Mesh Nebulizer Research Articles

Comparative study of the effects of mesenchymal stem cells with different delivery methods in an experimental model of lung fibrosis

Background: Transplantation of mesenchymal stem cells (MSCs) is one of the most promising directions in the treatment of idiopathic pulmonary fibrosis. In experimental small animal studies, intravenous and endobronchial (installation) techniques are used for the cell preparation delivery, while in humans inhalation of drugs is the simplest and most available method.
 Aim: The aim of the study was to determine the optimal type of a nebulizer for viability of MSCs during nebulization, followed by a comparison of the effects of inhalation and intravenous delivery methods in a standard model of bleomycin pulmonary fibrosis in rabbits.
 Methods: At the first stage, the survival of MSCs was assessed ex vivo after 10 minutes of compressor, ultrasound and mesh nebulization. Subsequently we used a nebulizer, which showed the best result in the cells, viability. At the next stage аfter bronchoscopic installation of bleomycin, 5 rabbits received intravenous transplantation of 2×106 allogeneic BMMSCs, other 5 rabbits — 2×107 MSCs inhaled via a compressor nebulizer; the control healthy and bleomycin groups included 5 animals each.
 Results: The highest degree of viability of MSC was maintained after passing via the compressor nebulizer (72%), a significantly lower survival rate was observed in ultrasonic nebulization (20%) and no live cells were detected after mesh nebulization. Both groups treated with MSC had a significantly lower fibrosis index on the Ashcroft morphometric scale than the control group of bleomycin fibrosis. Collagen expression in the lung tissue was significantly higher in all the groups with bleomycin injury, but in animals which underwent MSC inhalation, it was significantly different (0.51 point) from the bleomycin group without treatment (2.1 points). The level of neutrophils in the BAL fluid was significantly lower in animals which received the intravenous MSC therapy. The levels of TNF-α and TGF-β1 in the BAL fluids tended to decrease in the treatment groups, but did not differ significantly from control.
 Conclusions: The highest survival rate of MSCs is observed when using a compressor nebulizer, which apparently should be considered as the best way for delivering cells to the respiratory tract. Both inhalation and intravenous administration of MSCs cause similar effects of inhibiting the development of bleomycin-induced pulmonary fibrosis, which indicates the possibility of using both ways of cell delivery without loss of effectiveness.

Nasal high-flow bronchodilator nebulization: a randomized cross-over study

BackgroundThere is an absence of controlled clinical data showing bronchodilation effectiveness after nebulization via nasal high-flow therapy circuits.ResultsTwenty-five patients with reversible airflow obstruction received, in a randomized order: (1) 2.5 mg albuterol delivered via a jet nebulizer with a facial mask; (2) 2.5 mg albuterol delivered via a vibrating mesh nebulizer placed downstream of a nasal high-flow humidification chamber (30 L/min and 37 °C); and (3) nasal high-flow therapy without nebulization. All three conditions induced significant individual increases in forced expiratory volume in one second (FEV1) compared to baseline. The median change was similar after facial mask nebulization [+ 350 mL (+ 180; + 550); + 18% (+ 8; + 30)] and nasal high flow with nebulization [+ 330 mL (+ 140; + 390); + 16% (+ 5; + 24)], p = 0.11. However, it was significantly lower after nasal high-flow therapy without nebulization [+ 50 mL (− 10; + 220); + 3% (− 1; + 8)], p = 0.0009. FEV1 increases after facial mask and nasal high-flow nebulization as well as residual volume decreases were well correlated (p < 0.0001 and p = 0.01). Both techniques showed good agreement in terms of airflow obstruction reversibility (kappa 0.60).ConclusionAlbuterol vibrating mesh nebulization within a nasal high-flow circuit induces similar bronchodilation to standard facial mask jet nebulization. Beyond pharmacological bronchodilation, nasal high flow by itself may induce small but significant bronchodilation.

Delivery of pDNA Polyplexes to Bronchial and Alveolar Epithelial Cells Using a Mesh Nebulizer.

