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Parenchymal distribution of nebulized drug in healthy and diseased lungs has not, as evident from a literature review, been well characterized. We use a vibrating mesh nebulizer to deliver fluorescein solution in vivo to healthy or intratracheal‐lipopolysaccharide (LPS)‐instilled anesthetized rats in dorsal recumbency, or ex vivo to the lungs of LPS‐instilled rats. Following in vivo nebulization (healthy/LPS‐instilled), we quantify fluorescein intensity distribution by confocal microscopy in standard locations on the surface of freshly isolated lungs. Following LPS instillation (in vivo/ex vivo nebulization), we quantify fluorescein intensity in visibly injured locations. In standard locations, there is uniform, low‐intensity basal fluorescein deposition. Focal regions receive high deposition that is, in upper (cranial), middle, and lower (caudal) locations, 6.4 ± 4.9, 3.3 ± 3.0, and 2.3 ± 2.8 times greater, respectively, than average basal intensity. Following LPS instillation, deposition in moderately injured regions can be high or low; deposition in severely injured regions is low. Further, actively phagocytic cells are observed in healthy and LPS‐instilled lungs. And LPS particularly impairs mechanics and activates phagocytic cells in the male sex. We conclude that a low level of nebulized drug can be distributed across the parenchyma excepting to severely injured regions. [ABSTRACT FROM AUTHOR]

Aerosol drug administration has a long history as an important part of the treatment for different respiratory disorders in both adult and paediatric patients. The nebulization process permits the drug delivery directly to the upper and lower airways tracts, allowing increased local effectiveness, and avoids systemic side effects. The aerosol therapy is mainly used in pneumology for lower respiratory tract disorders, a series of drugs having a proven efficacy. Few publications present the efficacy and safety of ENT nebulization, despite its worldwide utilization. Topical drug delivery to the nasal cavities and paranasal sinuses via aerosols appears to be an interesting, but also a challenging alternative. The transport and deposition of drugs and aerosol particles into the sinuses is debatable due to several factors: sinuses are poorly perfused and virtually non-ventilated cavities; they are protected by the efficient particle filtration function of the nasal cavities. The review evaluates the efficacy and safety of aerosol therapy in rhinologic pathology. [ABSTRACT FROM AUTHOR]

Background: Post-operative sore throat (POST) is a very common anesthesia-related event which may hamper patient satisfaction and increase treatment cost. Aims and Objectives: This study aimed to compare the effectiveness of nebulization with dexamethasone and lignocaine to prevent POST. Materials and Methods: This randomized controlled study involved 135 patients randomly divided into three equal groups: Group D - (n=45) received 8 mg (2 mL) dexamethasone plus 3 mL of distilled water, Group L - (n=45) received 80 mg (4% lignocaine 2 mL) plus 3 mL distilled, and Group S - (n=45) received nebulization with 5 mL normal saline. Results: At 4 h postoperatively, the incidence of POST was 15.6% in the dexamethasone group, 33.3% in the lignocaine group, and 73.3% in the saline group. The score was significantly higher in the saline group (P=0.001) compared to the dexamethasone and lignocaine group, while it was comparable between dexamethasone and lignocaine group (P=0.188). Similarly, dexamethasone and lignocaine groups were comparable at immediately post-operative, 2, 8, 12, and 24 h post-operative time points. Post-operative hoarseness scores of all three groups were comparable at all-time points. A significant increase in the heart rate (HR) and mean arterial pressure (MAP) after intubation was observed in the saline and dexamethasone group as compared to the lignocaine group (P=0.001) while HR and MAP were comparable in dexamethasone and saline group (P=1.000). Conclusion: Dexamethasone and lignocaine nebulization are both effective and comparable prophylaxis for POST and lignocaine nebulization has added advantage of blunting pressor response to endotracheal intubation over dexamethasone nebulization. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location. [ABSTRACT FROM AUTHOR]

Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations. [ABSTRACT FROM AUTHOR]

Pulmonary drug delivery offers a minimally invasive and efficient method for treating lung conditions, leveraging the lungs' extensive surface area and blood flow for rapid drug absorption. Nebulized therapies aim to deliver drugs directly to the lung tissue. This study investigates the histological impact of nebulized tocilizumab—a monoclonal antibody targeting IL-6, traditionally administered intravenously for rheumatoid arthritis and severe COVID-19—on a murine model. Thirty BALB/c mice were nebulized with tocilizumab (10 mg, 5 mg, and 2.5 mg) and six controls were nebulized with saline solution. They were euthanized 48 h later, and their organs (lungs, nasal mucosa, and liver) were analyzed by a microscopic histological evaluation. The results indicate that all the mice survived the 48 h post-nebulization period without systemic compromise. The macroscopic examination showed no abnormalities, and the histopathological analysis revealed greater lung vascular changes in the control group than in the nebulized animals, which is attributable to the euthanasia with carbon dioxide. Additionally, increased alveolar macrophages were observed in the nebulized groups compared to controls. No significant histological changes were observed in the liver, indicating the safety of nebulized tocilizumab. In conclusion, these findings suggest the potential of nebulized tocilizumab for treating pulmonary inflammation, warranting further research to establish its efficacy and safety in clinical settings. [ABSTRACT FROM AUTHOR]

An effective method to deliver plasma‐activated water onto contaminated surfaces is with a surface acoustic wave (SAW) nebulizer that can efficiently produce plasma‐activated aerosols. While higher reactive species concentrations in the plasma‐activated aerosols promote more efficient bacterial inactivation and hence reduce the amount of aerosols needed to completely eradicate the bacteria colonies, higher concentrations of reactive species themselves are found to lead to lower nebulization rates due to the increased electrical conductivity of the solution. To circumvent this problem, it is shown that coating the SAW substrate with a thin insulating layer of silicon dioxide (SiO2) can significantly mitigate the nebulization rate reduction. Specifically, when the electrical conductivity increases from 0.25 to 4.0 mS cm−1, the 62% drop in the nebulization rate is observed with the uncoated SAW devices is substantially reduced to 19% simply with the SiO2 coating. This can be attributed to the synergistic effects of increased wettability and the suppression of the electrical body force acting on the liquid film. The concomitant increase in the bacterial colony reduction from 17% to 76% demonstrates this solution to be a facile yet effective way of enhancing the efficiency for spray‐based bacterial inactivation on contaminated surfaces. [ABSTRACT FROM AUTHOR]

