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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]

BACKGROUND: Little is known about the fate of expelled viral particulates during the aerosolization of inhaled medications during mechanical ventilation. We hypothesized that breathing patterns that generate a greater degree of shear stress and turbulent air flow will produce a greater concentration of exhaled viral RNA with the presence of a nebulizer during mechanical ventilation. METHODS: Eight ex vivo pig lungs were utilized as the physiological model. Each lung was dedicated to a specific breathing pattern that consisted of tidal breathing, respiratory distress, cough, and sneeze. Breath simulations were carried out through a commercial mechanical ventilator. Ninety mL of a bacteriophage stock at a concentration of 108 PFU/mL were introduced into the lungs during a 10-min sample collection session. The number of viral particles collected in exhalate was measured using quantitative polymerase chain reaction. The impact of breathing pattern on measured viruses was analyzed through two-way analysis of variance. RESULTS: The interaction effect between nebulization and breath pattern on exhaled viral quantity was not statistically significant P = .80, partial η² = 0.167. The analysis of the main effects indicated that the effects of the breathing pattern and nebulization phase were not statistically significant P = .26, partial η ² = 0.519; P = .98, partial η² = 0, respectively. There were no statistically significant differences among the breathing patterns related to measurable viral RNA. Coughing produced the most measurable increase in measured viral quantity during the nebulization phase and non-nebulization phase with a mean exhaled viral quantity (3.5 x 105 ng/μL [95% CI 1.6 x 105-5.5 x 105] and 2.7 x 105 ng/μL [95% CI 7.1 x 10³-5.5 x 105], respectively). Tidal breathing with the presence of a nebulizer and respiratory distress without a nebulizer produced the lowest measured viral quantities (M = 1.1 x 105 ng/μL [95% CI -1.7 x 105 to 3.9 x 105]; M = 1.2 x 105 ng/μL [95% CI -1.6 x 105 to 4.0 x 105]). CONCLUSIONS: In this ex vivo porcine model, the introduction of a nebulizer did not increase the mean viral RNA captured throughout all of the breathing patterns. [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]

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]

