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Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm lambs.

To evaluate the efficiency and distribution of ultrasonic nebulized versus instilled surfactant in the treatment of surfactant deficiency at varying degrees of maturation, twin or triplet lamb fetuses were delivered at 125 to 137 d gestational age and received nebulized natural surfactant (Neb Only), instilled surfactant followed by a second instilled dose (Inst/Inst), instilled surfactant followed by nebulized surfactant (Inst/Neb), or no surfactant (Control). The lambs were ventilated for 6 h. Twenty-eight lambs were categorized into two groups (low compliance versus moderate compliance) based on initial physiologic lung characteristics. Efficiency of deposition of nebulized surfactant directly correlated with the compliances and ventilatory efficiency indices measured at 15 min of age. The low-compliance group (Low Comp) had significantly lower efficiency of surfactant deposition (7.6 +/- 1.6%) than did the moderate-compliance group (Mod Comp) (23.4 +/- 2.5%) (p < 0.01). Overall, instilled surfactant had a reasonably homogeneous distribution, whereas nebulized surfactant had a less homogeneous distribution, except for the Low Comp, Inst/Neb group, which had a distribution pattern similar to that for instilled surfactant. The potential for nebulized surfactant therapy for respiratory distress syndrome (RDS) may be limited by the nonhomogeneous nature of ventilation in the preterm lung.

Administration, Inhalation↗

Dose response to ipratropium as a nebulized solution in patients with chronic obstructive pulmonary disease. A three-center study.

We performed a dose-response study of ipratropium bromide as a nebulized solution in patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind crossover format. Five doses from 0.05 to 0.6 mg of ipratropium bromide as a nebulized solution, the standard dose of ipratropium bromide by metered-dose inhaler, 40 micrograms, and placebo were given in random order on separate days. End points were the maximal increase in FEV1 and FVC, and the area under the FEV1 and FVC curves in the 8 h after administration of each of the seven treatments. Forty-two patients completed all seven study days. By each of the above end points for FEV1, 0.4 and 0.6 mg of nebulized ipratropium bromide achieved significantly more bronchodilatation than did each of the other treatments. These two doses were not significantly different from each other, suggesting that the optimal dose in this patient population is 0.4 mg. After this dosage, the FEV1 increased by 440 +/- 194 (mean +/- 1 SD) ml at peak effect between 1 and 2 h, and significant bronchodilatation persisted for 6.5 h. Ipratropium bromide by metered-dose inhaler (40 micrograms) was equivalent to approximately 0.1 mg by nebulized solution and achieved only 63 to 73% of the bronchodilatation achieved by optimal doses of the nebulized solution. In terms of FVC, all treatments with ipratropium were significantly better than with placebo. The area under the FVC curve was significantly greater after 0.4 and 0.6 mg of nebulized solution than after other treatments. No significant adverse experiences occurred with any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Lung deposition and efficiency of nebulized amikacin during Escherichia coli pneumonia in ventilated piglets.

Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg x kg-1, n = 10) or by intravenous infusion (15 mg x kg-1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 +/- 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 +/- 175 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x g-1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units. g-1 versus median = 5 x 10(2) colony forming units x g-1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.

Administration, Inhalation↗

Home nebulizers in childhood asthma. Parental perceptions and practices.

Seventy five percent of 91 parents of asthmatic children (aged 6 months to 15.4 years) with home nebulizers, responded to a questionnaire that sought to document parental experience with this form of therapy. The most common indications for acquiring a nebulizer were inability to use metered dose inhalers and poor response or intolerance to oral medications. When the children were classified into those who used the nebulizer daily (27/69) and those who used it less than daily (42/69), we found that the daily users were more likely to be in the severest category of asthma, by parental assessment, prior to the home nebulization program (p = 0.0035). Retrospective, uncontrolled comparison before and after the acquisition of a home nebulizer showed significant decreases both in hospital admissions (1.7 vs 0.7; p less than 0.001) and total in-patient days (4.1 vs 1.7; p less than 0.0001). Home nebulizers are well tolerated by parents and children alike and may be associated with decreased morbidity.

Adolescent↗

Possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest.

