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Prevalence and survival of microbial contaminants in heated nebulizers.

Over a 2-year period, 600 cultures of fluid in heated nebulizers in use by patients in the Peter Bent Brigham Hospital were performed. The most commonly isolated microorganisms were Pseudomonas and Alcaligenes species. Pseudomonas aeruginosa was never isolated. Three types of heated nebulizers were in use, and their contamination rate was significantly different (45 percent, 21 percent, and 8 percent, respectively; p less than 0.001). In the course of the study, the overall contamination rate decreased from 47 percent to 10 percent. This was mainly due to elmination of the type of heated nebulizer that was most prone to contamination. Five types of currently available large-reservoir nebulizers were inculated with various organisms and growth patterns studied. The various nebulizing equiment differed in its ability to inhibit or eliminate microbial growth; 1 of the heated nebulizers appeared to enhance growth of some of the inoculated bacteria.

Acinetobacter↗

Effect of nebulized ipratropium bromide on intraocular pressures in children.

STUDY OBJECTIVE: To evaluate the effects of nebulized ipratropium bromide on intraocular pressures and pupillary responses in children with asthma. DESIGN: A double-blind, randomized, crossover study. SETTING: Children's Hospital of Winnipeg, University of Manitoba. PATIENTS OR PARTICIPANTS: Age 6 to 17 years with asthma. INTERVENTION: Nebulized ipratropium bromide added to albuterol sulfate, albuterol alone, or saline solution was given by face mask and nebulizer. Before and 0.5 h after nebulization, intraocular pressures (mm Hg), pupillary size (mm), and pupillary responses were measured. In a subsequent open study, patients who had been admitted to hospital with acute asthma who were treated with nebulized ipratropium bromide were recruited for measurement of intraocular pressures, pupillary size, and pupillary responses. MEASUREMENTS AND RESULTS: Twenty patients completed the double-blind study, and 26 patients completed the open study. There were no changes in intraocular pressures, pupillary size, or pupillary response after any treatment on any study day in either the double-blind or the open studies. CONCLUSION: In children with asthma, who have no pre-existing ocular abnormalities, the risk of an adverse reaction to nebulized ipratropium bromide delivered by face mask inadvertently absorbed in the eye is extremely small.

Adolescent↗

The response of two different dosages of beclometasone dipropionate suspension for nebulization versus a standard dose of beclometasone dipropionate via a metered-dose inhaler on bronchoprovocation testing in adults with asthma.

The objective of this double-blind, randomized, placebo-controlled, parallel-group study was to compare the pharmacodynamic effects and safety of beclometasone dipropionate (BDP) given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 1-week run-in period, 40 patients, aged 18-60 years, with intermittent bronchial asthma were randomized to one of four treatment groups for 3 weeks (n = 10 in each group): beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. via a nebulizer, BDP suspension for nebulization 3,200 microg day(-1) b.i.d. via a nebulizer, BDP 800 microg day(-1) b.i.d. via a metered-dose inhaler (MDI) plus spacer, or placebo. At study end, comparable effects were reported for all active treatment groups on the primary pharmacodynamic endpoint of FEV1 in response to methacholine bronchial provocation testing, with a statistically significant improvement shown in the BDP 3,200 microg day(-1) suspension for nebulization group compared with pre-treatment for other parameters, including FEV1 and peak expiratory flow rates. All treatments were comparable. All treatments were equally well tolerated. No significant effects on cortisol levels were reported in any of the treatment groups.

Administration, Inhalation↗

An evaluation of nebulized levalbuterol in stable COPD.

BACKGROUND: Levalbuterol, the R-isomer of albuterol, has advantages over racemic albuterol in asthma; however, the effectiveness of this beta-agonist in COPD has received little attention. OBJECTIVES: To evaluate the effectiveness of a single dose of nebulized levalbuterol in COPD. DESIGN: A randomized, double-blind, placebo-controlled trial comparing nebulized levalbuterol to racemic albuterol, combined racemic albuterol and ipratropium, and placebo. PATIENTS: Thirty patients with stable COPD (FEV(1) between 45% and 70% of predicted) were studied. METHODS: After withholding usual bronchodilator medications for appropriate washout periods, patients were randomized on separate visits to receive single doses of each the following nebulized bronchodilator medications: (1) levalbuterol, 1.25 mg; (2) racemic albuterol, 2.5 mg; (3) combined racemic albuterol, 2.5 mg, and ipratropium, 0.5 mg; or (4) placebo. FEV(1), FVC, pulse rate, and oxygen saturation were measured at baseline, 0.5 h following nebulization, and hourly for 6 h. Hand tremor, using a 7-point scale, was measured at baseline, 0.5 h, 1 h, and 2 h. Treatment-placebo differences were analyzed using repeated-measures analysis of variance and least-squares means. RESULTS: The mean age (+/- SD) of patients was 69 +/- 15 years. Mean FEV(1) was 1.15 +/- 0.49 L. By 0.5 h following study drug administration, all three nebulized bronchodilator treatments led to similar, significant improvements in FEV(1) compared to placebo. These effects persisted at 1 h and 2 h for all three treatments; however, by 3 h, only the combined albuterol/ipratropium group had a mean change in FEV(1) significantly greater than placebo. There were no significant differences between bronchodilator groups at any time period. A mild increase in pulse rate was observed in all treatment groups. There were no significant treatment-placebo differences in oxygen saturation or hand tremor. CONCLUSION: For single-dose, as-needed use in COPD, there appears to be no advantage in using levalbuterol over conventional nebulized bronchodilators.

