Mesh Nebulizer Research Articles

Nebulization of extracellular vesicles: A promising small RNA delivery approach for lung diseases.

Small extracellular vesicles (sEVs) are a group of cell-secreted nanovesicles with a diameter up to 200nm. A growing number of studies have indicated that sEVs can reflect the pathogenesis of human diseases and mediate intercellular communications. Recently, sEV research has drastically increased due to their drug delivery property. However, a comprehensive method of delivering exogenous small RNAs-loaded sEVs through nebulization has not been reported. The methodology is complicated by uncertainty regarding the integrity of sEVs after nebulization, the delivery efficiency of aerosolized sEVs, their deposition in the lungs/cells, etc. This study demonstrates that sEVs can be delivered to murine lungs through a vibrating mesh nebulizer (VMN). In vivo sEV tracking indicated that inhaled sEVs were distributed exclusively in the lung and localized primarily in lung macrophages and airway epithelial cells. Additionally, sEVs loaded with small RNAs were successfully delivered into the lungs. The administration of siMyd88-loaded sEVs through inhalation reduced lipopolysaccharide (LPS)-induced lung injury in mice, supporting an application of this nebulization methodology to deliver functional small RNAs. Collectively, our study proposes a novel method of sEVs-mediated small RNA delivery into the murine lung through nebulization and presents a potential sEV-based therapeutic strategy for human lung diseases.

Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics

Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 μm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability.

Performance and Feasibility of Therapeutic Vibrating Mesh Nebulizer for Ventilation Lung Scan

PurposeThis study aimed to evaluate the performance of a therapeutic vibrating mesh-type nebulizer for the pulmonary delivery of radioaerosols for lung scintigraphy in healthy subjects.MethodsSix healthy subjects (mean age of 28.7 ± 6.2 years) inhaled 2 mL Tc-99m diethylenetriaminepentaacetic acid and normal saline solution (20 mCi) via a therapeutic vibrating mesh-type nebulizer (DK010, DELBio, Taipei, Taiwan). The nebulizer’s mass median aerodynamic diameter was between 2.3 and 5.0 µm (3.47 ± 0.37 µm), and the nebulization rate was greater than 0.2 mL/min. Scintigraphy was performed to count radioaerosols in the regions of interest to determine the total and regional lung deposition and extrathoracic airway deposition of aerosols, penetration of aerosols, and radioactivity count balance (RCB).ResultsThe total lung depositions of aerosols were 21.2% ± 5.2% (% ex-valve dose), 27.4% ± 8.0% (% ex-device dose), and 13.8% ± 4.1% (% initial dose) in the nebulizer. The extrathoracic airway deposition was 4.8% ± 1.1%. The RCB was 5.4% ± 3.0%. The ratio of outer over inner lung deposition (O/I ratio, or penetration index) was 1.89 ± 0.55.ConclusionThe delivery efficiency and penetration of aerosols to the peripheral lung, which were achieved by the DELBio DK010 vibrating mesh-type nebulizer, were similar to the commercialized jet-type nebulizers dedicated for radioaerosol lung scintigraphy nebulizer. The therapeutic vibrating mesh-type nebulizer (DELBio DK010) is feasible for radionuclide lung ventilation scintigraphy.

Pharmacokinetic Characteristics of Nebulized Colistimethate Sodium Using Two Different Types of Nebulizers in Critically Ill Patients with Ventilator-Associated Respiratory Infections.

Background: Rising antimicrobial resistance has led to a revived interest in inhaled colistin treatment in the critically ill patient with ventilator-associated respiratory infection (VARI). Nebulization via vibrating mesh nebulizers (VMNs) is considered the current standard-of-care, yet the use of generic jet nebulizers (JNs) is more widespread. Few data exist on the intrapulmonary pharmacokinetics of colistin when administered through VMNs, while there is a complete paucity regarding the use of JNs. Methods: In this study, 18 VARI patients who received 2 million international units of inhaled colistimethate sodium (CMS) through a VMN were pharmacokinetically compared with six VARI patients who received the same drug dose through a JN, in the absence of systemic CMS administration. Results: Surprisingly, VMN and JN led to comparable formed colistin exposures in the epithelial lining fluid (ELF) (median (IQR) AUC0-24: 86.2 (46.0-185.9) mg/L∙h with VMN and 91.5 (78.1-110.3) mg/L∙h with JN). The maximum ELF concentration was 10.4 (4.7-22.6) mg/L and 7.4 (6.2-10.3) mg/L, respectively. Conclusions: Based on our results, JN might be considered a viable alternative to the theoretically superior VMN. Therapeutic drug monitoring in the ELF can be advised due to the observed low exposure, high variability, and appreciable systemic absorption.

Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitor, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, blocks respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We use a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptide to the respiratory tract and demonstrate the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevents MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional means to fight against respiratory infection in non-vaccinated people, that can be readily translated to human trials. It presents a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure.

Quantifying the effectiveness of ultraviolet-C light at inactivating airborne Mycobacterium abscessus

Mycobacterium abscessus (MABS) group are environmental organisms that can cause infection in people with cystic fibrosis (CF) and other suppurative lung diseases. There is potential for person-to-person airborne transmission of MABS among people with CF attending the same care centre. Ultraviolet light (band C, UV-C) is used for Mycobacterium tuberculosis control indoors; however, no studies have assessed UV-C for airborne MABS. To determine whether a range of UV-C doses increased the inactivation of airborne MABS, compared with no-UVC conditions. MABS was generated by a vibrating mesh nebulizer located within a 400L rotating drum sampler, and then exposed to an array of 265nm UV-C light-emitting diodes (LED). A six-stage Andersen Cascade Impactor was used to collect aerosols. Standard microbiological protocols were used for enumerating MABS, and these quantified the effectiveness of UV-C doses (in triplicate). UV-C effectiveness was estimated using the difference between inactivation with and without UV-C. Sixteen tests were performed, with UV-C doses ranging from 276 to 1104μWs/cm2. Mean (±SD) UV-C effectiveness ranged from 47.1% (±13.4) to 83.6% (±3.3). UV-C led to significantly greater inactivation of MABS (all P-values ≤0.045) than natural decay at all doses assessed. Using an indoor model of the hospital environment, it was estimated that UV-C doses in the range studied here could be safely delivered in clinical settings where patients and staff are present. This study provides empirical in-vitro evidence that nebulized MABS are susceptible to UV-C inactivation.

In Vitro Characterization of Aerosolized Albuterol Generated by a Jet Nebulizer and Delivered through a Heated Flow Nasal Cannula System.

Pediatric patients receiving respiratory support with heated flow nasal cannula (HFNC) systems frequently receive inhaled medications. Most available data have been obtained with vibrating mesh nebulizers that are expensive. Data are lacking regarding the feasibility of using less expensive devices such as continuous output jet nebulizers. The characteristics of the aerosols generated by jet nebulizers operated at different conditions (6 and 9 L/min) were studied alone and connected to a HFNC system and different size cannulas using a cascade impactor and spectrophotometry (276 nm). Aerosol characteristics changed while traveling through the HFNC system. Initial size selection occurred at the exit of the circuit (before connecting to the cannula) with all aerosol <5 µm. Nasal cannula size further selected aerosols and reduced drug delivery. The operating flow of the nebulizer did not affect the delivered mass but higher flows generated smaller particle size aerosols. The addition of supplemental flow significantly reduced the delivered mass. The measured aerosol characteristics would likely result in intrapulmonary deposition. The delivery of aerosolized albuterol generated by a continuous output nebulizer placed in the inlet of a HFNC system and connected to large or XXL cannulas is feasible.

Position of different nebulizer types for aerosol delivery in an adult model of mechanical ventilation.