OBJECTIVE: To report a case of possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest and to review the involvement of various preservative agents in paradoxical bronchoconstrictive reactions. DATA SOURCES: Reference articles, case reports, and editorials are identified in the text. DATA SYNTHESIS: Many pharmacologic agents are available for nebulization. In addition to the active drug, these nebulizer solutions may contain preservatives. We describe a case of respiratory arrest in a 64-year-old man following nebulization therapy with albuterol and ipratropium solutions. These solutions contain benzalkonium chloride as a preservative. We are aware of only one report describing two deaths associated with such a severe reaction attributable to nebulization therapy. However, many reports of milder paradoxical bronchoconstriction are available in the medical literature. CONCLUSIONS: Clinicians should be aware of the possibility of paradoxical bronchoconstrictive reactions when patients are treated with nebulized bronchodilators.

Benzalkonium Compounds↗

Nebulization and anti-Pseudomonas aeruginosa activity of colistin.

Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.

Administration, Inhalation↗

Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Bioassay by histamine bronchoprovocation.

The results of previous studies comparing bronchodilatation from beta agonists administered by metered-dose inhaler (MDI) and nebulizer solution have been conflicting. We therefore evaluated a range of albuterol doses administered by these two methods, using histamine bronchoprovocation as a bioassay for the amount of drug reaching the beta 2 receptors in the lung. Twelve stable asthmatic volunteers received, in a double-blind, randomized, crossover design on different days, placebo or one, two, four, or six puffs from an MDI attached to an InspirEase device (90 micrograms per puff) or 0.625, 1.25, 2.5, or 5.0 mg of solution delivered in 2 ml of buffered saline through a Hudson Updraft II nebulizer. The histamine concentration required to decrease FEV1 by 20 percent (PC20) was measured 1 h before and 30 min after administration of each treatment and expressed as the increase in PC20 from baseline. The dose-response curves for change in PC20 indicated that the higher doses of the nebulizer solution delivered more drug to beta 2 receptors in the lung than the lower doses from the MDI. For example, the geometric mean increase in PC20 was 1.1 +/- 1.6 (SD) after placebo, 7.5 +/- 2.7 after two puffs from the MDI, and 20.0 +/- 2.1 after 2.5 mg of nebulizer solution (p less than 0.05). Using this bioassay method and administration technique, we estimated that ten puffs from the MDI (0.9 mg) would deliver approximately the same amount of albuterol to lung receptors as 2.5 mg of the nebulizer solution. Taking into account previously published reports and the results of the present study, we conclude that differences in dose, administration technique, nebulizer system efficiency, and severity of airway obstruction can alter the amount of drug reaching the beta 2 receptors in the lungs and, thus, the clinical response.

Adult↗

Emergency department treatment of severe asthma. Metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer.

STUDY OBJECTIVE: To compare the effectiveness of administration of albuterol by nebulizer or by a metered-dose inhaler having a holding chamber attachment (hereafter "inhaler") for treatment of acute asthma in an emergency department (ED). DESIGN: A randomized, double-blind, placebo-controlled intervention study conducted at two sites. SETTING: The EDs of a large municipal hospital and a university teaching hospital. PATIENTS: Thirty-five patients 10 to 45 years of age seeking treatment at an ED for acute asthma. INTERVENTIONS: Patients were randomly assigned to receive either albuterol by nebulizer plus placebo by inhaler (n = 20) or albuterol by inhaler plus placebo by nebulizer (n = 15). The dose was repeated every 30 min until the FEV1 was at least 80 percent of predicted, the patient became asymptomatic, or 6 doses had been given. MEASUREMENTS AND RESULTS: All references in this article to spirometric measurements of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) represent percentages of the predicted normal value. No significant (p > 0.58) differences occurred in baseline mean FEV1, FVC, or PEFR for the two groups. For both groups, significant improvement occurred in mean FEV1 at 30 min (p < 0.02) and at 60 min (p < 0.02), and in maximum mean FEV1 (p < 0.001). However, no significant (p > 0.6) differences occurred between groups in mean FEV1, FVC, or PEFR at 30 and 60 min, or in maximum improvement attained. The sample size was sufficiently large to detect a 12 percent difference in improvement with a power of 90 percent. Thirty-three of 35 patients were treated successfully with the study protocol, became asymptomatic, and were discharged home. One patient from each group required further treatment. CONCLUSIONS: There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for treatment of acute asthma. There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for the treatment of acute asthma when the dose was titrated to clinical response. When compared with nebulizer, the metered-dose inhaler with holding chamber delivers a full dose of albuterol more quickly and at no higher cost.

Administration, Inhalation↗

A comparison of commercial jet nebulizers.

