Comparison of nebulized magnesium sulfate plus albuterol to nebulized albuterol plus saline in children with acute exacerbations of mild to moderate asthma

A prospective, randomized, double blinded study was conducted to determine whether a combination of nebulized magnesium sulfate and albuterol as a single dose adds any benefit in management of children with mild to moderate asthma when compared to nebulized albuterol with saline. The difference in FEV1 was significant at 10 and 20 min after a single dose of the combined treatment with magnesium and albuterol when compared with the albuterol and saline group (1.41 L +/- 0.53 vs. 1.13 L +/- 0.34, respectively, p = 0.03). The addition of magnesium to albuterol seems to provide short-term benefits in children with acute exacerbations of mild to moderate asthma.     

pH-responsive polymeric nanoparticles with tunable sizes for targeted drug delivery

Biodegradable nanoparticles (NPs) have shown great promise as intracellular imaging probes, nanocarriers and drug delivery vehicles. In this study, we designed and prepared amphiphilic cellulose derivatives via Schiff base reactions between 2,3-dialdehyde cellulose (DAC) and amino compounds. Polymeric NPs were facilely fabricated via the self-assembly of the as-synthesized amphiphilic macromolecules. The size distribution of the obtained NPs can be tuned by changing the amount and length of the grafted hydrophobic side-chains. Anticancer drugs (DOX) were encapsulated in the NPs and the drug-loaded NPs based on cellulose derivatives were stable in neutral and alkaline environments for at least a month. They rapidly decomposed with the efficient release of the drug in acidic tumor microenvironments. These drug-loaded NPs have the potential for application in cancer treatment.

Novel nanoparticles for efficient drug delivery were designed and constructed using polymeric 2,3-dialdehyde cellulose (DAC). The drug DOX was encapsulated into nanoparticles and underwent thoroughly controlled release in acidic tumor microenvironments.     

A randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma

Multiple studies have examined adding nebulized ipratropium bromide to intermittent albuterol for the treatment of acute asthma. Although continuous nebulized treatments in themselves offer benefits; few data exist regarding the efficacy of adding ipratropium bromide to a continuous nebulized system. To compare continuous nebulized albuterol alone (A) vs. albuterol and ipratropium bromide (AI) in adult Emergency Department (ED) patients with acute asthma, a prospective, randomized, double-blind, controlled clinical trial was conducted on a convenience sample of patients (IRB approved). The setting was an urban ED. Consenting patients > 18 years of age with peak expiratory flow rates (PEFR) < 70% predicted, between October 15 and December 28, 1999, were randomized to albuterol (7.5 mg/h) + ipratropium bromide (1.0 mg/h), or albuterol alone via continuous nebulization using the Hope Nebulizer (B&B Technologies Inc., Orangevale, CA) for 2 h. Main outcome measures were changed in mean improvement at 60 and 120 min PEFR compared to baseline (time 0). Secondary measures were admission rates. Data were analyzed using appropriate parametric and non-parametric tests (p < 0.05 statistically significant). Sixty-two patients (30 women) completed enrollment: 32 in (AI) and (30) in (A). Four (A) and 2 (AI) patients are without 120 min data: 3 (A) and 1 (AI) were discharged after 60 min, whereas one each (A) and (AI) worsened and were admitted before 120 min. There were no statistically significant differences between treatment groups in age, sex, predicted or initial PEFR. Thirteen (19.4%) patients were admitted. There was no statistically significant difference in improvement of mean PEFR at 60 min or 120 min compared to baseline, between groups, using repeated measures analysis of variance. Mean improvement in PEFR at 60 min compared to baseline (time 0): (A) = 93.2 L/min (95% confidence interval [CI] 64.5-121.8), (AI) = 86.6 L/min (95% CI 58.9-114.3); mean improvement in PEFR at 120 min compared to baseline (time 0) (A) = 116.5 L/min (95% CI 84.5-148.5), (AI) = 126.4 L/min (95% CI 95.4-157.4). There was no statistically significant difference in admission rates between groups: 5/30 (A) and 8/32 (AI) (p = 0.62). There were no significant differences in mean improvement of PEFR at either 60 or 120 min between ED patients with acute asthma receiving continuous albuterol alone vs. those receiving albuterol in combination with ipratropium bromide.     

