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PubMedDate not supplied

Evaluation of different nebulized bronchodilators on clinical efficacy and hypokalemia in asthmatic children.

Acute asthma attack continues to be a major cause for children admitted to the emergency room. Nebulized beta 2-adrenergic agonists are still the first-line drugs for a rapid bronchodilation effect and an easily administered drug during acute asthma attack. The bronchodilator-induced hypokalemia is thought significant in adult group, but is often ignored in children group. In this study, we conducted a randomized study to compare the laboratory and clinical effects between nebulized salbutamol and terbutaline. We found that both salbutamol and terbutaline nebulization induced a significant hypokalemia (p < 0.05). Terbutaline nebulization also significantly improved the peak expiratory flow rate (PEFR) and respiratory rate (RR), but not venous partial pressure of oxygen (PvO2), venous carbon dioxide tension (PvCO2) and O2 saturation in venous blood (SvO2). In contrast, salbutamol improved not only PEFR and RR, but also PvO2, PvCO2, and SvO2 30 minutes of administration. In conclusion, the nebulized salbutamol, although induced a hypokalemic effect which is similar to terbutaline group, has a better effect on improving O2 saturation than nebulized terbutaline with the same dose 30 minutes after administered for children with acute asthma attack.

Administration, Inhalation↗

PubMed2002

Assessing nebulizer performance.

The quality of the aerosol generated by a nebulizer system is a function of its design, operating parameters, and the drug formulation to be aerosolized. The aerosolized drug dose inhaled from a nebulizer is determined by the patient's breathing pattern. The site of deposition of the aerosol in the lung is primarily influenced by the inspiratory flow rate and additionally by the nature of the lung disease. Thus, tests of performance that incorporate these different variables will provide data that give a better understanding of overall nebulizer performance. As discussed in this paper, a number of in vitro and in vivo laboratory tests can be undertaken to measure the characteristics of the delivery system as well as the quality and quantity of the aerosolized drug provided. With this information one can estimate the dose of drug that will be inhaled and deposited below the larynx. The accuracy of these predictions can additionally be improved with the use of breath simulators and standard breath patterns. Breath monitors that capture and feed actual patient breathing patterns into the simulator to mimic nebulizer operation during actual patient use further increase the accuracy of dose estimation. With the vast number of nebulizers available and also in development, a comparison of information obtained from different nebulizers is key in making an informed decision when selecting an aerosol delivery system that can provide an efficacious dose of a particular drug to a specific patient population.

Aerosols↗

PubMed2002

Nebulizers that use a vibrating mesh or plate with multiple apertures to generate aerosol.

Several electronic nebulizer devices that use a vibrating mesh or plate with multiple apertures to generate a fine-particle, low-velocity aerosol have been marketed or will shortly become available for clinical use. These devices have a high efficiency of delivering aerosol to the lung, such that the nominal dose of drugs to be administered could be substantially reduced. Moreover, the volume of drug solution left in these new devices when the nebulization has ceased is negligible, so there is potential to improve the cost-effectiveness of administering expensive medications. Because these devices nebulize at a faster rate than conventional jet or ultrasonic nebulizers, the duration of each treatment could be shortened. These devices efficiently nebulize solutions and suspensions; they have been successfully used for aerosolizing insulin, other proteins and peptides, and fragments of DNA. They could be employed for a wide variety of clinical applications, including the delivery of aerosols for systemic therapy and gene transfer. These devices have overcome many of the limitations associated with conventional jet and ultrasonic nebulizers, and they offer the versatility to modify the aerosol characteristics according to the clinical application for which they are employed. With these devices clinicians will be able to precisely control drug delivery to the respiratory tract.

Administration, Inhalation↗

PubMed2003

Comparison of the efficacy and safety of nebulized beclometasone dipropionate and budesonide in severe persistent childhood asthma.

Inhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in paediatric patients (aged 6 months to 6 years) with severe persistent asthma. Beclometasone dipropionate (BDP) 800 microgday(-1) suspension for nebulization and budesonide (BUD) 750 microg day(-1) given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters. The primary efficacy endpoint was the number of patients who did not experience any major exacerbation, this being 40.4% and 51.7% in the BDP and BUD groups respectively in the ITT population (P = 0.28), and the mean number of global exacerbations (major plus minor) decreased respectively by -37.5% in the BDP group and -23.3% in the BUD group. Both treatments were also associated with marked reductions in the number of nights with wheezing and the number of days of oral steroid use. Moreover, the two treatment groups had a similar adverse-event incidence and profile. Only 11 adverse events were reported, and no serious adverse events were related to treatment. Urinary cortisol and the time course of height and weight were unaffected by both treatments, and BDP was confirmed to have a neutral effect on bone metabolism. In conclusion, this study demonstrates that both BDP 800 microg day(-1) suspension for nebulization and BUD 750 microgday(-1) administered by nebulization are effective, with an acceptable safety profile, for treatment of severe persistent asthma in infants and young children.

Administration, Inhalation↗

PubMedDate not supplied

Comparison of breath-actuated and conventional constant-flow jet nebulizers in treating acute asthmatic children.

To compare the therapeutic effects of two small-volume jet nebulization devices, a breath-actuated nebulizer (BAN) and a constant-flow nebulizer (CFN), this study was conducted. Seventy-two asthmatic patients, aged 5 to 15, were randomly enrolled into this study (39 to the CFN group, 33 to the BAN group). Nebulization treatment with terbutaline solution (5.0 mg /2 ml) diluted with 2 ml isotonic saline for 10 minutes was performed after measurements of baseline spirometry, SaO2, and pulse rate. Measurements of spirometry, SaO2 and pulse rate were repeated at 0, 5, 15 and 30 minutes after the end of the nebulization treatment. After treatment, for within-group comparison, all the spirometric parameters (including FEV1, PEF and FEF25-75%) and SaO2 at various time points of both groups significantly improved. The pulse rate also significantly increased (only at 15 and 30 min for the CFN group). For between-group comparison, the BAN group had greater improvement in all the data of spirometric parameters and SaO2 at various time points, but only reached statistical significance at some time points in PEF, FEF25-75% and SaO2. The pulse rate of the BAN group was significantly higher than that of the CFN group beginning 5 minutes after treatment. In conclusion, the BAN device is better than the CFN device in improving the spirometric parameters and oxygen saturation of asthmatic children during an equal 10-minute nebulization therapy. These results, associated with the higher pulse rate evoked in the BAN group, suggest a higher lung deposition ratio in the BAN device.

Acute Disease↗

PubMed2005

Acute effect of nebulized budesonide in asthmatic children.

The acute anti-inflammatory effects of inhaled steroids at high doses and their use at home and as emergency treatment of acute asthma attacks in children have been evaluated in many clinical studies. However very little is known about their additional bronchodilator response to systemic steroids plus nebulized salbutamol in the early management in children. Asthmatic patients aged between 5-15 years were investigated in a double-blind, placebo-controlled fashion. Both the study group (Group I) and the control group (Group II) received three consecutive doses of nebulized salbutamol (0.15 mg/kg/dose) and one dose of parenteral methylprednisolone (1 mg/kg/dose, intramuscularly). After this treatment, nebulized budesonide (1 mg/dose) was administered to patients in the study group and placebo (nebulized saline) was administered to patients in the control group. Pulmonary index scoring and peak flow meter was performed to both groups before and after the treatment. There were twelve patients in Group I (mean age: 7.90 +/- 2.34 years) and fourteen patients in Group II (mean age: 9.36 +/- 2.55 years). There was no difference between the two groups with respect to age (p = 0.1421), gender (p = 1.000) and inhaled steroid prophylaxis rate (p = 0.2177). No statistically significant difference was detected between the two groups with respect to the pulmonary index score (p = 0.3528). Yet, there was a statistically significant difference between the two groups with respect to the increase in PEFR (p = 0.0155). The positive acute effect of nebulized budesonide in addition to systemic steroids and nebulized salbutamol in improving the spirometric indices in asthmatic children is an encouraging finding for further investigations of its routine use in the pediatric emergency department.

