Method Of Aerosol Delivery Research Articles

Aerosol Delivery to Simulated Spontaneously Breathing Tracheostomized Adult Model With and Without Humidification.

Optimal aerosol delivery methods for spontaneously breathing patients with a tracheostomy remain unclear. Thus, we aimed to assess the impact of nebulizer placement, flow settings, and interfaces on aerosol delivery by using a vibrating mesh nebulizer and a jet nebulizer in line with unheated humidification. An 8.0-mm tracheostomy tube was connected to the lung model that simulates adult breathing parameters via a collecting filter. Albuterol sulfate (2.5 mg/3 mL) was administered via a vibrating mesh nebulizer and a jet nebulizer, which was placed in line with unheated humidification provided by a large-volume nebulizer, with FIO2 set at 0.28, with gas flows of 2 L/min versus 6 L/min. Nebulizers were placed in line distal and proximal to the lung model by using a tracheostomy collar and a T-piece. Conventional nebulization was tested using a vibrating mesh nebulizer and a jet nebulizer directly connected to the tracheostomy tube bypassing the humidification device. The drug was eluted from the collecting filter and assayed with ultraviolet spectrophotometry (276 nm). During in-line nebulizer placement with unheated humidification, the inhaled dose was 2-4 times higher with a gas flow of 2 L/min than 6 L/min, regardless of nebulizer type, placement, or interface (all P < .05). At 6 L/min, the inhaled dose was higher with proximal than distal placement when using both interfaces, but, at 2 L/min, the inhaled dose was lower with proximal placement. With a jet nebulizer, the tracheostomy collar generated a higher inhaled dose at proximal placement compared with the T-piece, whereas the T-piece resulted in a higher inhaled dose than the tracheostomy collar with distal placement, regardless of the flow settings. Compared with conventional nebulization using a vibrating mesh nebulizer, an in-line vibrating mesh nebulizer with a large-volume nebulizer at 2 L/min had a similar inhaled dose, regardless of nebulizer placement and interface. In contrast, the in-line jet nebulizer was influenced by both placement and interface. Aerosol delivery with an in-line vibrating mesh nebulizer and jet nebulizer with unheated humidification was affected by nebulizer placement, interface, and gas flow settings.

Comparison of Aerosol Delivery Methods in Mechanically Ventilated Patients: Evaluating Differences in Drug Deposition, Patient Outcomes, and Side Effects

Background: Aerosol delivery methods vary in effectiveness and patient tolerance, particularly in mechanically ventilated patients. This study aims to compare Metered-Dose Inhalers (MDIs) with spacers, nebulizers, and Dry Powder Inhalers (DPIs) in terms of drug deposition, pulmonary function improvement, patient outcomes, and side effects. Methods: A mixed-methods approach was used, combining quantitative analysis of drug deposition, pulmonary function tests (PFTs), patient outcome scores, and side effect reporting with qualitative interviews from patients and clinicians. Data were collected from a sample of 120 mechanically ventilated patients across three hospitals. Results: Nebulizers demonstrated the highest mean drug deposition (45.8%) and pulmonary function improvement (22.3% change in FEV1), followed by MDIs with spacers (30.2% deposition, 15.5% improvement) and DPIs (25.0% deposition, 12.4% improvement). Nebulizers also had the highest patient outcome score (8.1), though with a higher incidence of side effects (22%). MDIs and DPIs had lower side effect rates (18% and 10%, respectively) and were preferred for their ease of use and quicker treatment times, despite lower efficacy. Conclusion: Nebulizers are more effective in delivering medication and improving pulmonary function but are associated with higher side effects. MDIs and DPIs, while less effective, offer benefits in terms of side effect profiles and patient convenience. Clinicians should weigh these factors when choosing aerosol delivery methods for mechanically ventilated patients.

A direct injection technique for investigation of lung sensory properties and reflex functions.