Seventeen commercially available jet nebulizers from 15 commercial sources were studied (Acorn-I, Acorn-II, AquaTower, AVA-NEB, Cirrhus, Dart, DeVilbiss 646, Downdraft, Fan Jet, MB-5, Misty Neb, PARI LC JET, PARI-JET, Salter 8900, Sidestream, Updraft-II, Whisper Jet). All nebulizers were filled with 2 ml of saline solution plus 0.5 ml of albuterol and powered with the same source (DeVilbiss PulmoAide). We compared total output (TO), time for total output (TTO), and percent output in respirable range (PORR). The TO was obtained by weighing before nebulization and at the point of eight-fold decline in output. The TTO was calculated from initiation of nebulization to the point of eightfold decline in output. The PORR was measured by a laser particle analyzer in continuous nebulization to the same point of abrupt drop in output. The TO varied from 0.98 To 1.86 ml (p < 0.0001) with the Acorn-I, Acorn-II, Updraft-II, and Sidestream, significantly greater than the others (p < 0.05). The TTO varied from 2.28 to 20.95 min (p < 0.0001). The AquaTower, PARI LC JET and PARI-JET, DeVilbiss, and Dart were significantly shorter than the others (p < 0.05). The PORR varied from 21.89 to 71.95 percent (p < 0.0001). The Sidestream was significantly greater than all others (p < 0.05). The PARI LC JET and PARI-JET were, in turn, significantly greater than the remaining models (p < 0.05). To combine these characteristics, we calculated respirable particle delivery rate (RPDR) by dividing TO by TTO and multiplying by PORR. The RPDR varied from 0.03 ml/min to 0.26 ml/min (p < 0.0001). The PARI LC JET (0.24 ml/min) and the PARI-JET (0.26 mg/min) had a RPDR that was significantly greater than the other models except the AquaTower, which, however, had a markedly variable performance. The Sidestream (0.19 mg/ml) did not differ significantly from the above group, nor from the DeVilbiss and Downdraft. All other models had significantly lower outputs (p < 0.05). We conclude that the output characteristics of commercial nebulizers vary greatly and will impact on the time required for treatment as well as the total amount of drug delivered to the lungs.

Aerosols↗

Aerosol delivery during continuous nebulization.

BACKGROUND AND OBJECTIVES: Continuous administration of aerosolized beta 2-agonists has been suggested as an effective treatment for severe reversible airways disease. To facilitate continuous therapy and avoid a feed system for small-volume nebulizers (SVNs), a large-volume medication nebulizer (Vortran HEART) was developed. The goal of this study was to determine actual drug delivery of the HEART and conventional SVNs for both adult and pediatric breathing patterns. DESIGN: Output studies were conducted on comparable samples of CIS-US AeroTech II and Hospitak PowerMist SVNs and Vortran HEART large-volume continuous nebulizers. To duplicate clinical aerosol delivery via an aerosol mask, drug particles were inhaled through the mouth of a model of a human face for two test breathing patterns (adult = tidal volume (Vt) of 500 mL, 20 breaths/min, duty cycle of 40%; pediatric = VT of 100 mL, 35 breaths/min, duty cycle of 40%), generated by a ventilator. Radiolabeled particles of saline solution, confirmed to behave identically to albuterol, were collected on absolute filters at the mouth of the face to measure the actual mass of albuterol particles delivered to the airway opening. RESULTS: The AeroTech II and PowerMist SVNs delivered 5.14 and 3.74 mg/h, respectively, for the adult breathing pattern and 2.97 and 2.48 mg/h, respectively, for the pediatric breathing pattern. Drug delivery rates of the HEART were a function of drug concentration and ranged from 0.87 to 3.48 mg/h for the adult breathing pattern. For the pediatric breathing pattern, drug delivery rate was a function of drug concentration and inspired minute ventilation and ranged from 0.41 to 1.83 mg/h. CONCLUSION: Our data demonstrate that drug delivery to the patient, expressed as inhaled mass over time, is similar for continuous nebulization (HEART system) and intermittently filled SVNs. In addition, for all nebulizers, the influence of the pediatric breathing pattern needs to be considered. Continuous nebulization permits the redistribution of health-care personnel and may reduce the costs of therapy.

Adrenergic beta-Agonists↗

Effect of regular use of high-dose nebulized beta2-agonists on resting energy expenditure, weight, and handgrip strength in patients with chronic airflow limitation.