BackgroundThe optimal positions of different types of nebulizer for aerosol delivery remain unclear.MethodsThree ICU ventilators employing three types of nebulizer were separately connected to a simulated lung to simulate nebulization during invasive ventilation. Assist/control-pressure control (A/C-PC) mode was utilized, with inspiratory pressure (Pi) set to 12 cmH2O and positive end expiratory pressure (PEEP) set to 5 cmH2O, and with a target Vt of 500 ml. The bias flow of all the ventilators was set to 2 L/min. The three nebulizers were the continuous jet nebulizer (c-JN), the inspiratory synchronized jet nebulizer (i-JN), and the vibrating mesh nebulizer (VMN). The five nebulizer positions were as follows: at the Y-piece (position 1) and 15 cm from the Y-piece (position 2) between the endotracheal tube and the Y-piece, at the Y-piece (position 3) and 15 cm from the Y-piece (position 4) in the inspiratory limb; and at the humidifier inlet (position 5). Aerosols were collected with a disposable filter placed at the simulated lung outlet (n = 3) and were measured by UV spectrophotometry (276 nm). The measurements were compared under different experimental conditions.ResultsThe aerosol delivery of c-JN, i-JN, and VMN was 5.33 ± 0.49~11.12 ± 0.36%, 7.73 ± 0.76~13.75 ± 0.46% and 11.13 ± 56–30.2 ± 1.63%, respectively. The higher aerosol delivery: for c-JN~Positions 2 (10.95 ± 0.15%), fori-JN~Positions 1 or 2 (12.91 ± 0.88% or 13.45 ± 0.42%), for VMN~Positions 4(29.03 ± 1.08%); the lower aerosol delivery: for c-JN~Positions 1, 3 or 5, fori-JN~Positions 4 or 5, for VMN~Positions 5.The highest aerosol delivery:For c-JN at Position 2 (10.95 ± .15%), for i-JN at Position 1 or 2 (12.91 ± .88% or 13.45 ± .42%), for VMN at Positions 4 (29. 03 ± 1.08%); the lower aerosol delivery: for c-JN at Positions 1, 3 or 5, for i-JN at Positions 4 or 5, for VMN at Positions 5. The highest aerosol deliveryof c-JN was lower than that of i-JN while the VMN was the highest (all P < .05). However, no differences were observed between the highest aerosol delivery with c-JN and the lowest aerosol delivery with i-JN. Similar results were found between the lowest aerosol delivery with VMN and the highest aerosol delivery with c-JN /i-JN in the Avea ventilator. There were no differences in the highest aerosol delivery of each nebulizer among the different ventilators (all p > 0.05).ConclusionDuring adult mechanical ventilation, the type and position of nebulizer influences aerosol delivery efficiency, with no differences between ventilators.

Mesh nebulizers enabling transnasal pulmonary delivery of medical aerosols to infants and toddlers: Roles, challenges, and opportunities

The development of mesh nebulizer technology has expanded the ability to deliver medical aerosols to infants and small childrenvianasal cannula and prongs. Mesh nebulizers do not require compressed gas to generate aerosols and have a smaller, lighter profile facilitating placement in delivery circuits, unlike ultrasonic nebulizers. Prior to this century, aerosol delivery with the nasal interface to 1–4 kg infants or surrogate animal models was limited to low single-digit deposition.In vitroand animal studies with the enabling mesh technology increase inhaled dose by upwards of 14% when nasal continuous positive airway pressure ventilation is in use. Recently, investigations of transnasal aerosol delivery to the lung have expanded to include nasal cannula interfaces with both high and low flow oxygen administration, nasal continuous positive airway pressure therapy, and nasal noninvasive ventilation in treating respiratory distress, respiratory insufficiency, and acute respiratory failure of infants and toddlers. We will first examine the progression of testing transpulmonary delivery of medical aerosols fromin vitromodels toin vivoanimal and human studies. Then, we will explain current and developing applications in clinical practice to view future directions and opportunities.

Antimicrobial Performance of an Innovative Technology of Atmospheric Plasma Reactors against Bioaerosols: Effectiveness in Removing Airborne Viable Viruses

Reducing the exposure to airborne contaminants, including bioaerosols containing viruses, is a key challenge in the context of indoor air quality. This study aims to assess the effectiveness of innovative Atmospheric Plasma Reactor (APR) technology, which can be included in air cleaner devices, as an engineering control tool for reducing the concentration of viable airborne viruses. We investigated the KillViDTM APR technology that uses ultra-high electric fields and pulsed power plasma to directly electroporate living cells and produce advanced oxidizing species in situ within the micro-droplet aerosols containing the pathogens to be treated. An experimental setup was developed in order to aerosolize a high concentration of virus suspension directly into the air cleaner, containing 3 or 6 modules of 215 atmospheric plasma micro-reactors. As a virus surrogate, we used the phi11 bacteriophage which was aerosolized using a vibrating mesh nebulizer. The viability of airborne viruses after a single pass through the air cleaner was assessed by quantifying the lysis of a specific Staphylococcus aureus host strain. We were able to demonstrate that our virucidal results were robust and showed a 5-log reduction (99.999%) in terms of virucidal activity for the 3-module configuration, while we observed at least a 6-log reduction (from an initial viral load of 9.25 × 105 PFU to 0) for the 6-module configuration.

