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SUMMARY Background During manual resuscitation, nebulizer therapy may be used to deliver therapeutics to patients in respiratory distress. However, the devices used to generate and deliver these medical aerosols have the potential to release these therapeutics into the local environment and expose caregivers to unwanted medical aerosols. Aim To quantify the levels of fugitive medical aerosol released into the environment during aerosol drug delivery using a manual resuscitation bag with and without filtration. Methods Time-varying fugitive aerosol concentrations were measured using an aerodynamic particle sizer placed at a position designed to mimic a caregiver. Two nebulizer types were assessed, a vibrating mesh nebulizer and a jet nebulizer. The aerosol dose delivered to the simulated patient lung was also quantified. Findings Filtration of the exhalation port of the manual resuscitation bag was seen to reduce fugitive medical aerosols to ambient levels for both nebulizer types. The vibrating mesh nebulizer delivered the greatest quantity of aerosol to the simulated adult patient (18.44 ± 1.03% versus 3.64 ± 0.26% with a jet nebulizer). Conclusions The results highlight the potential for exposure to fugitive medical aerosols released during the delivery of aerosol therapy with a manual resuscitation bag and also the potential for significant variation in patient lung dose depending on nebulizer type.

Background Efficient methods for the detection and repair of pleural defects are crucial for preventing postoperative air leaks; however, there are few studies on sealing test methods. We developed a new sealing test method that involves the administration of aerosolized indocyanine green into the airway. This experimental study aimed to confirm whether this method could identify alveolar-pleural fistulas. Methods Thoracotomy was performed on 6 beagles under general anesthesia. Pleural defects accompanying air leaks were created in the cranial and caudal lobes. Using a pediatric jet nebulizer kit, 5 mL of 2.5 mg/mL aerosolized indocyanine green solution was administered to the entire lung through a catheter placed in the trachea. Pleural defects were observed using a near-infrared light scope, and the time until confirmation of the defect sites was measured. Results Of the 25 pleural defect sites created, 24 could be identified under a near-infrared light camera. The average time required for confirming the site of pleural defect was 13.8 seconds (95% confidence interval, 7.32-16.8 seconds). Conclusions By administering aerosolized indocyanine green into the airway, the site of alveolar-pleural fistula could be identified with a near-infrared light camera in a canine pleural defect model. This method could be a valid sealing test and is suitable for video-assisted thoracic surgery, as it allows for observation of the lung in a collapsed state with a long observation time. Further studies are needed to determine the optimal dose of indocyanine green and to confirm the method’s applicability and efficacy in humans.

Pickering emulsions based on biologically oriented compounds are highly appreciated in a variety of applications, such as food, cosmetics, and pharmaceuticals. Here, we develop the dual ultrasonic nebulizer spray method to efficiently produce alginate particles (APs) that can be used as eco-friendly and biocompatible Pickering stabilizers. This custom-designed method enables one-step preparation of chitosan-coated APs (CAPs) and direct encapsulation of magnetic nanoparticles within CAPs. The size of the resulting CAPs is about 5 μm in diameter, which is ideal for emulsion stabilizers. Unlike conventional APs production based on nozzle spraying, the developed method does not cause clogging problems, allowing large-scale production of APs-based Pickering stabilizers with a narrow size distribution. In addition, various CAPs-stabilized Pickering emulsions are demonstrated to be extremely stable against coalescence and drying upon exposure to air.

Croup treatment usually involves a single dose of systemic dexamethasone combined with nebulized epinephrine. However, the optimal dose of l-epinephrine remains unclear. We examined whether a low dose (0.1 mg/kg) was inferior to the conventional dose (0.5 mg/kg) of 1:1000 nebulized l-epinephrine in patients with moderate to severe croup.This randomized double-blind clinical non-inferiority trial was conducted in three pediatric emergency departments from May 2015 to October 2017. Children 6 months to 5 years old with moderate to severe croup (Westley scale scores 3-11) were eligible. Subjects were randomly assigned to the conventional dose (0.5 mg/kg: maximum 5 mg) or low dose (0.1 mg/kg; maximum 1 mg) group. All subjects received 0.6 mg/kg dexamethasone. Croup scores and other vital signs were measured before and at 30, 60, 90, and 120 min after nebulized l-epinephrine administration. The primary outcome was the change in croup score after 30 min.The final analysis included 84 patients. The groups did not differ significantly in terms of demographic parameters. At 30 min after treatment with nebulized l-epinephrine, the croup scores in both groups were significantly reduced from the baseline values (p 0.05) and did not differ between the two groups (p = 0.42). Neither blood pressure nor heart rate differed between the two groups.Low-dose 1:1000 l-epinephrine was not inferior in croup score reduction to the conventional dose in patients with moderate to severe croup. Clinical trial No: NCT01664507, KCT0002318.

Background The daily burden of health maintenance for children and families with cystic fibrosis (CF) is immense with respect to time and complexity of care. Infection control practices, specifically nebulizer cleaning and disinfection, are a recommended component of home health care for CF families due to colonization of home respiratory equipment with lung pathogens. To better inform education interventions at our center, we were interested in studying how families' views on infection prevention and awareness of CF Foundation infection prevention and control (IP&C) guidelines correlate with actual home nebulizer care and the presence of microorganisms on their nebulizers. Methods Twenty families who have children with CF were surveyed to better understand attitudes toward infection prevention, awareness of CFF IP&C guidelines and nebulizer cleaning and disinfection practices in the home. Their nebulizers were also cultured for microbes to correlate recovery with infection control behaviors. Results A subset of families recognizes the importance of germ avoidance but do not recognize nebulizer cleaning and disinfection as very important for infection control practices. Decreased frequency of disinfection, but not cleaning, was correlated with the recovery of organisms on the nebulizers. Conclusions The study questionnaire results identify a gap between recognizing the importance of infection prevention and consistently implementing CFF IP&C guidelines in the home. This demonstrates the need at our center for new educational interventions to promote cleaning and disinfection of home nebulizers after each use as recommended by the CFF.

Home healthcare is a growing area of employment. Assessment of occupational health risks to home health care workers (HHCWs) is important because in many cases the unique characteristics of the home environment do not facilitate the level of exposure control afforded to caregivers in hospitals and other fixed patient care sites. This assessment is focused on health risks to HHCWs from exposure to pharmaceutical drugs used to treat asthma and other respiratory diseases, which are commonly administered to patients in aerosolized form via nebulizers. We developed risk-based exposure limits for workers in the form of occupational exposure limits (OEL) values for exposure to nebulized forms of the three most common drugs administered by this method: albuterol, ipratropium, and budesonide. The derived OEL for albuterol was 2 μg/day, for ipratropium was 30 μg/day, and for budesonide was 11 μg/day. These OELs were derived based on human effect data and adjusted for pharmacokinetic variability and areas of uncertainty relevant to the underlying data (human and non-human) available for each drug. The resulting OEL values provide an input to the occupational risk assessment process to allow for comparisons to HHCW exposure that will guide risk management and exposure control decisions.