Heliox-driven albuterol nebulization for asthma exacerbations: an overview

Our understanding of albuterol nebulization driven by helium-oxygen mixture (heliox) has matured with recent advances in clinical therapy, delivery systems, and understanding of dosing; this has led to substantial improvements in delivery as well as refinements of research protocols for asthma exacerbations. This review begins with heliox inhalation therapy and then addresses heliox as a driving gas for nebulization. Technical considerations are reviewed, including optimal gas mixtures, flow-rate adjustment factors, and nebulizer setup.     

Retrospective comparison of nebulized levalbuterol and albuterol for adverse events in patients with acute airflow obstruction

The objective of this study was to retrospectively compare the mean change in heart rate (HR) of patients with acute airflow obstruction treated with nebulized levalbuterol vs. albuterol. The study was conducted at the Akron General Medical Center, a 537-bed adult tertiary care teaching and research medical center. The participants were patients (> or = 18 years old) presenting to the emergency department with acute airflow obstruction. This was a retrospective chart review. Treatment groups received either levalbuterol (0.63 mg) or albuterol (2.5 mg). Respiratory care notes record HRs before and after nebulization of levalbuterol or albuterol. Primary analysis was conducted on days 1 and 3 of therapy to determine whether there is a difference between levalbuterol and albuterol with regard to mean change in HR with each treatment. In the primary analysis data, 35 subjects in each treatment group were compared. The mean age (+/- SD) was 65 +/- 16.4 and 68 +/- 16.5 for levalbuterol and albuterol, respectively. On day 1 of therapy, the difference in the mean change in HR with albuterol compared with levalbuterol was 1.0 bpm (95% CI, -1.6 to 3.7). On day 3, a statistically significant difference occurred in mean change in HR between treatment groups at 2.7 bpm (95% CI, 0.02 to 5.4). An increase in HR of 2.7 bpm by albuterol compared with levalbuterol on day 3 of therapy was the only significant finding among the analyses. However, this finding did not demonstrate dangerous elevations in HR following treatment with albuterol. Even the upper end of the confidence interval range at 5.4 bpm does not support a clinically significant difference in tachycardia with the pure isomer compared with the racemic mixture during acute airway obstruction.     

A method for increasing jet nebulizer delivery efficiency for aerosol drug delivery in ventilated newborns: an in vitro study

BACKGROUND: A substantial percentage of the aerosol produced by a nebulizer is lost down the expiratory limb of the ventilator circuit. We describe a method for the capture, return, and re-aerosolization of that undelivered aerosol. METHODS: We designed an expiratory-limb setup in which an "entraining jet" of gas accelerates unused aerosol and propels it toward an impaction surface. The deposited solution is then returned to the nebulizer reservoir via a feedback tube. As a result, more of the initial dose is delivered to the patient. The fraction of the dose delivered to a filter connected to a passive neonatal test lung was measured with and without the aerosol-recycling components activated. We used a deltaP (difference between the peak inspiratory pressure and the positive-end-expiratory pressure) of approximately 7.5 cm H2O, tidal volume of approximately 6 mL, respiratory rate of 40 breaths/min, and an inspiratory-expiratory ratio of 1:2.3. RESULTS: There was a statistically significant improvement with the feedback return to the reservoir, with up to nearly 60% more aerosol delivered. CONCLUSION: This improvement in aerosol delivery is encouraging, but more comprehensive studies are needed before such a device could be implemented clinically.     