In this study, a cell penetrating peptide was used as an uptake enhancer for pDNA delivery to the lungs. Polyplexes were prepared between pDNA and CPP. Intracellular delivery of pDNA was assessed in both alveolar (A549) and bronchial (Calu-3) epithelial cells. Aerosol delivery was investigated using a mesh nebulizer. Efficient intracellular delivery of pDNA occurs in both A549 and Calu-3 cells when delivered as polyplexes. Protection against nucleases and endosomal escape mechanism occurs when pDNA is formulated within the polyplexes. For aerosol delivery, 1% (w/v) mannitol was able to protect naked DNA structure during nebulization with a significant increase in fine particle fraction (particles <5μm). The structure of polyplexes when delivered via a mesh nebulizer using 1% (w/v) mannitol could partially withstand the shear forces involved in aerosolization. Although some loss in functionality occurred after nebulization, membrane-associated fluorescence was observed in A549 cells. In Calu-3 cells mucus entrapment was a limiting factor for polyplex delivery. The presence of CPP is essential for efficient intracellular delivery of pDNA. The polyplexes can be delivered to lung epithelial cells using mesh nebulizer. The use of different excipients is essential for further optimization of these delivery systems.

Synergy of nebulized phage PEV20 and ciprofloxacin combination against Pseudomonas aeruginosa

Nebulization is currently used for delivery of antibiotics for respiratory infections. Bacteriophages (or phages) are effective predators of pathogens including Pseudomonas aeruginosa commonly found in the lungs of patients with cystic fibrosis (CF). It is known that phages and antibiotics can potentially show synergistic antimicrobial effect on bacterial killing. In the present study, we investigated synergistic antimicrobial effect of phage PEV20 with five different antibiotics against three P. aeruginosa strains isolated from sputum of CF patients. The antibiotics included ciprofloxacin, tobramycin, colistin, aztreonam and amikacin, which are approved by U.S Food and Drug Administration (FDA) for inhaled administration. Phage and antibiotic synergy was determined by assessing bacterial killing performing time-kill studies. Among the different phage-antibiotic combinations, PEV20 and ciprofloxacin exhibited the most synergistic effect. Two phage-ciprofloxacin combinations, containing 1/4 and 1/2 of the minimum inhibitory concentration (MIC) of ciprofloxacin against P. aeruginosa strains FADD1-PA001 (A) and JIP865, respectively were aerosolized using both air-jet and vibrating mesh nebulizers and the synergistic antibacterial activity was maintained after nebulization. Air-jet nebulizer generated droplets with smaller volume median diameters (3.6–3.7 µm) and slightly larger span (2.3–2.4) than vibrating mesh nebulizers (5.1–5.3 µm; 2.1–2.2), achieving a higher fine particle fraction (FPF) of 70%. In conclusion, nebulized phage PEV20 and ciprofloxacin combination shows promising antimicrobial and aerosol characteristics for potential treatment of respiratory tract infections caused by drug-resistant P. aeruginosa.

Efficient Nose-to-Lung Aerosol Delivery with an Inline DPI Requiring Low Actuation Air Volume.

To demonstrate efficient aerosol delivery through an in vitro nasal model using a dry powder inhaler (DPI) requiring low actuation air volumes (LV) applied during low-flow nasal cannula (LFNC) therapy. A previously developed LV-DPI was connected to a LFNC system with 4mm diameter tubing. System connections and the nasal cannula interface were replaced with streamlined components. To simulate nasal respiration, an in vitro nasal model was connected to a downstream lung simulator that produced either passive or deep nasal respiration. Performance of a commercial mesh nebulizer system was also considered. For the optimized system, steady state cannula emitted dose was 75% of the capsule loaded dose. With cyclic nasal breathing, delivery efficiency to the tracheal filter was 53-55% of the loaded dose, which was just under the design target of 60%. Compared with a commercially available mesh nebulizer, the optimal LV-DPI was 40-fold more efficient and 150 times faster in terms of delivering aerosol to the lungs. The optimized LV-DPI system is capable of high efficiency lung delivery of powder aerosols through a challenging nasal cannula interface.

Effects of Fill Volume and Humidification on Aerosol Delivery During Single-Limb Noninvasive Ventilation.