Home-attending healthcare workers (HHCWs), one of the most rapidly growing occupations worldwide, are exposed to a wide range of aerosol contaminants, including pharmaceuticals administered to patients in their homes by nebulizer treatment. The aerosol concentration and exposure patterns may be vastly different from those identified in hospital environments. Inhalation exposure of healthcare professionals to nebulized medications has not been quantified. This pilot simulation study was conducted to measure particles released from a commercially available nebulizer-based aerosol delivery system into the indoor environment. Aerosolized medications such as Ipratropium Bromide, Budesonide, and Albuterol Sulfate (all suspended in a NaCl solution), and NaCl (used as medication to treat respiratory symptoms) were evaluated in individual trials. Deionized water was used as a control. The aerosols were measured using an Electrical Low Pressure Impactor at three locations of the HHCW-simulating manikin relative to the aerosol source. Exposure to all four selected aerosolized medications was significant (exceeding background control by one to four orders of magnitude). The particle size distributions measured for the four aerosols at a fixed distance from the source demonstrated similar trends with no significant differences identified in most cases. Although the total aerosol mass concentration in the breathing zone of the simulated HHCW ranged widely, from 2.29 to 10.2 μg/m3, it was not significantly affected by medication type. Therefore, we concluded that NaCl can serve as a surrogate for assessing aerosol exposures, at least for the selected nebulizer-administered medications.

Background Beneficial effects from non-invasive ventilation (NIV) in acute COPD are well-established, but the impact of nebulization during NIV has not been well described. Aim To compare pulmonary deposition and distribution across regions of interest with administration of radiolabeled aerosols generated by vibrating mesh nebulizers (VMN) and jet nebulizer (JN) during NIV. Methods A crossover single dose study involving 9 stable subjects with moderate to severe COPD randomly allocated to receive aerosol administration by the VMN Aerogen and the MistyNeb jet nebulizer operating with oxygen at 8 lpm during NIV. Radiolabeled bronchodilators (fill volume of 3 mL: 0.5 mL salbutamol 2.5 mg + 0.125 mL ipratropium 0.25 mg and physiologic saline up to 3 mL) were delivered until sputtering during NIV (pressures of 12 cmH2O and 5 cmH2O - inspiratory and expiratory, respectively) using an oro-nasal facemask. Radioactivity counts were performed using a gamma camera and regions of interest (ROIs) were delimited. Aerosol mass balance based on counts from the lungs, upper airways, stomach, nebulizer, circuit, inspiratory and expiratory filters, and mask were determined and expressed as a percentage of the total. Results Both inhaled and lung doses were greater with VMN (22.78 ± 3.38% and 12.05 ± 2.96%, respectively) than JN (12.51 ± 6.31% and 3.14 ± 1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ± 1.3% versus 46.44 ± 5.83%, p = 0.001). Peripheral deposition of radioaerosol was significantly lower with JN than VMN. Conclusions VMN deposited > 3 fold more radioaerosol into the lungs of moderate to severe COPD patients than JN during NIV.

Background The protection against aerosol transmission provided by masks vs face shields or in combination when speaking indoors is not well understood. Methods To simulate a human source, an aerosol generating system was made using a bacterial suspension in a nebulizer attached to an oxygen cylinder. A fan connected to the nebulizer created aerosols. Transmitted aerosols were detected using blood agar plates at 0.1524 and 1.8288 meters from source, simulating exposed person. The study was performed under controlled conditions at room temperature in a biohazard hood with high-efficiency particulate air (HEPA) filter and UV light. Results When face shields were used alone, significant numbers of bacterial colonies grew on blood agar plates. When a mask used alone for both the subjects (source and exposed), the blood agar yielded minimal colony forming units at both distances. When face shields were used in combination with masks, no significant improvement was observed as compared to masks alone. Discussion Our results were similar to what have been observed in related studies. Conclusions Surgical masks alone provided good protection, surpassing the protection provided by face shields alone. Both used together provided the best protection, although the combined protection was similar to surgical masks use alone.

Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being5 μm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.

The purpose of this research is to study the process of ultrasonic aerosol generation by finite element modeling and validate it by experimental method. This understanding leads to downsize nebulization droplets and improve the drug delivery effectiveness. The finite element model of an ultrasonic nebulizer consists of a cylindrical chamber (filled with liquid), air, and a piezoelectric actuator at the bottom of the chamber. Many physical interactions including piezoelectric structural vibration, pressure acoustic in fluid, two-phase flow and droplet separation are analyzed and simulated. In validation, the ultrasonic nebulizer is attached to Andersen cascade impactor (ACI) with a vacuum pump for classifying the aerosol droplet size. The inductively coupled plasma optical emission spectrometry (ICP-OES) technique is used to determine droplet size distribution. The simulation results have shown that the major distribution of droplet size is in a range of 1.64–2.70 µm. Accordingly, the experimental results based on the ACI cutoff diameter stages depict that the major volume distribution of droplet size should be in a range of 1.10–3.29 µm. Submicron droplets (0.56–0.90 µm) are occurred in the simulation, and are also detected in the experiment at the ACI submicron cutoff diameters at 0.4 µm and 0.7 µm. This agreement has proved that the multiphysics model of the ultrasonic nebulizer can predict the size of generated aerosol. The relationship of ultrasonic nebulization parameters could be extended to conceive a new ultrasonic nebulizer design that would achieve submicron droplet size in rendering better drug delivery effectiveness.

Metal speciation analysis of microsamples in the clinical, biological and forensic fields is important for elucidating the metals’ toxicity, mobility and metabolic behaviors of metals. Such analysis may be achieved by nanoliter high-performance liquid chromatography (nanoHPLC) hyphenated with inductively coupled plasma mass spectrometry (ICP-MS). In this work, an in-column high-pressure nebulizer (ICHPN) was developed to enhance the sensitivity and the separation efficiency of the sheathless nanoHPLC-ICP-MS coupling. The ICHPN consists of two concentric fused-silica capillaries with tapered tips connected via a PEEK tee, where C18 silica particles with a size of 5 μm were packed in the tapered inner capillary based on the keystone effect. Combining a heated single pass spray chamber with a makeup gas, the ICHPN was capable of independently optimizing the nebulization efficiency and the transport efficiency. The ICHPN offered high sensitivities, low detection limits and good precision at nanoflow rates. Compared with commercial nebulizers, the ICHPN fabrication was simple, rapid, reproducible and inexpensive. By implementing the ICHPN, we achieved rapid separation of four mercury species, i.e., Hg2+ and methyl-, ethyl- and phenylmercuric chloride, within 8.0 min with good resolution (2.0–13.9). Detection limits of 0.044-0.13 μg L−1 were obtained with precisions of peak heights and areas ranging from 1.5 to 3.5% for a 50 μg L−1 standard solution. Good agreement between the determined and certified values of mercury species in a certified reference material of caprine blood (SRM 955c) together with good recoveries (93–101%) validated the accuracy of the method.

