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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]

Delivering antibiotics directly to the respiratory tract through inhalation to address lung infections has garnered clinical and scientific interest for decades, given the potential favorable pharmacokinetic profile of this administration route. Among critically ill patients, the burden of healthcare-associated pulmonary infections particularly drove continued interest in delivering inhaled antibiotics to intubated patients. We present a concise overview of the existing rationale and evidence and provide guidance for implementing inhaled antibiotics among ventilated critically ill patients, emphasizing insights from recent literature. [ABSTRACT FROM AUTHOR]

The laryngeal adductor reflex (LAR) is a brainstem reflex that closes the vocal fold and constitutes a new method for continuously monitoring the vagus and laryngeal nerves during different surgeries. Previous reports concluded that topical lidocaine in spray inhibited LAR responses. However, topical anesthesia in the upper airway may be necessary in awake intubation. We present six patients who underwent neck endocrine surgery due to an intrathoracic goiter that compromised the airway. Before awake intubation, a nebulization of lidocaine 5% was applied for at least 10 min. The intubation procedure was well tolerated, and bilateral LAR with suitable amplitudes for monitoring was obtained in all cases. In our series, the nebulization of lidocaine 5% did not affect the laryngeal adductor reflex. Laryngoscope, 134:4161–4164, 2024 [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]

Glutathione (GSH), a tripeptide synthesized intracellularly, serves as a pivotal antioxidant, neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) while maintaining redox homeostasis and detoxifying xenobiotics. Its potent antioxidant properties, particularly attributed to the sulfhydryl group (-SH) in cysteine, are crucial for cellular health across various organelles. The glutathione-glutathione disulfide (GSH-GSSG) cycle is facilitated by enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR), thus aiding in detoxification processes and mitigating oxidative damage and inflammation. Mitochondria, being primary sources of reactive oxygen species, benefit significantly from GSH, which regulates metal homeostasis and supports autophagy, apoptosis, and ferroptosis, playing a fundamental role in neuroprotection. The vulnerability of the brain to oxidative stress underscores the importance of GSH in neurological disorders and regenerative medicine. Nebulization of glutathione presents a novel and promising approach to delivering this antioxidant directly to the central nervous system (CNS), potentially enhancing its bioavailability and therapeutic efficacy. This method may offer significant advantages in mitigating neurodegeneration by enhancing nuclear factor erythroid 2-related factor 2 (NRF2) pathway signaling and mitochondrial function, thereby providing direct neuroprotection. By addressing oxidative stress and its detrimental effects on neuronal health, nebulized GSH could play a crucial role in managing and potentially ameliorating conditions such as Parkinson's Disease (PD) and Alzheimer's Disease (AD). Further clinical research is warranted to elucidate the therapeutic potential of nebulized GSH in preserving mitochondrial health, enhancing CNS function, and combating neurodegenerative conditions, aiming to improve outcomes for individuals affected by brain diseases characterized by oxidative stress and neuroinflammation. [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]

The present pilot study is as a part of Ph.D. Programme under THE TAMILNADU Dr. M.G.R Medical University. The study was designed to assess the effectiveness of Novel Designed Nebulizer (NDN) Compliance among Pre- schoolers undergoing nebulization in selected Hospital, Salem. Quasi experimental research design was adopt- ed. 20 children (10 experimental, 10 control group) who were admitted in pediatric wards with respiratory con- ditions and receiving nebulization between the age group of 3 to 6 years were selected by purposive sampling. Nebulization was given to experimental group with Novel Designed Nebulizer (NDN) and control group with routine nebulization. The results showed that the post test scores reveal that experimental group all 10(10%) the preschoolers were having high level of compliance and in control group all 10(10%) the preschoolers were having Medium level of compliance to nebulization procedure.The Friedman test value is 9.235 which is greater than the table value which indicates that the Novel designed nebulization is effective in increasing the compli- ance in experimental group.overall mean and SD in Experimental group is 2.31±0.23and the overall mean and SD in control group is 4.19 ±0.46. The mean difference is 1.88. The Z value is 3.800 which is higher than the table value which shows that the Novel designed nebulization is effective in improving the compliance among Preschoolers in experimental group. [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]

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]