Administration, Inhalation↗

PubMed2006

Comparison of the effects of nebulized terbutaline with or without intravenous betamethasone on exhaled nitric oxide in children with acute asthma attack.

BACKGROUND AND PURPOSE: Exhaled nitric oxide (eNO), a non-invasive marker that reflects the degree of airway inflammation, may be useful for assessing the response to anti-inflammatory treatment of asthma. The purpose of this randomized prospective study was to compare the effect of a nebulized terbutaline plus a single intravenous dose of betamethasone at baseline followed by a second of terbutaline at 6 h with the effect of the same protocol of nebulized terbutaline alone on airway inflammation of acute asthmatic children as demonstrated by eNO levels. METHODS: Children visiting the emergency department due to acute asthma attack were recruited. All enrolled patients had fluorescent assay-proven hypersensitivity to Dermatophagoides pteronyssinus. Patients were randomized to receive either nebulized terbutaline plus intravenous betamethasone (experimental group, n = 11) or nebulized terbutaline alone (control group, n = 11) at baseline followed by a second dose of nebulized terbutaline alone 6 h later. RESULTS: Exhaled NO concentrations were significantly reduced in the experimental group at 7 h (40.25 +/- 12.43 vs 28.88 +/- 18.02 ppb; p = 0.005) and 12 h (40.25 +/- 12.43 vs 30.11 +/- 18.16 ppb; p = 0.007) after treatment. The eNO level in the experimental group was also reduced at 7 h (28.88 +/- 18.02 vs 38.12 +/- 16.50 ppb; p = 0.034) and 12 h (30.11 +/- 18.16 vs 39.36 +/- 17.63 ppb; p = 0.035) compared to the control group. The change of eNO concentration was correlated to the change of peak expiratory flow rate (PEFR) [r = -0.678; p = 0.022] and pulmonary index scores (r = 0.606; p = 0.048) at 7 h after treatment in the betamethasone group. CONCLUSION: Nebulized terbutaline given at baseline and 6 h later was significantly more effective in improving PEFR and asthmatic symptoms (pulmonary index scores) for at least 12 h when the initial dose was administered in combination with intravenous betamethasone.

Acute Disease↗

PubMed1990

Output characteristics of DeVilbiss No. 40 hand-held jet nebulizers.

DeVilbiss No. 40 hand-held nebulizers are widely used for quantifying airway responsiveness in large populations using pharmacological agents. We examined the aerosol characteristics of five nebulizers. Within each device, the aerosol output and droplet size were reasonably stable over a wide range of bulb pressures, although there were considerable differences in output characteristics between nebulizers. The droplet size was very large compared to conventional aerosol delivery systems, with a mass median diameter greater than 10 microns for three of the five devices. Between 28-50% of the output was in particles sufficiently small for airway deposition (less than 6.2 microns). A more vigorous compression of the bulb caused a small increase output and a reduction in droplet size, resulting in a much bigger variation in the output of the respirable aerosol (less than 6.2 microns) with changes in bulb pressure. The loss due to evaporation was about 3.5%, causing a similar rise in the osmolality of the nebulizer solution. In view of the variable nebulizer output and the marked between-operator variation in bulb pressure, the characteristics of individual DeVilbiss No. 40 nebulizers should be evaluated by individual operators before use in clinical practice or research.

Aerosols↗

PubMedDate not supplied

[Respiratory failure after nebulized terbutaline treatment in severely wheezy infants: report of three cases].