Being advertised and distributed as attractive substitutes of cannabis, synthetic cannabinoids (SC) are gaining increasing relevance in forensic and clinical toxicology. As no data from controlled human studies are available, SC are sold and consumed without the knowledge of their toxicokinetic (TK) and toxicodynamic properties. Hence, animal models coupled with mathematical approaches should be used to ascertain those properties. Therefore, a controlled pig TK study allowing for extrapolation to human data was performed. For this purpose, eleven pigs received a single pulmonary dose of 200 µg/kg body weight each of Δ9-tetrahydrocannabinol (THC), 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210) as well as 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4) via an ultrasonic nebulizer. Blood and urine samples were repeatedly drawn over 8 h. Serum-concentration-time profiles of the parent compounds were determined using LC-MS/MS. Urine specimens were analyzed by LC-HR-MS/MS in order to elucidate the main metabolites. Maximum serum concentrations were reached 10–15 min after beginning of nebulization and amounted to 66 ± 36 ng/mL for THC, 41 ± 11 ng/mL for JWH-210, and 34 ± 8.9 ng/mL for RCS-4. The serum-concentration-time profiles of THC, JWH-210, and RCS-4 were best described by three-compartment models with first order absorption and elimination processes. Absorption from the lungs to serum was modeled by first-order processes. The determination of the bioavailability yielded 23.0%, 24.2%, and 45.7% for THC, JWH-210, and RCS-4, respectively. Furthermore, the developed THC model was upscaled to humans using allometric scaling techniques. A successful prediction of human concentration-time profiles could be done. Also the metabolic patterns were in good agreement with human data. In conclusion, these findings are the first reported regarding the TK properties of SC after pulmonary administration to pigs. The presented method of TK serves as an appropriate predictor of human TK of cannabinoids.

Backgrounds Substituting 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. Methods In-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. Results Data-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. Conclusions Modeling 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.

The use of antifungals in birds is characterized by interspecies and interindividual variability in the pharmacokinetics, affecting drug safety and efficacy. Oral antifungal drug absorption is a complex process affected by drug formulation characteristics, gastrointestinal anatomy, and physiology. New antifungal drug delivery systems can enhance drug stability, reduce off-target side effects, prolong residence time in the blood, and improve efficacy. Topical administration of antifungals through nebulization shows promising results. However, therapeutic output is highly influenced by drug formulation and type of nebulizer, indicating these factors should be taken into account when selecting this medication route.

Introduction Projects comparing bronchodilator response by aerosol devices in the ED are limited. Evidence suggests that the vibrating mesh nebulizer (VMN) provides 5-fold greater aerosol delivery to the lung as compared to a jet nebulizer (JN). The aim of this project was to evaluate a new nebulizer deployed in an Emergency Department. Methods A quality improvement evaluation using a prospectively identified data set from the electronic medical record comparing all ED patients receiving aerosolized bronchodilators with the JN during September 2015 to those receiving aerosolized bronchodilators with the VMN during October 2015. Results 1594 records were extracted, 879 patients received bronchodilators via JN and 715 patients via the VMN. Admission rates in the VMN group were 28.1% and in the JN group at 41.4%. The total albuterol dose administered was significantly lower in the VMN group compared to the JN (p 5 mg albuterol to control symptoms (85% of the VMN group received only 2.5 mg) whereas dosing in the JN group was higher in some patients (with 47% receiving only 2.5 mg). The use of VMN was also associated with a 13% (37 min) reduction in median length of stay in the ED. Conclusions The VMN was associated with fewer admissions to the hospital, shorter length of stay in the ED and a reduction in albuterol dose. The device type was a predictor of discharge, disposition and amount of drug used. Randomized controlled studies are needed to corroborate these findings.

Spray pyrolysis process has been used for the synthesis of non-oxide ceramic powders from liquid precursors in the Si/C/N system. Particles with a high thermal stability and with variable composition and size distribution have been obtained. In this process, the mechanisms involved in precursor decomposition and gas phase recombination of species are still unknown. The final aim of this work consists in improving the whole process comprehension by an experimental/modelling approach that helps to connect the synthesized particles characteristics to the precursor properties and process operating parameters. It includes the following steps: aerosol formation by a piezoelectric nebulizer, its transport and the chemical-physical phenomena involved in the reaction processes. This paper focuses on the aerosol characterization to understand the relationship between the liquid precursor properties and the liquid droplet diameter distribution. Liquids with properties close to the precursor of interest (hexamethyldisilazane) have been used. Experiments have been performed using a shadowgraphy technique to determine the drop size distribution of the aerosol. For all operating parameters of the nebulizer device and liquids used, bimodal droplet size distributions have been obtained. Correlations proposed in the literature for the droplet size prediction by ultrasonic nebulization were used and adapted to the specific nebulizer device used in this study, showing rather good agreement with experimental values.

Coenzyme Q(10) (CoQ(10)) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ(10) nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ(10) formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60 nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ(10) delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02 mu m). Stability tests showed that the most stable formulation, after 90 days, was the one containing vitamin-E TPGS, followed by the CoQ(10)-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ(10).

Nebulizers 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.Ten 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.10 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).These 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.

Currently, cystic fibrosis patients require daily nebulized treatments to achieve optimal lung health. Growth of pathogenic bacteria in patient nebulizers is well known, and disinfection guidelines have been established. In this short communication, we sought to discover what effect, if any, repeated nebulization/disinfection cycles had on nebulizer output. We nebulized saline repeatedly after exposure to boiling water, steam, and alcohol disinfection methods. While alcohol disinfection did not affect nebulizer output, boiling water and steam significantly decreased nebulizer output from baseline, 74.1 ± 5.9% (p = 0.022) and steam 63.6 ± 6.5% (p = 0.0048) after 60 cycles respectively. This decrease in nebulizer output could significantly increase the duration of nebulizer treatment time and negatively impact the burden of care on patients with cystic fibrosis.

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.

Clinically, the particle size and size distribution of inhaled drug play an extremely important role in airway drug deposition and therapeutic outcome. It is necessary to fully understand the spatial distribution of inhaled drugs, which will contribute to the drug development. However, all spatial information is lost in the sample processing of conventional pharmacokinetic study. Mass spectrometry imaging (MSI) is a powerful tool for visualization of spatial localization of biological molecules or metabolites in tissue section without the procedure of any tagging or labeling chemistry. In this study, we have established a quantitative DESI imaging to detect the drug concentration in lung and the results of two administration methods (inhalation and oral) were compared. In addition, the spatial localization of inhaled drug was also visualized, and the in vitro in vivo correlations (IVIVCs) of lung distribution of inhaled drug were explored. Our results indicated that the spatial localization of drug aerosol delivered by the Pari nebulizer at the lung parenchyma has a tendency to be higher than the results obtained by Omron nebulizer. The signal intensity in the primary bronchi by Omron nebulizer was significantly higher than that result of Pari nebulizer. In vitro particle characterization, the ratio of small particles produced by the Pari nebulizer is higher than the results of Omron nebulizer. The in vivo and in vitro results show a consistency. The quantitative DESI-MSI is a potential tool for analysis and quantify the drug concentration in lung tissue.