Background: Some experts recommend specific ventilator settings during nebulization for mechanically ventilated patients, such as inspiratory pause, high inspiratory to expiratory ratio, and so on. However, it is unclear whether those settings improve aerosol delivery. Thus, we aimed to evaluate the impact of ventilator settings on aerosol delivery during mechanical ventilation (MV). Methods: Salbutamol (5.0 mg/2.5 mL) was nebulized by a vibrating mesh nebulizer (VMN) in an adult MV model. VMN was placed at the inlet of humidifier and 15 cm away from the Y-piece of the inspiratory limb. Eight scenarios with different ventilator settings were compared with endotracheal tube (ETT) connecting 15 cm from the Y-piece, including tidal volumes of 6–8 mL/kg, respiratory rates of 12–20 breaths/min, inspiratory time of 1.0–2.5 seconds, inspiratory pause of 0–0.3 seconds, and bias flow of 3.5 L/min. In-line suction catheter was utilized in two scenarios. Delivered drug distal to the ETT was collected by a filter, and drug was assayed by an ultraviolet spectrophotometry (276 nm). Results: Compared to the use of inspiratory pause, the inhaled dose without inspiratory pause was either higher or similar across all ventilation settings. Inhaled dose was negatively correlated with inspiratory flow with VMN placed at 15 cm away from the Y-piece (rs = −0.68, p < 0.001) and at the inlet of humidifier (rs = −0.83, p < 0.001). The utilization of in-line suction catheter reduced inhaled dose, regardless of the ventilator settings and nebulizer placements. Conclusions: When VMN was placed at the inlet of humidifier, directly connecting the Y-piece to ETT without a suction catheter improved aerosol delivery. In this configuration, the inhaled dose increased as the inspiratory flow decreased, inspiratory pause had either no or a negative impact on aerosol delivery. The inhaled dose was greater with VMN placed at the inlet of humidifier than 15 cm away the Y-piece. [ABSTRACT FROM AUTHOR]

This study aimed to explore the underlying mechanism of nebulized dexmedetomidine (DEX) in ameliorating ventilator-induced lung injury (VILI)-induced oxidative stress in rats. Forty 7 to 8-week-old Sprague-Dawley rats at the specific pathogen-free level were randomized into the control group, model group, nebulized dexmedetomidine (WH-YM) group, and dexmedetomidine intravenous infusion (JM-YM) group, each containing 10 rats. Except for the control group, rats in the other groups underwent mechanical ventilation (tidal volume, 40 mL/kg; respiratory rate, 70 breaths per minute; inspiratory-to-expiratory ratio, 1:2; fraction of inspired oxygen, 21%; positive end-expiratory pressure, 0 cmH2O). Nebulized DEX (6.3 µg/kg), and isodose intravenous DEX were given to rats of WH-YM and JM-YM groups prior to ventilation. Post 4-hour ventilation, rats were euthanized. Lung tissue wet-to-dry weight ratio, H&E staining for assessing diffuse alveolar damage (DAD), and expression levels of Nrf2 and Keap1 detected by qRT-PCR and Western blot were compared. Inflammatory markers TNF-α, IL-2, and IL-6, and oxidative stress indices malondialdehyde (MDA) and superoxide dismutase (SOD), were quantified in lung tissues and serum samples using commercial kits. Rats in the WH-YM and JM-YM groups demonstrated significant ameliorations in the wetto- dry weight ratio and DAD score, decreased Keap1, TNF-α, IL-2, and IL-6 levels in lung tissues and serum samples, but increased Nrf2 and SOD level than those of controls. These changes were more pronounced in the WH-YM group than in the JM-YM group. DEX effectively alleviates VILI-induced oxidative stress and inflammation via the Keap1- Nrf2-ARE signaling pathway., especially in the nebulized administration. [ABSTRACT FROM AUTHOR]

It is common for the anesthesiologist to cope with patients in the immediate postoperative period with moderate to severe amount of pain after laparoscopic cholecystectomy. The nebulization of local anesthetics in the abdominal cavity during laparoscopic surgery seems to be a promising procedure to reduce pain in the postoperative period thus reducing the number of analgesics and opioids administered to patients. We present the case of a 35-year-old woman who underwent a laparoscopic cholecystectomy, nebulizing ropivacaine in the abdominal cavity at the end of it, significantly reducing postoperative pain until the patient's discharge. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes. ANIMALS: 10 healthy experimental Beagles. METHODS: This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test. RESULTS: Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754). CLINICAL RELEVANCE: A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood. [ABSTRACT FROM AUTHOR]

Changes in the quantitative content and specific activity of hyaluronidase enzyme after ultrasonic treatment of solutions of bovhyaluronidase azoximer were studied. Solutions of the finished dosage form of bovhyaluronidase azoximer (Longidase® lyophilizate for preparation of solution for injection, 3000 IE) and bovhyaluronidase azoximer drug substance (Longidase® substance-lyophilizate) were studied. The aim of the study was to determine the effect of ultrasound (US) on the stability of bovhyaluronidase azoximer determined from the measured quantitative content and enzymatic activity of the substance in solution. US at a radiation intensity of 61.4 W/L during treatment in an ultrasonic bath did not significantly affect the quantitative content of the bovhyaluronidase azoximer drug substance in solution, while the decrease in the enzymatic activity of the active substance in Longidase solution after 20 and 30 min of ultrasonic treatment was statistically significant. At the same time, the enzymatic activity of the active substance determined by a biochemical method differed significantly (residual activity from 99.70% to 59.27%) depending on the design features of the nebulizers and the nebulization time after nebulization of the bovhyaluronidase azoximer solution in mesh nebulizers from various manufacturers. Nebulization times of min were least associated with the risk of significant loss of stability of bovhyaluronidase azoximer. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable "muco‐trapping" variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections. [ABSTRACT FROM AUTHOR]

Background & objective: Nasogastric (NG) tube insertion is a frequently performed medical procedure. Most of the time, the oropharyngeal discomfort is usually underestimated, and insertions are carried out with just regular lubricant jelly and no additional painkillers, which results in less-than-ideal pain management. We compared the effectiveness of preemptive use of nebulized ketamine and dexamethasone in preventing post-operative sore throat following NG tube insertion in laparoscopic surgery. Methods: This prospective randomized double-blind controlled study was carried on 108 patients of both sexes with ASA physical status I-II. aged 20-60 years, undergoing laparoscopic abdominal surgeries under general anesthesia. Patients were randomized into 3 equal groups. Group D received a dose of 8 mg nebulized dexamethasone. Group K received 50 mg nebulized ketamine. Group S received 5 ml of nebulized saline. NG tube was passed after induction of general anesthesia. Postoperative sore throat was enquired from the patients at full recovery (zero hour), then at 2, 8, 12 and 24 h. Computer software (SPSS 15.0.1. for Windows; SPSS Inc, Chicago, IL, 2001) was used for data analysis. Non-parametric quantitative data, median, range, percentages, and numbers are given for qualitative data. The appropriate analysis was conducted in line with the data obtained. P < 0.05 was regarded as significant. Results: The incidence of postoperative sore throat (POST) was lower with both nebulized dexamethasone and nebulized ketamine compared with nebulized saline; and significantly lower with dexamethasone compared with ketamine at 0 h (P < 0.001), 2 h (P < 0.001), 8 h (P < 0.001), 12 h (P < 0.001), and 24 h (P < 0.001). Conclusion: The current study revealed that preoperative nebulized dexamethasone was more effective than nebulized ketamine in reducing postoperative sore throat. [ABSTRACT FROM AUTHOR]