自然分娩影响因素的定性分析

目的了解目前影响产妇选择自然分娩的因素。方法采用小组访谈法进行资料收集,访谈对象包括10名医疗机构管理人员。结果影响自然分娩服务的因素包括：政策层面、人力资源以及社会因素。结论为了促进自然分娩,需要进一步针对政策、助产人力资源及教育、孕妇认知及社会舆论导向层面的因素进行相应的研究和干预。     

Respiratory response to salbutamol (albuterol) in ventilator-dependent infants with chronic lung disease: pressurized aerosol delivery versus intravenous injection

Objective To compare the effects of intravenously injected with inhaled salbutamol in ventilator dependent infants with chronic lung disease (CLD).Design Prospective randomized study in which each patient served as his/her own control.Setting Multidisciplinary neonatal and pediatric ICU.Patients 8 ventilator dependent premature infants with CLD.Interventions Salbutamol, 10 g/kg was given intravenously, and 10–19 h later, twice 100 g as pressurized aerosol, or vice versa, sequence randomized. The pressurized aerosol was delivered by a metered dose inhaler into a newly developed aerosol holding chamber, integrated into the inspiratory limb of the patient circuit. Respiratory system mechanics were assessed by the single breath occlusion method before and 10 and 60 min after drug administration.Measurements and results Compliance improved significantly after intravenous injection (0.48±0.18 to 0.67±0.16, p<0.01 and 0.59±0.23 ml/cmH₂O/kg, NS, (mean±1 SD) and after inhalation (0.46±0.19 to 0.64±0.32,p<0.01 and 0.56±0.31 ml/cmH₂O/kg, NS). Resistance decreased after i.v. use (0.38±0.17 to 0.25±0.11,p<0.001 and 0.25±0.10 cmH₂O/ml/s, NS) and after inhalation (0.35±0.12 to 0.27±0.09,p<0.01 and 0.28±0.12 cmH₂O/ml/s, NS). Heart rate increased significantly after both routes of application, whereas mean arterial pressure, respirator settings, FIO₂, transcutaneous SO₂ and capillary PCO₂ did not change.Conclusions Inhaled and intravenous salbutamol improves pulmonary mechanics to the same extent with comparable side effects, and may therefore be used to facilitate weaning from respirators.     

Evaluation of poly(acrylic acid-co-ethylhexyl acrylate) films for mucoadhesive transbuccal drug delivery: factors affecting the force of mucoadhesion.

Based on the premise that similar surface properties between the adhesive and the substrate would yield a strong adhesive bond, copolymers of acrylic acid (AA) and 2-ethylhexyl acrylate (EHA), P(AA-co-EHA), were designed and synthesized for buccal mucoadhesion. A series of linear copolymers with varying feed ratios of the two monomers (AA and EHA) were synthesized through free radical copolymerization at 69+/-0.5 degrees C using azobis(isobutyronitrile) (AIBN) as initiator. The reactions were carried out in THF under nitrogen for 24 h. The glass transition temperatures, T(g), of the copolymers were determined using DSC. The adhesion studies were conducted to determine the effects of copolymer composition, contact time between the substrate and the adhesive, and crosshead speed on mucoadhesive performance of the copolymer films using a computer interfaced Instron material testing system. The glass transition temperature of the copolymers decreased with increasing EHA content. Wet glass surface as substrate was shown not to be a good substrate model for adhesion determination studies. The copolymer composed of 46:54 mol.% AA:EHA (an almost 1:1 ratio in the repeat units) yielded the highest mucoadhesive force in contact with porcine buccal mucosa which was significantly greater (P<0.05) than that of poly(acrylic acid) (PAA) (used as positive control). The mucoadhesive force for all copolymers studied was significantly (P<0.05) greater than that of the negative control (backing material without copolymer film) except for the EHA homopolymer. Crosshead speed increased mucoadhesive force linearly and had a more pronounced effect on the mucoadhesive performance than time of contact between the adhesive and the substrate.     