Administration, Inhalation↗

[Metered-dose inhalers with home-made spacers versus nebulizers to treat moderate wheezing attacks in children].

OBJECTIVE: To compare the effectiveness of salbutamol administration by metered-dose inhaler with a home-made spacer versus jet nebulizer in children with moderate wheezing attacks. MATERIAL AND METHODS: A randomized, single-blinded trial was performed with a convenience sample of children presenting wheezing. The children were enrolled in an emergency room and randomly assigned to one of two treatment groups: home-made spacer group or nebulizer group. Clinical scores and oxygen saturation were recorded at baseline and 15 minutes after salbutamol administration. Treatment with salbutamol (100 microg/3 kg in the spacer group, and 250 microg/3 kg in the nebulizer group) was repeated at 20-minute intervals, until the child was considered to have improved significantly, with no need of any further dose, or until three doses were delivered. Treatment cost, time spent to prepare and deliver the drug, and level of parental satisfaction with the treatment were recorded. RESULTS: Fifty-four children with age between 22 days and 11.7 years were enrolled--27 in each group. Baseline and demographic characteristics were similar for both groups. The spacer was as effective as the nebulizer in terms of clinical score and oxygen saturation. The different doses (100 microg/3 kg with the spacer, and 250 microg/3 kg with the nebulizer) were shown to be clinically equivalent. Treatment cost was significantly lower in the spacer group, as was the time to prepare and deliver the drug. Parental satisfaction was similar for both inhaler devices. CONCLUSION: The home-made spacer with a metered-dose inhaler is a cost-effective alternative to a jet nebulizer in the delivery of salbutamol to children with moderate wheezing attacks.

Albuterol↗

Long-lasting protective effect of slow-release theophylline on asthma induced by ultrasonically nebulized distilled water.

We investigated the intensity and duration of the effect of a single dose of slow-release theophylline on bronchial hyperresponsiveness to ultrasonically nebulized distilled water in asthma. In six subjects with a history of mild asthma, we measured airway responsiveness to ultrasonically nebulized distilled water and serum theophylline at 4, 8, and 12 hours after treatment with placebo or slow-release theophylline (10 +/- 1 mg/kg, orally). To assess bronchial responsiveness, dose-response curves were established by plotting the baseline value of FEV1 and the largest FEV1 after each doubling dose of nebulized distilled water against the dose of nebulized water. The degree of bronchoconstriction induced by ultrasonically nebulized distilled water was significantly inhibited at 4, 8, and 12 hours after treatment with theophylline, at serum levels of 14.8 +/- 4.6, 14.4 +/- 2.8, and 12.0 +/- 2.5 micrograms/mL theophylline (mean +/- SD). Tremor occurred in three patients and was associated with nausea, epigastric pain, and tachycardia in one of them. We conclude that a single dose of slow-release theophylline has a prolonged protective effect on bronchoconstriction induced by ultrasonically nebulized distilled water, but in some subjects is associated with side effects that limit its clinical usefulness.

Asthma↗

Domiciliary nebulized beta-agonists. Long-term treatment in asthmatics, and drug intake and plasma levels in acute asthma.

Long-term domiciliary treatment with nebulized salbutamol was studied in 27 patients (mean age 55 years, range 25-77) suffering from severe chronic bronchial asthma. At the end of the treatment period (mean 2.7 years, range 0.9-3.9) three patients had returned their Pari Inhalierboy nebulizers, two because of improvement, one because of moving from the area. Two patients died at home from status asthmaticus. Of the rest, about a third experienced an improved quality of life, and six of 9 patients depending on oral corticosteroids could be transferred to metered dose aerosols. No significant changes of the number of days in hospital or on sick-leave, number of hospitalizations or number of outpatient consultations between corresponding periods before and after the start of nebulizing therapy at home were found. In another study, drug intake 24 h before hospital admission and plasma levels of beta-agonists were recorded in 45 asthmatics (mean age 52 years, range 20-74) on arrival at hospital with acute asthma (PEFR less than 50% predicted normal value, pulse rate greater than 100). In 22 of the 64 acute episodes recorded, domiciliary nebulized beta-agonists were used. No significant differences in the oral doses taken 24 h before arrival or the plasma concentrations of beta-agonists were found between patients with and without nebulized beta-agonists. The studies demonstrate the feasibility of home-treatment with beta-agonists via nebulizers.