The aim of this work was to determine the effect of fill volume and humidification change on aerosol delivery during single-limb noninvasive ventilation (NIV). Four groups were recruited, each consisting of 12 subjects (6 females) with COPD receiving NIV. Groups 1 and 3 received inhaled salbutamol with a vibrating mesh nebulizer, and Groups 2 and 4 received inhaled salbutamol with a jet nebulizer. The in vivo study was carried out on days 1 and 3. In groups 1 and 2, 2 fill-volumes were delivered to each subject; 1 mL 5,000 μg/mL salbutamol respirable solution used as it is or diluted to a total of 2 mL using normal saline. In groups 3 and 4, 1 mL 5,000 μg/mL salbutamol respirable solution diluted to 2 mL total volume using normal saline was delivered to each subject with and without humidification. Unchanged salbutamol in urine at 30 min (USAL0.5) and in pooled urine at 24 h (USAL24) was determined. On day 2, the ex vivo study was carried out on subjects using the same experimental setting with a filter placed proximal to their face mask for collection of total inhaled dose of salbutamol (aerosol emitted). The vibrating mesh nebulizer delivered higher USAL0.5, USAL24, and aerosol emitted compared to the jet nebulizer at all fill volumes and humidification conditions (P < .001). Increasing fill volume from 1 mL to 2 mL resulted in a significant increase in USAL0.5, USAL24, and aerosol emitted from the jet nebulizer (P < .05) with an insignificant effect on the vibrating mesh nebulizer. A 2-mL fill volume with the jet nebulizer delivered USAL24 and aerosol emitted comparable to those of 1 mL with the vibrating mesh nebulizer with significantly longer nebulization times (P < .001). Humidification had an insignificant effect on aerosol delivery. Increasing the fill volume of a jet nebulizer is essential to increase the amount of inhaled medication reaching a subject. In contrast, there is no need to increase fill volumes when using a vibrating mesh nebulizer. There is no need to switch off the humidifier while delivering aerosol through a single-limb NIV circuit.

P030 Modelled deposition of colistimethate sodium aerosol in the lungs of patients with cystic fibrosis using two different mesh nebulisers

P030 Modelled deposition of colistimethate sodium aerosol in the lungs of patients with cystic fibrosis using two different mesh nebulisers

In Vitro Determination of the Main Effects in the Design of High-Flow Nasal Therapy Systems with Respect to Aerosol Performance.

IntroductionThe use of concurrent aerosol delivery during high-flow nasal therapy (HFNT) may be exploited to facilitate the delivery of a variety of prescribed medications for inhalation. Until now, a systematic approach to determine the conditions required to yield an optimal emitted dose has not been reported. The aim of this study was to establish the effects of gas flow rate, input droplet size, and nebulizer position on the amount of aerosol exiting the nasal cannula during HFNT and thus becoming available for inhalation.MethodsTesting was completed according to a factorial statistical design of experiments (DOE) approach. Emitted dose was characterized with a vibrating mesh nebulizer (Aerogen Solo, Aerogen Ltd) for an adult model of HFNT at three clinically relevant gas flow rates, using three nebulizers producing varying input droplet sizes and placed at two different nebulizer positions.ResultsIncreasing the gas flow rate significantly lowered the emitted dose, with a dose of 7.10% obtained at 10 LPM, 2.67% at 25 LPM, and 1.30% at 40 LPM (p < 0.0001). There was a significant difference in emitted dose between nebulizers with different input droplet sizes, with increasing input droplet size associated with a reduced emitted dose (6.11% with an input droplet size of 3.22 µm, 2.76% with 4.05 µm, and 2.38% with 4.88 µm, p = 0.0002, Pearson’s r = − 0.2871). In addition, the droplet size exiting the nasal cannula interface was lower than that produced by the aerosol generator for all devices under test. Positioning the nebulizer immediately after the humidification chamber yielded a marginally greater emitted dose (3.79%) than when the nebulizer was placed immediately upstream of the nasal cannula (3.39%). Flow rate, input droplet size, and nebulizer position were at the 0.10 level of significance, indicating that all three factors had significant effects on emitted dose. According to the DOE model, flow rate had the greatest influence on emitted dose, followed by input droplet size and then nebulizer position.ConclusionOur findings indicate that in order to optimize the amount of aerosol exiting the nasal cannula interface during HFNT, it is necessary for gas flow rate to be low and the input droplet size to be small, while the nebulizer should be positioned immediately after the humidification chamber.FundingAerogen Limited.