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

Pulmonary delivery of nintedanib has noticeable advantages over the current oral administration in managing idiopathic pulmonary fibrosis (IPF). However, it remains a challenge to construct an efficient lung delivery system for insoluble nintedanib to resist nebulization instabilities and alveolar macrophage clearance. Herein, we attempted to develop nintedanib as inhalable nanocrystals stabilized with polysorbates. Different types of polysorbates (polysorbate 20, 40, 60, 80) and various drug-surfactant molar ratios (DSR = 10, 30, 60) were screened to determine the optimal nintedanib nanocrystal formulation. Most formulations (except those stabilized by polysorbate 40) could tailor nintedanib nanocrystals with sizes around 600 nm, and the nebulization-caused drug loss could be significantly reduced when DSR increased to 60. Meanwhile, all nanocrystals boosted the in vitro drug dissolution rate and improved the aerosol performance of nintedanib. Although nebulization-caused particle aggregation was found in most formulations, the nanocrystal stabilized with polysorbate 80 at DSR 60 presented no apparent size change after nebulization. This formulation exhibited superior alveolar macrophage evasion, enhanced fibroblast cluster infiltration, and improved fibroblast cluster inhibition compared with other formulations, indicating its significant potential for pulmonary nintedanib delivery. Overall, this study explored the potential of polysorbates in stabilizing nintedanib nanocrystals for nebulization and proposed practical solutions to transfer nintedanib from oral to lung delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Icariin (ICA)-loaded DSPE-PEG2000/DPPC disk-like micelles were synthesized utilizing the thin film hydration method to enhance the solubility and delivery of ICA to the lungs. The micellar formulation significantly improved the water solubility of ICA. This was attributed to the high encapsulation efficiency (95 %) and drug loading capacity (12 %) of the DSPE-PEG2000/DPPC micelles. Comprehensive characterization using Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Particle size analysis through dynamic light scattering (DLS) and transmission electron microscopy (TEM) demonstrated the formation of stable micelles with an average particle size around 10 nm. In vitro aerosolization studies using the next-generation impactor (NGI) revealed that the fine particle fraction was 63.5 ± 4 %, which means that over 60 % of the aerosolized ICA/DSPE-PEG2000/DPPC micelles were capable of reaching and targeting the deep lung alveoli, indicating their potential efficacy for pulmonary delivery. Cytotoxicity assessments via the MTT assay showed IC50 values of ICA-loaded DSPE-PEG2000/DPPC micelles were 117 ± 8 μg/mL, 29 ± 3 μg/mL, and 21 ± 1 μg/mL at 24, 48, and 72 h, respectively, highlighting the time-dependent cytotoxic effects of the ICA-loaded micelles on A549 cells. However, the IC50 values of free ICA were > 500 μg/mL, 252 ± 3 μg/mL, and 109 ± 2 μg/mL, respectively at three different time points. That indicated that ICA-loaded nano micelles enhanced the cytotoxicity of ICA. Furthermore, the cellular uptake of the nano micelles by A549 cells was visualized and confirmed using EVOS fluorescence imaging and flow cytometry techniques. In addition, RAW 264.7 M2 polarization studies indicated ICA loaded DSPE-PEG2000/DPPC micelles have potential for treating pulmonary fibrosis. These findings suggest that DSPE-PEG2000/DPPC micelles significantly enhance the solubility and delivery of ICA, presenting a promising nanocarrier system for targeted pulmonary fibrosis therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The present study examined the duration of bronchodilation induced by nebulized glycopyrronium bromide (GB) and compared its effectiveness and incidence of any side effects with the combination of salbutamol and ipratropium bromide (SI) in critically ill mechanically ventilated chronic obstructive pulmonary disease (COPD) patients., Patients and Methods: This prospective, observational study was conducted in mechanically ventilated adult patients of COPD (18-75 years). Data of two groups of patients were collected for 12 hours each for three consecutive days after the nebulization - Group I: those who received 25 µg of GB, and Group II: those who received 1.25 mg of levo-salbutamol and 500 µg of ipratropium by nebulization., Results: A significantly higher number of patients in group II had copious secretions. The mean static compliance was comparable at all time intervals, whereas the mean airway pressure was significantly lower in group II from 15 minutes to 4 hours post-nebulization. In group I, the onset of bronchodilation was 30 minutes on days 1 and 3, and 60 minutes on day 2, whereas, in group II, it was 60 minutes on days 1 and 2 and 30 minutes on day 3. In group I, bronchodilation was 10 hours on day 1 and 12 hours each on days 2 and 3, whereas in group II, bronchodilation was 4 hours on day 1 and 6 hours each on day 2 and 3., Conclusion: Compared with SI, GB nebulization resulted in lesser respiratory secretions, a longer duration of action in terms of lowered airway resistance, and no adverse effects like hypertension, tachycardia, or desiccation of respiratory secretions., How to Cite This Article: Priya P, Nath SS, Kumar V, Kumar S. Comparison of Nebulized Glycopyrronium with a Combination of Salbutamol and Ipratropium on Ventilatory Parameters in Critically Ill Mechanically Ventilated Patients of Chronic Obstructive Pulmonary Disease: An Observational Study. Indian J Crit Care Med 2024;28(10):963-969., Competing Interests: Source of support: Nil Conflict of interest: None Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.Conflict of interest: None, (Copyright © 2024; The Author(s).)

