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The study aimed to develop and evaluate budesonide inhalation micro‐suspension to target inflammation in the lower trachea and bronchi. Initially, the slurry phase is prepared by dispersing the drug (0.25 and 0.5 mg ml−1) in the Water for Injection with polysorbate 80. The slurry is mixed with the aqueous phase comprising other excipients. The mixture is further subjected to the treatment with homogenizer. The prepared formulations are subjected to various physio‐chemical analysis like description, density, pH, osmolality, viscosity, shelf life, impurities, assay, particle size, etc. Andersen cascade impactor is used to estimate the aerodynamic performance. In vivo analysis is initiated with the induction of Asthma in Sprague Dawley rats by ovalbumin challenge intranasally and the treatment is given with the aid of a nebulizer. Lastly, the biochemical estimations are carried out in blood and bronchoalveolar lavage fluid (BALF). The lungs are also subjected to morphological and histological evaluations. The physio‐chemical and analytical examination indicated a stable formulation that is compliant with the standard guidelines. The D90 value of the test formulation is ≤4.5 µm. Cascade impactor evaluation estimated almost, 2–10% higher amount of budesonide reaching the target region as compared to the marketed product. Test formulation attenuated the manifestation of ovalbumin‐induced asthma through suppression of inflammatory cell count in blood and BALF, and modulation of Lactate dehydrogenase and Alkaline Phosphatase levels which is further confirmed by histopathological analysis. The formulated budesonide micro‐suspension demonstrated stability, safety, and efficient delivery to the target site. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Intubated patients with methicillin‐resistant Staphylococcus aureus pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15–20 μg/mL) in 38–79% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit.Airway pharmacokinetics of optimized IV and inhaled vancomycin in infected clinically stable prolonged mechanically ventilated patients were measured. First, IV vancomycin was given until optimized concentrations were achieved (15–20 μg/mL), and, at the same time point, sputum vancomycin concentrations were measured. Then, sputum concentrations were re‐assessed after 4 treatments of inhaled vancomycin (120 mg/2 mL) via a previously characterized nebulizing system that deposited 18 ± 2 mg in the lungs. Vancomycin post‐distribution phase serum peak and trough concentrations were also obtained. Serum albumin was measured to assess binding to vancomycin.Mean serum trough concentration was 18.4 ± 6.5 μg/mL. Sputum concentrations were affected by serum albumin. Only patients with severe hypoalbuminaemia had penetration of drug leading to therapeutic (15.7–17 μg/mL) sputum concentrations. Following inhaled vancomycin, sputum concentrations increased significantly to 199 ± 37.0 μg/mL (P = .002) exceeding minimum inhibitory concentration by 2 orders of magnitude.Despite optimized serum concentrations, patients with albumin near normal had suboptimal concentrations of vancomycin in their sputum. Inhaled therapy may be clinically important for successful treatment of ventilator‐associated methicillin‐resistant Staphylococcus aureus infection. Further studies of inhaled therapy are needed to define their role as adjunctive therapy in ventilator‐associated pneumonia and as single therapy in tracheobronchitis. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionAsthma is a chronic respiratory disorder characterized by airway inflammation and narrowing often leading to acute exacerbations that necessitate a visit to the emergency department (ED). While life threatening cases usually require bronchodilator delivery by nebulizers, mild to moderate acute asthma exacerbations can be treated by bronchodilators delivered either by metered dose inhalers (MDI). Numerous studies have attempted to compare between the two modalities and have drawn similar conclusions in that both are comparable in efficacy with minimal differences. What is evident, however, is that physicians remain inclined to favor nebulizers in the majority of acute asthma exacerbations.In this questionnaire-based study, a survey was distributed to physicians who treat asthma exacerbations to examine demographics, knowledge, beliefs, and current practice in regard to bronchodilator therapy.The majority (90.8%) of physicians prefer short-acting beta agonists via nebulizer, with 9.2% favoring MDI + spacer. Participants include consultants, residents, and specialists across various emergency disciplines. While 90.1% find MDI + spacer equally effective as nebulizers, advantages cited include cost-effectiveness (49.6%), shorter ED stays (63.4%), quicker administration (67.9%), and ease of use (58.8%). Challenges include availability (66.4%) and ineffectiveness in younger patients (45%). Despite this, 65.6% are willing to switch to MDI for initial asthma management in the ED, while 34.4% are resistant.Concerns about availability and effectiveness in younger patients remain barriers. However, a significant number are willing to adopt MDIs with spacers, indicating potential for broader use with better availability and training. [ABSTRACT FROM AUTHOR]

Background: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. Results: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. Conclusion: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks. [ABSTRACT FROM AUTHOR]

The increasing use of hexavalent chromium (Cr(VI)) has exposed large populations to this environmental and occupational carcinogenic agent. Therefore, researchers have been interested in removing this substance through adsorbents. This study aimed to investigate the efficiency of natural zeolite in the direct adsorption of Cr(VI) from airflow and its adsorption modeling. In this study, a nebulizer device produced the Cr(VI) mist. The efficiency of natural zeolite in Cr(VI) adsorption from airflow, modeling of fixed column adsorption, and the effective parameters on adsorption efficiency including the initial concentration of chromium, airflow rate, and adsorption bed depth were studied. To facilitate the prediction of the performance of natural zeolite’s adsorption column, Yoon–Nelson, Thomas, BDST, and Buhart–Adams models were used. The results showed that the adsorption capacity diminished with increased airflow rate and initial concentration, while it increased with elevated height of the adsorption bed. Yoon–Nelson, Thomas, and BDST models corresponded to experimental data with a correlation coefficient of 0.9933, but the information of the Buhart–Adams model had a lower correlation coefficient (around 0.6677). In conclusion, natural zeolite can be used as an efficient low-cost adsorbent for directly Cr(VI) removing from the airflow in a fixed bed column. [ABSTRACT FROM AUTHOR]

Abstract Background Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC)

Abstract The increasing use of hexavalent chromium (Cr(VI)) has exposed large populations to this environmental and occupational carcinogenic agent. Therefore, researchers have been interested in removing this substance through adsorbents. This study aimed to investigate the efficiency of natural zeolite in the direct adsorption of Cr(VI) from airflow and its adsorption modeling. In this study, a nebulizer device produced the Cr(VI) mist. The efficiency of natural zeolite in Cr(VI) adsorption from airflow, modeling of fixed column adsorption, and the effective parameters on adsorption efficiency including the initial concentration of chromium, airflow rate, and adsorption bed depth were studied. To facilitate the prediction of the performance of natural zeolite’s adsorption column, Yoon–Nelson, Thomas, BDST, and Buhart–Adams models were used. The results showed that the adsorption capacity diminished with increased airflow rate and initial concentration, while it increased with elevated height of the adsorption bed. Yoon–Nelson, Thomas, and BDST models corresponded to experimental data with a correlation coefficient of 0.9933, but the information of the Buhart–Adams model had a lower correlation coefficient (around 0.6677). In conclusion, natural zeolite can be used as an efficient low-cost adsorbent for directly Cr(VI) removing from the airflow in a fixed bed column.