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during the aerosolization of liquids or powders and the role of aerosol flow dynamics in the RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Through an analysis of existing technical limitations, selected strategies aimed at enhancing the effectiveness of targeted aerosol delivery to the RS have been identified and presented. These strategies also include the use of smart inhaling devices and systems with built-in AI algorithms. [ABSTRACT FROM AUTHOR]

General anaesthesia with endotracheal intubation results in postoperative sore throat. We studied the effectiveness of nebulization with ketamine which is a NMDA receptor antagonist, on the incidence and severity of sore throat in patients undergoing surgery under general anaesthesia. Institutional ethical committee approval obtained. 100 consenting patients scheduled for middle ear surgeries were randomly allocated to two groups of 50 each to receive 50mg of Ketamine or saline nebulization 15 minutes before the induction. Sore throat was less in 0, 2, 4, and 6hrs (p<0.02). Ketamine nebulization before intubation reduces incidence and severity of sore throat. [ABSTRACT FROM AUTHOR]

Background and Objective: Endotracheal intubation is part of general anesthesia, and probably the most commonly performed airway related procedure in operating rooms as well as intensive care units. It may be a causative factor in about 74% of patients who experience postoperative sore throat (POST) due to airway mucosal injury. This doubleblind randomized clinical trial assessed the effectiveness of nebulized dexmedetomidine in preventing POST by comparing with a control group. Methodology: In this randomized, double‐blind clinical trial, we enrolled 56 patients, who were to undergo general anesthesia with endotracheal intubation. Patients were randomly divided into two groups of 28 each. Group A received dexmedetomidine nebulization, and Group B had normal saline nebulization, both for 15 min before induction. POST was assessed at 1, 2, 4, 6, 12, and 24 h after extubation using a POST scale. Data were collected and statistically analyzed Results: The overall incidence of POST was 60.3%: Control group experienced POST by 28 (96.6%) patients, compared to 7 (24,1%) patients in dexmedetomidine group (P = 0.0001). Differences were significant at recording times postoperatively. The dexmedetomidine group had milder sore throats, less coughing, and lower heart rates/blood pressures compared to the control group. Conclusion: Patients who were nebulized with dexmedetomidine, experienced lower rates and intensity of postoperative sore throat compared to the control group. Administering dexmedetomidine via nebulization before intubation can be considered a safe and effective method for reducing postoperative sore throat, with less postintubation hemodynamic derangement. [ABSTRACT FROM AUTHOR]

Background: Nebulized drug delivery is commonly used in pediatric clinical practice. The growing number of literatures have reported the application of nebulized ketamine in pediatric sedation in recent years. This meta-analysis of randomized controlled trials comparing the efficacy and safety of nebulized ketamine versus different pharmacological approaches was conducted to estimate the effects of this technique in pediatric sedation. Methods: We searched PubMed, Embase, and Cochrane Library from inception to Feb 2023. All randomized controlled trials used nebulized ketamine as presurgical and pre-procedural sedatives in children were included. Sedative effects and various adverse events were considered as the outcomes. Results: Ten studies with 727 pediatric patients were enrolled. Compared to nebulized dexmedetomidine, using of ketamine via nebulization showed similar sedation satisfaction (54.79% vs. 60.69%, RR = 0.88, with 95%CI [0.61, 1.27]), success rate of parental separation (57.27% vs. 73.64%, RR = 0.81, with 95%CI [0.61, 1.08]), and mask acceptability (37.27% vs. 52.73%, RR = 0.71, with 95%CI [0.45, 1.10]). However, the using of combination of two medications (nebulized ketamine plus nebulized dexmedetomidine) was associated with better sedative satisfaction (33.82% vs. 68.11%, RR = 0.50, with 95%CI [0.27, 0.92]) and more satisfactory mask acceptance (45.59% vs. 71.01%, RR = 0.69, with 95%CI [0.56, 0.86]). Compared with nebulized ketamine, using of nebulized dexmedetomidine was associated with less incidence of emergence agitation (18.18% vs. 3.33%, RR = 4.98, with 95%CI [1.88, 13.16]). Conclusions: Based on current evidences, compared to nebulized dexmedetomidine, nebulized ketamine provides inconspicuous advantages in pediatric sedation, and it has a relatively high incidence of emergence agitation. Combination of nebulized ketamine and dexmedetomidine might be considered as one preferred option in pediatric sedation as it can provide more satisfactory sedative effects. However, there is insufficient evidence regarding nebulized ketamine versus ketamine administered through other routes and nebulized ketamine versus other sedatives. The overall low or moderate quality of evidence evaluated by the GRADE system also calls for more high-quality studies with larger sample sizes in future. Research registration: The protocol of present study was registered with PROSPERO (CRD42023403226). [ABSTRACT FROM AUTHOR]

Introduction: A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. Methods: In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler® and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. Results: Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5 × 106 copies/mL. Two out of the 10 samples from the fugitive aerosol collected were positive to SARS-CoV-2. Conclusion: The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. Objectives: To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat Escherichia coli induced ARDS. Methods: Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in E. coli. Purified proteins were evaluated in in vitro assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an E. coli-induced ARDS rat model. Results: SOD proteins exhibited high SOD activity in vitro and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an E. coli-induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. Conclusions: Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates E. coli induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS. [ABSTRACT FROM AUTHOR]

