Vibrating Mesh Nebulizer Research Articles

Analytical model of the dynamic behavior of a vibrating mesh nebulizer for optimal atomization efficiency

This work deals with the assessment of optimal working condition of a mesh nebulizer on-demand droplet generation. The purpose of this paper is to introduce a model of vibrating mesh nebulizer to identify optimal working regime from a mechanical point of view. The influence of geometrical parameters and mechanical properties of both the piezoelectric component, vibrating plate and geometry of perforations is investigated and discussed based on an analytical model of stepped plate. This model is validated by 2D-axisymmetric finite element computations. The main trends identified by the model are recovered by the simulation and enable to formulate design rules to maximize the atomization efficiency with respect to a given set of mechanical and geometrical parameters.

Gelatin Stabilizes Nebulized Proteins in Pulmonary Drug Delivery against COVID-19.

Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to the lungs efficiently following nebulization. We have developed a high-affinity angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD-62) that can be used as a medication to inhibit infection with SARS-CoV-2 and its variants. In this study, we established a nebulization protocol for drug delivery by inhalation using two commercial vibrating mesh (VM) nebulizers (Aerogen Solo and PARI eFlow) that generate similar mist size distribution in a size range that allows efficient deposition in the small respiratory airway. In a series of experiments, we show the high activity of RBD-62, interferon-α2 (IFN-α2), and other proteins following nebulization. The addition of gelatin significantly stabilizes the proteins and enhances the fractions of active proteins after nebulization, minimizing the medication dosage. Furthermore, hamster inhalation experiments verified the feasibility of the protocol in pulmonary drug delivery. In short, the gelatin-modified RBD-62 formulation in coordination with VM nebulizer can be used as a therapy to cure SARS-CoV-2.

In-Vitro Comparison of Single Limb and Dual Limb Circuit for Aerosol Delivery via Noninvasive Ventilation.

The effect of single- and dual-limb circuits on aerosol delivery during noninvasive ventilation (NIV) in adult models is unclear. A noninvasive ventilator equipped with a single-limb circuit or an ICU ventilator equipped with a dual-limb circuit was connected to a simulated lung. Ventilator parameters were adjusted to maintain a tidal volume at ∼500 mL. Aerosol deposition with different placements of a vibrating mesh nebulizer and humidification conditions were compared. Additional experiments by using a non-vented mask or a vented mask were compared in the single-limb circuit only. Aerosol was collected by a disposable filter placed between the simulated lung and the head model (n = 3), and measured by ultraviolet spectrophotometry (276 nm). The aerosol deposition varied between 4.12 ± 0.22% and 20.75 ± 0.95%. The greatest aerosol delivery during NIV when using a non-vented mask was found when a vibrating mesh nebulizer was placed between the mask and 15 cm from the exhalation port in the humidified single-limb circuit, and 15 cm from the Y-piece in the inspiratory limb of the humidified dual-limb circuit, and no significant difference of aerosol deposition was found between the two optimal positions (20.03 ± 1.48% vs 18.04 ± 0.93%, respectively; P =.042). There was no difference of aerosol delivery in dry versus humidified circuits, except when a vibrating mesh nebulizer was placed at the humidifier inlet in a dual-limb circuit. When using a vented mask, the aerosol deposition was poor (6.56 ± 0.41 ∼ 8.02 ± 0.39%), regardless of vibrating mesh nebulizer positions and humidification types. During NIV, the aerosol delivery was optimal when a vibrating mesh nebulizer was placed between the non-vented mask and 15 cm from the exhalation port in the single-limb circuit or 15 cm from the Y-piece in the inspiratory limb of the dual-limb circuit; no significant difference was found between the two optimal placements. Humidification had little effect on aerosol delivery. Aerosol delivery was poor in the single-limb circuit with a vented mask.

Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients

BackgroundContinuous Positive Airway Pressure (CPAP), BiPhasic Positive Airway Pressure (BiPAP), and high flow nasal cannula (HFNC) show some evidence to have efficacy in COVID-19 patients. Delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The present work aimed to compare the effect of BiPhasic Positive Airway Pressure (BiPAP) mode at two different pressures; low BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 10/5 cm water) and high BiPAP (IPAP/EPAP of 20/5 cm water), with HFNC system on pulmonary and systemic drug delivery of salbutamol. On the first day of the experiment, all patients received 2500 μg salbutamol using Aerogen Solo vibrating mesh nebulizer. Urine samples 30 min post-dose and cumulative urinary salbutamol during the next 24 h were collected on the next day. On the third day, the ex-vivo filter was inserted before the patient to collect the delivered dose to the patient of the 2500 μg salbutamol. Salbutamol was quantified using high-performance liquid chromatography (HPLC).ResultsLow-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Low-pressure BiPAP showed the highest delivered systemic delivery amount followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP. The ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP.ConclusionsOur results of pulmonary, systemic, and ex-vivo drug delivery were found to be consistent. The low BiPAP delivered the highest amount followed by the HFNC then the high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP.

Pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following nebulisation of CMS among patients with ventilator-associated pneumonia

There has been accumulating interest in nebulised colistin methanesulfonate (CMS) for the treatment of ventilator-associated pneumonia (VAP). In this study, pulmonary and systemic pharmacokinetics following nebulisation of CMS at a dose of 3 MIU and 5 MIU, using a vibrating mesh nebuliser, for VAP caused by extensively drug-resistant Gram-negative pathogens was assessed. Blood samples and mini-bronchoalveolar lavage (mini-BAL) was performed post-dose at 1, 4 and 8 h. Concentrations of CMS and formed colistin in mini-BAL and plasma were determined by liquid chromatography–tandem mass spectrometry, and pharmacokinetic analysis was conducted using a population approach. The study population included three groups (n = 10 per group): (A) intravenous CMS and concomitantly nebulised CMS at a dose of 3 MIU (30 min duration); (B) nebulised CMS at a dose of 3 MIU (30 min duration) as monotherapy; and (C) nebulised CMS 5 MIU (45 min duration) as monotherapy. Mean plasma formed colistin concentrations were <1 mg/L following CMS nebulisation as monotherapy (groups B and C). Predicted trough concentrations of formed colistin in the epithelial lining fluid (ELF) following 24-h dosing of 3 MIU and 5 MIU nebulised CMS were 120.4 mg/L and 200.7 mg/L, respectively. The model predicted that concomitant intravenous CMS (group A) had minimal impact on the formed colistin concentration in ELF. This study demonstrated high ELF formed colistin concentrations following nebulised CMS (constantly above colistin MICs), while plasma concentrations were lower than those associated with nephrotoxicity. Our results provide important information for optimisation of nebulised colistin therapy.

Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study.

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.

Preliminary bronchodilator dose effect on aerosol-delivery through different nebulizers in noninvasively ventilated COPD patients

Objectives: This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. Method: COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose. Results: The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens(p < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery (p < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN (p < 0.001). Conclusion: Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.

Effect of IFN-α and other commonly used nebulization drugs in different nebulization methods on the resistance of breathing circuit filters under invasive mechanical ventilation.

BackgroundInterferon (IFN) is widely used in clinical practice and nebulization inhalation is one of the commonly used routes of administration. However, nebulization drugs such as interferon-α (IFN-α) with large molecular weights may deposit in the membrane of the breathing filters, causing its resistance to gradually increase. Thus, our study explores the effect of IFN-α and other nebulization drugs on the resistance of breathing circuit filters under invasive mechanical ventilation.MethodsWe divided 96 breathing filters into eight groups. The baseline group was not treated while the blank group was installed but were not nebulized. The remaining groups received jet nebulized or vibrating nebulized with either normal saline, Combivent, Amphotericin B, or IFN-α at a frequency of once every 12 hours separately and were removed from the breathing circuit after 24 hours. The resistance of the filter of each group was then measured and statistical comparisons were made.ResultsFilter resistance of the IFN-α jet nebulization group was greater than that of the other groups, and there were statistical differences except for the Amphotericin B jet nebulization group. Comparison of the resistance [cmH2O/(L·s)] of the IFN-α jet nebulization group vs. the baseline group showed 2.56 (2.40, 2.68) vs. 2.26 (2.03, 2.40), P=0.037; of the IFN-α jet nebulization group vs. the blank group showed 2.56 (2.40, 2.68) vs. 2.11 (1.98, 2.27), P=0.003; of the IFN-α jet nebulization group vs. the normal saline group: 2.56 (2.40, 2.68) vs. 2.16 (2.08, 2.32), P=0.023; of the IFN-α jet nebulization group vs. the Combivent jet nebulization group: 2.56 (2.40, 2.68) vs. 2.18 (2.14, 2.27), P=0.018; and of the IFN-α jet nebulization group vs. the Amphotericin B jet nebulization group: 2.56 (2.40, 2.68) vs. 2.33 (2.05, 2.45), P=0.221. The effect of jet nebulization and vibrating mesh nebulization on the resistance of breathing filters showed no significant statistical difference.ConclusionsJet nebulization with IFN-α significantly increased the resistance of the breathing filter within 24 hours and there was no significant difference in filter resistance between jet nebulization and vibrating mesh nebulization of IFN-α or Amphotericin B.