Aerosolized lung surfactant therapy during nasal continuous positive airway pressure (CPAP) support avoids intubation but is highly complex, with reported poor nebulizer efficiency and low pulmonary deposition. The study objective was to evaluate particle size, operational compatibility, and drug delivery efficiency with various nasal CPAP interfaces and gas humidity levels of a synthetic dry powder (DP) surfactant aerosol delivered by a low-flow aerosol chamber (LFAC) inhaler combined with bubble nasal CPAP (bCPAP). A particle impactor characterized DP surfactant aerosol particle size. Lung pressures and volumes were measured in a preterm infant nasal airway and lung model using LFAC flow injection into the bCPAP system with different nasal prongs. The LFAC was combined with bCPAP and a non-heated passover humidifier. DP surfactant mass deposition within the nasal airway and lung was quantified for different interfaces. Finally, surfactant aerosol therapy was investigated using select interfaces and bCPAP gas humidification by active heating. Surfactant aerosol particle size was 3.68 µm. Lung pressures and volumes were within an acceptable range for lung protection with LFAC actuation and bCPAP. Aerosol delivery of DP surfactant resulted in variable nasal airway (0-20%) and lung (0-40%) deposition. DP lung surfactant aerosols agglomerated in the prongs and nasal airways with significant reductions in lung delivery during active humidification of bCPAP gas. Our findings show high-efficiency delivery of small, synthetic DP surfactant particles without increasing the potential risk for lung injury during concurrent aerosol delivery and bCPAP with passive humidification. Specialized prongs adapted to minimize extrapulmonary aerosol losses and nasal deposition showed the greatest lung deposition. The use of heated, humidified bCPAP gases compromised drug delivery and safety. Safety and efficacy of DP aerosol delivery in preterm infants supported with bCPAP requires more research.

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

To develop a robust algorithm to accurately calculate 'daily complete dose counts' for inhaled medicines, used in percent adherence calculations, from electronically-captured nebulizer data within the CFHealthHub Learning Health System. A multi-center, cross-sectional study involved participants and clinicians reviewing real-world inhaled medicine usage records and triangulating them with objective nebulizer data to establish a consensus on 'daily complete dose counts.' An algorithm, which used only objective nebulizer data, was then developed using a derivation dataset and evaluated using internal validation dataset. The agreement and accuracy between the algorithm-derived and consensus-derived 'daily complete dose counts' was examined, with the consensus-derived count as the reference standard. Twelve people with CF participated. The algorithm derived a 'daily complete dose count' by screening out 'invalid' doses (those <60s in duration or run in cleaning mode), combining all doses starting within 120s of each other, and then screening out all doses with duration < 480s which were interrupted by power supply failure. The kappa co-efficient was 0.85 (0.71–0.91) in the derivation and 0.86 (0.77–0.94) in the validation dataset. The algorithm demonstrated strong agreement with the participant-clinician consensus, enhancing confidence in CFHealthHub data. Publishingdata processing methods can encourage trust in digital endpoints and serve as an exemplar for other projects. [ABSTRACT FROM AUTHOR]

Nebulizers generate aerosols from liquid-based solutions and suspensions. Nebulizers are particularly well suited to delivering larger doses of medication than is practical with inhalers and are used with a broad range of liquid formulations. When the same drug is available in liquid or inhaler form, nebulizers are applicable for use with patients who will not or cannot reliably use a pressurized metered-dosed inhaler (pMDI) or dry powder inhaler (DPI) due to poor lung function, hand-breath coordination, cognitive abilities (e.g., infants, elderly) or device preference. In a nebulizer, liquid medication is placed in a reservoir and fed to an aerosol generator to produce the droplets. A series of tubes and channels direct the aerosol to the patient via an interface such as mouthpiece, mask, tent, nasal prongs or artificial airway. All nebulizers contain these basic parts, although the technology and design used can vary widely and can result in significant difference in ergonomics, directions for use, and performance. While many types of nebulizers have been described, the three categories of modern clinical nebulizers include: (1) pneumatic jet nebulizers (JN); (2) ultrasonic nebulizers (USN); and (3) vibrating mesh nebulizers (VMN). Nebulizers are also described in terms of their reservoir size. Small volume nebulizers (SVNs), most commonly used for medical aerosol therapy, can hold 5 to 20 mL of medication and may be jet, ultrasonic, or mesh nebulizers. Large volume nebulizers, typically jet or ultrasonic nebulizers, hold up to 200 mL and may be used for either bland aerosol therapy or continuous drug administration. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) have shown significant potential for pulmonary administration of therapeutics for the treatment of chronic lung diseases in a localized and sustained manner. Nebulization is a suitable method of NP delivery, particularly in patients whose ability to breathe is impaired due to lung diseases. However, there are limited studies evaluating the physicochemical properties of NPs after they are passed through a nebulizer. High shear stress generated during nebulization could potentially affect the surface properties of NPs, resulting in the loss of encapsulated drugs and alteration in the release kinetics. Herein, we thoroughly examined the physicochemical properties as well as the therapeutic effectiveness of Infasurf lung surfactant (IFS)-coated PLGA NPs previously developed by us after passing through a commercial Aeroneb® vibrating-mesh nebulizer. Nebulization did not alter the size, surface charge, IFS coating and bi-phasic release pattern exhibited by the NPs. However, there was a temporary reduction in the initial release of encapsulated therapeutics in the nebulized compared to non-nebulized NPs. This underscores the importance of evaluating the drug release kinetics of NPs using the inhalation method of choice to ensure suitability for the intended medical application. The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics. [ABSTRACT FROM AUTHOR]