An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ12) and titanium dioxide nanoparticles (TiO2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM).Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ12 and TiO2 NM-105 particles showed good linearity (R2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12.This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials.

Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients.

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. Intraoperative management of patients at high risk of RV failure should aim to reduce RV afterload and optimize RV filling pressures, while avoiding systemic hypotension, to facilitate weaning from cardiopulmonary bypass (CPB). Inhaled epoprostenol and inhaled milrinone (iE&iM) administered in combination before CPB may represent an effective strategy to facilitate separation from CPB and reduce requirements for intravenous inotropes during cardiac surgery. Our primary objective was to report the rate of positive pulmonary vasodilator response to iE&iM and, second, how it relates to perioperative outcomes in cardiac surgery. This is a retrospective cohort study of consecutive patients with PH or RV dysfunction undergoing on-pump cardiac surgery at the Montreal Heart Institute from July 2013 to December 2018 (n = 128). iE&iM treatment was administered using an ultrasonic mesh nebulizer before the initiation of CPB. Demographic and baseline clinical data, as well as hemodynamic, intraoperative, and echocardiographic data, were collected using electronic records. An increase of 20% in the mean arterial pressure (MAP) to mean pulmonary artery pressure (MPAP) ratio was used to indicate a positive response to iE&iM. In this cohort, 77.3% of patients were responders to iE&iM treatment. Baseline systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.16 per 5 mm Hg; P = .0006) was found to be a predictor of pulmonary vasodilator response, while a European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score >6.5% was a predictor of nonresponse to treatment (≤6.5% vs >6.5% [reference]: OR, 5.19; 95% CI, 1.84-14.66; P = .002). Severity of PH was associated with a positive response to treatment, where a higher proportion of responders had MPAP values >30 mm Hg (42.4% responders vs 24.1% nonresponders; P = .0237) and SPAP values >55 mm Hg (17.2% vs 3.4%; P = .0037). Easier separation from CPB was also associated with response to iE&iM treatment (69.7% vs 58.6%; P = .0181). A higher proportion of nonresponders had a very difficult separation from CPB and required intravenous inotropic drug support compared to responders, for whom easy separation from CPB was more frequent. Use of intravenous inotropes after CPB was lower in responders to treatment (8.1% vs 27.6%; P = .0052). A positive pulmonary vasodilator response to treatment with a combination of iE&iM before initiation of CPB was observed in 77% of patients. Higher baseline SPAP was an independent predictor of pulmonary vasodilator response, while EuroSCORE II >6.5% was a predictor of nonresponse to treatment.

Aerosolterapia durante la aplicación de ventilación mecánica no invasiva o cánula nasal de alto-flujo en pacientes con asma y EPOC

Noninvasive mechanical ventilation (NIV) and high-flow nasal cannula (HFNC) are increasingly used in patients with exacerbated acute and chronic respiratory failure. Some patients receiving these therapies may also benefit from inhaled drug delivery. It is therefore attractive to combine treatment with aerosols and noninvasive respiratory support (NIRS). Aerosol therapy devices that can be adapted in line with NIRS are pressurized metered-dose inhalers (pMDIs) and nebulizers. In the subgroup of nebulizers are three types: jet nebulizers (NJ), ultrasonic nebulizers (NUs) and vibrating mesh nebulizers (VMN). The administration of aerosol therapy in line with HFNC seems a novel combination and of great applicability in selected patients. Based on the available evidence, the combination of providing NIV and aerosol therapy in patients with airflow obstruction without interrupting respiratory treatment seems appropriate. The aim of this article is to review the available literature on aerosol therapy during NIRS. In addition, to provide recommendations based on the available evidence.

Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis.

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 μm as measured by cascade impaction, and a volumetric median diameter of 4.09 μm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

Can mesh nebulizers improve prehospital aerosol therapy? An in vitro study on simulated prehospital emergency patients suffering from respiratory distress