Background Tonsillectomy is associated with significant pain, and postoperative pain control is often unsatisfactory. There have been several methods adopted to treat postoperative pain, but none of the methods were effective, with patients continuing to undergo severe postoperative pain. Hence, our study aimed to compare the efficacy of pre-emptive nebulized ketamine versus pre-emptive nebulized lidocaine with a control group receiving nebulized saline for pain control in children undergoing tonsillectomy. Methods In this prospective randomized clinical trial, 105 patients with American Society of Anesthesiologists (ASA) Ⅰ and Ⅱ undergoing tonsillectomy were enrolled and randomized into three groups, group K, group L, and group C, with 35 patients in each group, wherein pre-emptive nebulized ketamine, lidocaine, and saline were given to each group of patients, respectively. Faces Pain Scale-Revised (FPS-R), sedation scale scores, and the usage of rescue analgesia were noted postoperatively for the first six hours. Hemodynamic parameters were noted before and after nebulization. The primary objective was to determine the number of patients requiring rescue analgesia as an indicator of postoperative pain control. Results In this randomized clinical trial, pre-emptive nebulized ketamine significantly reduced the need for rescue analgesia compared to lidocaine and saline (p<0.05). Only 14.3% (n=5) of patients in the ketamine group required rescue analgesia compared to 85.7% (n=30) in the lidocaine group and 91.4% (n=32) in the control group. Nebulized ketamine given pre-emptively is an effective strategy for reducing postoperative pain in pediatric tonsillectomy. Conclusion Pre-emptive nebulized ketamine was found to be effective when compared with lidocaine nebulization in reducing postoperative pain in children undergoing tonsillectomy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Shri B M Patil Medical College Hospital and Research Centre issued approval BLDE (DU)/IEC/782/2022-23. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Seetharamaraju et al.)