Capillary electrophoresis (CE) is a powerful and sensitive tool for speciation analysis when combined with inductively coupled plasma mass spectrometry (ICP-MS); however, the performance of this technique can be limited by the nature of pneumatic nebulizers. This study compares two commercially available pneumatic nebulizers to a newly introduced vibrating capillary nebulizer (VCN) for on-line coupling of CE with ICP-MS. The VCN is a low-cost, non-pneumatic nebulizer that is based on the design of capillary vibrating sharp-edge spray ionization. As a piezoelectrically driven nebulization source, the VCN creates an aerosol independent of gas flows and does not produce a low-pressure region at the nebulizer orifice. To compare the systems, we performed replicate analyses of sulfate in river water with each nebulizer and the same CE and ICP-MS instruments and determined the figures of merit of each setup. With the CE-VCN-ICP-MS setup, we achieved around 2–4 times lower sensitivity compared to the commercial setups. However, the VCN-based setup provided lower noise levels and better linear correlation from the analysis of calibration standards, which resulted in indistinguishable LOD and LOQ values from the in-house-built VCN-based and commercial setups for CE-ICP-MS analysis. The VCN is found to have the highest baseline stability with a standard deviation of 3500 cts s−1, corresponding to an RSD of 2.7%. High reproducibility is found with the VCN with a peak area RSD of 4.1% between 3 replicate measurements. [ABSTRACT FROM AUTHOR]

Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. How can potential risks of infections during nebulization be mitigated? The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies. [ABSTRACT FROM AUTHOR]

The article discusses a study which compared bronchodilator therapy delivery with a vibrating mesh nebulizer (VMN) and jet nebulizer (JN) in subjects experiencing a severe asthma exacerbation. Cited are the importance of improvement in air flow after bronchodilator therapy, the ability of the vibrating mesh nebulizer to improve air flow more rapidly than the JN to treat severe asthma exacerbations, and the strengths and limitations of the study.

Nebulized therapy is the mainstay for treating obstructive airway diseases, but there is heightened concern about the potential risk for SARS-CoV-2 transmission during nebulization in COVID-19 patients. To investigate the effects of 0.9% saline nebulization on SARS-CoV-2 RNA spreading in 11 COVID-19 patients (five females, mean age 62.45 ± 9.31 years); also to ascertain whether saline nebulization changed the number of exhaled bio-aerosol particles in six out of the 11 patients. Air samples were collected using suction pumps equipped with 0.45 μm PTFE filters and positioned around the patient's bed. Exhaled particles were quantified by using an optical particle counter. At baseline (i.e. before nebulization) SARS-CoV-2 was detected more frequently in the pumps close to the patient than in those far away. After saline nebulization, the detection of SARS-CoV-2 in the pumps close to the patient was comparable to that observed at baseline. In the pumps far from the patient, saline nebulization slightly, but not significantly, increased SARS-CoV-2 RNA detection compared to baseline. Overall, no significant changes in the SARS-CoV-2 RNA detection were observed after saline nebulization. At baseline, exhaled particle emission varied among patients, with two of them showing higher emission of particles than the remaining patients. Saline nebulization induced a marked decrease in exhaled particles in the two patients who displayed high emission at baseline, whereas no changes were observed in the remaining patients. Saline nebulization did not significantly change SARS-CoV-2 RNA spreading. Saline nebulization does not significantly increase SARS-CoV-2 spreading. [ABSTRACT FROM AUTHOR]

The local delivery of therapeutic small interfering RNA or siRNA to the lungs has the potential to improve the prognosis for patients suffering debilitating lung diseases. Recent advances in materials science have been aimed at addressing delivery challenges including biodistribution, bioavailability and cell internalization, but an equally important challenge to overcome is the development of an inhalation device that can deliver the siRNA effectively to the lung, without degrading the therapeutic itself. Here, we report the nebulization of siRNA, either naked siRNA or complexed with polyethyleneimine (PEI) or a commercial transfection agent, using a miniaturizable acoustomicrofluidic nebulization device. The siRNA solution could be nebulised without significant degradation into an aerosol mist with tunable mean aerodynamic diameters of approximately 3 µm, which is appropriate for deep lung deposition via inhalation. The nebulized siRNA was tested for its stability, as well as its toxicity and gene silencing properties using the mammalian lung carcinoma cell line A549, which demonstrated that the gene silencing capability of siRNA is retained after nebulization. This highlights the potential application of the acoustomicrofluidic device for the delivery of efficacious siRNA via inhalation, either for systemic delivery via the alveolar epithelium or local therapeutic delivery to the lung.

Abstract Background The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery. Methods Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy. Results A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0–24.5) of the nominal dose in comparison to the three other groups (p

Background and purpose: Chronic obstructive pulmonary disease has a high prevalence in the world community and the majority of sufferers use inhalation sprays. There is a remarkable consensus that the choose the most appropriate method to deliver inhaled medicine in the control of chronic obstructive pulmonary disease is as important as the selected drug. Therefore, the purpose of the present study was to compare the effect of salbutamol through spray, spacer and the nebulizer on lung function in chronic obstructive pulmonary disease patients. Materials and methods: This randomized clinical trial was conducted on 66 patients with chronic obstructive pulmonary disease hospitalized in Shahada Qain Hospital in 2019. Research units were randomly assigned to spray, spacer, and nebulizer groups based on the inclusion criteria. After entering the data into SPSS software version 23, chi-square, Crosal-Wallis, ANOVA and repeated measurement statistical tests were used to analyze the data. Results: There was no significant difference between the three groups in terms of demographics and information related to the disease (P>0.05). The average respiratory indices including FVC, FEV1, SPO2, FEV1FVC and respiratory rate after the intervention in the spray group with spacer and the nebulizer group were significantly higher than the spray alone group (P