STUDY OBJECTIVES: A proportion of patients with chronic airflow limitation (CAL) have a raised resting energy expenditure (REE). The mechanism underlying this is not known. The question of whether the increased REE seen in some patients with CAL is due to beta2-agonist therapy has arisen, and the aim of this study was to examine REE, body composition, and peripheral muscle strength in patients before and after the use of regular high-dose beta2-agonists administered by nebulizer. DESIGN: Prospective observational study. SETTING: Respiratory outpatient clinic. PARTICIPANTS: Twenty outpatients with CAL being considered for a home nebulizer prescription. INTERVENTIONS: REE was measured by indirect calorimetry. Fat-free mass and handgrip strength were measured. Quality of life was assessed by the St. George's Hospital Respiratory Questionnaire. All subjects were assessed independently of this study for provision of a home nebulizer using a standard protocol. Based on the assessment, either standard-dose salbutamol therapy was continued or a nebulizer was provided with a prescription for high-dose salbutamol (5 mg qd). A mean of 8.1 months later (range, 3 to 16 months), 16 patients were restudied. MEASUREMENTS AND RESULTS: Eight patients had been taking regular high-dose nebulized salbutamol, and eight had continued taking standard-dose salbutamol by metered dose inhaler. There was no difference in baseline measures between the group who were later prescribed high-dose salbutamol and the group who were not. There were no changes in REE, anthropometric measures, or handgrip strength over time in either of the groups. CONCLUSIONS: The long-term use of high-dose nebulized beta2-agonists in patients with chronic airflow limitation has no effect on baseline REE, handgrip strength, weight, or body composition.

Administration, Inhalation↗

Effects of repetitive use and cleaning techniques of disposable jet nebulizers on aerosol generation.

STUDY OBJECTIVE: Patients with cystic fibrosis use disposable jet nebulizers for the self-administration of antibiotics, DNase, and bronchodilators several times per day. Most patients elect to reuse their disposable nebulizers. The purpose of this study was to determine if significant changes in particle size distribution or output (mL/min) occurred with reuse. DESIGN: In vitro studies were performed using four disposable models and one durable jet nebulizer for up to 100 runs; measurements of particle size and output were obtained at 10 run intervals, using saline solution alone, tobramycin, gentamicin, or a mixture of albuterol and cromolyn. Particle size determinations were made with a laser diffraction analyzer. RESULTS: There was no significant difference between the baseline performance of the four disposable models and the durable Pari LC, when measuring particle size distribution of the aerosol; the Pari LC had an output rate two to three times higher than the four disposable models. For each of the four solutes tested, there was no clinically significant change in performance for up to 100 cycles, when the nebulizers were properly cleaned between uses. Unwashed units containing tobramycin started to fail by 40 runs. CONCLUSIONS: When properly maintained, there was no trend of deterioration of performance with repeated use of disposable nebulizers. Microbial contamination was not addressed in this study and must be considered prior to recommendations for the reuse of disposable nebulizers.

Administration, Inhalation↗

In vitro comparison of DeVilbiss jet and ultrasonic nebulizers.

Output, droplet size (by laser instrument), and nebulization time have been compared in vitro for eight individual ultrasonic nebulizers (DeVilbiss Pulmosonic) and eight individual jet nebulizers (DeVilbiss 646), the latter operated by compressed air at flows of 6 and 12 L/min. A solution of hypertonic (7 percent) saline was nebulized. The ultrasonic nebulizer retained a higher "dead" volume of solution on completion of nebulization (p less than 0.05), but the increase in saline concentration was less marked than for the jet (p less than 0.01). The mass of NaCl released as aerosol was similar for the ultrasonic and for the jet at 6 L/min but was increased for the jet at 12 L/min (p less than 0.05). There was a fivefold interindividual variation in output for the ultrasonic. Droplet mass median diameters for the ultrasonic (mean 5.4 micron) were slightly lower than those for the jet at 6 L/min (mean 6.0 micron, p less than 0.05) but were higher than those for the jet at 12 L/min (mean 3.7 micron, p less than 0.01). The ultrasonic emitted virtually no droplets less than 2 micron diameter and may be unsuitable for applications requiring high yields of fine particles for delivery to the peripheral lung regions.

Aerosols↗

Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction.

Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction.

Adult↗

Effects of budesonide inhalation suspension compared with cromolyn sodium nebulizer solution on health status and caregiver quality of life in childhood asthma.