Purpose of Review: Inhaled antifungals achieve high lung concentrations with minimal systemic adverse events. Despite being available for over five decades, data supporting their use outside the mold-active prophylaxis setting are lacking. Herein, we review the recent evidence on inhaled antifungals in treating pulmonary aspergillosis (allergic, chronic, and invasive) and mucormycosis. Recent Findings: Several antifungals have recently been evaluated, including repurposed and newer inhaled agents (opelconazole). Inhaled amphotericin B deoxycholate (in pulmonary mucormycosis) and liposomal formulation (in invasive aspergillosis) were safely used in two recent randomized trials. However, both these small trials failed to demonstrate added benefit with adjunctive inhaled amphotericin. In allergic bronchopulmonary aspergillosis, nebulized amphotericin B may prolong the time-to-exacerbation when used in patients experiencing frequent exacerbations. Summary: The last decade has witnessed considerable progress in inhaled antifungals. Ongoing trials will likely offer hope for managing allergic and invasive pulmonary mycoses in the future. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Anestesiología is the property of Colegio Mexicano de Anestesiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

This article examines the effects of inhaled salbutamol on the cardiac electrical system in children. The study found that salbutamol inhalation led to changes in heart rate and certain electrocardiogram parameters, indicating a potential increased risk of arrhythmias. The study emphasizes the need for cautious use of high doses of salbutamol in children with asthma. The researchers also found that salbutamol can affect the T wave axis in the heart, increasing the risk of cardiac re-entry and arrhythmias. It is important to note that these findings may not apply to all populations and further research is needed. [Extracted from the article]

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP. [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: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. Objective: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. Design: A retrospective study. Methods: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 μg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV1 percentage predicted values (FEV1%pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV1 and/or FVC or >10% increase in FEV1%pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. Results: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV1 and increased FEV1 relative to the predicted value (ΔFEV1%pred) were significantly higher in patients <65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p < 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV1 (95% CI: 0.01–0.05, p = 0.004) and a 1.09% greater increase in ΔFEV1%pred (95% CI: 0.303–1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13–2.47, p = 0.009). Conclusion: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing. Plain language summary: Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing Bronchodilator responsiveness testing is commonly undertaken as an important part of spirometry testing to determine the degree of volume and airflow improvement after bronchodilator administration. BDR testing results may affect patients' diagnosis and treatment. This study compared the effects of two delivery models (a metered dose inhaler (MDI) with spacer and nebulization) on responsiveness to bronchodilators and the results of bronchodilator responsiveness testing among patients with chronic obstructive pulmonary disease. We found that the increment in forced expiratory volume in one second were significantly higher in patients aged <65 years and in those with severe spirometric abnormalities in the nebulization group than in those in the MDI group. The study provides evidence that salbutamol delivered by a nebulizer is preferable to an MDI with spacer in patients <65 years and in those with severe spirometric abnormalities and could increase positive responsiveness to bronchodilators. The study will assist in clinical decision-making by selecting the appropriate dosing regimen for different patients. [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]

Nanocarrier-assisted pulmonary drug delivery system has been widely employed for lung local disease treatment due to its enhanced drug lesion accumulation and reduced systematical side effects. However, the mucus barriers covered on the epithelia of trachea and bronchial tree construct a dense barrier for inhaled nanocarrier transport, which compromises the therapeutical effects. In this study, a lipid liquid crystalline nanoparticle NLP@Z with surface zwitterion material hexadecyl betaine (HB) modification and N-acetylcysteine (NAC) encapsulation was presented to exert the combination strategy of mucus-inert surface and mucus degradation. The HB modification endowed NLP@Z mucus-inert surface to inhibit the interaction between NLP@Z and mucins, and the encapsulated NAC could effectively degrade the mucins and further decrease the mucus viscosity. This combination strategy was proved to significantly promote the mucus penetration performance and enhance epithelial cell uptake. In addition, the proposed NLP@Z was equipped with desired nebulization property, which could be served as a potential pulmonary delivery nanoplatform. In summary, the proposed NLP@Z highlights the employment of the combination strategy for mucus penetration enhancement in pulmonary delivery, which may become a versatile platform for lung disease therapy. [ABSTRACT FROM AUTHOR]