A simple and rapid instantaneous nebulization dispersive liquid‐phase microextraction method was developed, and combined with high‐performance liquid chromatography for determination of the contents of seven analytes in traditional Chinese medicines. In this study, using the sprinkler device to achieve instantaneous synchronous dispersion and extraction, only one spray can rapidly achieve the concentration and enrichment of seven kinds of chalcone and isoflavones. The key factors affecting the extraction efficiency were optimized including the type and volume of extractant, the pH and salt concentration of the sample phase, and the number of dispersion. Under the optimal conditions, the enrichment factor of the target analytes ranged from 103.1 to 180.9, with good linearity and correlation coefficients above 0.9970. The limits of detection ranged from 0.02 to 0.15 ng/mL, with good accuracy (recoveries 91.1 to 108.9%) and precision (relative standard deviations 1.5–7.1%). This method has short extraction time (2 s), low organic solvent consumption and high enrichment effect, so it has a wide application prospects. [ABSTRACT FROM AUTHOR]

Postoperative peritoneal adhesions occur in the majority of patients undergoing intra-abdominal surgery and are one of the leading causes of hospital re-admission. There is an unmet clinical need for effective anti-adhesive biomaterials, which can be applied evenly across the damaged tissues. We examined three different responsive hydrogel types, i.e. a thermosensitive PLGA-PEG-PLGA, a pH responsive UPy-PEG and a shear-thinning hexapeptide for this purpose. More specifically, their potential to be homogeneously distributed in the peritoneal cavity by high pressure nebulization and prevent peritoneal adhesions was evaluated. Solutions of each polymer type could be successfully nebulized while retaining their responsive gelation behavior in vitro and in vivo. Furthermore, none of the polymers caused in vitro toxicity on SKOV3-IP2 cells. Following intraperitoneal administration, both the PLGA-PEG-PLGA and the hexapeptide hydrogels resulted in local inflammation and fibrosis and failed in preventing peritoneal adhesions 7 days after adhesion induction. In contrast, the pH sensitive UPy-PEG formulation was well tolerated and could significantly reduce the formation of peritoneal adhesions, even outperforming the commercially available Hyalobarrier® as positive control. To conclude, local nebulization of the bioresponsive UPy-PEG hydrogel can be considered as a promising approach to prevent postsurgical peritoneal adhesions. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0–1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude. [ABSTRACT FROM AUTHOR]

Pulmonary bacterial infections present a significant health risk to those with chronic respiratory diseases (CRDs) including cystic fibrosis (CF) and chronic-obstructive pulmonary disease (COPD). With the emergence of antimicrobial resistance (AMR), novel therapeutics are desperately needed to combat the emergence of resistant superbugs. Phage therapy is one possible alternative or adjunct to current antibiotics with activity against antimicrobial-resistant pathogens. How phages are administered will depend on the site of infection. For respiratory infections, a number of factors must be considered to deliver active phages to sites deep within the lung. The inhalation of phages via nebulization is a promising method of delivery to distal lung sites; however, it has been shown to result in a loss of phage viability. Although preliminary studies have assessed the use of nebulization for phage therapy both in vitro and in vivo, the factors that determine phage stability during nebulized delivery have yet to be characterized. This review summarizes current findings on the formulation and stability of liquid phage formulations designed for nebulization, providing insights to maximize phage stability and bactericidal activity via this delivery method. [ABSTRACT FROM AUTHOR]

Purpose: Niclosamide is approved as an oral anthelminthic, but its low oral bioavailability hinders its medical use requiring high drug exposure outside the gastrointestinal tract. An optimized solution of niclosamide for nebulization and intranasal administration using the ethanolamine salt has been developed and tested in a Phase 1 trial. In this study we investigate the pulmonary exposure of niclosamide following administration via intravenous injection, oral administration or nebulization. Methods: We characterized the plasma and pulmonary pharmacokinetics of three ascending doses of nebulized niclosamide in sheep, compare it to intravenous niclosamide for compartmental PK modelling, and to the human equivalent approved 2 g oral dose to investigate in the pulmonary exposure of different niclosamide delivery routes. Following a single-dose administration to five sheep, niclosamide concentrations were determined in plasma and epithelial lining fluid (ELF). Non-compartmental and compartmental modeling was used to characterize pharmacokinetic profiles. Lung function tests were performed in all dose groups. Results: Administration of all niclosamide doses were well tolerated with no adverse changes in lung function tests. Plasma pharmacokinetics of nebulized niclosamide behaved dose-linear and was described by a 3-compartmental model estimating an absolute bioavailability of 86%. ELF peak concentration and area under the curve was 578 times and 71 times higher with nebulization of niclosamide relative to administration of oral niclosamide. Conclusions: Single local pulmonary administration of niclosamide via nebulization was well tolerated in sheep and resulted in substantially higher peak ELF concentration compared to the human equivalent oral 2 g dose. [ABSTRACT FROM AUTHOR]

Background and Aims: Awake fibreoptic intubation is considered a safe approach in airway management of a patient with difficult airway. Awake fibreoptic endoscopy needs appropriate anaesthesia of airway to suppress airway reflexes and prevent discomfort. We planned this study to evaluate effect of adding dexmedetomidine to lignocaine nebulization on conditions for awake videoendoscopic intubation. Material and Methods: In this prospective randomized double blind controlled study, ninety six ASA grade I, II patients of either gender, aged 18-65 years, scheduled for elective surgeries under general anaesthesia, were randomly allocated into two groups, Group D and L to receive nebulization with 4% Lignocaine 5 ml + Dexmedetomidine 2 mcg/kg and 4% Lignocaine alone respectively, 20 min before procedure. Time taken to intubate the patient, ease of intubation assessed by cough severity score, patient comfort score, post-intubation patient satisfaction and hemodynamic changes were recorded and compared. Results: Group D and L had comparable intubation time (196.8 ± 61.2 s) and (205.8 ± 52.2 s) (p = 0.437). Cough severity, patient comfort and quality of procedure with post intubation patient satisfaction score were significantly better in Group D. Haemodynamics parameters were better post nebulization in group D as compared to group L. Conclusion: Addition of Dexmedetomidine 2 mcg/kg with 4% Lignocaine during nebulization improves intubating conditions during awake flexible videoendoscopy in terms of ease of intubation, cough severity, patients comfort and satisfaction along with providing stable Haemodynamics profile. [ABSTRACT FROM AUTHOR]