Background and Aims: Mild to moderate sedation during bronchoscopy is essential for patient safety, comfort during and after the procedure, and to facilitate the performance of the bronchoscopist. Dexmedetomidine is a highly selective, centrally acting a-2 agonist used to provide conscious sedation during various procedures. The aim of this study was to compare the efficacy of three different doses of dexmedetomidine nebulization as an adjuvant to lignocaine during bronchoscopy. Material and Methods: Ninety American Society of Anesthesiologists physical status I/II patients, aged from 18 to 60 years, scheduled for an elective bronchoscopy, were recruited. They were divided into three groups: 30 patients in each group. Group I: The patient was nebulized with a mixture of 4 ml of 4% lignocaine and dexmedetomidine 0.5 µg/kg. Group II: The patient was nebulized with a mixture of 4% lignocaine, 4 ml, and dexmedetomidine, 1 µg/kg. Group III: The patient was nebulized with 4% lignocaine 4 ml and dexmedetomidine 1.5 µg/kg. Results: The mean cough score was (1.17 ± 0.37), (1.40 ± 0.49), and (1.70 ± 0.75) in group III, group II, and group I, respectively. A significant difference was found between the groups. Patients were more comfortable with a statistically significant difference in the comfort score in group III as compared to group II and group I. Conclusion: Dexmedetomidine nebulization in a dose of 1.5 µg/kg (compared to 1 µg/kg or 0.5 µg/kg) as an adjuvant to lignocaine, provides better bronchoscopy conditions and patient satisfaction. [ABSTRACT FROM AUTHOR]

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10–50 μm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5–31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region. [ABSTRACT FROM AUTHOR]

Pulmonary drug delivery system is one of the most intriguing and beneficial route for drug delivery as it offers several advantages over the conventional oral route of administration. Many devices are being studied to achieve optimum drug delivery through pulmonary route. Nebulizers, dry powder inhalers, pressurized metered dose inhalers are developed and marketed to target delivery through the pulmonary system. Nebulizers are devices which convert liquid into aerosols of appropriate size for inhalation which can efficiently reach the pulmonary region. The different types of nebulizers include jet nebulizer, ultrasonic nebulizer, vibrating mesh nebulizer. They are further subdivided according to the modification in their structure. The advancement in science has led to the development of more ‘intelligent nebulizers’ which include I-neb nebulizer and AKITA nebulizer, they monitor the breathing pattern of the patient and release the drug accordingly resulting in minimal wastage of the drug. Nebulizers sales have shown growth in the market owing to an increase in the incidences of chronic obstructive pulmonary disorder, asthma in the young and elderly, thus, a combination of smart nebulizer and microparticle formulation will help in achieving the desired results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients receiving mechanical ventilation often require airway clearance and inhaled therapies. Intrapulmonary percussive ventilation (IPV) combines a high-frequency percussive ventilator with a jet nebulizer. Data on aerosol delivery efficiency of the device are scarce. We evaluated albuterol delivery efficiency while using an IPV in-line adapter under different conditions. METHODS: A pediatric lung model of invasive mechanical ventilation was used. The following independent variables were evaluated: lung condition (normal vs ARDS), ventilator mode (adaptive pressure ventilation vs pressure control), percent opening of adapter (0% vs 25% vs 50%), IPV driving pressure (25 psi vs 40 psi), IPV percussion setting (easy vs hard), and endotracheal tube (ETT) size (3.5 mm vs 5.5 mm). Albuterol delivery efficiency (mass captured in the filter expressed as percentage of loading dose) was selected as the dependent variable. Albuterol was captured on a filter at the tip of the ETT and quantified via spectrophotometry (276 nm). RESULTS: Albuterol delivery efficiency ranged from 0-2.89%. Median (interquartile range) and 95% CI around the median were 0.54% (0.37-1.00) and 0.50-0.63%, respectively. The coefficient of determination (R²) for the model including all variables was 0.363. The 2 main contributors were percent of adapter opening (R² 0.30) and IPV setting (R² 0.039). CONCLUSIONS: Albuterol delivery during invasive mechanical ventilation via in-line IPV in a pediatric lung model was inefficient. Alternative methods of delivering bronchodilators and other inhaled medications should be considered when IPV is used. [ABSTRACT FROM AUTHOR]

Background: The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery. Methods: Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy. Results: A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0–24.5) of the nominal dose in comparison to the three other groups (p < 0.01). Around 50 to 60% of lung doses reached the outer region of both lungs in all groups. Drug doses in inner and outer lung regions were significantly increased in the SCAT group (p < 0.01), except for the outer right lung region in the fourth group due to preferential drug trickling from the endotracheal tube and the trachea to the right bronchi. Similar lung delivery was observed whether the heated humidifier was switched off or left on. Inhaled doses measured in vitro correlated with lung doses (R = 0.768, p < 0.001). Conclusion: Optimizing the administration technique enables a significant increase in inhaled drug delivery to the lungs, including peripheral airways. Before adapting mechanical ventilation, studies are required to continue this optimization and to assess its impact on drug delivery and patient outcome in comparison to more usual settings. [ABSTRACT FROM AUTHOR]

The humidity of gases is an important topic within anaesthesia and intensive care medicine. An appreciation of the underlying physics helps to ensure that we monitor and deliver optimally humidified gases to our patients, thus minimizing the pathophysiological consequences when normal humidification processes are bypassed. In this article the different techniques and equipment used to measure humidity are illustrated, as well as the methods of humidification used in clinical practice. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) have shown significant potential for pulmonary administration of therapeutics for the treatment of chronic lung diseases in a localized and sustained manner. Nebulization is a suitable method of NP delivery, particularly in patients whose ability to breathe is impaired due to lung diseases. However, there are limited studies evaluating the physicochemical properties of NPs after they are passed through a nebulizer. High shear stress generated during nebulization could potentially affect the surface properties of NPs, resulting in the loss of encapsulated drugs and alteration in the release kinetics. Herein, we thoroughly examined the physicochemical properties as well as the therapeutic effectiveness of Infasurf lung surfactant (IFS)-coated PLGA NPs previously developed by us after passing through a commercial Aeroneb® vibrating-mesh nebulizer. Nebulization did not alter the size, surface charge, IFS coating and bi-phasic release pattern exhibited by the NPs. However, there was a temporary reduction in the initial release of encapsulated therapeutics in the nebulized compared to non-nebulized NPs. This underscores the importance of evaluating the drug release kinetics of NPs using the inhalation method of choice to ensure suitability for the intended medical application. The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics.