Subjective clinical observations have suggested that nebulized bronchodilators are helpful in the treatment of some wheezy infants. Although the role of beta 2-agonists in the management of acute asthma in infants and very young children remains controversial, the use of beta 2-adrenergic agents in this age group has been widespread. beta 2-agonists nebulization continues to be the first-line treatment for acute attack of asthma, irrespective of age, in some institutes, but their uses are not without side effect especially in young wheezy infants. We report three cases of respiratory failure occurred after treatment with nebulized beta 2 bronchodilator in infants with chronic lung disease and acute wheezing. All the 3 cases were victims of prematurity. Case 1 was a case of Wilson-Mikity syndrome; case 2 was a case of bronchopulmonary dysplasia; and case 3 was a case of repeatedly wheezing infant. All 3 cases had severely wheezy dyspnea with retraction before nebulized beta 2 bronchodilator treatment. Respiratory failure was found 5 to 10 minutes after the treatment. We suggest that it must be very careful in the treatment of severely wheezy infants with beta 2-agonist nebulization, especially in cases with histories of prematurity and chronic lung disease. It is necessary to carefully monitor the vital signs of the infants during beta 2 agonist nebulization.

Humans↗

PubMed1996

Aerosol production and aerosol droplet size distribution during mechanical ventilation (IPPV) with a new ultrasonic nebulizer.

Administration of drugs via the airway is increasingly practiced in ICU- and surgical patients. For this purpose, aerosols may be produced by either jet nebulization or ultrasonic droplet generation. In mechanically ventilated patients, aerosol delivery is often insufficient. The influence of the ventilatory pattern on nebulizer efficacy is poorly understood. In the present in vitro study we determined the efficacy of a new ultrasonic nebulizer in delivering aerosolized epoprostenol using defined ventilator settings. We determined aerosol delivery rates, the aerosol droplet size distribution and the impact of the connection tubing on drug delivery, applying adult and infant ventilation patterns. Aerosol production rates ranged from 0.28 to 0.57 ml per minute. Using an adult ventilator setting volume controlled ventilation (CMV) led to a higher aerosol production rate than pressure controlled ventilation (PCV) at identical tidal volumes and mean airway pressures (0.57 ml/min,CMV vs 0.39 ml/min, PCV). With an infant ventilator setting, nebulizer rates were lower than those found for the adult ventilator setting, but did not differ substantially between CMV and PCV mode (0.29 ml/min, CMV vs 0.28 ml/min, PCV). Aerosol delivery rates distal to the endotracheal tube changed according to aerosol production rates (adult mode: 0.18 ml/min, CMV vs 0.10 ml/min, PCV; infant mode: 0.03 ml/min, both CMV and PCV). In the infant ventilation mode, a higher percentage of the aerosol was trapped in the catheter mount as compared to the adult ventilation mode. Mass median droplet diameters for each of the four ventilator settings were almost identical (4.63 to 5.09 micron) and smaller than indicated in the product specifications (8 micron). Delivery rates and sizes of droplets delivered by the new ultrasonic nebulizer SUN 345(R) agree well with previously reported data from comparable settings using diverse nebulizer devices.

Adult↗

PubMedDate not supplied

Preservatives in nebulizer solutions: risks without benefit.