This article reviews a unique direct injection technique that complements the more conventional right atrial injection and aerosol delivery methods to study sensory and reflex effects of the lung sensors. Used in combination with other methods, this technique should contribute to the pulmonary sensory research. The lungs house sensory receptors (sensors) that mediate a variety of sensory and reflex responses to mechanical or chemical changes. These reflexes are mainly carried through pulmonary sympathetic and vagal afferent pathways. The chemosensors in the lung periphery are especially important in pulmonary diseases and their reflex responses have traditionally been studied either by aerosol delivery, which also activates receptors in the central airways, or by right atrial injection, which also activates receptors lying outside the lung. Thus, these techniques may confound the interpretation of sensory function. Our laboratory has developed a direct injection technique to deliver agents into the lung parenchyma, which complements the conventional techniques with some important advantages. This article reviews the technique.

Drug delivery systems for fluoroquinolones: New prospects in tuberculosis treatment

The review focuses on new delivery systems of fluoroquinolones, the highly active antibiotics, the therapeutic application of which is still limited due to low bioavailability and low solubility in biological media. The development of suitable delivery systems seems to be a promising solution to these problems. Here, we consider the delivery systems based on synthetic polymers (polylactic and polyglycolic acids and their copolymers, polycaprolactones, etc.) and natural polymers, in particular, polysaccharides. Oligosaccharide delivery systems, conjugates of fluoroquinolones with natural polymers, as well as lipid delivery systems, including liposomes, solid lipid particles, and hybrid particles, are also discussed. The characteristic features of oral, intravenous, and aerosol delivery methods for fluoroquinolones are revealed, which is especially important in the development of new drugs for the treatment of tuberculosis.

Inhaled salbutamol dose delivered by jet nebulizer, vibrating mesh nebulizer and metered dose inhaler with spacer during invasive mechanical ventilation

BackgroundPatient receiving invasive mechanical ventilation (IMV) may benefit from medical aerosol, but guidance on dosing with different aerosol devices is limited to in-vitro studies. The study was designed to compare aerosol delivery with five different types of aerosol generators during IMV. MethodIn randomized design, 60 (30 female) mechanically ventilated chronic obstructive pulmonary disease (COPD) patients were assigned to one of 5 groups. Groups 1–4 received 5000 μg salbutamol using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO vibrating mesh and jet nebulizers (JN), respectively, while group 5 received 800 μg (8 puffs) of salbutamol via metered dose inhaler with AeroChamber-MV (MDI-AC). All devices were place in the inspiratory limb of ventilator downstream from humidifier which was switched off while delivery. Patients received the inhaled dose on day 1 and provided urine 30 post dosing. They also recived the same inhaled dose with a filter before the endotracheal tube on day 2. Amount of salbutamol excreted in urine 30 min post inhalation and the amount deposited on the filter from all the COPD patients were determined as indeces of pulmonary deposition and systemic absorption, respectively. ResultsNo significant difference was found between the 3 vibrating mesh nebulizers (VMNs). The in-vivo and ex-vivo testing showed that all the VMNs resulted in better aerosol delivery compared to JN (p < 0.01). However, MDI-AC resulted in better aerosol delivery to VMNs but must be accompanied with careful attention and proper delivery of MDI-AC doses by healthcare provider. ConclusionsVMNs can be exchanged with each other, with no dose adjustment. However, dose adjustment is a must when replacing VMNs by JN or MDI-AC. This similarity and difference between the 5 aerosol delivery methods suggest that for IMV patients, aerosol delivery methods should be chosen or substituted with care.