Nebulized Antibiotics for Healthcare- and Ventilator-Associated Pneumonia.

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new β-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

Contamination of Aerosol with Pseudomonas Aeruginosa Introduced via Mouthpiece in Different Nebulizer Designs

Background: Nebulizers have been associated with bacterial and viral contamination likely from drooling or expulson of oral secretions into the nebulizer mouthpiece. We hypothesized that simulated “drooling” could result in contamination of the nebulizer medication resulting in aerosolization of potential pathogens. Method: We evaluated four nebulizers: Continuous jet nebulizer (CJN: MistyMax, Allegiance, USA), breath enhanced (BEN:LC Sprint; Pari, Germany), breath actuated (BAN; AeroEclipse Monaghan/Trudell, Canada) and vibrating mesh nebulizer (VMN; Aerogen with Ultra, Aerogen Ltd, Galway, Ireland) operated per manufacturer recommendations with 3 mL of NSS. Pseudomonas aeruginosa broth (2 mL) was pipetted into the mouthpiece of each nebulizer in an upright postion simulating a patient drooling into the device. Aerosol was produced for 30-60 seconds and collected on Triptic Soy Agar (TSA) plate, prior, immeadiately, and 4-5 hours post instillation. Colony counts were done post incubation (3-5 days). Results: P. aeruginosa colony counts prior, immediately, and four hours after instillation; BAN (0, 110, and 122 CFU/m); and BEN (0, Too Numerous To Count (TNC), and TNC), VMN: (0, 0, and 0 CFU/mL) and CJN (0, 0, and 0 CFU/mL), respectively. Conclusions: Nebulizer type and design influence impact of pathogen containing fluids passing through the mouthpiece contaminating the aerosol generated.

Efficacy and safety of inhalation of pulmonary surfactant using vibrating mesh nebulizers combined with nasal continuous positive airway pressure in the treatment of neonatal respiratory distress syndrome

To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS). A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO2/FiO2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO2/FiO2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO2/FiO2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found (P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO2/FiO2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.

Effect on Airflow of a Vibrating Mesh Nebulizer Compared to a Jet Nebulizer for Delivery of Bronchodilator Therapy to Acute Severe Asthma Patients in an Emergency Department

Effect on Airflow of a Vibrating Mesh Nebulizer Compared to a Jet Nebulizer for Delivery of Bronchodilator Therapy to Acute Severe Asthma Patients in an Emergency Department

Mitigating Fugitive Aerosols During Aerosol Delivery via High-Flow Nasal Cannula Devices.

Aerosol delivery via high-flow nasal cannula (HFNC) has attracted clinical interest in recent years. However, both HFNC and nebulization are categorized as aerosol-generating procedures (AGPs). In vitro studies raised concerns that AGPs had high transmission risk. Very few in vivo studies examined fugitive aerosols with nebulization via HFNC, and effective methods to mitigate aerosol dispersion are unknown. Two HFNC devices (Airvo 2 and Vapotherm) with or without a vibrating mesh nebulizer were compared; HFNC alone, surgical mask over HFNC interface, and HFNC with face tent scavenger were used in a random order for 9 healthy volunteers. Fugitive aerosol concentrations at sizes of 0.3-10.0 μm were continuously measured by particle sizers placed at 1 and 3 ft from participants. On a different day, 6 of the 9 participants received 6 additional nebulizer treatments via vibrating mesh nebulizer or small-volume nebulizer (SVN) with a face mask or a mouthpiece with/without an expiratory filter. In vitro simulation was employed to quantify inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 and Vapotherm. Compared to baseline, neither HFNC device generated higher aerosol concentrations. Compared to HFNC alone, vibrating mesh nebulizer via Airvo 2 generated higher 0.3-1.0 μm particles (all P < .05), but vibrating mesh nebulizer via Vapotherm did not. Concentrations of 1.0-3.0 μm particles with vibrating mesh nebulizer via Airvo 2 were similar with vibrating mesh nebulizer and a mouthpiece/face mask but less than SVN with a mouthpiece/face mask (all P < .05). Placing a surgical mask over HFNC during nebulization reduced 0.5-1.0 μm particles (all P < .05) to levels similar to the use of a nebulizer with mouthpiece and expiratory filter. In vitro the inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 was ≥ 6 times higher than vibrating mesh nebulizer via Vapotherm. During aerosol delivery via HFNC, Airvo 2 generated higher inhaled dose and consequently higher fugitive aerosols than Vapotherm. Simple measures, such as placing a surgical mask over nasal cannula during nebulization via HFNC, could effectively reduce fugitive aerosol concentrations.