Background: The hospitals of the Saint Alphonsus Health System (SAHS) have implemented a metered dose inhaler (MDI) to nebulization therapeutic interchange program in which all orders for albuterol/ipratropium and inhaled corticosteroid/long-acting beta agonists (ICS/LABA) MDIs are therapeutically interchanged to nebulizers by pharmacy. Objectives: The primary outcome measure is to assess the percent of albuterol/ipratropium and ICS/LABA inhalers therapeutically interchanged to nebulized solutions. Secondary outcomes include assessment of readmission rates, the percentage of patients discharged with the appropriate MDI, and a financial analysis of the implementation of the therapeutic interchange program. Methods: This retrospective observational cohort study was approved by the system's institutional review board and conducted between October 15, 2019, and February 15, 2020. Adult patients with history of asthma or COPD admitted to one of the SAHS hosptials with an order placed for ipratropium/albuterol, fluticasone/salmeterol, mometasone/formoterol, or budesonide/formoterol MDIs were eligible for inclusion. Patients were excluded if they were presumed to have or tested positive for COVID-19. Results: Therapeutic interchanges were successfully completed in 94.3% of the orders included in this evaluation. Discharge discrepancies occurred in 14.3% of orders assessed. No correlation was found between discharge discrepancies and 30-day readmissions. The MDI to nebulized solution interchanges saved $13,908.16 in medication cost in the sample population. Conclusion: The first phase of implementing the SAHS inhaler to nebulizer therapeutic interchange program was operationally and clinically successful. The program is projected to continue to reduce medication waste and provide cost savings for the health system. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aerosolized drug delivery via high-flow nasal cannula (HFNC) decreases as gas flow is increased. To improve aerosol delivery, breath-enhanced jet nebulizer may increase aerosol output. This study tested that hypothesis and compared breath-enhanced jet nebulizer to vibrating mesh nebulizer technology. METHODS: First, in an isolated circuit, breath-enhanced jet nebulizer and vibrating mesh nebulizer aerosol outputs were measured during simulated HFNC by using infused saline solution at rates of 5-60 mL/h. Limits were defined when nebulizer filling was detected. The devices were then tested by using 99mTc/saline solution to measure maximum rates of aerosol production. After the output experiments, drug delivery was measured in vitro by using a model that consisted of an HFNC circuit interfaced to a realistic 3-dimensional printed head. The 99mTc/saline solution was infused at rates of 5 to 60 mL/h for the breath-enhanced jet nebulizer and 5 to 20 mL/h for the vibrating mesh nebulizer with HFNC gas flows of 10 to 60 L/min. Aerosol delivery to the trachea was measured by using a shielded ratemeter, which defined the rate of drug delivery (lg NaCl/min). RESULTS: With increasing gas flow, breath-enhanced jet nebulizer output increased to a maximum of 50 mL/h, the vibrating mesh nebulizer maximum was 12 mL/h. At HFNC gas flow of 60 L/min, breath-enhanced jet nebulizer delivered 3.16 to 316.8 lg NaCl/min, the vibrating mesh nebulizer delivered 23.5 to 61.7 µg NaCl/min. For infusion pump flows of 5 to 12 mL/h, the rate of drug delivery was independent of nebulizer type (P = .19) and dependent on infusion pump flow (P < .001) and gas flow (P < .001). CONCLUSIONS: Increasing gas flow increased breath-enhanced jet nebulizer output, which demonstrated the effects of breath enhancement. At 60 L/min, breath enhanced jet nebulizer delivered up to 5 times more aerosol compared with conventional vibrating mesh nebulizer technology. Breath-enhanced jet nebulizer delivered a wide range of dose rates at all high flows. In patients who are critically ill, breath-enhanced jet nebulizer technology may allow titration of bedside dosing based on clinical response by simple adjustment of the infusion rate. [ABSTRACT FROM AUTHOR]

Practical relevance: Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy. Aim: As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats. Evidence base: In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease. [ABSTRACT FROM AUTHOR]

Rationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. Measurements and Main Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. Conclusions: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings. [ABSTRACT FROM AUTHOR]

Background: The conventional method of irrigation during laparoscopy and endoscopy is well documented in literature. The use of nebulizer or underwater sealed chest tube drain to achieve this has not been designed or studied in literature. Aim: To showcase an innovation using nebulizer and underwater sealed chest tube drain assembled for irrigation during laparoscopy and endoscopy procedures. Materials and methods: A prospective preliminary experimental study was conducted using a newly designed method of irrigation in laparoscopic and endoscopic surgeries performed from March 2021 to March 2022 in a tertiary center and a private hospital in South Southern, Nigeria. Ethical approval was obtained from the hospital ethics committee and informed consent was obtained from patients. The effectiveness of this new method was compared with standard irrigation machine as control. The patients were blocked into laparoscopy and colonoscopy procedures, respectively. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS version 26). Results: The results showed that the use of nebulizer underwater sealed chest tube drain assembly was very effective in laparoscopy and colonoscopy procedures. In three cases of fundoplication operations, five cases of cholecystectomies and 30 cases of hydro-jet insufflation colonoscopies were performed with good outcomes. Conclusion: This new novel method will serve a very good alternative irrigation method in laparoscopy and endoscopy procedures. It is currently being studied in other methods, such as hysteroscopy, cystoscopy, and therapeutic endoscopies. [ABSTRACT FROM AUTHOR]

The purpose of this meta‑analysis was to evaluate the efficacy of nebulised magnesium in the treatment of acute exacerbation of COPD. PubMed and Embase databases were searched for randomised controlled trials comparing any dose of nebulised magnesium sulphate with placebo for treatment of acute exacerbation of COPD, published from database inception till 30 June 2022. Bibliographic mining of relevant results was performed to identify any additional studies. Data extraction and analyses were done independently by review authors and any disagreements were resolved through consensus. Meta‑analysis was done using a fixed‑effect model at clinically significant congruent time points reported across maximum studies to ensure comparability of treatment effect. Four studies met the inclusion criteria, randomly assigning 433 patients to the comparisons of interest in this review. Pooled analysis showed that nebulised magnesium sulphate improved pulmonary expiratory flow function at 60 minutes after initiation of intervention compared to placebo [median difference (MD) 9.17%, 95% confidence interval (CI) 2.94 to 15.41]. Analysis of expiratory function in terms of standardised mean differences (SMD) revealed a small yet significant positive effect size (SMD 0.24, 95% CI 0.04 to 0.43). Among the secondary outcomes, nebulised magnesium sulphate reduced the need for ICU admission (risk ratio 0.52, 95% CI 0.28 to 0.95), amounting to 61 fewer ICU admissions per 1000 patients. No difference was noted in the need for hospital admission, need for ventilatory support, or mortality. No adverse events were reported. Nebulised magnesium sulphate improves pulmonary expiratory flow function and reduces the need for ICU admission in patients with acute exacerbation of COPD. [ABSTRACT FROM AUTHOR]