Vitamin D3 deficiency has been recognized as a pandemic with serious health consequences including chronic respiratory diseases. Unfortunately, improvement in this situation by using vitamin D supplementation has failed. The direct delivery of 1,25(OH)2-vitamin D3 and its precursor into the respiratory tract, by nebulization, seemed to be a better option, as verified in the presented study. To induce vitamin D deficiency, mice received a diet with 0.05 IU/g cholecalciferol, while control animals were given feed with 0.5 IU/g cholecalciferol. Vitamin-D-deficient mice were exposed to different doses of calcidiol or calcitriol via nebulization for at least 7 days. At the end of the experiment, whole-body plethysmography was conducted. Pulmonary and serum levels of calcitriol were examined using ELISA. The calcitriol concentrations in mice on standard vs. deficient diet were 30.31/18.20 pg/mg (lungs) and 132.24/98.61 pg/mL (serum), respectively. Restoration of the physiological level of calcitriol in vitamin-D-deficient mice required 1-week exposure to 100 pg/g of calcidiol or 5 pg/g of calcitriol. The inhalations did not cause any side changes in murine respiratory function. The presented study revealed the usefulness and safety of chronic inhalation with a bioactive form of vitamin D3 or its precursor for the restoration of physiological calcitriol levels in animals with vitamin D deficiencies. [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]

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]

The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by the lactic acid bacterium Leuconostoc mesenteroides B512F. Time of addition assays with SARS-CoV-2 pseudoviruses in in vitro models confirm the inhibitory activity of DSs in the early stages of viral infection (viral entry). In addition, this exopolysaccharide substance also reports broad-spectrum antiviral activity against several enveloped viruses such as SARS-CoV-2, HCoV229E, HSV-1, in in vitro models and in human lung tissue. The toxicity and antiviral capacity of DS from L. mesenteroides was tested in vivo in mouse models which are susceptible to SARS-CoV-2 infection. The described DS, administered by inhalation, a new route of administration for these types of polymers, shows strong inhibition of SARS-CoV-2 infection in vivo, significantly reducing animal mortality and morbidity at non-toxic doses. Therefore, we suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Aminoglycosides are a family of rapidly bactericidal antibiotics that often remain active against resistant Gram-negative bacterial infections. Over the past decade, their use in critically ill patients has been refined; however, due to their renal and cochleovestibular toxicity, their indications in the treatment of sepsis and septic shock have been gradually reduced. This article reviews the spectrum of activity, mode of action, and methods for optimizing the efficacy of aminoglycosides. We discuss the current indications for aminoglycosides, with an emphasis on multidrug-resistant Gram-negative bacteria, such as extended-spectrum β-lactamase-producing Enterobacterales, carbapenemase-producing Enterobacterales, multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii. Additionally, we review the evidence for the use of nebulized aminoglycosides. [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]

A jet nebulizer sprays a fine mist or aerosol directly into the lungs to reduce inflammation, expand airways, and make breathing easier for respiratory patients. Asthma, COPD, emphysema, and cystic fibrosis are treated with jet nebulizers. They are chosen over other nebulizers for their shorter treatment time and wider medication compatibility. For mechanically ventilated patients, jet nebulizers humidify oxygen to provide bronchodilators, antibiotics, and other respiratory medications. Additionally, they treat pneumonia, bronchitis, and other lung infections. Aerosol therapy requires medical jet nebulizers. However, experiment setup is time-consuming and challenging to enhance smaller droplet output. The study is aimed at enhancing the nebulizer and process parameters using numerical simulation and comparing the results to experimental data from the Malvern Spraytec™ laser diffraction system. This numerical model improves nebulization knowledge and predicts process parameters that affect output. Ansys Fluent was used to analyze a Creo-designed jet nebulizer solid model. The Spraytec™ experimental method was utilized to characterize fluticasone propionate’s aerosol output and build the best nebulizer. Laser diffraction and computational fluid dynamics (CFD) analysis measured the nebulizer aerosol output. Comparing particle size data between 2 and 5 μm. The results are similar, with a difference of 4.20%. Taguchi optimization found the optimal process parameter, and a conformation test enhanced the process parameter. The nebulizer generates 8.57% more fluticasone propionate at optimal particle size. The optimized nebulizer generates aerosols reliably and speeds up patient recovery. [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]