Adult↗

Continuous versus frequent intermittent nebulization of albuterol in acute asthma: a randomized, prospective study.

BACKGROUND: In acute severe asthma the optimal dose, frequency, duration and method of administration of beta-2 agonists is unknown. No study to date has evaluated the efficacy of high dose beta-2 agonists beyond the initial two hours. OBJECTIVE: (1) To determine whether high-dose continuous nebulization of albuterol (7.5 mg/h) is as safe and as efficacious as high-dose intermittent nebulization of albuterol (2.5 mg every 20 minutes) for four hours. (2) To evaluate whether there is a continual improvement using high dose therapy beyond two hours. METHODS: We devised a simple means of continuous nebulization calibrated to deliver 7.5 mg albuterol per hour. Twenty-two nonsmoking, patients with acute, severe asthma who presented to the emergency department with less than 60% predicted normal PEFR were randomized to either the continuous or intermittent group. All patients received intravenously 125 mg methyl prednisolone on initiation of the study. No theophylline was administered. Spirometry and vital signs were measured at baseline and every 30 minutes thereafter. Electrocardiograms were obtained on all patients and all patients had continuous cardiac monitoring. RESULTS: Both groups doubled their baseline spirometric values over the four-hour period (P < .0001). The FEV1 did not differ significantly between regimens at any time interval. Improvement from 120 minutes to 240 minutes was statistically significant (P < .0001). There was no significant difference in vital signs at the end of the study compared with baseline in either group, nor between the two groups at any time interval. CONCLUSION: High-dose continuous nebulization of albuterol is as safe and as efficacious as intermittent nebulization of albuterol in the early treatment of asthma in an emergency department. To our knowledge, this is the first study showing continued significant improvement beyond the initial two hours of therapy using high dose nebulized beta-2 agonists.

Acute Disease↗

The efficacy and safety of home nebulizer therapy for children with asthma.

We evaluated the efficacy and safety of nebulized beta-agonists used in the homes of 22 children with asthma. Patients served as their own controls for the comparison of asthma-related variables between periods of 12 months before and 12 months after the initiation of home nebulizer therapy. Significant reductions in the numbers of emergency department visits, hospital admissions, and short courses of prednisone therapy occurred when home nebulizer therapy was provided. The younger the patients, the more frequently improvement occurred. After the initiation of home nebulizer therapy there was no change in the severity of illness when patients presented to the emergency department or in the number of episodes of respiratory failure. Home nebulizer therapy for children with asthma appears safe and reduces the need for hospital care and short courses of prednisone therapy.

Adolescent↗

Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis.

Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.

Administration, Inhalation↗

Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

Administration, Inhalation↗

Importance of drug delivery system in steroid aerosol therapy via nebulizer.

Aim of our study was to evaluate if the type of nebulizer can influence the effects of steroid aerosol therapy. We considered 27 asthmatics allergic to grasses with FEV1<80% of the predictive value or methacholine PD20 FEV1<750 mcg. The patients were divided into three groups in relation to the type of nebulizer they used and treated 9 weeks by aerosol therapy with beclomethasone dipropionate bid (800 mcg). Respect to the values recorded at the beginning and at the end of the therapy we found different variations of spirometric indeces and PD20 values among the three groups. We can conclude that the type of nebulizer influences steroid aerosol therapy and, particularly, jet nebulizers seem more efficient than ultrasonic nebulizers.

Adult↗

Comparison of the bronchodilator effects of nebulized bitolterol mesylate and isoproterenol hydrochloride in steroid-dependent asthma.

This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.

Adult↗

Salbutamol output from two jet nebulizers.

Nebulized bronchodilators are commonly used in the management of patients with airflow obstruction, although there is little information available on the bronchodilator output from the nebulizer unit. We have examined the fluid and salbutamol outputs of a single jet nebulizer from two commercial manufacturers at 1 min intervals up to 12 min. The drug and fluid output continued throughout the study period, with a greater fluid output leading to an increase in the concentration of salbutamol remaining within the nebulizer unit. This suggests that weight change is not a good indicator of drug output. Furthermore, there was a marked difference in peak salbutamol output between the two nebulizer units, being 2.9 mg (55%) with the Micro-Neb unit and 1.98 mg (38.7%) with the System 22 unit.