Recently, many preclinical and clinical studies have been conducted on the delivery of therapeutic antibodies to the lungs using nebulizers, but standard treatment guidelines have not yet been established. Our objective was to compare nebulization performance according to the low temperature and concentration of immunoglobulin G (IgG) solutions in different types of nebulizers, and to evaluate the stability of IgG aerosols and the amount delivered to the lungs. The output rate of the mesh nebulizers decreased according to the low temperature and high concentration of IgG solution, whereas the jet nebulizer was unaffected by the temperature and concentration of IgG. An impedance change of the piezoelectric vibrating element in the mesh nebulizers was observed because of the lower temperature and higher viscosity of IgG solution. This affected the resonance frequency of the piezoelectric element and lowered the output rate of the mesh nebulizers. Aggregation assays using a fluorescent probe revealed aggregates in IgG aerosols from all nebulizers. The delivered dose of IgG to the lungs in mice was highest at 95 ng/mL in the jet nebulizer with the smallest droplet size. Evaluation of the performance of IgG solution delivered to the lungs by three types of nebulizers could provide valuable parameter information for determination on dose of therapeutic antibody by nebulizers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our institution was experiencing a respiratory therapy staffing crisis during the COVID-19 pandemic, in part due to excessive workload. We identified an opportunity to reduce burden by limiting use of 3% hypertonic saline and/or N-acetylcysteine nebulizer therapies (3%HTS/NAC). METHODS: Leveraging the science of de-implementation, we established a policy empowering respiratory therapists to discontinue 3%HTS/NAC not meeting the American Association for Respiratory Care (AARC) Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients. After a 3-month period of educating physicians and advanced practice practitioners the policy went to into effect. Outcomes measured included monthly number of treatments, orders, and full-time employees associated with administering nebulized 3%HTS/NAC. RESULTS: Post policy activation, the monthly mean 3%HTS/NAC treatments were significantly reduced to 547.5 ± 284.3 from 3,565.2 ± 596.4 (P < .001) as were the associated monthly mean of full-time employees, 0.8 ± 0.41 from 5.1 ± 0.86 (P < .001). The monthly mean 3%HTS/NAC orders also fell to 93.8 ± 31.5 from 370.0 ± 46.9 (P < .001). Monthly mean non-3%HTS/NAC treatments remained stable; post policy was 3,089.4 ± 611.4 and baseline 3,279.6 ± 695.0 (P = 1.0). CONCLUSIONS: Implementing a policy that empowers respiratory therapists to promote adherence to AARC Clinical Guidelines reduced low-value therapies, costs, and staffing needs. [ABSTRACT FROM AUTHOR]

Current guidelines recommend inhalation therapy as the preferred route of drug administration for treating patients with chronic obstructive pulmonary disease (COPD). Inhalation devices consist of nebulizers and handheld inhalers, such as dry-powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), and soft mist inhalers (SMIs). Although pMDIs, DPIs and SMIs may be appropriate for most patients with COPD, certain patient populations may have challenges with these devices. Patients who have cognitive, neuromuscular, or ventilatory impairments (and receive limited assistance from caregivers), as well as those with suboptimal peak inspiratory flow may not derive the full benefit from handheld inhalers. A considerable number of patients are not capable of producing a peak inspiratory flow rate to overcome the internal resistance of DPIs. Furthermore, patients may have difficulty coordinating inhalation with device actuation, which is required for pMDIs and SMIs. However, inhalation devices such as spacers and valved holding chambers can be used with pMDIs to increase the efficiency of aerosol delivery. Nebulized treatment provides patients with COPD an alternative administration route that avoids the need for inspiratory flow, manual dexterity, or complex hand-breath coordination. The recent approval of two nebulized long-acting muscarinic antagonists has added to the extensive range of nebulized therapies in COPD. Furthermore, with the availability of quieter and more portable nebulizer devices, nebulization may be a useful treatment option in the management of certain patient populations with COPD. The aim of this narrative review was to highlight recent updates and the treatment landscape in nebulized therapy and COPD. We first discuss the pathophysiology of patients with COPD and inhalation device considerations. Second, we review the updates on recently approved and newly marketed nebulized treatments, nebulized treatments currently in development, and technological advances in nebulizer devices. Finally, we discuss the current applications of nebulized therapy in patients with COPD.

The purpose of this meta-analysis was to evaluate the efficacy of nebulised magnesium in the treatment of acute exacerbation of COPD. PubMed and Embase databases were searched for randomised controlled trials comparing any dose of nebulised magnesium sulphate with placebo for treatment of acute exacerbation of COPD, published from database inception till 30 June 2022. Bibliographic mining of relevant results was performed to identify any additional studies. Data extraction and analyses were done independently by review authors and any disagreements were resolved through consensus. Meta-analysis was done using a fixed-effect model at clinically significant congruent time points reported across maximum studies to ensure comparability of treatment effect. Four studies met the inclusion criteria, randomly assigning 433 patients to the comparisons of interest in this review. Pooled analysis showed that nebulised magnesium sulphate improved pulmonary expiratory flow function at 60 minutes after initiation of intervention compared to placebo [median difference (MD) 9.17%, 95% confidence interval (CI) 2.94 to 15.41]. Analysis of expiratory function in terms of standardised mean differences (SMD) revealed a small yet significant positive effect size (SMD 0.24, 95% CI 0.04 to 0.43). Among the secondary outcomes, nebulised magnesium sulphate reduced the need for ICU admission (risk ratio 0.52, 95% CI 0.28 to 0.95), amounting to 61 fewer ICU admissions per 1000 patients. No difference was noted in the need for hospital admission, need for ventilatory support, or mortality. No adverse events were reported. Nebulised magnesium sulphate improves pulmonary expiratory flow function and reduces the need for ICU admission in patients with acute exacerbation of COPD.