Cell adherence and drug delivery from particle based mesoporous silica films

Spatially and temporally controlled drug delivery is important for implant and tissue engineering applications, as the efficacy and bioavailability of the drug can be enhanced, and can also allow for drugging stem cells at different stages of development. Long-term drug delivery over weeks to months is however difficult to achieve, and coating of 3D surfaces or creating patterned surfaces is a challenge using coating techniques like spin- and dip-coating. In this study, mesoporous films consisting of SBA-15 particles grown onto silicon wafers using wet processing were evaluated as a scaffold for drug delivery. Films with various particle sizes (100–900 nm) and hence thicknesses were grown onto trichloro(octadecyl)silane-functionalized silicon wafers using a direct growth method. Precise patterning of the areas for film growth could be obtained by local removal of the OTS functionalization through laser ablation. The films were incubated with the drug model 3,3′-dioctadecyloxacarbocyanine perchlorate (DiO), and murine myoblast cells (C2C12 cells) were seeded onto films with different particle sizes. Confocal laser scanning microscopy (CLSM) was used to study the cell growth, and a vinculin-mediated adherence of C2C12 cells on all films was verified. The successful loading of DiO into the films was confirmed by UV-vis and CLSM. It was observed that the drugs did not desorb from the particles during 24 hours in cell culture. During adherent growth on the films for 4 h, small amounts of DiO and separate particles were observed inside single cells. After 24 h, a larger number of particles and a strong DiO signal were recorded in the cells, indicating a particle mediated drug uptake. The vast majority of the DiO-loaded particles remained attached to the substrate also after 24 h of incubation, making the films attractive as longer-term reservoirs for drugs on e.g. medical implants.

Particle-based mesoporous silica films synthesized through a direct growth method were successfully used as a drug delivery system.     

Basic techniques for aerosol delivery during mechanical ventilation

Among the devices employed for aerosol generation (metered-dose inhalers, nebulizers, and dry powder inhalers) only metered-dose inhalers and nebulizers are routinely employed for aerosol delivery to mechanically ventilated patients. The ventilator circuit and artificial airway were previously thought to be major barriers to effective aerosol delivery to mechanically ventilated patients. In the past decade in vitro and in vivo investigations have contributed to a better understanding of the complex array of factors that influence inhaled drug delivery in mechanically-ventilated patients. Several investigators have shown that with careful attention to the administration technique aerosol delivery efficiency in mechanically-ventilated patients is comparable to that in ambulatory patients. The ability to efficiently deliver aerosols should lead to wider clinical application of inhaled therapies in patients receiving mechanical ventilation.     

A computational model for particle size influence on drug absorption during controlled-release colonic delivery.

The effect of particle size on the percent drug absorbed is computationally modeled for controlled-release dosage forms that deliver drug particles to the colon. The relative benefit of reducing particle size is mapped on a diagram of the drug's absorption rate constant (estimated from rat intestinal perfusion, CACO-2 or human intubation permeation rates) versus the drug's solubility. Some drugs fall into a limit of high percentage absorption even with large particles such that particle size reduction has little impact. Another group of drugs is solubility limited such that even with small particles, absorption is negligible. Between the two regions, only drugs with sufficiently high absorption rates are influenced by the drug dissolution rate and thereby the particle size. The size of this region is a function of dosing rate. Comparisons between calculated particle size effects on colon absorption as a function of colon volume suggest caution when using animal models to predict bioavailability from colonic drug delivery. This volume dependence also suggests that the particle size influence will vary as a function of the digestive cycle.     

New delivery systems for asthma drugs

The therapy of asthma requires great attention to detail by both doctor and patient since the technique of drug administration always needs care. New developments in drug delivery systems for asthma may make this task easier and lead to reduced morbidity.     

The importance of nonelectrostatic materials in holding chambers for delivery of hydrofluoroalkane albuterol