Efficacy of Various Mitigation Devices in Reducing Fugitive Emissions from Nebulizers.

Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo and mitigation of aerosol dispersion into the environment with various commercially available devices are not known. Nine healthy volunteers were given 3 mL saline with a small-volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved face mask for VMN, and a face mask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room with 2 particle counters positioned 1 and 3 ft from participants measuring aerosol concentrations at sizes of 0.3-10.0 μm at baseline, before, during, and after each treatment. Fugitive aerosol concentrations were higher with SVN than VMN and higher with a face mask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 μm in size for VMN and 0.3-3.0 μm for SVN (all P < .05). An Exhalo scavenger over the mask reduced 0.5-3.0 μm sized particle concentrations for SVN (all P < .05) but not VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosol concentrations regardless of the nebulizer type. SVN produced higher fugitive aerosol concentrations than VMN, whereas face masks generated higher aerosol concentrations than mouthpieces. Adding an exhalation filter to the mouthpiece or a scavenger to the face mask reduced aerosol concentrations for both SVN and VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosols as effectively as a mouthpiece with an exhalation filter. This study provides guidance for reducing fugitive aerosol emissions from nebulizers in clinical practice.

β Agonist Delivery by High-Flow Nasal Cannula During COPD Exacerbation.

Whereas high-flow nasal cannula (HFNC) oxygen therapy is increasingly used in patients with exacerbation of COPD, the effectiveness of β 2 agonist nebulization through HFNC has been poorly assessed. We hypothesized that salbutamol vibrating-mesh nebulization through HFNC improves pulmonary function tests in subjects with COPD. We conducted a physiological crossover study including subjects admitted to the ICU for severe exacerbation of COPD. After subject improvement allowing a 3-h washout period without bronchodilator, pulmonary function tests were performed while breathing through HFNC alone and after salbutamol vibrating-mesh nebulization through HFNC. The primary end point consisted in the changes in FEV1 before and after salbutamol nebulization. Secondary end points included the changes in FVC, peak expiratory flow (PEF), airway resistance, and clinical parameters. Among the 15 subjects included, mean (SD) FEV1 significantly increased after salbutamol nebulization from 931 mL (383) to 1,019 (432), mean difference +87 mL (95% CI 30-145) (P = .006). Similarly, FVC and PEF significantly increased, +174 mL (95% CI 66-282) (P = .004) and +0.3 L/min (95% CI 0-0.6) (P = .037), respectively. Airway resistances and breathing frequency did not significantly differ, whereas heart rate significantly increased after nebulization. In subjects with severe exacerbation of COPD, salbutamol vibrating-mesh nebulization through HFNC induced a significant bronchodilator effect with volume and flow improvement.

The Impact of High-Flow Nasal Cannula Device, Nebulizer Type, and Placement on Trans-Nasal Aerosol Drug Delivery.

Aerosol delivery via high-flow nasal cannula (HFNC) has been increasingly used in recent years. However, the effects of different HFNC devices, nebulizer types, and placement on aerosol deposition remain largely unknown. An adult manikin with anatomically correct upper airway was used with a collection filter placed between the manikin's trachea and a breathing simulator, composed of a dual-chamber model lung driven by a critical care ventilator. Three HFNC device configurations were compared, with vibrating mesh nebulizer and small-volume nebulizer placed at the humidifier (inlet for Optiflow and outlet for Airvo 2) and proximal to the nasal cannula at gas flows of 10, 20, 40 and 60 L/min, in quiet and distressed breathing patterns. Albuterol (2.5 mg) was nebulized for each condition (no. = 3). The drug was eluted from the collection filter and assayed with ultraviolet spectrophotometry (276 nm). At all settings, except when a nebulizer was placed proximal to the nasal cannula with the Optiflow and when the HFNC flow was set at 60 L/min, the vibrating mesh nebulizer generated a higher inhaled dose than did the small-volume nebulizer (all P < .05). With the exception of distressed breathing at an HFNC flow of 10 L/min, the inhaled dose with the vibrating mesh nebulizer placed at the humidifier was greater than with the vibrating mesh nebulizer placed proximal to the nasal cannula (all P < .05), Optiflow provided a higher inhaled dose than did Airvo 2 with either AirSpiral or 900PT501 circuits with the vibrating mesh nebulizer placed at the humidifier (all P < .05). During transnasal aerosol delivery, the vibrating mesh nebulizer generated a higher inhaled dose than did the small-volume nebulizer when the nebulizer was placed at the humidifier. With the vibrating mesh nebulizer placed at the humidifier and an HFNC flow > 10 L/min, the inhaled dose was higher than with the vibrating mesh nebulizer placed proximal to the nasal cannula, and the inhaled dose was higher with Optiflow than with Airvo 2.