Albuterol↗

Terbutaline inhalations by the Turbuhaler as replacement for domiciliary nebulizer therapy in severe chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are often treated with high dose inhalations of beta 2-agonists. We compared domiciliary therapy with terbutaline administered by the Turbuhaler and by a jet nebulizer. Forty nebulizer users with severe COPD were included in the randomized, double-blind, cross-over study. Terbutaline was inhaled t.i.d. for 2 weeks as dry powder (5 doses = 2.5 mg) by Turbuhaler or as solution (2 ml = 5 mg) by jet nebulizer (Pari Inhalierboy). The mean age of the 25 completing patients was 66 years (range: 54-81), the mean FEV1 was 0.73 l or 29% of predicted (range: 11-55%). The period where the Turbuhaler delivered the active drug was preferred by 16 patients, the nebulizer period by seven (P = 0.09). The median score concerning feeling of control over the disease--according to the Chronic Respiratory Disease Questionnaire--was better after the Turbuhaler period (P = 0.01). Other scores concerning disease related quality of life, the daily peak expiratory flow rates, the additional use of a metered dose inhaler were not significantly different for the two types of treatment. It is concluded that high dose domiciliary terbutaline treatment by Turbuhaler can replace nebulizer treatment in most patients with severe COPD.

Aged↗

Development of a slurry introduction method for multi-element analysis of antibiotics by inductively coupled plasma atomic emission spectrometry using various types of spray chamber and nebulizer configurations.

A direct sample introduction inductively coupled plasma atomic emission spectrometric (ICP-AES) method, for multi-element analysis of powdered antibiotic drugs was developed using the slurry formation technique. The slurry of powdered sample is formed in dilute nitric acid solution in presence of Triton X-100 surfactant. Two different configurations of spray chamber and nebulizer were tested for direct aspiration of slurry into the plasma: (i) cyclonic spray chamber combined with babington-type nebulizer and (ii) scott-type double-pass spray chamber combined with cross-flow nebulizer. The latter configuration proved to be less tolerable to slurry aspiration. RF power generator, nebulizer argon gas flow rate, nebulizer sample uptake flow rate and slurry sample concentration were optimized. The sensitivity of the proposed method was compared to the corresponding sensitivity obtained from aqueous solutions for each analyte. The performance characteristics of the slurry aspiration method were evaluated against the complete acid-digestion method followed ICP-AES. Finally, the proposed method was applied to the analysis of commercial antibiotics.

Aerosols↗

Inhalation therapy in asthma: nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.

OBJECTIVE: To compare lung deposition from a nebulizer and a pressurized metered-dose inhaler (pMDI)/holding chamber to determine their efficiency in aerosol delivery to children. STUDY DESIGN: Children with stable asthma (n = 17) aged 2 to 9 years inhaled in random order radiolabeled salbutamol from a nebulizer and a pMDI through a nonstatic holding chamber. Body and lung deposition of radiolabeled salbutamol was assessed with a gamma camera. RESULTS: Mean (absolute dose) total lung deposition expressed as a percentage of the nebulized dose was 5.4% (108 microg) in younger children (<4 years) and 11.1% (222 microg) in older children (>4 years). Mean (absolute dose) total lung deposition expressed as a percentage of the metered dose was 5.4% (21.6 microg) in younger and 9.6% (38.4 microg) in older children. CONCLUSIONS: For the same age groups we have shown equivalent percentages of total lung deposition of radiolabeled salbutamol aerosolized by either a nebulizer or a pMDI/holding chamber. However, the delivery rate per minute and the total dose of salbutamol deposited were significantly higher for the nebulizer.

Albuterol↗

Hypokalemic effects of intravenous infusion or nebulization of salbutamol in patients with chronic renal failure: comparative study.

To examine and compare the efficacy and safety of different routes of administration of salbutamol in treating hyperkalemia, 15 patients with chronic renal failure (blood urea nitrogen > 80 mg/dL, serum creatinine > 8.0 mg/dL) were enrolled to sequentially receive either intravenous infusion (0.5 mg) or nebulization (10 mg) of salbutamol. Five of these patients (33.3%) did not respond to the intravenous salbutamol and were excluded from the study. Both treatments significantly decreased plasma potassium in 10 patients and the decrease was sustained for at least 3 hours. After infusion, the maximal reduction in plasma potassium levels was 0.92 +/- 0.10 mEq/L and occurred after 30 minutes. On the other hand, the maximal reduction in plasma potassium after nebulization (0.85 +/- 0.13 mEq/L) was similar to that after infusion, but it occurred after 90 minutes. Insulin and blood glucose increased, whereas blood pH, PCO2, sodium, osmolality, and blood pressure did not change after either treatment. Heart rate increased significantly after both treatments, but less after nebulization than after infusion. It is concluded that both infusion and nebulization are simple, effective, and safe therapeutic modalities for the treatment of hyperkalemia in patients with chronic renal failure. Infusion should be used in patients requiring a rapid decrease in plasma potassium; nebulization, on the other hand, should be used in patients with coronary artery diseases.

Administration, Inhalation↗