AEROSOL THERAPY DURING NON-INVASIVE VENTILATION

Nowadays, the effectiveness of inhalation drug therapy during non-invasive ventilation (NIV) has been proved. The delivery of aerosol drugs during non-invasive ventilation depends on numerous factors, such as the choice of inhalation equipment and a mask, position of the leak port and position of the device in the respirator settings. Innovations in the field of inhalation therapy resulted in the development new devices able to optimize pulmonary deposition and reduce the time of inhalation therapy. Compared to standard jet nebulizers, mesh nebulizers can deliver the 4 fold higher dose of the drug to the patient's airways. Further research is needed in order to investigate the opportunities of aerosol therapy during high-flow oxygen therapy by means of nasal cannulae.

Nebulization of single-chain tissue-type and single-chain urokinase plasminogen activator for treatment of inhalational smoke-induced acute lung injury

Single-chain tissue-type plasminogen activator (sctPA) and single-chain urokinase plasminogen activator (scuPA) have attracted interest as enzymes for the treatment of inhalational smoke-induced acute lung injury (ISALI). In this study, the pulmonary delivery of commercial human sctPA and lyophilized scuPA and their reconstituted solution forms were demonstrated using vibrating mesh nebulizers (Aeroneb® Pro (active) and EZ Breathe® (passive)). Both the Aeroneb® Pro and EZ Breathe® vibrating mesh nebulizers produced atomized droplets of protein solution of similar size of less than about 5 μm, which is appropriate for pulmonary delivery. Enzymatic activities of scuPA and of sctPA were determined after nebulization and both remained stable (88.0% and 93.9%). Additionally, the enzymatic activities of sctPA and tcuPA were not significantly affected by excipients, lyophilization or reconstitution conditions. The results of these studies support further development of inhaled formulations of fibrinolysins for delivery to the lungs following smoke-induced acute pulmonary injury.

Fabrication and Characterization of Medical Mesh-Nebulizer for Aerosol Drug Delivery

In the field of drug delivery, a nebulizer is a device used to convert liquid drugs into tiny airborne droplets, such as aerosol or a mist form. These fine droplets are delivered to a patient’s lungs and airways and then spread throughout the body via blood vessels. Therefore, nebulization therapy is a highly-effective method compared with existing drug delivery methods. To enhance the curative influence of a drug, this study suggests the use of a new micro-porous mesh nebulizer consisting of a controllable palladium–nickel (Pd–Ni) membrane filter, piezoelectric element, and a cavity in the micro-pump. In this research, we optimize a biocompatible Pd–Ni membrane filter, such that it generated the smallest aerosol particles of various drugs. The pore size of the filter outlet is 4.2 μm ± 0.15 μm and the thickness of the Pd-Ni membrane filter is approximately 41.5 μm. In addition, the Pd–Ni membrane filter has good biocompatibility with normal cells. The result of a spray test with deionized (DI) water indicated that the size of a standard liquid droplet is 4.53 μm. The device has an electrical requirement, with a low power consumption of 2.5 W, and an optimal operation frequency of 98.5 kHz.

Modeling and optimization of nebulizers' performance in non-invasive ventilation using different fill volumes: Comparative study between vibrating mesh and jet nebulizers

BackgroundsSubstituting nebulisers by another, especially in non-invasive ventilation (NIV), involves many process-variables, e.g. nebulizer-type and fill-volume of respirable-dose, which might affect patient optimum-therapy. The aim of the present work was to use neural-networks and genetic-algorithms to develop performance-models for two different nebulizers. MethodsIn-vitro, ex-vivo and in-vivo models were developed using input-variables including nebulizer-type [jet nebulizer (JN) and vibrating mesh nebulizer (VMN)] fill-volumes of respirable dose placed in the nebulization chamber with an output-variable e.g. average amount reaching NIV patient. Produced models were tested and validated to ensure effective predictivity and validity in further optimization of nebulization process. ResultsData-mining produced models showed excellent training, testing and validation correlation-coefficients. VMN showed high nebulization efficacy than JN. JN was affected more by increasing the fill-volume. The optimization process and contour-lines obtained for in-vivo model showed increase in pulmonary-bioavailability and systemic-absorption with VMN and 2 mL fill-volumes. ConclusionsModeling of aerosol-delivery by JN and VMN using different fill-volumes in NIV circuit was successful in demonstrating the effect of different variable on dose-delivery to NIV patient. Artificial neural networks model showed that VMN increased pulmonary-bioavailability and systemic-absorption compared to JN. VMN was less affected by fill-volume change compared to JN which should be diluted to increase delivery.