An integrated in vitro in silico approach was employed to investigate albuterol administration to an adult lung airway. Particle size characterization of aerosolized albuterol generated by a jet- and vibrating mesh nebulizer was evaluated in vitro using an adult ventilator circuit that consisted of an endotracheal tube (ETT) connected to a cooled Next Generation Impactor. The aerosol particle size distribution sampled by spectrophotometry was used to predict particle deposition in an in silico patient-specific seven-generation airway model using computational fluid dynamics (CFD). A Lagrangian particle tracking algorithm was used to investigate the effect of nebulizer type and position on drug delivery and compare the efficacy of drug administration through endotracheal intubation and oral route. A vibrating mesh nebulizer produced a larger lung dose than the jet nebulizer, with the aerosol characteristics being dependent on the location of the nebulizer in the ventilator circuit. The CFD analysis showed that the vibrating mesh nebulizer placed at the ventilator had a lower global and local deposition fraction down to the 7th airway generation with higher penetration beyond. Besides, delivery through the ETT was more efficient than oral delivery for the studied conditions. Particle deposition patterns in the various lung lobes were evaluated. Placement of the nebulizer in an adult ventilator circuit could target different areas of the lung.

TOPIC: Respiratory Care TYPE: Original Investigations PURPOSE: Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyperresponsiveness. Current ERS guidelines recommend that measures should be taken to minimize technician exposure to methacholine aerosol, with added infection control concerns in the context of the ongoing COVID-19 pandemic. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb reduced expelled particle concentrations by 77-91% during MCT. Our aim was to evaluate whether this modification resulted in a change in the delivered dose of methacholine. METHODS: Following published industry testing standards for MCT, we connected a Hamilton-G5 mechanical ventilator and Michigan lung simulator in series with respiratory rate 15 breaths/min, tidal volume (VT) 500 mL, I:E ratio 1:1 with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson MicroMist and AeroEclipse II BAN nebulizers powered by either a dry gas source at 50 psi and 4.5 L/min or the Ombra compressor system, in addition to our current MCT protocol which utilizes Hudson MicroMist nebulizer with KoKo dosimeter (3 breaths). A filter placed in line between the nebulizer and test lung was weighed before and after 1 minute of nebulized methacholine delivery. Mean inhaled mass was calculated from three trials of each method with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles < 5 µm) and inhalation time. Unpaired t-test was used to compare methacholine dose delivery with and without viral filter placement. Due to multiple independent comparisons, Bonferroni correction was used and alpha level was set at 0.01. RESULTS: The addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using the 50 psi dry gas source, dose delivered with the Hudson MicroMist did not differ with (461.0 µg) or without (307.8 µg) a viral filter (P=0.11) or with the AeroEclipse II BAN with (580.8 µg) or without (678.4) a viral filter (P=0.59). Using the Ombra compressor, dose delivered with the Hudson MicroMist did not differ with (1063.3 µg) or without (947.5 µg) a viral filter (P=0.026) or with AeroEclipse II BAN with (843.8 µg) or without (648.3) viral filter (P=0.42). Dose delivery did not differ significantly when using the KoKo dosimeter and Hudson MicroMist with or without a viral filter (P=0.20) using a 3-breath protocol. CONCLUSIONS: The addition of a viral filter to the nebulizer expiratory limb did not result in a significant change in the in the delivered dose of methacholine. CLINICAL IMPLICATIONS: Based on these findings, use of a viral filter to limit the concentration of expelled aerosol during MCT should be considered to improve pulmonary function technician safety and potentially reduce the risk of infectious exposure during the ongoing COVID-19 pandemic. DISCLOSURES: No relevant relationships by Kaiser Lim, source=Web Response no disclosure submitted for todd meyer;No relevant relationships by Alexander Niven, source=Web Response No relevant relationships by Paul Scanlon, source=Web Response No relevant relationships by Yosuf Subat, source=Web Response No relevant relationships by Keith Torgerud, source=Web Response

Aerosol inhalation delivery of cefazolin, a broad-spectrum first-generation cephalosporin antibiotic, was investigated. Inhalation system based on ultrasonic nebulizer was developed for the generation of dry cefazolin aerosol within mean particle diameter range 0.5–3.0 μm and mass concentration 0.01–3 μg/cm3. Pharmacokinetic measurements were carried out for the aerosolized form of cefazolin delivered in mice using nose-only chamber. Cefazolin concentrations in blood serum and in the lungs of mice were measured as a function of time by means of high performance liquid chromatography. Body-delivered dose depending on particle size, concentration and inhalation time as well as other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized cefazolin was assessed through the aerosol inhalation treatment of mice infected with Klebsiella pneumoniae. Survival rate for infected mice after the treatment with cefazolin aerosol demonstrated high antibacterial efficiency of the inhalation delivery of cefazolin in comparison with intraperitoneal delivery.

A novel transparent airway model is presented, that simulates the geometry and airflow along all 23 bifurcation units of a representative pathway. The model is intended for the development of new aerosol/droplet based therapeutic techniques. The model is realized in fused quartz and thus allows the application of different optical measurement techniques for the analysis of aerosol propagation and deposition on microscopic level. In addition, it enables separate adjustment of the flow conditions for each individual bifurcation unit of the lung and therefore offers the possibility to simulate specific human breathing characteristic. The model can be rotated in two spatial directions to vary the local relevance of sedimentation for aerosol deposition. In this first study, the suitability of the model concept is investigated and evaluated by analyzing a predefined droplet aerosol during its propagation along the airway. A water aerosol is generated using a commercially available medical nebulizer and is actively inhaled by the lung model. Droplets within the airway are characterized in flight with regard to their mean size, velocity, and concentration as function of generation number and breathing characteristics using high-speed transmitted light microscopy. The present combination of measurement methodology and aerosol characteristics allows a quantitative analysis of the propagation of micro droplets up to the 10th generation of the respiratory tract. The data indicate that up to the 6th generation the droplets on average follow the respiratory flow almost with no slip and are deposited further downstream. The results underline the importance of airway models with a sufficiently high number of generations.