Edetate disodium (EDTA) and benzalkonium chloride (BAC) are often present as preservative or stabilizing agents in nebulizer solutions used to treat asthma and chronic obstructive pulmonary disease. Benzalkonium chloride is a potent bronchoconstrictor when inhaled in concentrations similar to those in which it is present in these solutions. Inclusion of BAC (together with EDTA) in the ipratropium bromide (Atrovent) nebulizer solution resulted in paradoxic bronchoconstriction in some asthmatic patients and an overall reduction in bronchodilator efficacy. The presence of BAC in albuterol nebulizer solutions does not affect the short-term bronchodilator response to a single dose, although case reports suggest that its repeated use in patients with severe asthma may result in paradoxic bronchoconstriction. When inhaled by asthmatic subjects, EDTA also causes dose-dependent bronchoconstriction, although it is less potent than BAC. The use of preservative-free bronchodilator nebulizer solutions does not result in clinically significant bacterial contamination if they are dispensed in sterile unit-dose vials, in volumes and concentrations that do not require modification by the user. Despite this evidence, in the United States a number of solutions, including some preparations of albuterol, contain either BAC or EDTA. Current regulations do not require that the concentration of preservatives be documented on the product; however, considerably different doses of BAC are delivered with different products. For example, a standard 2.5-mg dose of albuterol nebulizer solution contains 50 microg of BAC when administered from the multidose dropper bottle and 300 microg from the unit-dose screw-cap product. Furthermore, it is legal for pharmacists to substitute or compound solutions containing high concentrations of BAC when the physician has prescribed a preservative-free product. We recommend that the United States follow the practice of most Western countries and withdraw bronchodilator nebulizer solutions that contain preservatives such as BAC. We further recommend that the solutions should be prepared under sterile conditions, formulated preservative free, and made available in unit-dose vials.

Benzalkonium Compounds↗

PubMed1996

A new nebulizer for atomic spectrometry.

The rotating disc nebulizer has been redesigned with respect to the principle parameters that determines its analytical performance. The flow pattern of the aerosol attained has been optimized by altering the shape of the inner chamber of the nebulizer to obtain optimum aerodynamic characteristics. The optimum angle of impact and "free flight" distance has been established using particle size distribution and mass transport efficiency as criteria. Analytical characteristics have been determined by monitoring the emission signal from aqueous standards. The accuracy has been assessed by using reference steel samples. Using standard solutions of different viscosity the performance of the nebulizer with respect to viscosity changes of the sample has been compared with that of a commercial Meinhardt nebulizer. The rotating disc nebulizer has been less affected by changes in viscosity making it possible to use this nebulizer with slurry and oil samples.

Journal Article↗

PubMed1999

Effect of nebulized albuterol on circulating leukocyte counts in normal subjects.

Nebulized beta 2-receptor agonists may cause neutrophil demargination and result in misleading total circulating leukocyte counts (WBCs) in patients with acute bronchospasm. Varying underlying adrenergic stimulation in these patients also makes interpretation of these data difficult. This study examined the direct effect of these agents on the measured WBCs of healthy adults without evidence of bronchospasm or illness. A prospective, blinded, randomized study of 30 healthy volunteers (aged 18-50 years) was performed in a controlled environment. Subjects were excluded if they were pregnant, had a known underlying medical disorder or have had a prior reaction to albuterol or similar medications. Participants in the study were given either a nebulized albuterol treatment or nebulized normal saline (control group). Leukocyte counts were then obtained before and after treatments. Paired data were analysed using a one-tailed t-test while considering an increase of 40% in WBCs to be significant, P = 0.05, and beta = 0.10. Mean leukocyte counts were 5.9 (+/- 1.2) before treatment as compared to 6.0 (+/- 1.3) after albuterol nebulization. Using the coefficient of variance of WBCs in normal humans as c. 50% (6000 +/- 3000 cells mm-1) we were unable to demonstrate a significant difference in variation in post-nebulized leukocyte counts between the control group and the nebulized albuterol group. While there is concern that the treatment of patients experiencing acute bronchospasm with beta 2 agonists may result in factitious elevations in peripheral leukocyte counts, were found no direct effect of these agents on measured counts in normal subjects.

Adolescent↗

PubMed2001

Nebulized prostacyclin (PGI2) in acute respiratory distress syndrome: impact of primary (pulmonary injury) and secondary (extrapulmonary injury) disease on gas exchange response.