Nebulized therapy in children

Nebulization is widely used in treating respiratory disorders in younger patients and critically ill children.Jet nebulizers, ultrasonic nebulizers and vibrating mesh nebulizers are the main types of small volume nebulizers used in emergency room and pediatric intensive care unit.Glucocorticoids, bronchodilators, mucolytic agents can be administered via nebulization.Different compatibilities exist among these therapeutic agents. Key words: Child; Nebulization; Small volume nebulizer; Nebulizable drug

Comparability of methacholine challenge test results between two jet nebulizers

ABSTRACTRATIONALE: To improve standardization of methacholine challenge testing, all nebulizers must be characterized in a manner that allows data comparability between test sites regardless of the protocol or equipment used. In response to issues concerning the highly standardized Wright jet nebulizer, other devices, which may or may not be characterized, have been used for testing. One such device is the Bennett Twin jet nebulizer, which has been assumed to produce equivalent results to the Wright based on a small, unpublished data set.OBJECTIVE: Determine if the Wright and Bennett Twin jet nebulizers produce equivalent methacholine challenge test results.METHODS AND MEASUREMENTS: As an addition to a larger, multi-site study comparing the Wright jet nebulizer and the Aerogen® Solo vibrating mesh nebulizer for standard use in methacholine challenge testing, our test site (n = 20) included a crossover study arm that entailed testing with the Bennett Twin in mild-to-moderate asthmatics. The two jet nebulizer models were calibrated with the same methodology (weight loss of 0.13 g/min) and were operated per the two-minute tidal breathing protocol. Test results in the form of the PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) were compared. MAIN RESULTS: The two jet nebulizer models produced equivalent PC20 results, with geometric mean data of 2.3 mg/mL and 1.8 mg/mL for the Wright and Bennett Twin, respectively.CONCLUSION: These findings suggest that, like the Wright, the Bennett Twin is suitable for standard use in methacholine challenge testing.

Pharmacokinetics and Pharmacodynamics of Nebulized and Intratracheal Milrinone in a Swine Model of Hypercapnia Pulmonary Hypertension

Milrinone pulmonary administration is used currently for the treatment of pulmonary hypertension. Several methods are available: simple jet nebulization, vibrating mesh nebulization, intratracheal instillation, and intratracheal atomization. The aim of this study was to explore the concentration-effect relationship of milrinone for each of these methods. Observational open-label pharmacokinetic/pharmacodynamics cohort study. Single-center, hospital animal laboratory. Twelve swine. After hypercapnia pulmonary hypertension, swine were administered equivalent inhaled milrinone doses of 15 or 50 µg/kg through simple jet nebulization, vibrating mesh nebulization, intratracheal instillation, and intratracheal atomization. Blood and urine samples were taken up to 360 minutes postadministration. The ratio of mean systemic arterial pressure to mean pulmonary arterial pressure was monitored continuously. Right heart echographies were taken before and after hypercapnia and after drug administration. Mean elimination half-lives were similar for the 4 administrations. Mean percent changes in the ratio were of 37 (60%), 18 (31%), 17 (36%), and 20 (20%), for simple jet nebulization, vibrating mesh nebulization, intratracheal instillation, and intratracheal atomization, respectively. Mean maximum plasma concentrations for intratracheal administrations were reached at 8 and 45 min for atomization and instillation, respectively. Significant increases in right atrial diameter and right ventricular end-diastolic area were witnessed during pulmonary hypertension as well as a return to baseline values after milrinone administration. The intratracheal methods, particularly intratracheal atomization, showed less hemodynamic effect than nebulizations and, in the case of intratracheal instillation, unpredictable drug exposure. Nebulization methods on the other hand, especially simple jet nebulization, suggest better efficacy and sensitivity but are less fit for emergency situations.

Mesh nebulizers have become the first choice for new nebulized pharmaceutical drug developments.