Background New guidelines for methacholine challenge testing recommend reporting the test outcome as dose rather than concentration. Jet nebulizers have historically been used for methacholine challenge testing, but much of the weight loss, often (incorrectly) referred to as aerosol output, is actually evaporation. The Wright nebulizer is well characterized and still widely used, but its availability is unclear, and it is nondisposable. We developed a novel method using a vibrating mesh nebulizer (Solo). This method was compared with the standard 2-min tidal breathing method using the Wright nebulizer. Repeatability within and between nebulizers was also tested. Methods Fifteen patients with mild asthma completed four methacholine challenges (two with the Solo vibrating mesh nebulizer and two with the Wright jet nebulizer). Challenges with the same nebulizer were 24 h apart, and challenges between nebulizers were separated by 1 week. Standard 2-min tidal breathing methods were used with the Wright nebulizer. For the Solo nebulizer, the tidal breathing method was modified by nebulizing to completion 0.5 mL of doubling concentrations of methacholine at 5-min intervals. Results Geometric mean methacholine doses required to cause a 20% fall in FEV 1 were similar (96 vs 110 μg; P > .05); methacholine concentrations that caused a 20% fall in FEV 1 were significantly lower with the vibrating mesh nebulizer (0.48 vs 4.4 mg/mL; P 1 within and between nebulizers was excellent (intraclass correlation coefficient > 0.92). Conclusions We have developed a novel, simple, repeatable method for conducting methacholine challenges using new nebulizer technology. Importantly, the method meets recommendations set out in the new guidelines. Trial Registry ClinicalTrials.gov; No.: 02965482; URL: www.clinicaltrials.gov.

The size of airborne particles determines their deposition pattern within the lungs and therefore, the efficacy of inhalation therapy. The present study analyzed factors affecting liquid atomization performed by vibrating-membrane technology. First, the process of vibrating-membrane nebulization (eFlow®rapid and Aeroneb® Pro) was challenged with numerous inorganic salts and active pharmaceutical ingredients. All investigated samples caused a sigmoidal decrease in aerosol droplet size upon an increase in concentration. Calculated dose-effect curve characteristics (i.e., half maximal effective sample concentration inducing a halfway drop of the droplet size) indicated distinct molar "potency" amongst the utilized samples with respect to generation of "adequate" inhalation aerosols. Second, the employed solvent (aqueous vs. organic) was shown to amplify the electrolyte effect on vibrating-membrane technology (i.e., dose-effect curve characteristics and overall aerosol droplet size). Third, besides the sample and solvent type, the nozzle composition (diverse metal and polymer coatings) induced a strong impact on the current mode of nebulization. Here, coating materials were identified, which necessitated higher and lower electrolyte concentrations in order to decrease the aerosol droplet size in comparable manner to plain nebulizer membranes. Thus, depending on the employed sample type and concentration, solvent and nozzle composition, a delivery of "inadequate" or "adequate" aerosols for inhalation purpose was observed. Overall, the current observations could be used to compile suggestions for the rational design of aerosol formulations and nebulizer devices meeting the specific requirements for successful inhalation therapy.

Cardiopulmonary bypass triggers an ischemia-reperfusion injury with endothelial dysfunction in the pulmonary circulation which can result in pulmonary hypertension. Inhaled milrinone reduces this reperfusion phenomenon and two methods commonly available for administering it are simple jet and vibrating mesh nebulizations. However, neither their generated milrinone particle size profiles, nor their ability to aid endothelial relaxation have been compared. Simple jet and vibrating mesh particle size distributions of milrinone were verified through cascade impaction and their efficacy was tested on a cardiopulmonary bypass (CPB) swine model. Post-nebulizations, animals underwent 90 min of CPB, followed by 60 min of reperfusion and lung excision. Pulmonary arterial endothelium-dependent relaxations to acetylcholine and bradykinin were then performed on pulmonary vasculature rings and were subsequently modeled as inhibitory Emax functions. In vitro studies showed lower emitted and inhaled doses from the simple jet nebulizer and its particle size distribution indicated upper and middle airway targeting. During in vivo studies, milrinone pre-treated, unlike saline groups maintained baseline pulmonary pressures up to 30 min post-CPB. Ex vivo studies showed better endothelial relaxation of arteries from the two milrinone groups over those from the control group in an administration/pathway-dependent manner, favoring simple jet administration.

In an effort to better understand the droplet evaporation characteristics in nebulizer based humidification and aerosol based drug delivery, this paper investigates the variation in the droplet size distribution and the amount of water evaporated from the droplets. The experimental part was conducted on droplets generated by an ultrasound atomizer and delivered to a stream of air flowing along a conduit as is typically found in medical respiratory therapy devices. For the theoretical part a poly-disperse droplet evaporation model was developed and validated by the experimental results. A feature of this investigation is the consideration of the changes to different droplet size ranges (lower, middle and upper) within the droplet size distribution to better understand the evaporation process and also provide a more detailed comparison with the analytical model. As expected the experimental results show that increasing the air temperature and conduit length increase the amount of water evaporated and cause a shift in the droplet size distribution. However, changes to the droplet size distribution are also attributed to the fact that large droplets are possibly being removed from the air stream due to settling in the apparatus. The poly-disperse evaporation model accurately predicted water evaporation and changes to the median droplet sizes in the distribution.

The aim of this study was to determine the-effect of fill-volume, heat-and-humidification on aerosol-delivery and fugitive-aerosol-emissions from nebulizers placed proximal to the patient in single-limb-non-invasive-ventilation (NIV) adult-model. We compared a vibrating-mesh-nebulizer (VMN) and jet-nebulizer (JN) placed proximal to breathing-simulator with adult-settings (I:E 1:3, 15 breaths.min −1 , tidal-volume 500 mL). Ventilator was set to (20 cm.H 2 O peak-inspiratory-pressure, peak-expiratory-pressure 5cmH 2 O) in spontaneous-mode. Each nebulizer was used to compare total-inhaled-dose (TID) collected in inhalation-filter of 3 different fill-volumes (5000 μg salbutamol diluted to 1, 2 and 4 mL using normal-saline) and 3 heat-and-humidification-conditions (no-heat and no-humidification, humidification with no-heat and heat-with-humidification) using 1 mL respirable-solution containing 5000 μg salbutamol diluted to 2 mL using normal-saline. TID with 1, 2 and 4 mL fill-volumes were similar with VMN but increased upto twofold with JN (p Efficiency of JN varied with fill-volume. In contrast, the lower-residual-volume of VMN produced similar efficiency across fill-volumes with higher TID than JN. No need to switch-off the humidifier for aerosol-delivery in NIV, since variations of heat-and-humidity did not impact TID with both nebulizer. However, fugitive-aerosol-emissions represent a potential-risk to both healthcare-providers and acute-care-environment.