Introduction: Arterial hypoxia is one of the most common findings in critically ill patients. Inhaled medications in ventilated patients can reduce airway resistance, facilitate dilution, and prevent airway infections. This study aimed to examine the effects of nebulized Eucalyptus (NE) on arterial blood gases (ABG) and physiologic indexes of patients receiving mechanical ventilation (MV). Methods: The current randomized clinical trial was performed in three intensive care units (ICUs) of Al-Zahra Hospital in Isfahan, Iran. Using purposive sampling method, 70 intubated patients were selected and randomly divided into NE (n=35) and control (n=35) groups. NE group received 4 ml (5%) Eucalyptus in 6 mL normal saline (NS) every 8 hours since intubation to 3 days by a nebulizer. Control group received 10 mL NS in the same way. Glasgow Coma Scale (GCS) and ABG parameters (pH, BE, HCO3, PCO2, SaO2, and PaO2), and the peak inspiratory pressure (PIP) and tidal volume (TV) were equally assessed in both intervention and control groups. Data were analyzed using SPSS software version 13. Results: There was no significant difference between the patients of both groups in terms of vital signs (blood pressure, temperature, respiratory rate, and pulse rate), GCS, pH, BE, HCO3, PCO2, SaO2, PaO2, PIP, and TV before the study. Amongst the parameters of ABG, there was a significant difference between PaO2 and SaO2 and PIP in the intervention and control groups 3 days after intervention. Conclusion: Inhaled Eucalyptus can improve oxygenation and reduce airway pressure in patients undergoing MV.

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) drew substantial attention as a potential COVID-19 treatment based on its antiviral and immunomodulatory effects in vitro. However, HCQ showed a lack of efficacy in vivo, and different groups of researchers attributed this failure to the insufficient drug concentration in the lung following oral administration (HCQ is only available in the market in the tablet form). Delivering HCQ by inhalation represents a more efficient route of administration to increase HCQ exposure in the lungs while minimizing systemic toxicity. In this pilot study, the safety, tolerability, and pharmacokinetics of HCQ nebulizer solution were evaluated in healthy volunteers. Methods: Twelve healthy participants were included in this study and were administered 2 mL of HCQ01 solution (equivalent to 25 mg of HCQ sulfate) through Aerogen® Solo, a vibrating mesh nebulizer. Local tolerability and systemic safety were assessed by forced expiratory volume in the first and second electrocardiograms, clinical laboratory results (e.g., hematology, biochemistry, and urinalysis), vital signs, and physical examinations. Thirteen blood samples were collected to determine HCQ01 systemic exposure before and until 6 hours after inhalation. Results: The inhalation of HCQ01 was well tolerated in all participants. The mean value of Cmax for the 12 participants was 9.66 ng/mL. Tmax occurred at around 4.8 minutes after inhalation and rapidly decreased thereafter. The reported systemic exposure was very low with a mean value of 5.28 (0.6–15.6) ng·h/mL. Conclusion: The low systemic concentrations of HCQ01 of 9.66 ng/mL reported by our study compared with 1 μg/mL previously predicted after 200 mg BID oral administration, and the safety and tolerability of HCQ01 administered as a single dose through nebulization, support the assessment of its efficacy, safety, and tolerability in further studies for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Microbial contamination of aerosol facemasks could be a source of nosocomial infections during nebulization therapy in hospital, prompting efforts to identify these contaminants. Identification of micro-organisms in medical devices has traditionally relied on culture-dependent methods, which are incapable of detecting the majority of these microbial contaminants. This challenge could be overcome with culture-independent sequencing-based techniques that are suited for the profiling of complex microbiomes. To characterize the microbial contaminants in aerosol facemasks used for nebulization therapy, and identify factors influencing the composition of these microbial contaminants with the acquisition and analysis of comprehensive microbiome-scale profiles using culture-independent high-throughput sequencing. Used aerosol facemasks collected from hospitalized patients were analysed with culture-independent 16S rRNA gene-based amplicon sequencing to acquire microbiome-scale comprehensive profiles of the microbial contaminants. Microbiome-based analysis was performed to identify potential sources of microbial contamination in facemasks. Culture-independent high-throughput sequencing was demonstrated for the capacity to acquire microbiome-scale profiles of microbial contaminants on aerosol facemasks. Microbial source identification enabled by the microbiome-scale profiles linked microbial contamination on aerosol facemasks to the human skin and oral microbiota. Antibiotic treatment with levofloxacin was found to reduce contamination of the facemasks by oral microbiota. Sequencing-based microbiome-scale analysis is capable of providing comprehensive characterization of microbial contamination in aerosol facemasks. Insight gained from microbiome-scale analysis facilitates the development of effective strategies for the prevention and mitigation of the risk of nosocomial infections arising from exposure to microbial contamination of aerosol facemasks, such as targeted elimination of potential sources of contamination. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is the most common microorganism found in the sputum culture of Cystic fibrosis (CF) patients causing the pulmonary destruction. Aminoglycosides have a low diffuse rate from lipid membranes, and respiratory system secretions. Regarding the burden of pulmonary exacerbation caused by the pseudomonas aeruginosa in cystic fibrosis patients in the long term and the limited number of clinical trials focused on appropriate treatment strategies, the present study evaluated the concurrent inhaled and intravenous aminoglycoside antibiotics for pulmonary exacerbation caused by the pseudomonas aeruginosa as a safe and effective treatment in children. Method: This study was a blinded, randomized clinical trial phase conducted in a tertiary referral pediatric teaching hospital from May 2021 to May 2022. The patients were randomly allocated to receive intravenously administered ceftazidime and Amikacin alone or with inhaled Amikacin. Forced expiratory volume (FEV1), Amikacin via the level, kidney function tests, audiometry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), hospital stay, and bacterial eradication rate were compared in two therapy groups. Results: the average FEV1 has increased by 47% in Neb + group compared to Neb- group following treatment. Hospital stay was lower in Neb + group. No renal toxicity or ototoxicity was observed in both therapy groups. Pseudomonas aeruginosa eradication rate Neb- and Neb + groups were 44% and 69%, respectively (p-value = 0.15). Conclusion: Concurrent inhaled and intravenous Amikacin is safe and effective to treat Pseudomonas aeruginosa exacerbation in CF patients. Moreover, co-delivery antibiotics' route treatment increased the eradication rate. Although not statistically significant, never the less, it is clinically relevant. The intervention reduced the length of hospitalization in this group. [ABSTRACT FROM AUTHOR]