In the 24 years since first being marketed, the mesh nebulizer has been developed by five main manufacturers into a viable solution for the delivery of high-value nebulized drugs. Mesh nebulizers provide increased portability, convenience and energy efficiency along with similar lung deposition and increased ease of use compared with jet nebulizers. An analysis of EU and US clinical trial databases has shown that mesh nebulizers are now preferred over jet nebulizers for clinical trials sponsored by pharmaceutical companies. The results show a strong preference for the use of mesh nebulizers in trials involving high cost and niche therapy areas. Built-in capability to optimize the way patients use their mesh nebulizer and manage their disease will further increase uptake. [Formula: see text].

Comparison of the Clinical Efficacy of Salbutamol with Jet and Mesh Nebulizers in Asthmatic Children

Background Ultrasonic, jet, and mesh nebulizers have all been used in the treatment for asthma. Mesh nebulizers reportedly offer the best inhalation efficiency. Methods This study aimed to clarify the utility of the mesh nebulizer, compared to jet nebulizers, in the treatment of pediatric asthma patients. Participants included 88 children <6 years old who were receiving treatment for asthma at Murayama Pediatric Clinic. Heart rate, peripheral oxygen saturation in arterial blood, and Mitsui symptom scores were compared before and after treatment with a mesh nebulizer (n = 43) or jet nebulizer (n = 45) using a salbutamol inhalation solution (0.2 ml for children ≧ 2 years old, n = 51; 0.1 ml for children < 2 years old, n = 37). Results Other than required inhalation time, clinical findings did not differ between mesh and jet groups. In both groups, heart rate increased significantly in patients treated with 0.2 ml (1000 microg) of salbutamol. Conclusions and Clinical Relevance The required inhalation time of the mesh nebulizer was superior to the jet nebulizer. Children ≧ 2 years with mild asthma attacks experienced a significantly increased heart rate in both groups. The dose of salbutamol (0.2 ml for ≧2 years) used for asthma attacks should be reconsidered in mild asthma.

Vibrating Mesh Nebulisers – Can Greater Drug Delivery to the Airways and Lungs Improve Respiratory Outcomes?

Aerosols are an increasingly important mode of delivery of drugs, particularly bronchodilators, for the treatment of respiratory diseases, notably asthma and chronic obstructive pulmonary disease. The most common type of nebuliser is the jet nebuliser (JN); they have been in use for more than a century but these devices can be cumbersome to use and may sometimes deliver insufficient amounts of drug. A more recent development in aerosol therapy is the vibrating mesh nebuliser (VMN) which is very user friendly and is more efficient than the JNs due to an extremely low residual volume. Scintigraphy images from studies of volunteer subjects using radio-labelled aerosol treatment show that VMN-generated aerosols deliver more drug to patients in a shorter period of time than JN-generated aerosols. Various bench, animal model and small clinical studies have shown that VMNs are more efficient than JNs in drug delivery, potentially improving clinical outcomes. These studies have included various breathing circuits used in mechanical ventilation (MV), non-invasive ventilation, high-flow nasal cannula systems and devices for spontaneously breathing patients. The efficiency of drug delivery was affected by factors including the position of the nebuliser in the circuit and humidity. Some studies have shown potential substantial savings by hospitals in the cost of MV treatments after switching from metered dose inhalers to VMNs. VMNs have also been shown to be effective for the administration of inhaled antibiotics, corticosteroids and other drugs. Larger studies of the effects of VMNs on patient outcomes are needed but they are likely to be an increasingly important means of administering therapies to a burgeoning population with respiratory disease.

Aerosol delivery during spontaneous breathing with different types of nebulizers- in vitro/ex vivo models evaluation