OBJECTIVE: To compare the effects of 2 nebulizable controller asthma medications on caregiver and pediatric quality of life. METHODS: In this 52-week, randomized trial, children aged 2 to 6 years with mild to moderate persistent asthma received budesonide inhalation suspension 0.5 mg (total daily dose) once or twice daily (n = 168) or cromolyn sodium nebulizer solution 20 mg 4 times daily (n = 167) for 8 weeks, with dosage adjustment thereafter at the investigators' discretion. The Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), Compliance/Caregiver Satisfaction Questionnaire (CCSQ), Modified Child Health Questionnaire-Parent Form 50 (CHQ-PF50), and Functional Status-II(R) (FS-II[R]) Questionnaire were administered at baseline and weeks 8, 28, and 52. Global assessments of ease of asthma management and child health status were obtained from caregivers and physicians at the end of the study. RESULTS: Improvements from baseline in domain-specific (activities and emotional function) and total PACQLQ scores were greater at each time point (weeks 8, 28, and 52) for caregivers of patients treated with budesonide compared with caregivers of patients receiving cromolyn sodium. Only the budesonide group met the criterion for a clinically important improvement (>or=0.5 unit change) in all PACQLQ domains by week 8, which was maintained at weeks 28 and 52. Moreover, improvements surpassed the criterion for moderate clinical importance (1.0 unit change) in all PACQLQ domains for the budesonide group, but this level of improvement was only achieved in the activities domain (at week 28) for the cromolyn sodium group. Based on the CCSQ, budesonide resulted in greater caregiver satisfaction, treatment convenience, ease of use, and compliance compared with cromolyn sodium. Thus, 90.7% of caregivers in the budesonide group were "completely or very satisfied" compared with 53.4% in the cromolyn sodium group. Over half (54.6%) of caregivers in the budesonide group rated budesonide "highly or very convenient" compared with 23% for cromolyn sodium; 77% rated budesonide "extremely or very easy" to use compared with 47% for cromolyn. Adherence with daily medication regimens was reported for 76% of children in the budesonide group compared with 57% in the cromolyn sodium group. Child health status, as indicated by mean FS-II(R) scores, showed improvements from baseline in both groups at weeks 8, 28, and 52. There was a trend for these improvements to be superior in the budesonide group. Additionally, budesonide was superior to cromolyn sodium in caregiver and physician global assessments. At the end of the study, 76% of caregivers of children receiving budesonide reported asthma management to be "a great deal easier" compared with the start of the study, and 74% rated the overall health status of their child as "much better now than 1 year ago." In contrast, only 29% and 37% of caregivers whose children received cromolyn sodium provided these respective ratings. CONCLUSIONS: Budesonide inhalation suspension improved the quality of life for caregivers of children with asthma. Caregivers of children treated with budesonide had significantly fewer limitations in daily activities and emotional functioning compared with caregivers of children treated with cromolyn sodium nebulizer solution. The improvements in caregiver quality of life occurred earlier with budesonide compared with cromolyn sodium. Only caregivers in the budesonide group had a clinically important mean change from baseline in all PACQLQ domains by week 8. These benefits were maintained at week 52. Children treated with budesonide inhalation suspension and cromolyn sodium experienced improvements in health status, assessed using the FS-II(R). The greatest differences between treatments were seen in the disease-specific portion of the FS-II(R), which relates impairments in functional status to the child's illness. Caregiver and physician global assessment indicated significantly better overall child health after 1 year of treatment with budesonide, supporting an improvement in health status. Clinical trials in children 4 to 16 years of age with asthma have demonstrated greater effectiveness of inhaled corticosteroids versus cromolyn sodium on several clinical measures of efficacy. Measures of asthma control in this study, reported in detail elsewhere [Leflein et al. Pediatrics 2002;109:866-872], also have shown greater improvements with budesonide therapy. Treatment with budesonide inhalation suspension resulted in a significantly lower mean rate of asthma exacerbations, significantly longer times to first asthma exacerbation, significantly longer times to first additional use of chronic asthma therapy, and significant improvements in asthma symptom scores and breakthrough medication use compared with cromolyn sodium therapy. Additionally, children receiving budesonide inhalation suspension experienced more symptom-free days and episode-free days compared with children receiving cromolyn sodium. Safety profiles were similar between the 2 treatment groups. Budesonide inhalation suspension was associated with significantly greater caregiver satisfaction, convenience, ease of use, and compliance compared with cromolyn sodium nebulizer solution. This greater caregiver satisfaction and quality of life may be related to the greater asthma control achieved in children treated with budesonide therapy compared with cromolyn sodium. In addition, the convenience of once- or twice-daily dosing with budesonide inhalation suspension, compared with 3- or 4-times-daily dosing of cromolyn sodium, may decrease caregiver burden and enhance the willingness of caregivers to adhere to treatment regimens prescribed for their young children with asthma. This effect on caregiver adherence could further improve treatment effectiveness. This is the first clinical trial comparing the effects of a nebulized corticosteroid with that of an alternative nebulized therapy on quality of life in young children with asthma and their families. Compared with nebulized cromolyn sodium, budesonide inhalation suspension not only provides better overall child health status and asthma management, but greater caregiver quality of life and greater caregiver satisfaction, convenience, ease of use, and compliance.