Performance of different add-on devices in dual limb non-invasive mechanically ventilated circuit

Aerosol delivery is thought to be improved by giving one or two pMDI puffs before the prescribed nebulizer dose during non-invasive ventilation (NIV). The aim of the present study was to in-vitro evaluate the efficiency of aerosol delivery using newly developed spacers versus standard T-piece in dual limb NIV circuit.Three add-on devices were evaluated: Combihaler, Minimhal, and standard T-piece which were connected to a vibrating mesh nebulizer (VMN), jet nebulizer (JN), or pMDI within NIV circuit. Three experimental setts were evaluated. Firstly, two pMDI puffs were actuated before nebulization of 1 ml of salbutamol respirable solution by VMN using Combihaler, and Minimhal; the second was the actuation of 10 pMDI puffs only without nebulization.; and the third was the nebulization of 1 ml respirable solution by either VMN or JN without the preliminary pMDI puffs. The amount of aerosol deposited on the inhalation filter was quantified by high-performance liquid chromatography.The Combihaler + VMN delivered the highest TID. Aerosol delivery by Combihaler + pMD and Minimhal + pMDI was significantly higher than that of T-piece + pMDI (p = 0.009 and 0.025, respectively). No significant difference was found between the TID of Minimhal + JN and T-piece + JN. No significant effect was found upon using 2 puffs before the nebulized dose with both Minimhal and Combihaler.Combihaler delivered higher aerosol from VMN and pMDI compared to Minimhal, and standard T-piece. Minimhal delivered higher aerosol from pMDI compared to standard T-piece. Introducing two puffs of pMDI before nebulization with both Minimhal and Combihaler insignificantly affected aerosol delivery.

Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients.

Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. Retrospective review and analysis. Stanford University Hospital, a 605-bed tertiary care center. Patients receiving inhaled epoprostenol in 2019. No interventions. Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

Particle Dynamics and Bioaerosol Viability of Aerosolized Bacillus Calmette-Guérin Vaccine Using Jet and Vibrating Mesh Clinical Nebulizers.

Background: Bacillus Calmette-Guérin (BCG) is a vaccine used to protect against tuberculosis primarily in infants to stop early infection in areas of the world where the disease is endemic. Normally administered as a percutaneous injection, BCG is a live significantly attenuated bacteria that is now being investigated for its potential within an inhalable vaccine formulation. This study investigates the feasibility and performance of two jet and two vibrating mesh nebulizers aerosolizing BCG and the resulting particle characteristics and residual viability of the bacteria postaerosolization. Methods: A jet nebulizer (Collison), outfitted either with a 3- or 6-jet head, was compared with two clinical nebulizers, the vibrating mesh Omron MicroAir and Aerogen Solo devices. Particle characteristics, including aerodynamic particle sizing, was performed on all devices within a common aerosol chamber configuration and comparable BCG innocula concentrations. Integrated aerosol samples were collected for each generator and assayed for bacterial viability using conventional microbiological technique. Results: A batch lot of BCG (Danish) was grown to titer and used in all generator assessments. Aerosol particles within the respirable range were generated from all nebulizers at four different concentrations of BCG. The jet nebulizers produced a uniformly smaller particle size than the vibrating mesh devices, although particle concentrations by mass were similar across all devices tested with the exception of the Aerogen Solo, which resulted in a low concentration of BCG aerosols. Conclusions: The resulting measured viable BCG aerosol concentration fraction produced by each device approximated one another; however, a measurable decrease of efficiency and overall viability reduction in the jet nebulizer was observed in higher BCG inoculum starting concentrations, whereas the vibrating mesh nebulizer returned a remarkably stable viable aerosol fraction irrespective of inoculum concentration.

177 Aerosol Delivery Evaluation of a Vibrating Mesh Nebulizer and a Jet Nebulizer During Breath Actuated and Continuous Nebulization Modes in Spontaneously Breathing Adult and Pediatric Models

177 Aerosol Delivery Evaluation of a Vibrating Mesh Nebulizer and a Jet Nebulizer During Breath Actuated and Continuous Nebulization Modes in Spontaneously Breathing Adult and Pediatric Models