Combining oxygen therapy with aerosol delivery within High flow nasal cannula oxygen therapy (HFNC) is an attractive practice. Delivered dose (DD) was found to decrease with increasing gas flow rates and with smaller sized cannulas. The aim of this study was to quantify amount of aerosol emitted at the cannula outlet using different aerosol generators at low oxygen flow. Aerogen Solo vibrating mesh (SOLO), jet nebulizers, Combihaler connected to metered dose inhaler (MDI) and SOLO, MDI connected AeroChamber Vent and MDI connected AeroChamber Mini were used to deliver aerosol in HFNC in-vitro setting. SOLO with its T-piece delivers DD∼35% of nebulizer charge with high fine-particle-dose (FPD). Both Combihaler and jet-nebulizer delivered∼18% with lower FPD. MDI with both spacers delivers only 2.1 and 1.3% of nominal dose, respectively. Mass median aerodynamic diameters were small for the SOLO, Combihaler and jet nebulizers and high for the two spacers. Inhaled aerosols can be delivered efficiently at low oxygen flow using SOLO, with both T-piece and Combihaler, and jet nebulizer in HFNC system. While MDIs with spacers delivers negligible amounts of drug below that expected for clinical response at this flow.

Background Chronic infections with Pseudomonas aeruginosa are a leading cause of morbidity in patients with cystic fibrosis (CF). Tobramycin nebulizer solution (TNS) is indicated for maintenance therapy in CF patients. TOBI® is a tobramycin nebulizer solution (TNS) approved by FDA for maintenance therapy for patient with CF. Adherence to recommended therapy in CF has always been a challenge and new generation nebulizers are increasingly used “off label” to reduce the time required for inhalation, potentially improving patient compliance. Objectives To assess the performance of selected recent nebulizer delivery systems for determination the optimum combinations to deliver TOBI®. Using the relative lung bioavailability of TOBI® to the lungs in healthy volunteers, following inhalation from selected nebulizer delivery systems, using a urinary pharmacokinetics method. In vitro aerodynamic characteristics of the nebulized dose were also determined. Methods Serial urine samples were collected from 12 healthy volunteers up to 24 h post-inhalation of TOBI® inhaled solution following delivery by Pari LC Plus®, Sidestream®, NE-U22-E Omron® and Aeroneb® Go nebulizers. In vitro aerodynamic characteristics of the nebulized dose were also determined according to the CEN (Committee European de Normalization) method. Results The mean (SD) relative lung bioavailability from Pari LC Plus®, Sidestream®, Omron®, and Aeroneb® Go nebulizers was 4.9 (0.5), 3.9 (0.5), 7.1 (1.3), and 7.7 (0.7) %, respectively. The mean (SD) mass median aerodynamic diameter (MMAD) of the drug particles from the same systems was 2 (0.2), 2 (0.2), 1.2 (0.03) and 2.0 (0.1) μm, and the corresponding fine particle doses (FPD) were 2.2 (0.23), 1.5 (0.2), 3.44 (0.3) and 2.8 (0.3) mg. Conclusion The data obtained from in-vitro and in-vivo studies reflect poor relative lung bioavailability of tobramycin following jet nebulization.

A method based on continuous-microflow ultrasonic nebulizer quadruple-mode micro-capillary system (μ-USN/QCS-HG) has been used for the efficient generation of As, Bi, Ge, Sb, Se and Sn hydrides directly formed at vibrating quartz plate before detection by microwave induced plasma-optical emission spectrometry (MIP-OES). The ultrasonic nebulizer incorporates four solution capillaries with independent liquid feeding and a common gas inlet. The μ-USN/QCS-HG allowed the hydride generation directly into the cyclonic spray chamber without using any additional device either for solution and gas control or for gas phase separation. The μ-USN/QCS-HG-MIP OES makes feasible the implementation of an on-line internal standard (IS) calibration strategy and Ge was suggested as internal standard. A univariate approach and the simplex optimization procedure were used to achieve optimized conditions and derive analytical figures of merit. Analytical performance of the ultrasonic nebulization system was characterized by determination of the limits of detection (LODs) and precision (RSDs) with the μ-USN/QCS-HG-MIP OES observed at a 50 μL min− 1 flow rate. The experimental concentration detection limits for simultaneous determination, calculated as the concentration giving a signal equal to three times of the standard deviation of the blank (LOD, 3σblank criterion, peak height) were 1, 5, 2, 3 and 2 ng mL− 1 for As, Bi, Sb, Se and Sn, respectively. The method offers good precision (RSD ranged from 2% to 3%) for micro-sampling analysis. The potential application of this system was demonstrated by successfully analyzing several certified reference environmental samples (CRM DOLT-2, SRM 2710 and SRM 1643e) with satisfactory results. The measured of contents of elements in certified reference materials were in good agreement with the certified values, according to the t-test, for a confidence level of 95%.

Using inhaler devices, drug delivery to the lung has been practiced for a long time to treat respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). The key question in this practice is how to deliver the drug to the regions of interest efficiently. Significant efforts have been made to develop models of depositional behavior of inhaled particles. The semi-experimental International Commission on Radiological Protection (ICRP) model is frequently used to predict depositional behavior of inhaled particles. Here, we have tried to adapt this model for predicting deposition of pharmaceutical particles that are inhaled through dry powder inhalers (DPIs) and nebulizers. We attempted to use a more proper extrathoracic deposition formula accounting for breath holding and bolus timing (in case of DPIs) and possible evaporation of droplets (in case of nebulizers). Two computer programs for DPIs and nebulizers were developed which can be freely accessed through e-mail contact to the first author.

The analytical potential of a coupled continuous-micro-flow ultrasonic nebulizer quadruple-mode micro-capillary system (μ-USN-QCS)-argon-helium microwave induced plasma-optical emission spectrometry (MIP-OES) has been evaluated for the purpose of determination of inorganic elements (Ba, Ca, Cd, Cu, Fe, Mg, Mn, Pb, Sr, Zn). The nebulizer incorporates four solution capillaries with independent liquid feeding and a common gas inlet. Four different spray chambers were evaluated and the geometry of the best performing one was optimized. A univariate approach and the simplex optimization procedure were used to achieve optimized conditions and derive analytical figures of merit. Analytical performance of the ultrasonic nebulization system was characterized by a determination of the limits of detection (LODs) and precision (RSDs) with the μ-USN-QCS-MIP-OES observed at a 40 μL min − 1 flow rate. The experimental concentration detection limits for simultaneous determination, calculated as the concentration giving a signal equal to three times of the standard deviation of the blank (LOD, 3σ blank criterion, peak height) were in the range from 2.8 ng mL − 1 for Cu to 30 ng mL − 1 for Ba. The method offers relatively good precision (RSD ranged from 6% to 8%) for micro-sampling analysis. The methodology was validated through determination of elements in certified reference materials (NRCC DOLT-2, NRC GBW 07302, NIST 2710 and NIST 1643e) and by the aqueous standard calibration technique. The measured of contents of elements in the reference materials were in satisfactory agreement with the certified values.