Nowadays, due to a higher resistance to drugs, antibiotics, and antiviral medicaments, new ways of fighting pathogens are intensively studied. The alternatives for synthesized compositions are natural products, most of which have been known in natural medicine for a long time. One of the best-known and intensively investigated groups are essential oils (EOs) and their compositions. However, it is worth noting that the method of application can play a second crucial part in the effectiveness of the antimicrobial activity. EOs possess various natural compounds which exhibit antimicrobial activity. One of the compositions which is based on the five main ingredients of eucalyptus, cinnamon, clove, rosemary, and lemon is named "five thieves' oil" (Polish name: olejek pięciu złodziei) (5TO) and is used in natural medicine. In this study, we focused on the droplet size distribution of 5TO during the nebulization process, evaluated by the microscopic droplet size analysis (MDSA) method. Furthermore, viscosity studies, as well as UV-Vis of the 5TO suspensions in medical solvents such as physiological salt and hyaluronic acid, were presented, along with measurements of refractive index, turbidity, pH, contact angle, and surface tension. Additional studies on the biological activity of 5TO solutions were made on the P. aeruginosa strain NFT3. This study opens a way for the possible use of 5TO solutions or emulsion systems for active antimicrobial applications, i.e., for surface spraying. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid (TA) is used to control bleeding in patients with hemoptysis. However, the effectiveness of the different routes of TA administration has not been studied.Research Question: Does nebulized route of Tranexamic Acid (TA) administration reduce the amount of hemoptysis compared to intravenous route in patients presenting to emergency department (ED) with hemoptysis?Methods: We conducted a pragmatic, open labelled, cluster randomized, parallel single centered pilot trial of nebulized TA (500mg tid) versus intravenous TA (500mg tid) in adult patients presenting to emergency department with active hemoptysis. The primary outcome was cessation of bleeding at 30 min. Secondary outcome included amount of hemoptysis at 6h, 12h and 24 h; interventional procedures and side effects of TA. Patients who were hemodynamically unstable or requiring immediate interventional procedure or mechanical ventilation were excluded from the study.Results: Of the 55 patients in each arm, hemoptysis cessation at 30 minutes after TA administration was significantly higher in nebulized arm (n=40) compared to intravenous arm (n=28) [X2 (1, n=110)=5.55, p=0.0019]. Also, hemoptysis amount reduced significantly in nebulization arm at all time periods of observation (P value 30min=0.011, at 6h=0.002, 12h=0.0008, 24h=0.005). Fewer patients in nebulized arm required bronchial artery embolization (13 vs 21, P value=0.024) and thereby higher discharge rates from the ED (67.92% vs 39.02%, P value=0.005). Two patients in nebulized arm had asymptomatic bronchoconstriction which resolved after short acting beta agonist nebulization. No patient discharged from ED underwent any interventional procedure or revisited the ED with rebleed during the 72 hours follow up period.Interpretation: Nebulized TA may be more efficacious than intravenous TA in reducing the amount of hemoptysis and need for ED interventional procedures. Future larger studies are needed to further explore the potential of nebulized TA compared to intravenous TA in patients with mild hemoptysis. [ABSTRACT FROM AUTHOR]

Bacteriophages have been identified as a potential treatment option to treat lung infection in the context of antibiotic resistance. We performed a preclinical study to predict the efficacy of delivery of bacteriophages against Pseudomonas aeruginosa (PA) when administered via nebulization during mechanical ventilation (MV). We selected a mix of four anti-PA phages containing two Podoviridae and two Myoviridae, with a coverage of 87.8% (36/41) on an international PA reference panel. When administered via nebulization, a loss of 0.30–0.65 log of infective phage titers was measured. No difference between jet, ultrasonic and mesh nebulizers was observed in terms of loss of phage viability, but a higher output was measured with the mesh nebulizer. Interestingly, Myoviridae are significantly more sensitive to nebulization than Podoviridae since their long tail is much more prone to damage. Phage nebulization has been measured as compatible with humidified ventilation. Based on in vitro measurement, the lung deposition prediction of viable phage particles ranges from 6% to 26% of the phages loaded in the nebulizer. Further, 8% to 15% of lung deposition was measured by scintigraphy in three macaques. A phage dose of 1 × 109 PFU/mL nebulized by the mesh nebulizer during MV predicts an efficient dose in the lung against PA, comparable with the dose chosen to define the susceptibility of the strain. [ABSTRACT FROM AUTHOR]

The efficiency of lung drug delivery of nebulized drugs is governed by aerosol quality, which depends both on the aerosolization process itself but also on the properties of aerosol precursors. This paper determines physicochemical properties of four analogous micro-suspensions of a micronized steroid (budesonide, BUD) and seeks relationships between these properties and the quality of the aerosol emitted from a vibrating mesh nebulizer (VMN). Despite the same BUD content in all tested pharmaceutical products, their physicochemical characteristics (liquid surface tension, viscosity, electric conductivity, BUD crystal size, suspension stability, etc.) are not identical. The differences have a weak influence on droplet size distribution in the mists emitted from the VMN and on theoretical (calculated) regional aerosol deposition in the respiratory system but, simultaneously, there is an influence on the amount of BUD converted by the nebulizer to aerosol available for inhalation. It is demonstrated that the maximum inhaled BUD dose is below 80–90% of the label dose, depending on the nebulized formulation. It shows that nebulization of BUD suspensions in VMN is sensitive to minor dissimilarities among analogous (generic) pharmaceutics. The potential clinical relevance of these findings is discussed. [ABSTRACT FROM AUTHOR]

Maintaining proper asepsis and hygiene conditions in spaces intended for veterinary surgery remains a paramount for compliance with professional ethics. Moreover, environmental surfaces can contribute to the spread of cross-infections, and therefore constitute a likely transitory site for the accumulation of microorganisms. The aim of the current study was to evaluate, implement and measure the efficacy of a novel nebulization technique method for surface disinfection. The procedure was carried out in ten enclosed spaces used as surgery rooms within veterinary clinics. Disinfection was performed using Cube Atomizers, a nebulizer with a revolutionary spraying system, which transforms the biocide substance into microparticles that persist in the air for a long period of time, ensuring decontamination of the treated volume (air and all types of surfaces). Thus, using an approved biocide, the device ensured a successful disinfection of spaces, eliminating bacteria, and other biological pathogens. The microbiological tests were carried out before and after disinfection on different growth mediums (Agar for the total bacteria count, Chapmann for Staphylococcus, Holmes for Streptococcus, Levine for Gram-negative Cocci and Sabouraud for fungi). An increased efficiency of disinfection was observed, with a significant decrease in total bacteria count of almost 90-97% and the value of colony-forming units reaching 0 after nebulization in some cases; for Staphylococcus (Chapmann) there was a significant decrease, between 85-95%; for Streptococcus (Holmes) the decrease was almost 90-99%; for Gram-negative Cocci (Levine) the decrease was almost 92-99%; and for fungi (Sabouraud) the decrease was around 50%. The Cube Atomizers device is easy to use, can be fitted anywhere and guarantees safety for the user, environment, and all treated materials. Its revolutionary system ensures decomposition of the biocide into microparticles, leaving no residues. [ABSTRACT FROM AUTHOR]