INTRODUCTION: Electrostatic attraction of aerosolized particles to the inner walls of an aerosol holding chamber (HC) made from a nonconducting material can reduce medication delivery, particularly if there is a delay between actuation and inhalation. OBJECTIVE: Compare total emitted mass and fine-particle mass (mass of particles < 4.7 microm) of hydrofluoroalkane-propelled albuterol from similar-sized HCs manufactured from conductive material (Vortex), charge-dissipative material (AeroChamber Max), and nonconductive material (OptiChamber Advantage, ProChamber, Breathrite, PocketChamber, and ACE), with and without wash/rinse pretreatment of the HC interior with ionic detergent, and with 2-s and 5-s delays between actuation and inhalation. METHODS: All the HCs were evaluated (1) directly from their packaging (with no wash/rinse pretreatment) and (2) after washing with ionic detergent and rinsing and drip-drying. We used an apparatus that interfaced between the HC mouthpiece and the induction port of an 8-stage Andersen cascade impactor to simulate a poorly coordinated patient, with delays of 2 s and 5 s between actuation and inhalation/sampling, at 28.3 L/min. RESULTS: With the 2-s delay, the delivered fine-particle mass per actuation, before and after (respectively) wash/rinse pretreatment was: AeroChamber Max: 23.8 +/- 4.8 microg, 21.5 +/- 3.2 microg; Vortex: 16.2 +/- 1.7 microg, 15.5 +/- 2.0 microg; OptiChamber Advantage: 2.6 +/- 1.2 microg, 6.7 +/- 2.3 microg; ProChamber: 1.6 +/- 0.4 microg, 5.1 +/- 2.5 microg; Breathrite: 2.0 +/- 0.9 microg, 3.2 +/- 1.8 microg; PocketChamber: 3.4 +/- 1.6 microg, 1.7 +/- 1.6 microg; ACE: 4.5 +/- 0.9 microg, 5.4 +/- 2.9 microg. Similar trends, but greater reduction in aerosol delivery, were observed with the 5-s delay. Significantly greater fine-particle mass was delivered from HCs made from conducting or charge-dissipative materials than from those made from nonconductive polymers, even after wash/rinse pretreatment (p < 0.01). The fine-particle mass was also significantly greater from the AeroChamber Max than from the Vortex, irrespective of wash/rinse pretreatment or delay interval (p < 0.01). CONCLUSION: HCs made from electrically conductive materials emit significantly greater fine-particle mass, with either a 2-s or 5-s delay, than do HCs made from nonconducting materials, even with wash/rinse pretreatment.     

Efficacy of nebulized albuterol and cromolyn sulfate for acute wheezing and stridor in children: a prospective, randomized study

A number of respiratory tract illnesses may produce acute wheezing and stridor in children, and treatment may vary, depending on the specific illness. These illnesses, however, may be difficult to differentiate solely on clinical grounds. A uniform therapeutic approach for children with acute wheezing or stridor independent of the specific etiology can be employed. In this prospective study, 246 children received aerosolized albuterol and cromolyn sulfate. Children who remain in distress after aerosolized medications should be admitted to the hospital. Those with partial improvement may be treated with home aerosol treatments after intramuscular injection of dexamethasone.     

Cavitation-enhanced extravasation for drug delivery

A flow-through tissue-mimicking phantom composed of a biocompatible hydro-gel with embedded tumour cells was used to assess and optimize the role of ultrasound-induced cavitation on the extravasation of a macromolecular compound from a channel mimicking vessel in the gel, namely a non-replicating luciferase-expressing adenovirus (Ad-Luc). Using a 500 KHz therapeutic ultrasound transducer confocally aligned with a focussed passive cavitation detector, different exposure conditions and burst mode timings were selected by performing time and frequency domain analysis of passively recorded acoustic emissions, in the absence and in the presence of ultrasound contrast agents acting as cavitation nuclei. In the presence of Sonovue, maximum ultraharmonic emissions were detected for peak rarefactional pressures of 360 kPa, and maximum broadband emissions occurred at 1250 kPa. The energy of the recorded acoustic emissions was used to optimise the pulse repetition frequency and duty cycle in order to maximize either ultraharmonic or broadband emissions while keeping the acoustic energy delivered to the focus constant. Cell viability measurements indicated that none of the insonation conditions investigated induces cell death in the absence of a therapeutic agent (i.e. virus). Phase contrast images of the tissue-mimicking phantom showed that short range vessel disruption can occur when ultra-harmonic emissions (nf0/2) are maximised whereas formation of a micro-channel perpendicular to the flow can be obtained in the presence of broadband acoustic emissions. Following Ad-Luc delivery, luciferase expression measurements showed that a 60-fold increase in its bioavailability can be achieved when broadband noise emissions are present during insonation, even for modest contrast agent concentrations. The findings of the present study suggest that drug delivery systems based on acoustic cavitation may help enhance the extravasation of anticancer agents, thus increasing their penetration distance to hypoxic regions and poorly vascularised tumour regions.