OBJECTIVES: To examine the hypothesis that the response to inhaled prostacyclin (PGI2 on oxygenation and pulmonary hemodynamics may be related to different morphologic features that are supposed to be present in acute respiratory distress syndrome (ARDS) originating from pulmonary (primary ARDS [ARDS(PR)]) and from extrapulmonary disease (secondary ARDS [ARDS(SEC)]). DESIGN: Prospective, nonrandomized interventional study. SETTING: Multidisciplinary intensive care unit, secondary care center. PATIENTS: Fifteen consecutive, mechanically ventilated patients with ARDS and severe hypoxemia, defined as PaO2/FIO2 of <150 torr at the time of admission. INTERVENTIONS: After an initial stable period of at least 60 mins, patients received nebulized PGI2 in 15-min steps; the drug was titrated to find the dose with the best improvement of PaO2, starting with 2 ng/kg/min up to an allowed maximum dose of 40 ng/kg/min. MEASUREMENTS AND MAIN RESULTS: Blood gas, gas exchange, and hemodynamic measurements were performed at the following time points: a) baseline; b) during the optimal or maximum dose of PGI2; and c) 1 hr after withdrawal of the drug. Patients underwent a computed tomographic (CT) scan using a basal CT section to compute the mean CT numbers and the density histogram. Patients were considered responders to PGI2 if an increase in PaO2 of > or =7.5 torr or an increase in PaO2/FIO2 ratio of > or =10% occurred. For the group as a whole, mean pulmonary artery pressure decreased from 32 +/- 1 to 29 +/- 1 mm Hg during PGI2 nebulization, whereas pulmonary vascular resistance decreased 1 hr after withdrawal of nebulization from 177 +/- 18 to 153 +/- 16 dyne x sec/cm5; oxygenation did not change significantly. Eight patients responded to PGI2 nebulization on oxygenation (all were in the ARDS(SEC) subgroup), whereas seven did not (all but one were in the ARDS(PR) subgroup). Among the physiologic variables examined to assess any difference between the two ARDS groups at time of PGI2 nebulization, there was a significant difference concerning the mean CT density number, which was -445 +/- 22 Hounsfield Units in the ARDS(SEC) group and -258 +/- 16 Hounsfield Units in the ARDS(PR) group. In patients presenting with an ARDS(PR), PGI2 induced a reduction in PaO2/FIO2 and a reduction in PaO2 from 87 +/- 2 to 79 +/- 2 torr, whereas in patients with an ARDS(SEC) there was an increase in PaO2/FIO2 and in PaO2 from 76 +/- 4 to 84 +/- torr with a decrease in mean pulmonary artery pressure. CONCLUSIONS: Based on the data from this study, the clinical recognition of the two types of the syndrome together with the CT number frequency distribution analysis may be associated with a prediction of the PGI2 nebulization response on oxygenation.

Adult↗

PubMed2002

Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department.