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of selfdosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARSCoV-2 and other respiratory pathologies. [ABSTRACT FROM AUTHOR]

Objective: Chronic obstructive pulmonary disease (COPD) is associated with many health complications, including pulmonary hypertension (PH). Although oral calcium channel blockers have shown promising results in managing COPD‐induced PH, significant systemic side effects may limit their use in this population. Administering verapamil through nebulization can be an alternative approach. We aim to assess the possible therapeutic effects of verapamil inhalation in out‐patients with pulmonary hypertension (PH) secondary to COPD. Methods: A double‐blind, randomized placebo‐controlled clinical trial was conducted. Patients with PH were randomly assigned to two groups of 15 participants. The intervention group received a short‐term single dose of 10 mg nebulized verapamil (4 ampoules of 2.5 mg/ml verapamil solutions). The control group received nebulized distilled water as a placebo in addition to their standard treatment throughout the study. Results: Systolic pulmonary artery pressure (sPAP) did not improve as a primary outcome significantly in patients receiving nebulized verapamil compared with those on placebo (p = 0.89). Spirometry results showed a significant improvement in FVC in the intervention group from 1.72 ± 0.63 to 1.85 ± 0.58 L (p = 0.00), and FEV1/FVC ratio decreased significantly after verapamil administration (p = 0.027). Conclusion: Verapamil did not improve any of the pulmonary artery or RV parameters in patients with COPD‐associated, but it did improve SpO2 and increase FVC, which revealed us possibility of verapamil in treating V/Q mismatch. The improved gas exchange may have been due to improvements in FVC as reflected in the improved spirometry. Higher doses of verapamil may be more efficacious and can be the subject of future trials. [ABSTRACT FROM AUTHOR]

Introduction: Salbutamol is used in bronchodilator response testing (BDRT), which is an important diagnostic tool in bronchial obstructive diseases. Most available studies compare the bronchodilator response of salbutamol administered with a pressurized metered-dose inhaler and salbutamol in a nebulization solution. Aim: The spirometric evaluation of the bronchodilator response of two methods of salbutamol nebulization in asthmatic children. Material and methods: A randomized, open, comparative study was conducted in which 132 children with partially controlled asthma and current bronchial obstruction determined by spirometry were enrolled. BDRT was conducted using salbutamol solution administered with either a continuous jet nebulizer (CON) or a breath-actuated jet nebulizer (BAN). The BAN group received half the dose of the drug compared to the CON group, i.e. 2.5 mg. Changes in FEV1 and FEF25-75 after drug administration were calculated in relation to the baseline values. Results: The change in FEV1 after salbutamol administration was 16.9 ±9.7% in the BAN group and was statistically significantly higher than in the CON group (12.6 ±8.8%) (p = 0.026). The change in FEF25-75 was 37.7 ±23.2% in the BAN group and 32.7 ±25.5% in the CON group (p = 0.061). There were no statistically significant differences in the frequency of adverse events between the compared groups. Conclusions: Salbutamol inhaled from BAN results in a better bronchodilator response than twice the nominal dose of this drug inhaled from CON, which is due to the absence of drug loss during the expiratory phase and therefore greater pulmonary deposition. [ABSTRACT FROM AUTHOR]

Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (w/w) as oil, Labrasol:Poloxamer-407 (2:1) (w/w) as surfactant mixture (Smix) and water. The optimum formulation P2TD resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2TD demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2TD promising for the treatment of pediatric PAH. [ABSTRACT FROM AUTHOR]

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery. [Display omitted] • Icariin reacts with phospholipid to form phospholipid complex with self-assembly ability. • Icariin-phospholipid complex (IPC) is stable during autoclaving and nebulization processes. • IPC sustains drug release, enhances lung affinity and slows lung clearance. • Intratracheal delivery of IPC improves and extends drug exposure to lung tissues and immune cells in lungs. • Instilled IPC prolongs pulmonary anti-inflammatory effects and increases the survival rate of mice with ARDS. [ABSTRACT FROM AUTHOR]

Background and Aims: Dexmedetomidine is a highly selective α-2 adrenoreceptor agonist and has been found to be an effective premedication agent when administered via the intranasal route. We aimed to compare the efficacy of dexmedetomidine premedication administered via intranasal route and through nebulization in pediatric patients. Material and Methods: This non-inferiority randomized controlled trial was conducted after getting approval from institutes ethics committee and informed written parental consent. Sixty-four children aged 2-8 years scheduled for elective surgery under general anesthesia were enrolled and were divided into two groups. Group I (Intranasal, n = 33) received 2 mcg/kg dexmedetomidine via intranasal route and group N (Nebulized, n = 31) received 2 mcg/kg dexmedetomidine through nebulization. The primary outcome was number of patients with satisfactory sedation 30 minutes after premedication at separation from parent. The secondary outcome included ease of medication acceptance, anxiety at parental separation, acceptance of anesthesia mask, perioperative hemodynamics, emergence agitation during recovery and adverse effects. Data collected was analyzed using Chi-square test, Student "t" test and Mann-Whitney U test with the help of SPSS 22. A one tailed P value < 0.025 was considered significant. Results: Demographic profile was comparable between groups. On arrival in OR 27 (81.8%) patients in group I and 21 (67.7%) patients in group N had satisfactory sedation score (P = 0.19). The median (IQR) sedation score was comparable between group I and group N (P = 0.057). Patients in Group I showed significantly better medication and mask acceptance scores (P < 0.0001, P = 0.001 respectively), parental separation anxiety score (P < 0.0001) and emergence agitation score (P = 0.001). There were no significant differences in hemodynamic parameters and adverse effects between the groups. Conclusion: Although nebulized dexmedetomidine is non-inferior to intranasal dexmedetomidine in providing desired level of sedation but intranasal administration had better acceptance of medication and anesthesia mask with lesser anxiety at parental separation and postoperative emergence agitation. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) disorders, such as psychiatric disorders, neurodegeneration, chronic pain, stroke, brain tumor, spinal cord injury, and many other CNS diseases, would hugely benefit from specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to the brain is challenging due to their low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit peptides' clinical application and explain the interest in alternative routes of peptide administration, particularly nose-to-brain (N-to-B) delivery, which allows protein and peptide drugs to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure; the olfactory and trigeminal nerves provide a unique pathway to the brain and the external environment. This review highlights the intranasal delivery of drugs, focusing on peptide delivery, illustrating various clinical applications, nasal delivery devices, and the scope and limitations of this approach. [ABSTRACT FROM AUTHOR]