Background & aims: Gold nanoparticles (AuNPs) are useful tools for noninvasive drug delivery. AuNP nebulization has shown poor deposition results, and AuNP tracking postadministration has involved methods inapplicable to clinical settings. The authors propose an intratracheal delivery method for minimal AuNP loss and computed tomography scans for noninvasive tracking. Materials & methods: Through high-frequency and directed nebulization postendotracheal intubation, the authors treated rats with AuNPs. Results & conclusion: The study showed a dose-dependent and bilateral distribution of AuNPs causing no short-term distress to the animal or risk of airway inflammation. The study demonstrated that AuNPs do not deposit in abdominal organs and show targeted delivery to human lung fibroblasts, offering a specific and noninvasive strategy for respiratory diseases requiring long-term therapies. This study presents an alternative method for drug delivery involving gold nanoparticle aerosolization directly into the major airways. Direct nebulization prevents particle loss and avoids drug administration through the blood. The particles can be detected successfully via upper body scans, which are noninvasive and allow for on-demand monitoring. Nanoparticles are flexible tools that can be modified to target specific cells of interest and can be excreted upon completion of their function. These results could represent an alternative method of drug administration in patients needing repeated cytotoxic therapies with known off-target effects. [ABSTRACT FROM AUTHOR]

Background: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. Objective: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. Design: A retrospective study. Methods: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 μg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV1 percentage predicted values (FEV1%pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV1 and/or FVC or >10% increase in FEV1%pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. Results: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV1 and increased FEV1 relative to the predicted value (ΔFEV1%pred) were significantly higher in patients >65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p > 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV1 (95% CI: 0.01-0.05, p = 0.004) and a 1.09% greater increase in ΔFEV1%pred (95% CI: 0.303-1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13-2.47, p = 0.009). Conclusion: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing. Plain language summary Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing Bronchodilator responsiveness testing is commonly undertaken as an important part of spirometry testing to determine the degree of volume and airflow improvement after bronchodilator administration. BDR testing results may affect patients' diagnosis and treatment. This study compared the effects of two delivery models (a metered dose inhaler (MDI) with spacer and nebulization) on responsiveness to bronchodilators and the results of bronchodilator responsiveness testing among patients with chronic obstructive pulmonary disease. We found that the increment in forced expiratory volume in one second were significantly higher in patients aged >65 years and in those with severe spirometric abnormalities in the nebulization group than in those in the MDI group. The study provides evidence that salbutamol delivered by a nebulizer is preferable to an MDI with spacer in patients >65 years and in those with severe spirometric abnormalities and could increase positive responsiveness to bronchodilators. The study will assist in clinical decision-making by selecting the appropriate dosing regimen for different patients. [ABSTRACT FROM AUTHOR]

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32–57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100–164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75–14] vs. 7 [4–13] days, OR (95% CI): 1.069 (1.003–1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies. [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]

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]

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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]

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]

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]

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]

Osimertinib (OB) is a third-generation irreversible tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), overexpressed in non-small cell lung cancer. Systemic administration of drug often results in poor drug levels at the primary tumor in the lungs and is associated with systemic side effects. In this study, we developed inhalable OB liposomes that can locally accumulate at the tumor site thereby limiting systemic toxicity. OB was loaded into liposomes via active and passive loading methods. The OB active liposomes achieved a higher encapsulation (78%) compared to passive liposomes (25%). The liposomes (passive and active) exhibited excellent aerosolization performance with an aerodynamic diameter of 4 µm and fine particle fraction of 82%. In H1975 cells, OB active and passive liposomes reduced IC50 by 2.2 and 1.2-fold, respectively, compared to free drug. As the OB active liposomes demonstrated higher cytotoxicity compared to OB passive liposomes, they were further investigated for in vitro anti-cancer activity. The OB active liposomes inhibited tumor cell migration and colonization as determined by the scratch assay and clonogenic assay, respectively. Furthermore, the 3D spheroid studies showed that the liposomes were successful in inhibiting tumor growth. These results highlight the potential of OB liposomes to suppress lung cancer. Owing to these attributes, the inhalable OB liposomes can potentially promote better therapeutic outcomes with limited systemic toxicity. [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]

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]