BACKGROUND: In acute severe asthma, treatment must be initiated early to reverse the pathophysiology that may render airways less responsive to bronchodilation. The addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether this approach results in earlier hospital discharge. The early use of bolus intravenous salbutamol has also been shown to improve outcome, including earlier discharge. We therefore assessed the relative benefits of intravenous salbutamol and nebulized ipratropium bromide in the early management of acute severe asthma in children by a double-blind, randomized, controlled trial. METHODS: This study was undertaken at a tertiary children's hospital, The Children's Hospital at Westmead, The Royal Alexandra Hospital for Children, Westmead, Sydney, Australia. Only children with severe acute asthma as determined by the National Asthma Campaign guidelines criteria and pulmonary index were included. All children received initial nebulized salbutamol therapy (2.5-5 mg salbutamol in 4 mL of normal saline depending on age) at initial emergency department presentation. If asthma remained severe 20 mins later, an intravenous cannula was inserted and intravenous methylprednisolone (1 mg/kg) was administered to all children receiving nebulized salbutamol every 20 mins. Children were then randomized to one of three groups: intravenous salbutamol (15 microg/kg as a single bolus over 10 mins), ipratropium bromide (250 microg), or intravenous salbutamol plus ipratropium bromide. All observers were blinded to treatment groups. Children were randomly assigned to receive a single-dose intravenous bolus of either saline or salbutamol and either nebulized saline or ipratropium bromide determined by a number generated randomly in the hospital pharmacy. The primary outcomes were recovery time and discharge time of each group. Respiratory and hemodynamic monitoring were continuous during the first 2 hrs of the study and then children were monitored clinically for 24 hrs. RESULTS: A total of 55 children with acute severe asthma were entered into the study over an 18-month period. The three groups were similar demographically, with a mean age of 5.9 yrs, and mean duration of attack of 19.6 hrs. No side effects or treatment intolerance were reported. Children in the groups that received intravenous salbutamol had a significant reduction in recovery time to achieving second hourly inhaled salbutamol (p =.008) compared with those administered inhaled bronchodilator alone. The addition of ipratropium bromide to intravenous salbutamol provided no significant further benefit in terms of nebulizer therapy (intravenous salbutamol compared with intravenous salbutamol plus ipratropium bromide). Children administered intravenous salbutamol ceased supplemental oxygen therapy earlier than those administered ipratropium alone at 12 hrs post-randomization (p =.0003). Children administered intravenous salbutamol could be discharged from the hospital 28 hrs earlier than those administered ipratropium bromide (p =.013). CONCLUSION: Children administered intravenous salbutamol for severe acute asthma showed a more rapid recovery time, which resulted in earlier discharge from the hospital than those administered inhaled ipratropium bromide. There was no additional benefit obtained by combining ipratropium bromide and intravenous salbutamol administration.

Adolescent↗

PubMed1979

Comparison of histamine bronchial challenges with the Wright nebulizer and the dosimeter.

In twenty adult asthmatics studied in a stable state, histamine bronchial challenges were carried out at one-week intervals with the Wright nebulizer and with the dosimeter-DeVilbiss apparatus. Dose-response curves were analysed for sensitivity, defined as the minimal histamine dose causing a 20% fall in FEV1 (PC20), and for reactivity, defined as the slope of the dose-response curve once the reaction starts to occur. A significant relationship (r=0.80) was found for the sensitivity obtained with the two nebulizers. PC20 was indeed reproducible within a two folds concentration of histamine in sixteen of the twenty patients. A significant difference (P less than 0.01) was found in the reactivity to the two different apparatus, reactivity being greater with the Wright nebulizer in twelve out of fifteen patients so tested. Sensitivity and reactivity showed a borderline relationship (r=0.47) with the Wright nebulizer but not with the dosimeter. A significant correlation (P less than 0.05) was found to exist between the initial FEV1 (in % of the predicted value) and the observed sensitivity and reactivity as assessed with the Wright nebulizer, but not as assessed with the dosimeter. We conclude that histamine bronchial challenges with the Wright nebulizer and with the dosimeter yield reproducible results if the threshold of a 20% fall in FEV1 is taken as positive. However, the two methods produce different results in terms of reactivity.

Adolescent↗

PubMed1997

Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution.

Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes. The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium (99mTc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1.98 microns and 2.02, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2: lipid:HSA) demonstrated a close correlation of size distributions (r = 0.9445; P < 0.001). The entrapment of interleukin 2 in liposomes was 93 +/- 4.3% before nebulization and 90 +/- 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean +/- s.d. central lung-to-peripheral lung deposition was 1.12 +/- 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen. The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers.

Aerosols↗

PubMed2004

Effects of a nebulized NONOate, DPTA/NO, on group B streptococcus-induced pulmonary hypertension in newborn piglets.

NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions. When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury. To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4-10 d). They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension. Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 x 10(8) CFU/min). Methemoglobin levels were measured at baseline and 60 min. A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p <0.001). Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p <0.01). Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups. These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization. The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature. Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates.

Adult↗