In-vitro/in-vivo comparison of inhaled salbutamol dose delivered by jet nebulizer, vibrating mesh nebulizer and metered dose inhaler with spacer during non-invasive ventilation

ABSTRACTBackground: Patients receiving noninvasive ventilation (NIV) may benefit from medical aerosol, but most guidance on dosing with different aerosol devices is limited to in-vitro studies. The study was designed to in-vitro, ex-vivo, and in-vivo compare aerosol delivery during bilevel NIV with three types of aerosol generators: metered dose inhaler with AeroChamber-MV spacer (AC), Aerogen Pro vibrating mesh nebulizer (PRO), and Sidestream jet nebulizer (SIDE). Materials and Method: A bilevel ventilator with dry single limb circuit and fixed expiratory port was set in spontaneous mode with initial inspiratory and expiratory pressures of 20 and 5 cmH20, 1:3 inspiratory-expiratory ratio, and 15 breaths.min−1. Aerosol generators were placed proximal to facial mask of NIV chronic obstructive pulmonary disease (COPD) patients. 1 mL salbutamol nebulizer solution (5 mg/mL) was nebulized using PRO and SIDE. 12MDI doses, containing 100μg salbutamol each, were delivered using AC. In-vitro aerosol fate and aerodynamic droplet characteristics, in-vivo amount of salbutamol excreted 30 mins and pooled up to 24 h post inhalation in urine from 12 COPD patients (as indices of pulmonary deposition and systemic absorption, respectively) and amount of salbutamol deposited on ex-vivo filters (expected inhalable amount) was determined. Results: The in-vitro, in-vivo and ex-vivo testing showed that PRO had better aerosol delivery compared to SIDE (p < 0.01). However, with smaller nominal dose MDI with AC resulted in similar aerosol delivery to PRO suggesting better aerosol delivery stress on careful attention and proper delivery by health care provider. Conclusions: These similarities and differences between the three aerosol generators tested suggest that aerosol delivery methods should be carefully chosen or substituted in non-invasive ventilated patients.

Cellular response to the deposition of diesel exhaust particle aerosols onto human lung cells grown at the air–liquid interface by inertial impaction

The pathogenesis of disease resulting from exposure to diesel exhaust particles (DEP) is often studied using cultured lung cells. Frequently, researchers expose cells to DEP by spiking a suspension of particles in liquid onto the apical surface. This is not representative of in vivo exposure, where aerosols are deposited onto cell surfaces at the air–liquid interface (ALI). Inertial impaction provides an opportunity to deliver high doses of particles with aerodynamic diameters >∼1μm to the surface of cells in seconds in a reproducible and predictable manner.A custom device was constructed to deposit DEP aerosols onto the surface of Calu-3 and A549 cells grown at the ALI. The pro-inflammatory and toxic cellular response to exposure to the deposited DEP aerosols was measured and compared to the response of cells exposed to DEP as suspensions. Calu-3 cells showed evidence of an oxidative stress response for both exposure types, while there was strong evidence to suggest that the method of aerosol delivery was harmful to the A549 cells.

Pharmaceutical and biotechnological aerosols for cystic fibrosis therapy

This review addresses different aerosol therapies used to treat the underlying cause and symptoms of cystic fibrosis (CF) during the past two decades. A summary of the current methods of aerosol delivery and suggestions that may improve the efficacy of the current treatments are provided.

Aerosol delivery of virulent Mycobacterium bovis to cattle

Setting: Although animal models of aerosol inoculation of Mycobacterium tuberculosis and M. bovis have been reported using laboratory animals, a model of aerosol delivery of M. bovis to cattle has not been reported previously. Objective: Develop and characterize a model of aerosol delivery of M. bovis to cattle, and compare the distribution of lesions in cattle infected with either of two different strains of M. bovis, one isolated from cattle (HC2005T), and the other isolated from white-tailed deer (1315). Design: Cattle ( n=20, female and castrated males) aged 4 months, were infected with 1×10 3 ( n=5) or 1×10 5 ( n=5) colony-forming units (CFU) of M. bovis 1315 or 1×10 3 ( n=5) or 1×10 5 ( n=5) CFU of M. bovis HC2005T. Calves were infected using a commercially available aerosol delivery system. One hundred fifty-five days after infection, calves were euthanized, examined and tissues collected for microscopic analysis and bacteriologic culture. Results: Nineteen of 20 calves developed tuberculosis. Typical tuberculous lesions were most pronounced in the lungs and tracheobronchial and mediastinal lymph nodes. Conclusion: The system described provides a reliable method of aerosol delivery of M. bovis to cattle. Lesion distribution suggests that the aerosolized inoculum was delivered deep into pulmonary alveoli and thus represents true aerosol exposure. Disease was more severe in groups receiving the highest dose of either inoculum strain; however, differences between strains were not seen. Published by Elsevier Science Ltd.

Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits.

The deposition efficiency of three methods of aerosol delivery of salbutamol into lungs of ventilated rabbits was compared: 1) metered dose inhaler (MDI) with holding chamber (HC), 2) jet nebulizer (JN), and 3) ultrasonic (US) nebulizer. The latter system was tested using two different sized medication reservoirs, a large (20 mL) cup (US20) and a small (10 mL) cup (US10). After delivery of technetium-99m-labeled salbutamol aerosol, deposition in the lungs, trachea, and ventilator circuit were estimated by a gamma counter. Total pulmonary deposition [mean(SEM)] as a percentage of the prescribed drug was: MDI + HC 0.22(0.05)%; JN 0.48(0.05)%; US20 0.90(0.13)%; US10 3.05(0.49)%. Only the deposition from the US10 was statistically significantly higher than the other modes (p < 0.05). Dynamic scintigraphy showed that, among the nebulizers, the US10 continued to deliver medication for longer than either the JN or the US20. We conclude that the US10 appears to be more efficient in delivering aerosol to the lung in this rabbit model and merits further evaluation for clinical efficiency.

Repeatability of methacholine challenges in 2- to 4-year-old children with asthma, using a new technique for quantitative delivery of aerosol.

To determine the repeatability of bronchial responsiveness in awake young children, two methacholine challenge tests were performed on separate days in 16 children with stable asthma (mean age, 3 3/4 years). Methacholine was administered using a new method for quantitative delivery of aerosol that eliminates the effect of dilution of the aerosol by entrainment of air and enables quantitative delivery of aerosol according to body weight. Respiratory function was monitored by measurement of respiratory resistance by the interrupter technique (Rint), respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique, transcutaneous measurements of oxygen (PtcO2), and specific airway resistance (sRaw). Repeatability was evaluated by determining the provocative dose that caused a defined percentage of change relative to baseline (PD%: Rint PD30, Rrs5 PD30, Xrs5 PD80, PtcO2 PD10, and sRaw PD80. Repeatability was estimated from the difference between the PD% obtained at the time of the two tests. Using the numeric value of these differences, the repeatability of Xrs5 PD60, PtcO2 PD10, and sRaw PD50 was [mean (SD)]: [0.8 (0.5)] [0.5 (0.4)] and [0.7 (0.6)] doubling doses, respectively. Rint PD30 and Rrs5 PD30 proved to be less reproducible: [1.2 (1)] and [1.6 (0.9)] doubling doses, respectively. The new method of aerosol delivery offers a means of standardizing the bronchoconstrictor stimulus, and the results show that estimates of bronchial responsiveness in young children can be obtained reproducibly within one doubling dose of methacholine.

Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients.

Metered-dose inhalers (MDIs) provide several advantages over nebulizers, including ease of administration, decreased cost, reliability of dosing, and freedom from contamination. However, this method of aerosol delivery has been considered ineffective in mechanically-ventilated patients because most of the aerosol deposits in the endotracheal tube and ventilator circuit. A smaller amount of aerosol from a MDI is deposited in the lower respiratory tract of mechanically-ventilated patients than in ambulatory patients, although recent studies show that a significant bronchodilator effect can still be achieved. When employed optimally, significant bronchodilation occurs with as little as 4 puffs of a sympathomimetic aerosol. Multiple factors influence the efficacy of MDIs in mechanically-ventilated patients. The method of connecting the MDI canister to the ventilator circuit has a marked effect on aerosol delivery, and other factors include the timing of MDI actuation, ventilator mode, tidal volume, circuit humidity, and duty cycle. With a proper technique of administration, a MDI serves as an effective, convenient, and safe method for delivering bronchodilator aerosols in mechanically-ventilated patients.