Administration, Inhalation↗

Nebulization of S-carboxymethylcysteine does not adversely affect the mucociliary system in the paranasal sinus and trachea of the healthy rabbit.

Chronic sinusitis is a persistent inflammatory impairment of the paranasal sinus. Disturbance of the mucociliary function in the paranasal sinus is the most common finding in chronic sinusitis. S-carboxymethylcysteine (S-CMC) has been shown to directly enhance the ciliary activity of the chronic sinusitis mucosa. Direct contact of the disturbed cilia with S-CMC may recover the reduced beating activity of cilia in chronic sinusitis and the mucosal pathology of the disease can thus be improved. Before S-CMC as medicine for nebulization in the treatment of chronic sinusitis can be clinically applied, however, it should be experimentally established whether nebulization of S-CMC has any adverse effects on the mucociliary system of the respiratory mucosa. The present study was designed to experimentally examine the safety of nebulization of S-CMC especially with regard to the respiratory mucosa. Rabbits were treated with nebulization of three different concentrations of S-CMC solution for 20 min a day for 14 successive days, and their mucosal pathology of the sinus and trachea was examined and compared with that of healthy animals. Nebulization of concentrations of 0.5-10% of S-CMC solution did not affect the ciliary activity in the sinus and tracheal mucosa, nor did this treatment induce pathological changes such as epithelial injury and inflammatory cell accumulation. It is therefore concluded that concentrations of 0.5-10% S-CMC solution are quite safe for the use of nebulization in the treatment of chronic sinusitis.

Animals↗

Design characteristics for drug nebulizers.

Drug nebulizers should be designed to produce an aerosol which efficiently targets drug to the respiratory tract. In this article we review the basic principles of aerosol generation from both jet and ultrasonic nebulizers, and the factors governing respiratory tract penetration and deposition. We review methods for accurate measurement of aerosol dose and size, with emphasis on evaporative effects and the implications to drug nebulizer design. We identify three forms of drug aerosol waste attributable to: generation of non-respirable aerosol, losses to the environment, and dead volume solution; and we consider how each may be minimized through good nebulizer design. Finally, we compare the relative merits of jet and ultrasonic nebulizers, and conclude by predicting a new trend in future drug nebulizer therapy.

Aerosols↗

Effectiveness of a positive expiratory pressure device in conjunction with beta2-agonist nebulization therapy for bronchial asthma.

Patients with asthma often show increased airway hyperreactivity and mucus hypersecretion. Although beta2-agonist therapy is one of the most common and effective ways used to relieve airway obstruction, the use of a positive expiratory pressure device (PEPD) is also effective in mucus clearance. However, no previously reported study has examined the effectiveness of these two therapies used in combination. This study assessed the effectiveness of a PEPD on beta2-agonist nebulization therapy by measuring the pulmonary function before and after nebulization therapy in 54 asthmatic patients. The results show that the use of PEPD after beta2-agonist nebulization therapy improved pulmonary function compared with the use of beta2-agonist nebulization therapy alone, as shown by the increases in forced midexpiratory flow and forced vital capacity (FVC). Patients with forced expiratory volume in 1 sec (FEV1) below 85% FVC obtained a significant improvement in FEV1 and FVC after using PEPD. When PEPD was used before beta2-agonist nebulization therapy, there were no obvious direct bronchodilative effects. The use of PEPD after beta2-agonist therapy, however, significantly enhanced the bronchodilative effect of beta2-agonist therapy in patients with an FEV1 below 85% FVC. The additional effect of PEPD use in improving pulmonary function after beta2-agonist nebulization therapy might be a result of an enhancement in mucus clearance.

Adolescent↗