The outbreak of SARS-CoV-2 has emphasized the need for a deeper understanding of infectivity, spread, and treatment of airborne viruses. Bacteriophages (phages) serve as ideal surrogates for respiratory pathogenic viruses thanks to their high tractability and the structural similarities tailless phages bear to viral pathogens. However, the aerosolization of enveloped SARS-CoV-2 surrogate phi6 usually results in a >3-log10 reduction in viability, limiting its usefulness as a surrogate for aerosolized coronavirus in “real world” contexts, such as a sneeze or cough. Recent work has shown that saliva or artificial saliva greatly improves the stability of viruses in aerosols and microdroplets relative to standard dilution/storage buffers like suspension medium (SM) buffer. These findings led us to investigate whether we could formulate media that preserves the viability of phi6 and other phages in artificially derived aerosols. Results indicate that SM buffer supplemented with bovine serum albumin (BSA) significantly improves the recovery of airborne phi6, MS2, and 80α and outperforms commercially formulated artificial saliva. Particle sizing and acoustic particle trapping data indicate that BSA supplementation dose-dependently improves viral survivability by reducing the extent of particle evaporation. These data suggest that our viral preservation medium may facilitate a lower-cost alternative to artificial saliva for future applied aerobiology studies. IMPORTANCE We have identified common and inexpensive lab reagents that confer increased aerosol survivability on phi6 and other phages. Our results suggest that soluble protein is a key protective component in nebulizing medium. Protein supplementation likely reduces exposure of the phage to the air-water interface by reducing the extent of particle evaporation. These findings will be useful for applications in which researchers wish to improve the survivability of these (and likely other) aerosolized viruses to better approximate highly transmissible airborne viruses like SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products. [ABSTRACT FROM AUTHOR]

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This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99mTc-DTPA (radiolabel aerosol) were used to assess the intrasinus aerosol deposition on a nasal cast. Two commercial medical devices (PARI SINUS nebulizer and NL11SN ATOMISOR nebulizer) and various nasal delivery techniques (one or two nostrils connected to the aerosol inlet, the patient with the soft palate closed or open during the acoustic administration of the drug, the presence or not of flow resistance in the nostril opposite to the one allowing the aerosol to be administered) were evaluated. The closed soft palate condition showed a significant increase in drug deposition even though no significant difference in the rest of the nasal fossae was noticed. Our results clearly demonstrated a higher intrasinus aerosol deposition (by a factor 2–3; respectively 0.03 ± 0.007% vs. 0.003 ± 0.0002% in the right maxillary sinus and 0.027 ± 0.006% vs. 0.013 ± 0.004% in the left maxillary sinus) using the acoustic airflow generated by the PARI SINUS compared to the NL11SN ATOMISOR. The results clearly demonstrated that the optimal conditions for aerosol deposition in the maxillary sinuses were obtained with a closed soft palate. Thus, the choice of the nebulizing technology (and mainly the frequency of the pulsating aerosol generated) and also the recommendation of the best nasal delivery technique are key factors to improve intrasinus aerosol deposition. [ABSTRACT FROM AUTHOR]

BackgroundMesenchymal stem cells (MSC) have shown immense therapeutic promise in a range of inflammatory diseases, including acute respiratory distress syndrome (ARDS), and are rapidly advancing through clinical trials. Among their multimodal mechanisms of action, MSCs exert strong immunomodulatory effects via their secretome, which contains cytokines, small molecules, extracellular vesicles, and a range of other factors. Recent studies have shown that the MSC secretome can recapitulate many of the beneficial effects of the MSC itself. We aimed to determine the therapeutic capacity of the MSC secretome in a rat bacterial pneumonia model, especially when delivered directly to the lung by nebulization which is a technique more appropriate for the ventilated patient.MethodsConditioned medium (CM) was generated from human bone marrow derived MSCs in the absence of antibiotics and serum supplements. Post-nebulization lung penetration was estimated through nebulization of CM to a cascade impactor and simulated lung and quantification of collected total protein and IL-8 cytokine. Control and nebulized CM was added to a variety of lung cell culture models and injury resolution assessed. In a rat E. coli pneumonia model, CM was instilled or administered by nebulization and lung injury and inflammation assessed at 48 h.ResultsMSC-CM was predicted to have good distal lung penetration and delivery when administered by nebulizer. Both control and nebulized CM reduced NF-κB activation and inflammatory cytokine production in lung cell culture, while promoting cell viability and would closure in oxidative stress and scratch wound models. In a rat bacterial pneumonia model, both instilled and nebulizer delivered CM improved lung function, increasing blood oxygenation and reducing carbon dioxide levels compared to unconditioned medium controls. A reduction in bacterial load was also observed in both treatment groups. Inflammatory cytokines were reduced significantly by both liquid and aerosol CM administration, with less IL-1β, IL-6, and CINC1 in these groups compared to controls.ConclusionMSC-CM is a potential therapeutic for pneumonia ARDS, and administration is compatible with vibrating mesh nebulization.

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10–50 μm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5–31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region.

Background:Pseudomonas aeruginosa is the most common microorganism found in the sputum culture of Cystic fibrosis (CF) patients causing the pulmonary destruction. Aminoglycosides have a low diffuse rate from lipid membranes, and respiratory system secretions. Regarding the burden of pulmonary exacerbation caused by the pseudomonas aeruginosa in cystic fibrosis patients in the long term and the limited number of clinical trials focused on appropriate treatment strategies, the present study evaluated the concurrent inhaled and intravenous aminoglycoside antibiotics for pulmonary exacerbation caused by the pseudomonas aeruginosa as a safe and effective treatment in children.Method: This study was a blinded, randomized clinical trial phase conducted in a tertiary referral pediatric teaching hospital from May 2021 to May 2022. The patients were randomly allocated to receive intravenously administered ceftazidime and Amikacin alone or with inhaled Amikacin. Forced expiratory volume (FEV1), Amikacin via the level, kidney function tests, audiometry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), hospital stay, and bacterial eradication rate were compared in two therapy groups.Results: the average FEV1 has increased by 47% in Neb + group compared to Neb− group following treatment. Hospital stay was lower in Neb + group. No renal toxicity or ototoxicity was observed in both therapy groups. Pseudomonas aeruginosa eradication rate Neb− and Neb + groups were 44% and 69%, respectively (p-value = 0.15).Conclusion: Concurrent inhaled and intravenous Amikacin is safe and effective to treat Pseudomonas aeruginosa exacerbation in CF patients. Moreover, co-delivery antibiotics’ route treatment increased the eradication rate. Although not statistically significant, never the less, it is clinically relevant. The intervention reduced the length of hospitalization in this group.Clinical Trial Registration:clinicaltrials.gov, identifier [IRCT20120415009475N10].