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl β-cyclodextrin (HP) and sulfobutyl ether β-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS–CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD–DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS–CD inclusion complexes against SARS-CoV-2 via nebulization. [ABSTRACT FROM AUTHOR]

Background: Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19. Methods: A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated. Results: Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the duration of hospitalization for mild cases of COVID-19 pneumonia. Conclusions: Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020. [ABSTRACT FROM AUTHOR]

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

The SARS‐CoV‐2 pandemic, which suddenly appeared at the beginning of 2020, revealed our knowledge deficits in terms of ventilation and air pollution control. It took many weeks to realize that aerosols are the main route of transmission. The initial attempt to hold back these aerosols through textile masks seemed almost helpless, although there is sufficient knowledge about the retention capacity of fabric filters for aerosols. In the absence of a sufficient number of permanently installed heating, ventilation, and air conditioning systems, three main approaches are pursued: (a) increasing the air exchange rate by supplying fresh air, (b) using mobile air purifiers, and (c) disinfection by introducing active substances into the room air. This article discusses the feasibility of these different approaches critically. It also provides experimental results of air exchange measurements in a school classroom that is equipped with a built‐in fan for supplying fresh air. With such a fan and a window tilted at the appropriate distance, an air exchange rate of 5/h can be set at a low power level and without any significant noise pollution. Heat balance calculations show that no additional heat exchanger is necessary in a normal classroom with outside temperatures above 10°C. Furthermore, a commercial mobile air purifier is studied in a chamber and a test room setup in order to examine and evaluate the efficiency of such devices against viable viruses under controlled and realistic conditions. For this purpose, bacteriophages of the type MS2 are used. Both window ventilation and air purifiers were found to be suitable to reduce the concentration of phages in the room. [ABSTRACT FROM AUTHOR]

Background: Awake fiberoptic intubation (AFOI) is the gold standard for managing a difficult airway. To make the patient comfortable and cooperative during the procedure, many drugs such as benzodiazepines, opioids, or dexmedetomidine are used. Most of these intravenously given drugs may cause respiratory depression and hypoxia. Aim: We compared the efficacy of dexmedetomidine through nebulization and transtracheal route with intravenous routes with the primary aim of comparing patient tolerance score (PTS) and secondary objectives of comparing sedation score, cough score, and total duration required for awake fiberoptic nasotracheal intubation. Settings and Design: This study was a prospective randomized double-blind study. Subjects and Methods: Seventy-six patients, scheduled for elective surgery requiring AFOI between 18 and 75 years, were included in the study. They were randomly divided into two groups of 38 each. Group I patients received intravenous dexmedetomidine 1 μg.kg−1 and Group L patients received local dexmedetomidine through nebulization 0.5 μg.kg−1 and transtracheal injection 0.5 μg.kg−1. Statistical Analysis Used: Statistical Package for the Social Sciences version 22 was used. Results: Patients who received dexmedetomidine through nebulization and transtracheal route have significantly better PTSs and less cough scores as compared to patients who received dexmedetomidine by intravenous route (P < 0.05). Hemodynamic parameters and sedation scores between the two groups were statistically insignificant (P > 0.05). The time required for the procedure was significantly less in Group L compared to Group I (P < 0.05). Conclusion: Dexmedetomidine by nebulization and transtracheal route provides optimal conditions for AFOI with good patient tolerance and less cough score as compared to the intravenous route. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of quantitative data on healthcare professionals' (HCPs) time dedicated to nebulized chronic obstructive pulmonary disease (COPD) therapy in inpatient and long-term care (LTC) settings. Using time and motion methodology, we quantified HCP time and opportunity costs (time and materials) associated with nebulized COPD therapy in inpatient and LTC settings and estimated efficiencies of changing to once-daily therapy. Methods: A case report form was built to reflect local nebulization workflow. Primary outcomes were mean active HCP time per predefined task and mean total active HCP time associated with short-acting beta agonist (SABA) and SABA/short-acting muscarinic antagonist (SAMA) combination nebulization processes. Results: Twenty observations occurred within each setting. Inpatient observations included three SABA and 17 SABA/SAMA (from 18 different patients), and LTC observations included five SABA and 15 SABA/SAMA (from eight different patients). Mean total process time was 16.12 min in the inpatient setting (95% CI 14.48–17.76) and 21.0 min in the LTC setting (95% CI 18.8–23.2), with the actual nebulization comprising over 50% of process time for both. In LTC, CIs suggest a difference by cognitive impairment status: mean 24.1 min (95% CI 21.3–26.9) if cognitively impaired versus 19.0 min (95% CI 16.1–21.8) if not. In the inpatient setting, the estimated process time/admission was 7.8 h; a once-daily nebulized drug would require only 2.3 h. In LTC, the estimated process time was 32.1 h/month; a once-daily nebulized drug would require only 13.7 h/month. Estimated nebulization cost was $243/admission for current versus $72 for once-daily dosing in inpatient, and $1177/month versus $504 in LTC. Conclusions: The nebulization process for COPD patients in both inpatient and LTC settings consumes considerable HCP time. A switch from SABA or SABA/SAMA to a drug with a once-daily nebulization frequency could generate substantial time savings depending on the setting and site characteristics. [ABSTRACT FROM AUTHOR]

Objective: To compare preoperative Ketamine nebulization versus saline nebulization in reducing the frequency and severity of sore throat postoperatively. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Anesthesia, Combined Military Hospital, Bahawalpur Pakistan, from Jan to Jun 2022. Methodology: A total of 120 patients (60 in each group) with different surgeries filling the inclusion criteria were considered in the study. Adult patients of 20-60 years with ASA class 1-2 who were planned for elective surgery of less than 2 hours were included. Group-A patients underwent nebulization with Ketamine while in Group-B nebulization was done with normal saline. Results: A total of patients included were 120 (60 each group). Twenty-eight (23.3%) patients developed Post-Operative Sore Throat at some time after extubation. The frequency of Post-Operative Sore Throat with Ketamine was 13.3% and with saline it was 33.3%. Twenty (71.42%) patients of Post-Operative Sore Throat developed sore throat at 2 hours after extubation, of which 15 patients belong to Saline Group (p-value 0.01). Twenty-one patients of Post-Operative Sore Throat had mild sore throat of which 14 patients were of Saline Group (p-value 0.006). Conclusion: Ketamine nebulization postoperatively leads to reduced frequency and severity of Post-Operative Sore Throat in early post-operative period in patients in which endotracheal intubation was done for GA. [ABSTRACT FROM AUTHOR]