At this paper the effect of aeration on the droplet size distribution of the aerosol have been analyzed. The atomization process was carried out using a pneumatic nebulizer which was equipped with a modified nebulizer cup. This modified nebulizer cup was combined with an additional source of gas bubbles. The measurements of the droplet sizes obtained by the use of the digital microphotography method and analyzed by Image-Pro Plus software. The analysis of the experimental studies proved that an increase in the flow rates of additional gas leads to the increase in the number of small droplets and the decrease of the number of drops of large diameter. Additionally, the mean droplet diameter decreases with the increase of the flow rate of aeration gas. A correlation equation was proposed, which describes the relationship between the mean diameter of droplet and the volumetric flow rate of additional gas. The increase in the bubble volume discharging through a single orifice causes the increase of the flow rate of aeration gas. The modifications of construction of atomizer lead to the better effectiveness of nebulization.

Metal element detection technologies for seawater analysis are very important in the fields of marine scientific investigation and environmental monitoring. The current technologies cannot meet the requirements of detection capabilities, such as online, real-time, multi-element and highly sensitive while used in the above fields on-site. A newly developed sensor named online ultrasonic nebulizer assisted laser induced breakdown spectroscopy (OUN-LIBS) is introduced in this paper which is expected to be used for on-site seawater analysis. The core design idea of this sensor is to combine an online ultrasonic nebulizing auxiliary device with a traditional LIBS system to nebulize the liquid samples into aerosol for LIBS detection in order to realize a continuously, highly sensitive, stable and fast on-site detection. Based on this idea, a hardware system composed of an adapter module, a nebulizing module and an optical module and a software system with communication, control and display functions were designed. The laboratory experiments and marine field testing were carried out to assess the sensor. Under the status of continuous online detection, the LODs of the 6 target elements are lower than 1 ppm and the stability of spectral line intensity of Ca is lower than 0.38%. Besides the traditional calibration curve method, an online and on-site standard sample calibration method is adopted in the concentration quantitative analysis. The results of research show that the accuracy of online quantification analysis is very impressive even in the marine field testing.

The aim of this work was to investigate the photocatalytic inactivation efficiencies of eight phages infective to lactic acid bacteria (LAB) contained in bioaerosols. Studies were performed in a semi-pilot scale equipment, which consists of a stainless steel camera, in which air containing the phage particles circulates, and an acrylic reactor with twenty UV-A lamps and six borosilicate plates covered with the catalytic film (TiO2). Phages (ALQ13.2, ATCC 15807-B1, ATCC 8014-B1, BYM, CHD, LDG, Ln-9 and MLC-A) were nebulized into the camera using the 6-jet Collison nebulizer, being assays performed for a total time of 100 min. Sampling by impact of air on a glass slide was carried out. Some conditions of equipment operation (phage suspension concentration, nebulization method, influence of relative humidity) using phage ATCC 8014-B1 were previously adjusted. Phages ALQ13.2, ATCC 15807-B1, BYM and CHD were not detected in the air because of loss of their infectivity after nebulization when assays in absence of catalyst and UV radiation were conducted. On the other hand, it was possible to achieve a complete inactivation (

Introduction Different aerosol generators are used during mechanical ventilation connected to spacers or adapters. The design and volume of these connections can significantly affect aerosol delivery. This study aimed to evaluate the impact of a variety of connections on aerosol delivery in invasive mechanical ventilation (IMV) setting. Methods A ventilator was set at volume-controlled mode (Vt = 500 ml, f = 15/min, PEEP = 5 cm H20), and connected to a test lung model to simulate intubated mechanically ventilated adults with a 1:3 ratio of inspiratory to expiratory phase. An endotracheal tube of 8 mm inner diameter was used in this model, inserted between Y-piece and the breathing simulator. Ventilator settings were selected typically as those indicated for COPD patients in the intensive care unit when IMV is prescribed during acute exacerbations. Aerosol-generator was placed in dual limb IMV at Y-piece in the inspiratory limb. For nebulizer delivery; 1 ml respirable solution was nebulized using vibrating mesh nebulizer with three connection settings; I: T-piece, II: Combihaler (new and old version), and III: Combihaler with a pressurized metered-dose inhaler (pMDI). Only with connection III, two pMDI puffs, 100 μg salbutamol each, were actuated before nebulization of 1 ml of salbutamol solution. For pMDI delivery; pMDI puffs (100 μg per puff) were delivered using two connection settings I: pMDI T-piece adapter (2 and 5 pMDI salbutamol puffs), and II: Combihaler (2 pMDI salbutamol puffs only). 2 and 5 pMDI salbutamol puffs were delivered by pMDI T-piece adapter to determine the possible effect of aerosolized drug condensation on the T-piece. Fates of nebulized, and actuated-doses were determined. Results No significant difference was observed between old and new Combihalers used to deliver nebulized doses with and without pMDI. The pMDI T-piece adapter delivered significantly higher pMDI aerosol than Combihaler (p Conclusions The antistatic property of the new Combihaler affected pMDI delivered dose similar to conventional spacer but does not affect the nebulized dose. Further clinical studies are needed to determine the bronchodilator effect of the pre-nebulization pMDI puffs on the nebulized dose.

Treprostinil palmitil (TP) is an inhaled long-acting pulmonary vasodilator prodrug of treprostinil (TRE) that has been formulated for delivery as a suspension (treprostinil palmitil inhalation suspension; TPIS) and as a dry powder (treprostinil palmitil inhalation powder; TPIP). In humans, tachyphylaxis is frequently observed with continuous intravenous (IV) or subcutaneous (SC) infusion of TRE and requires dosage escalation to maintain activity. The aim of the present study was to determine whether tachyphylaxis occurs with repeat daily administration of inhaled TPIS.Experiments were performed in male Sprague-Dawley rats prepared with a telemetry probe implanted into the right ventricle to measure the change in right ventricular pulse pressure (ΔRVPP) induced by exposure to a 10% oxygen gas mixture. TPIS (6 mL) at concentrations of 0.25, 0.5, and 1 mM was given by nose-only inhalation using an Aeroneb Pro nebulizer, either as a single administration or daily for 16 or 32 consecutive days. In studies involving consecutive daily administrations of TPIS, the delivered TP dosage was 140.3 μg/kg at 1 mM and ranged from 40.2 to 72.2 μg/kg at 0.5 mM. A separate cohort of telemetered rats received continuous IV infusion of TRE via an Alzet mini-pump at a dosage rate of 250 ng/kg/min for 16 days. Blood and lung tissue samples were obtained, and the concentration of TRE in the plasma and TRE and TP in the lungs were measured approximately 1 h after TPIS administration.Dose-response studies with TPIS administered as a single administration inhibited the hypoxia-induced increase in RVPP in both a concentration-dependent (0.25, 0.5, and 1 mM) and time-dependent (1-24 h) manner. TPIS, given QD or BID at inhaled doses ranging from 40.2 to 140.3 μg/kg for 16 or 32 consecutive days, produced statistically significant (P .05) inhibition of the increase of RVPP due to hypoxia over the full duration of the dosing periods. By contrast, the inhibition of the hypoxia-induced increase in RVPP observed with IV TRE infusion (250 ng/kg/min) disappeared after 16 days of infusion. The plasma concentrations of TRE were significantly higher after IV TRE (range, 2.85-13.35 ng/mL) compared to inhaled TPIS (range, 0.22-0.73 ng/mL) CONCLUSIONS: There was no evidence of tachyphylaxis with repeat daily dosing of TPIS for a period of up to 32 days. The absence of tachyphylaxis with TPIS is likely related to its local vasodilatory effects within the lungs, combined with an absence of sustained high plasma concentrations of TRE.