HintergrundMedikamentenvernebler im Rettungsdienst sollten eine hohe Vernebelungsleistung haben, um schnell eine therapeutische Wirkstoffkonzentration des vernebelten Medikaments zu erreichen. Eine Umfrage im süddeutschen Rettungsdienst zeigte allerdings, dass fast ausschließlich die wenig effizienten Jet-Vernebler zum Einsatz kommen.Ziel der ArbeitZiel der vorliegenden In-vitro-Studie war es herauszufinden, ob der Einsatz von Mesh-Verneblern die prähospitale Aerosoltherapie verbessern könnte.Material und MethodenDie Vernebelungsleistung eines Jet-Verneblers (Cirrus™ 2, Fa. Intersurgical®) und 2 mobil einsatzbarer Mesh-Vernebler (Aerogen Solo®, Fa. Aerogen Limited, M‑Neb® mobile, NEBU-TEC International med. Produkte Eike Kern GmbH) wurde in einem In-vitro-Modell spontan atmender Notfallpatient*innen mit 4 unterschiedlichen Atemmustern bei verschiedenen Sauerstoffflussraten getestet.ErgebnisseDie Mesh-Vernebler zeigten im Vergleich zum Jet-Vernebler eine signifikant höhere Verneblungsleistung und Salbutamol-Filterdeposition, wobei der M‑Neb® mobile die höchsten Werte für Leistung und Deposition erreichte. Der Sauerstofffluss hatte den größten Einfluss auf die Leistung des Jet-Verneblers, wirkte sich aber kaum auf die Mesh-Vernebler aus. Die Deposition wurde zudem stark vom Atemmuster beeinflusst.DiskussionDer Einsatz von Mesh-Verneblern mit hoher Verneblungsleistung konnte in einem In-vitro-Modell die Aerosoltherapie von prähospitalen Notfallpatient*innen verbessern. Sie waren dem Jet-Vernebler in Bezug auf die Verneblungsleistung und die Lungendeposition überlegen und ermöglichten zudem eine bedarfsangepasste Sauerstofftherapie. Die höchste Medikamentendeposition wurde bei den tachypnoischen Patient*innen erreicht, welche in der praktischen Anwendung auch am meisten von einem erhöhten Medikamentenspiegel profitieren würden.Zusatzmaterial onlineZusätzliche Informationen sind in der Online-Version dieses Artikels (10.1007/s00101-022-01183-y) enthalten (weitere Tabellen).

Inhaled aprotinin reduces viral load in mild‐to‐moderate inpatients with SARS‐CoV‐2 infection

Inhaled aprotinin reduces viral load in mild‐to‐moderate inpatients with SARS‐CoV‐2 infection

Evaluation of aerosol drug delivery with concurrent low- and high-flow nasal oxygen.

Question addressed by studyAdministration of aerosol to patients receiving high-flow nasal oxygen (HFNO) ranges from concurrent aerosol delivery by mouthpiece to aerosol via cannula alone. This study examines the conditions to provide optimal aerosol delivery with low- or high-flow nasal oxygen with concurrent mouthpiece or through nasal cannula alone, and the impact on fugitive aerosols.Materials and methodsA vibrating mesh nebuliser delivered salbutamol via mouthpiece, aerosol holding chamber and nasal cannula to an adult head model simulating relaxed breathing. The mean±sd inhaled dose (%) was assayed from a filter distal to the trachea. Optical particle sizers were used to measure fugitive aerosol concentrations during aerosol delivery.ResultsConcurrent low-flow nasal oxygen (LFNO) and aerosol delivery with a mouthpiece and aerosol holding chamber increased the inhaled dose (%) available, 31.44±1.33% when supplemented with 2 L·min−1 of nasal oxygen. Concurrent HFNO above 30 L·min−1 resulted in a lower inhaled dose (%) compared to aerosol delivered through HFNO alone. The addition of concurrent LFNO or HFNO resulted in no increase in aerosol levels in the test room.Answer to question posedConcurrent LFNO with a mouthpiece and aerosol holding chamber is an effective and safe means of aerosol delivery.

Aqueous dispersions of oxygen nanobubbles for potential application in inhalation therapy

Inhalation is a non-invasive method of local drug delivery to the respiratory system. This study analyzed the potential use of aqueous dispersion of oxygen nanobubbles (ADON) as a drug carrier with the additional function of oxygen supplementation to diseased lungs. The suitability of the membrane-based method of ADON preparation and, next, the stability of ADON properties during storage and after aerosolization in nebulizers of various designs (jet, ultrasonic, and two vibrating mesh devices) was investigated. The increased oxygen content in the aerosol generated in two mesh nebulizers suggests that the proposed concept may be helpful in the oxygen supplementation during drug delivery by aerosol inhalation without using an additional oxygen source. This application can increase the overall effectiveness of lung disease treatment and pulmonary rehabilitation.