Conflicting guidance exists regarding the characterization of nebulization as an aerosol-generating procedure and subsequent risk of transmission of SARS-CoV-2 to healthcare workers.This study sought to address whether SARS-CoV-2 viral load distribution was impacted by bronchodilator delivery via nebulizer versus metered-dose inhaler (MDI).Adults infected with COVID-19 were enrolled and received a single dose of albuterol sulfate nebulized solution (2.5 mg/3 mL via breath-actuated nebulizer with filtered mouthpiece) or albuterol sulfate hydrofluoroalkane inhalation aerosol (90 µg/actuation; two puffs via MDI with spacer) in a randomized crossover sequence. Air and surfaces were sampled at predefined locations within patients’ hospital rooms to assess SARS-CoV-2 dispersion over three periods (baseline, MDI, and nebulizer).Eleven patients received crossover therapy. Six patients had detectable SARS-CoV-2 RNA during one treatment period (n = 3 each for MDI and nebulizer) and one during both treatment periods. No viral RNA was found in the rooms of four (36.4%) patients. Overall, few environmental samples (17/397; 4.3%) contained detectable viral RNA, with no meaningful differences in positivity rate across periods; RNA genome copy numbers were low in positive samples. No correlation between dispersion and patient clinical status or environmental parameters was observed.In this first prospective trial evaluating viral load distribution following use of nebulizer versus MDI in hospitalized patients with COVID-19, low environmental contamination was found regardless of administration method. Findings support the use of either device when needed to treat patients with COVID-19. [ABSTRACT FROM AUTHOR]

Patients with COVID-19 may complicate their evolution with thromboembolic events. Incidence of thromboembolic complications are high and also, patients with the critically-ill disease showed evidence of microthrombi and microangiopathy in the lung probably due to endothelial damage by directly and indirectly injured endothelial and epithelial cells. Pulmonary embolism, deep venous thrombosis and arterial embolism were reported in patients with COVID-19, and several analytical abnormal coagulation parameters have been described as well. D-dimer, longer coagulation times and lower platelet counts have been associated with poor outcomes. The use of anticoagulation or high doses of prophylactic heparin is controversial. Despite the use of anticoagulation or high prophylactic dose of heparin have been associated with better outcomes in observational studies, only in patients with non-critically ill disease benefits for anticoagulation was observed. In critically-ill patient, anticoagulation was not associated with better outcomes. Other measures such as antiplatelet therapy, fibrinolytic therapy or nebulized anticoagulants are being studied in ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate ocular surface status and corneal higher‐order aberrations after a new ocular nebulization therapy combined with meibomian gland massage for the treatment of meibomian gland dysfunction (MGD). Patients and methods: This prospective randomized study involved 38 patients diagnosed with MGD. Subjects were classified into two groups: the nebulization and meibomian gland massage group (or NB group, 14 patients, 28 eyes) and the eye drop group (or ED group, 24 patients, 48 eyes). Azithromycin solution and esculin and digitalis glycoside eye drops were tested in the therapy. Best‐corrected visual acuity (BCVA) testing; noncontact tonometry; fundoscopy; the Ocular Surface Disease Index (OSDI) questionnaire; tear film assessment encompassing tear meniscus height (TMH) and non‐invasive keratograph breakup time (NIKBUT); corneal fluorescein staining; the Schirmer I test (SIT); and anterior, posterior and total corneal aberrations were evaluated at 1 and 3 months after treatment. Results: At 3 months, the NB group showed significantly better improvement than the ED group in terms of TMH (0.23 ± 0.04 versus 0.19 ± 0.05, p = 0.002) and first breakup time (f‐BUT; 7.42 ± 2.49 versus 5.53 ± 2.12, p = 0.001). The average breakup time (Av‐BUT) of the NB group was significantly longer than that of the ED group at 1 month (9.52 ± 2.70 versus 8.02 ± 2.33, p = 0.013) and 3 months (5.53 ± 2.12 versus 8.35 ± 2.38, p = 0.018). Both groups achieved improvement in corneal fluorescein staining (CFS) and SIT results at 1 and 3 months (p < 0.05). At the 3‐month follow‐up, anterior corneal trefoil aberrations decreased significantly in the NB group (p = 0.008), and improvements in anterior corneal coma aberrations and posterior corneal higher‐order aberrations (HOAs) were observed in the ED group (p < 0.05) over the 4 mm pupil zone. Over a 6 mm zone at 3 months, anterior, posterior and total trefoil aberrations as well as total HOAs were significantly decreased in the NB group (p < 0.05), while posterior HOAs and trefoil aberrations were found to be decreased in the ED group (p < 0.05). For individual Zernike terms, anterior and total corneal Z(3, −3) showed decreases over the 4 and 6 mm zones, while no improvement was detected in the NB group at 3 months. Conclusion: In terms of comfort and visual quality, nebulization therapy combined with meibomian gland massage to deliver azithromycin solution and esculin and digitalis glycoside eye drops appears to be more effective in treating clinical symptoms and signs of MGD than simply applying esculin and digitalis glycoside eye drops. [ABSTRACT FROM AUTHOR]

Background: Allaying anxiety and providing calm children in the operating room is a challenging task for anesthesiologists. This study was designed to compare the use of nebulized dexmedetomidine and ketamine for premedication in pediatric patients under general anesthesia. Methods: Seventy patients, aged 2 to 8 years of both sexes, with American Society of Anesthesiologists physical status I/II scheduled for hernia repair surgery under general anesthesia, were randomized to two equal groups using a computer-generated random number table. Patients in group D received dexmedetomidine (2 μg/kg), and patients in group K received ketamine (2 mg/kg) by a jet nebulizer before the induction of anesthesia. The study’s primary objective was comparing the level of sedation, which was achieved at 30 min after a study drug administration using the Ramsay sedation scale, between the two groups. The secondary objectives were the two-group comparison of parental separation anxiety scale, acceptance of the mask, hemodynamic variables, recovery time, incidence of emergence agitation, and adverse events. Results: The median Ramsay sedation scale at 30 min was 3 (1–4) in group D and 3 (1–3) in group K (P = 0.002). Patients in group D had a more acceptable parental separation anxiety scale (P = 0.001) and a satisfactory mask acceptance scale (P = 0.042). Conclusions: Nebulized dexmedetomidine (2 μg/kg) provided better sedation along with smooth parental separation and satisfactory mask acceptance during induction of anesthesia with a similar emergence agitation profile and adverse reactions compared to nebulized ketamine in pediatric patients. [ABSTRACT FROM AUTHOR]