Simple concepts that control the amount of analyte, solvent aerosol and solvent vapor that enter the plasma are used to explain changes in analyte transport efficiency as a function of sample uptake rate in pneumatic nebulizer/spray chamber sample introduction systems. These include droplet-droplet collision/coalescence, evaporation of solvent from the sample aerosol and droplet impact on the walls of the spray chamber. We show that even small (2 to 5 μm diameter) droplets have a poor (

Awareness of the risk of airborne transmission of SARS-CoV-2 makes patients hesitant about using inhaled medications that are considered as a potential source of viral transmission and immunosuppression. However, patients with asthma or COPD should continue all prescribed inhaled medications. Apparently, inhalers, including pMDIs, DPIs, or SMIs, have a low risk of contamination although characteristics of drug formulation can precipitate cough, whereas some researchers do not rule out the probability that nebulizer treatments may increase the risk of infection transmission via droplet nuclei and aerosols. Considering that aerosol therapy generates fugitive emissions that are not inhaled by the patient and are released from the device during expiration, several international professional bodies have provided recommendations for drug delivery via inhalers and in particular, nebulizers. Unfortunately, these recommendations are often in conflict with each other and do not clarify whether it is appropriate to use nebulizers during this COVID-19 pandemic. Considering what is available in literature, there are no known infection-related hazards to an uninfected patient and also a patient with COVID-19 that preclude the use of a nebulizer at home, but it fundamental that all patients, regardless of whether or not suffering from COVID-19, always follow some practical advices., Highlights • Droplets or aerosols predominate in the transmission of SARS-CoV-2. • Established treatments for both asthma and COPD are generally administered by inhalation. • There are no known infection-related hazards that preclude the use of a nebulizer at home. • All patients must always follow some practical advices.

The Flow Focusing Pneumatic Nebulizer (FFPN) working at low liquid flow rates was evaluated for the elemental analysis in slurried samples by argon-helium microwave induced plasma optical emission spectrometry (MIP-OES). The obtained results achieved were compared with commercially available V-groove Babington type nebulizer (VBPN). A univariate approach and the simplex optimization procedure were used to achieve optimized conditions and derive analytical figures of merit. Analytical performance of the micro nebulization system was characterized by a determination of the limits of detection (LODs), the precision (RSDs) and the wash-out times for Ba, Ca, Cd, Cu, Fe, Mg, Mn, Pb and Sr. The experimental concentration detection limits for simultaneous determination, calculated as the concentration giving a signal equal to three times of the standard deviation of the blank (LOD, 3σ blank criterion, peak height) were 0.9, 0.2, 0.3, 0.2, 0.3, 0.1, 0.2, 0.4, 0.4 and 0.3 ng mL −1 for Ba, Ca, Cd, Cu, Fe, Mg, Mn, Pb and Sr, respectively. The method offers relatively good precision (RSD ranged from 5% to 8%) for micro-slurry sampling analysis. Analyses of the certified reference materials (NRCC DOLT-2, GBW 07302 and SRM 2710) were performed in order to determine the accuracy available with the presented nebulization systems. The measured contents of elements in the reference materials were in satisfactory agreement with the certified values. In addition, these elements were determined in two real samples. Slurry concentration up to 3% m/v (particles

Coenzyme Q10 (CoQ10) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this study was to investigate the feasibility of preparing phospholipid-stabilized dispersions of the anticancer agent for continuous pulmonary delivery using a vibrating-mesh nebulizer. We determined the physicochemical properties (drug particle size distribution in dispersion, zeta potential, surface tension, and rheology) and compared the aerosolization profiles (nebulization performance, aerodynamic drug deposition and total emitted dose) of dispersions of CoQ10 prepared with different phospholipids. The hydrodynamic sizes of the drug particles in dispersion were primarily in the submicron range, but formulations with drug particle sizes greater than the aperture size of the nebulizer presented superior aerosolization profiles. At high shear rates, certain formulations presented increased shear-thickening behavior, which was connected to a decrease in mass and drug output over time, and with decreased aerodynamic and geometric sizes. Other formulations presented shear-thinning behavior and showed similarly high drug depositions. In this investigation, we found that dispersed formulations of CoQ10 presented different in vitro performance for pulmonary delivery based on their rheological behavior. In conclusion, this characterization methodology provides an innovative approach to screen formulations of poorly-water soluble compounds for continuous (no clogging) active vibrating-mesh nebulization.

ZnO thin films were deposited onto glass substrates using a simple and low-cost homemade nebulizer spray technique by keeping the substrate temperature at 350, 400 and 450 °C. Their ammonia gas sensing property at room temperature under darkness was studied. The results show that the ZnO films deposited at 400 °C substrate temperature exhibit the best response time as well as shortest recovery time. The large number of oxygen vacancies presents in this film and the suitable surface morphology with increased surface to volume ratio may be the reasons for the enhanced gas sensing property of this sample. The photoluminescence, FESEM and XRD results are correlated appropriately with the gas sensing properties of the samples.

A suitable aerosol droplet size and formulation output rate is essential for the therapy of lung diseases under application of nebulizers. The current study investigated the potential of amine-modified poly(vinyl alcohol)s as excipients for inhalation delivery. A change of conductivity (effective at0.1mg/ml) and viscosity (effective at0.1mg/ml) of samples that were supplemented with charge-modified polymers had a significant influence on the generated droplet size (shift from ~8 to ~4 μm) and formulation throughput rate (shift from ~0.2 to ~1.0 g/min), where polymers with a higher amine density (and molecular weight) showed an elevated activity. Biocompatibility assessment of polymers in A549 cells and an isolated lung model resulted in cell lysis and lung edema formation dependent on the type (degree of amine substitution) and dose of polymer applied. Suitable compositions and concentrations of amine-modified poly(vinyl alcohol)s were identified with respect to an optimized nebulizer performance and acceptable biocompatibility. Charge-modified polymers represent novel excipients with potential to improve inhalation therapy.