BackgroundNebulizers for spontaneous breathing have been evaluated through different study designs. There are limitations in simulated bench models related to patient and nebulizer factors. The aim of this study was to determine the correlation of inhaled drug mass between in vitro and ex vivo studies by testing aerosol deposition of various types of nebulizers. MethodsTen healthy subjects were recruited to receive aerosol therapy with five nebulizers in random order: 1) a jet nebulizer (JN); 2) a breath-enhanced nebulizer (BEN); 3) a manually triggered nebulizer (MTN), 4) a breath-actuated nebulizer (BAN), and 5) a vibrating mesh nebulizer (VMN) with valved-adapter. A unit dose of salbutamol containing 5 mg in 2.5 mL was placed into the nebulizer and administered for 10 min. For the ex vivo study, minute ventilation of healthy subjects was recorded for 1 min. For the in vitro study a breathing simulator was utilized with adult breathing patterns. Aerosolized drug from the nebulizers and the accessory tubes was captured using inspiratory and expiratory collecting filters. Captured drug was eluted, measured and expressed as inhaled and exhaled mass using spectrophotometry at a wavelength of 276 nm. Results10 healthy subjects were recruited, aged 20.8 ± 0.7 years old, with a mean height of 166.2 ± 9.2 cm and weight of 64.7 ± 12.4 kg. There was no significant difference in the inhaled drug dose between the JN and BEN (15.0 ± 1.94% and 17.74 ± 2.65%, respectively, p = .763), yet the inhaled doses were lower than the other three nebulizers (p < .001). The VMN delivered greater inhaled dose than the other four nebulizers (p < .01). The respiratory rate of the cohorts was significantly correlated with the inhaled drug dose. For the in vitro model, the JN delivered a lower inhaled dose (11.6 ± 1.6, p < .001) than the other nebulizers, whereas the MTN and BAN deposited significantly lower exhaled doses (1.7 ± 0.4 and 2.7 ± 0.2, respectively, p < .001). The VMN demonstrated a greater drug dose with the in vitro study than the ex vivo model (44.0 ± 0.9% and 35.5 ± 6.3% respectively, p = .003), whereas the JN in the ex vivo model resulted in a greater inhaled drug dose (15.0 ± 1.9% for ex vivo vs 11.6 ± 1.6% for in vitro, p = .008). ConclusionsThese in vitro/ex vivo model comparisons of nebulizers performance indicated that breath-related nebulizers can be estimated using an in vitro model; however, the JN and VMN delivered inhaled drug mass differed between models. There was a significant correlation between respiratory rate and inhaled mass, and the inhaled drug dose generated by VMN correlated with minute ventilation. This study demonstrated that the VMN produced greater inhaled drug dose and lowest residual dose, whereas the BEN, BAN, and MTN produced lower exhaled drug dose in both in vitro and ex vivo models.

Albuterol Delivery Efficiency in a Pediatric Model of Noninvasive Ventilation With Double-Limb Circuit.

Noninvasive ventilation (NIV) is used to treat respiratory failure in patients with concomitant need for aerosol delivery. Limited pediatric data are available on aerosol delivery efficiency, and none at all regarding aerosol delivery efficiency with a double-limb circuit. We compared the effect of position in the double-limb ventilator circuit, types of nebulizer, and ventilator settings on aerosol delivery efficiency in a pediatric model of NIV. We hypothesized that placing a vibrating mesh nebulizer at the ventilator and using the highest inspiratory pressures would increase aerosol delivery efficiency. A breathing simulator was connected in series to a low dead-space filter holder (lung dose) and to an anatomically correct head/airway model of a 5-year-old child. A non-vented mask connected the model to a ventilator operated on noninvasive bi-level mode and assembled with a double-limb, heated-wired adult circuit. Inspiratory pressures of either 15 or 20 cm H2O and an expiratory pressure of 5 cm H2O were used. Two different vibrating mesh nebulizers and 2 different jet nebulizers loaded with albuterol solution were studied. Albuterol was measured with spectrophotometry. Aerosol delivery efficiency was calculated as lung dose expressed as a percentage of the nominal dose. A vibrating mesh nebulizer before the mask or Y-piece provided the highest delivery efficiency and outperformed a vibrating mesh nebulizer integrated into the mask. Vibrating mesh nebulizers delivered more drug than jet nebulizers, regardless of their position in the circuit. Increasing the inspiratory pressure only improved aerosol delivery efficiency with a jet nebulizer placed at the ventilator. In a pediatric model of NIV, the effect of nebulizer position on aerosol delivery efficiency depends on the type of device and its placement in the ventilator circuit. A vibrating mesh nebulizer placed at the mask or before the Y-piece of the double-limb circuit provided the highest aerosol drug delivery during NIV. Data generated with invasive ventilation models should not be generalized to NIV models.