Pulmonary deposition of a nebulised aerosol during mechanical ventilation.

There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (99mTc HSA (50 micrograms); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2.2 (0.8)% with 1.5% and 0.7% depositing in the right and left lungs respectively; 0.9% of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients.

Metered Dose Inhalers for Bronchodilator Delivery in Intubated, Mechanically Ventilated Patients

We determined the relative efficacy of two bronchodilator aerosol delivery methods in 18 intubated mechanically ventilated patients with airways obstruction. Two treatment arms, consisting of albuterol 270 micrograms (three puffs) from a metered dose inhaler and albuterol 2.5 mg from a saline solution nebulized with an updraft inhaler, were compared in a single blind, randomized crossover design. Pulmonary function was evaluated using an interrupter technique. Changes in passive expiratory flow at respiratory system recoil pressures between 6 and 10 cm H2O provided the therapeutic endpoints. Paired measurements were made before and 30 minutes after drug delivery. The MDI and NEB resulted in similar improvements in iso-recoil flow (mean increase for both groups = 0.1 L/s). Treatment sequence, severity of obstruction, and bronchodilator responsiveness had no effect on relative efficacy. Albuterol caused a small but significant increase in heart rate that was similar following both delivery methods. We conclude that bronchodilator aerosol delivery with metered dose inhalers provides a viable alternative to nebulizer therapy in intubated mechanically ventilated patients and may result in a cost savings to hospitals and patients.

Aerosol delivery in lung disease

Metered-dose inhalers are the preferred method of aerosol delivery under normal circumstances because of their convenient size, ease of use and better patient compliance. Where poor coordination exists a spacer device, breath-activated inhaler or powder inhalation should be used and if muscular weakness presents a problem a Haleraid should be tried. A clinical air pump with jet nebuliser is appropriate if these methods prove unsatisfactory; where wet aerosol has been shown to result in clearly superior effects; for very small children; and for the "brittle" asthmatic prone to sudden life-threatening attacks, especially patients living in isolated conditions. Regular checks on aerosol techniques and efficacy of therapy are important aspects of follow up and education of all patients with airflow obstruction.

Pressurized bronchodilator aerosol technique: Influence of breath-holding time and relationship of inhaler to the mouth

Twenty-seven patients with reversible airways obstruction have been studied to determine the effect of two methods of aerosol delivery on bronchodilator response to fenoterol. There was no significant difference in response after inhaling with the mouth open or closed, and breath-holding for 10 seconds offered no significant advantage compared to 4 seconds.

Pressurized bronchodilator aerosol technique: Influence of breath-holding time and relationship of inhaler to the mouth

Twenty-seven patients with reversible airways obstruction have been studied to determine the effect of two methods of aerosol delivery on bronchodilator response to fenoterol. There was no significant difference in response after inhaling with the mouth open or closed, and breath-holding for 10 seconds offered no significant advantage compared to 4 seconds.

The tube spacer in children with asthma.

ABSTRACT. We compared the use of a standard metered aerosol actuator with the tube spacer in delivering 500 micrograms of terbutaline sulphate to the airways of seven children with clinical asthma. Each child used the standard metered aerosol in his usual way and the tube spacer with a 5 second delay between actuation and inhalation on separate occasions. Response was measured by change in forced expiratory volume in one second (FEV1). We found no significant difference in bronchodilatation between the two methods of aerosol delivery. We conclude that the tube spacer is an effective way of delivering a metered aerosol and that it has the advantage of allowing up to 5 seconds between actuation and inhalation. The tube spacer has particular application in young children who have difficulty in co‐ordinating their inspiration with metered aerosol actuation.