COMBINED BOLUS AND CONTINUOUS NEBULIZATION DURING MECHANICAL VENTILATION: DUAL THERAPY FOR RESPIRATORY FAILURE

TYPE: Abstract TOPIC: Critical Care PURPOSE: This study tests nebulizers configured to deliver multiple medications during continuous nebulization without interruption or circuit disconnection. METHODS: A prototype i-AIRE dual-medication port breath-enhanced jet nebulizer (BEJN) was compared to Aerogen Solo vibrating mesh nebulizers (VMN). VMN were stacked; one for infusion, the second for bolus drug delivery. Radiolabeled saline was infused over 4 hr at 5 & 10 mL/h with 3 mL and 6 mL radiolabeled saline bolus injections into the circuit at 30 and 120 min respectively. Inhaled Mass expressed as % of initial syringe activity (IM%/min) was monitored in real time with a ratemeter. All delivered radioaerosol was collected on a filter at the airway opening. Transients in aerosol delivery were documented. RESULTS: IM %/h during continuous infusion was linear, with BEJN and VMN delivering 3-4 %/hr. BEJN functioned without incident. VMN stopped nebulizing spontaneously 50% of the time but tapping restarted VMN function during 3 of 4 continuous runs and 7 of 9 bolus delivery runs. Bolus delivery IM% (mean ± SD): 22 ± 8%, 14 ± 11 % for BEJN and VMN, respectively. CONCLUSIONS: Simultaneous continuous and bolus nebulization without circuit disconnection is possible for both jet and mesh technology. CLINICAL IMPLICATIONS: Continuous nebulization of pulmonary vasodilators is an off-label therapy for critically ill patients with hypoxemia. This study indicates that additional drugs (bronchodilators/antibiotics) can be given by bolus nebulization without circuit disconnection. Monitoring of VMN devices may be necessary in case of spontaneous interruption of nebulization. DISCLOSURE: Stony Brook University owns patents on inhaled therapy in intubated patients licensed to InspiRx, Inc. Dr. Smaldone consults to InspiRx and is a member of the Advisory Board. Ms Cuccia has served as a consultant to InspiRx. Dr. Lee and Mr. McPeck have no KEYWORD: nebulization

Real-Time Analysis of Dry-Side Nebulization With Heated Wire Humidification During Mechanical Ventilation.

Recent observational studies of nebulizers placed on the wet side of the humidifier suggest that, after some time, considerable condensation can form, which triggers an occlusion alarm. In the current study, an inline breath-enhanced jet nebulizer was tested and compared in vitro with a vibrating mesh nebulizer on the humidifier dry-inlet side of the ventilator circuit. Two duty cycle breathing patterns were tested during continuous infusion (5 or 10 mL/h) with and without dynamic changes in infusion flow and duty cycle, or bolus delivery (3 or 6 mL) of radiolabeled saline solution. Inhaled mass (IM) was measured by a real-time ratemeter (µCi/min) and analyzed by multiple linear regression. During simple continuous infusion, IM increased linearly for both nebulizer types. IM variability was attributable to the duty cycle (P < .001) (34%) and infusion flow (P < .001) (32%) but independent of nebulizer technology (P = .38) (7%). Dynamic continuous infusion studies that simulate clinical scenarios with ventilator and pump flow changes demonstrated a linear increase in the rate of aerosol that was dependent on pump flow (P < .001) (63%) and minimally dependent on the duty cycle (P = .003) (8%). During bolus treatments, IM increased linearly to plateau. IM variability was attributable to the duty cycle (P < .001) (40%) and residual radioactivity in the nebulizer (P < .001) (20%). Separate analysis revealed that the vibrating mesh nebulizer residual volume contributed 16% of the variability and inline breath-enhanced jet nebulizer contributed 5%. IM variability was independent of bolus volume (P = .82) (1%). System losses were similar (the inline breath-enhanced jet nebulizer: 32% residual in nebulizer; the vibrating mesh nebulizer: 34% in circuitry). Aerosol delivery during continuous infusion and bolus delivery was comparable between the inline breath-enhanced jet nebulizer and the vibrating mesh nebulizer, and was determined by pump flow and initial ventilator settings. Further adjustments in ventilator settings did not significantly affect drug delivery. Expiratory losses predicted by the duty cycle were reduced with placement of the nebulizer near the ventilator outlet.