

During the six months from January-June 1994, 10 cases of severe and 11 of less severe pulmonary infection caused by Pseudomonas aeruginosa were diagnosed in patients with chronic obstructive airways disease. Possible sources were evaluated. P. aeruginosa was isolated from four of the 22 nebulizers tested. The relationship of isolates from the patients and nebulizers was confirmed by sero- and phage-typing, and by arbitrarily-primed polymerase chain reaction (AP-PCR). Three types were identified and the distribution of types in patients with severe infection was as follows (one patient had a multiple infection). Type I was isolated from two nebulizers and from sputa, and/or blood and/or bronchial protected specimen brush samples or bronchial lavage fluid from four patients. Type II came from the sputa of three patients and a third nebulizer; and type III from sputa and/or blood of four further patients and another nebulizer. The data provided evidence for the relation between P. aeruginosa as a cause of infection and the contamination of the nebulizers. When nebulizer mouthpieces were changed every 24 h and sterilized between patients, no more contamination occurred, and the outbreak ceased.

Aged↗

A trial of nebulized magnesium sulfate to reverse bronchospasm in asthmatic patients.

STUDY OBJECTIVE: To test the hypothesis that nebulized magnesium sulfate reverses methacholine-induced bronchospasm in asthmatic patients. DESIGN: Randomized, double-blind, crossover clinical trial. SETTING: Center for Asthma and Allergic Diseases, Children's Hospital of Pittsburgh. TYPE OF PARTICIPANTS: Ten patients who were 21 to 37 years old and had stable asthma. INTERVENTIONS: Patients withheld asthma medications for 24 hours before each study day. Patients with baseline forced expiratory volume in one second (FEV1) of less than 80% were excluded. All subjects underwent bronchial methacholine challenge to produce bronchospasm. They then received one of three different nebulized treatments: 2.5 mg albuterol in 3 mL saline, 3 mL magnesium sulfate (268 mmol/L, pH 6.4), or 3 mL normal saline. Patients repeated spirometry 15 minutes after completing the study drug and then received albuterol by metered-dose inhaler. Spirometry was repeated after the metered-dose inhaler. Each patient made three separate visits to receive each of the three medications. MEASUREMENTS AND RESULTS: Methacholine reduced each patient's FEV1 by at least 20% at each testing session. Post-methacholine treatment with nebulized albuterol improved FEV1 by a mean of 56% (SD, 19.6%). Nebulized normal saline led to a mean increase in FEV1 of 29% (SD, 26.5%). Nebulized magnesium sulfate improved FEV1 by a mean of 12% (SD, 12.0%) (P = .054 by paired t-test compared with normal saline). CONCLUSION: Nebulized magnesium sulfate has a minimal bronchodilatory effect in asthmatic patients with methacholine-induced bronchoconstriction. Responsiveness to magnesium sulfate may be dependent on the mechanism of induction of bronchospasm, and there probably is no role for nebulized magnesium sulfate in the treatment of acute bronchospasm due to cholinergic stimulation.

Adult↗

Drug output of unvented jet nebulizers as a function of time.

Nebulizer drug output rate increases during the nebulization. For unvented jet nebulizers, a physical and mathematical model based on the efficiency of the nebulization process is presented for this phenomenon. Formulas are derived for the cumulative drug output and the drug output rate of the nebulization process. The model is compared with the model proposed by Coates et al. [J. Aerosol. Med. 11 (1998) 101]. Both models are supported by experimental literature data. Both models predict the experimental values well but the proposed model allows more easy prediction of the influence of small changes in the nebulization conditions and the calculation of the cumulative drug output for a related process. From literature data it is shown that the efficiency of an unvented jet nebulization process of diluted aqueous solutions is relatively insensitive to small changes in the concentration as well as to small changes in aspiration flow but is sensitive to the humidity of the compressor gas only.

Mathematics↗

Effect of cryoprotectants on the stability and aerosol performance of nebulized aviscumine, a 57-kDa protein.

Nebulization of aqueous drug solutions is a suitable delivery system for pulmonary application of proteins because it can easily produce droplets small enough to reach the alveolar region. However, proteins are sensitive to nebulization. Therefore, stabilizers need to be added which on the other hand influence the aerosol performance, such as average droplet size or mass output. This research presents the effect of various cryoprotectants such as Na-polyphosphate, CaCl(2) x 6H(2)O and MgSO(4) x 7H(2)O on the stability and aerosol performance of freeze-dried aviscumine after reconstitution and nebulization using three different nebulizers. Formulations containing Tris-buffer, polysorbate 80, Na(2)-EDTA and HES450 were lyophilized and reconstituted with a buffered isotonic solution containing 100 mmol/l Tricine-buffer pH 8, 0.03% (w/v) octanoyl-N-methylglucamide, 150 mmol/l NaCl and a cryoprotectant. The aviscumine activity was determined by a binding assay. The addition of 0.2% Na-polyphosphate to the reconstitution medium led to retention of approx. 73% of the aviscumine activity after 20 min nebulization with the Systam ultrasonic nebulizer. It has been observed that 84 and 72% of the activity were retained by the addition of 10 mmol/l CaCl(2) x 6H(2)O using PariBoy air-jet and Multisonic ultrasonic nebulizer, respectively. In addition, a decrease in the mean droplet size with increasing the cryoprotectant concentration has been observed. A relationship between the average droplet size, surface tension and viscosity depending on the used cryoprotectant type and concentration could be established.

Aerosols↗

Nebulized sodium cromoglycate in preterm infants--protection against water challenge-induced bronchoconstriction.

Nebulized water is an effective bronchoprovocative agent in asthmatic adults and children. The aim of this study was to assess the bronchoconstrictor effect of this agent in preterm infants studied at follow-up and if their response to it was altered by pre-treatment with nebulized sodium cromoglycate. Lung function, thoracic gas volume and airway resistance, was measured by whole body plethysmography and specific conductance (SGAW) calculated. Measurements were made before and after nebulized saline, nebulized water (first water challenge), nebulized sodium cromoglycate and again nebulized water (second water challenge). There was no significant change in SGAW following either normal saline or sodium cromoglycate. In nine infants SGAW deteriorated by more than 16% (twice the coefficient of variation of the measurement) after the first water challenge but only in one after the second water challenge (P < 0.01). We conclude that nebulized water is an effective bronchoconstrictor in preterm infants and that sodium cromoglycate can protect against this challenge.

Bronchi↗