Phages are known as a promising method to combat antimicrobial resistance (AMR) in the human and veterinary sector. Use of phage aerosols enormously increases the application field, although the impact on the infectivity of phages during nebulization needs to be evaluated. In this study S. infantis was treated on plates and chicken skin with nebulized phage particles of the Myoviridae type, identified by transmission electron microscopy, using a commercial nebulizer primarily used for H 2 O 2 disinfection. The reduction of bacterial number by aerosol applied phage particles was evaluated. It could clearly be shown that the phage particles were able to infect Salmonella after being nebulized using ultrasound technology. Further studies on other types of phages as well as other conditions must be performed to standardize the aerosolic application of phages., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Background: Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration., Methods: Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored., Findings: Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy., Conclusions: Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation., Funding: This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation., Competing Interests: Declaration of interests P.D.-C. is cofounder of Evolving Therapeutics SL and a member of its scientific advisory board, and P.E.T. is cofounder of Felix Biotechnology, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To study the efficacy of oxygen atomization inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) for preventing oral mucositis in patients following hematopoietic stem cell transplantation., Methods: Data from patients who received hematopoietic stem cell transplantation and were treated with GM-CSF for the prevention/treatment of oral mucositis in our hospital from June 2021 to June 2023 were collected. The enrolled patients were divided into an observation group and a control group according to the use of GM-CSF. The WHO Mucositis Scale Assessment Criteria were utilized to evaluate the characteristics of patients with oral mucositis (OM) from the beginning of the pretreatment period until they were discharged from the hospital. The general data, preconditioning protocol, transplantation method, overall grade and duration of oral mucositis, pain score, nutritional score and number of days of parenteral nutrition use, oral mucosal infection status and antibiotic use intensity, the granulocyte and megakaryocyte reconstruction time, and adverse reaction reports of the patients were collected and summarized through the medical records system., Results: A total of 143 patients were included in this study, including 75 patients in the observation group. In the observation group, there were 36 males and 39 females aged 22-67 years. There were 45 patients who received autologous transplantation and 30 patients who received allogeneic transplantation. In terms of the disease distribution, there were 33 cases of leukemia, 24 cases of lymphoma, 11 cases of multiple myeloma, and 8 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 2 cases of myelofibrosis, 1 case of POEMS syndrome). There were 68 patients in the control group, including 33 males and 35 females; the control group patients were aged 25-74years. Forty-one patients received autologous transplantation, and 27 patients received allogeneic transplantation. The disease distribution included 29 cases of leukemia, 17 cases of lymphoma, 12 cases of multiple myeloma, and 7 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 1 case of myelofibrosis, 1 case of POEMS syndrome). There were no significant differences between the two groups concerning age, sex, disease distribution or the transplantation method (P > 0.05). In the observation group, 13 cases did not develop oral mucositis, and 32 cases developed oral mucositis (16 cases of Grade I, 14 cases of Grade II, 2 cases of Grade III, and 0 cases of Grade IV). In the control group, there were 5 cases without mucositis and 36 cases with oral mucositis (6 cases of Grade Ⅰ, 16 cases of Grade Ⅱ, 8 cases of Grade Ⅲ, and 6 cases of Grade Ⅳ), the difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). In the observation group, 8 patients did not develop oral mucositis, and 22 patients developed oral mucositis (13 cases of Grade I, 7 cases of Grade II, 1 case of Grade III, and 1 case of Grade IV). In the control group, 1 case did not develop mucositis, and 26 cases developed oral mucositis (3 cases of Grade Ⅰ, 10 cases of Grade Ⅱ, 9 cases of Grade Ⅲ, and 4 cases of Grade Ⅳ). The difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral mucosal infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). No adverse reactions were reported in either group., Conclusion: In both autologous transplantation and allogeneic transplantation patients, GM-CSF atomized inhalation can improve the prevention and treatment of oral mucositis in stem cell transplantation patients, reduce the incidence of oral infection, reduce the intensity of antibiotic use and the number of days of parenteral nutrition use, and thus promote the process of hematopoietic reconstruction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The delivery of mRNA into the lungs is the key to solving infectious and intractable diseases that frequently occur in the lungs. Since inhalation using a nebulizer is the most promising method for mRNA delivery into the lungs, there have been many attempts toward adapting lipid nanoparticles for mRNA inhalation. However, conventional lipid nanoparticles, which have shown great effectiveness for systemic delivery of mRNA and intramuscular vaccination, are not effective for pulmonary delivery due to their structural instability during nebulization and their inability to adapt to the pulmonary microenvironment. To address these issues, we developed an ionizable liposome-mRNA lipocomplex (iLPX). iLPX has a highly ordered lipid bilayer structure, which increases stability during nebulization, and its poly(ethylene glycol)-free composition allows it to infiltrate the low serum environment and the pulmonary surfactant layer in the lungs. We selected an inhalation-optimized iLPX (IH-iLPX) using a multistep screening procedure that mimics the pulmonary delivery process of inhaled nanoparticles. The IH-iLPX showed a higher transfection efficiency in the lungs compared to conventional lipid nanoparticles after inhalation with no observed toxicity in vivo . Furthermore, analysis of lung distribution revealed even protein expression in the deep lungs, with effective delivery to epithelial cells. This study provides insights into the challenges and solutions related to the development of inhaled mRNA pulmonary therapeutics.

Disulfiram (DS) has an excellent anti-viral activity; however, its low water-solubility and first-pass metabolism are limiting its clinical applications. Cyclodextrins (CDs) have been used as solubility enhancers and carriers of DS proposed for inhalation to treat SARS-CoV-19. Two types of CDs (hydroxypropyl β-cyclodextrin and sulfobutyl ether β-cyclodextrin) were used to form inclusion complexes with DS, and drug solubility was assessed using spectrophotometric analytical method. Formulations were freeze-dried and characterized using DSC, TGA and FTIR. Nebulization technique was used to assess the potential for generating aerosols. All inclusion complexes are proved to be suitable for inhalation, therefore, potentially effective therapy for further investigation against SARS-CoV-19 is shown.

Objective: To compare the effects of nebulized Ketamine versus nebulized Magnesium Sulfate to prevent post-operative sore throat. Study Design: Quasi-Experimental Study. Place and Duration of Study: Department of Anaesthesia, Combined Military Hospital, Rawalpindi Pakistan, from Sep 2020 to Feb 2021. Methodology: A total of 154 patients who underwent general anaesthesia for elective procedures were randomly included in the study. These patients were divided into two equal Groups, i.e., Group-A (n=77), who received Magnesium Sulphate 250mg in 5ml saline and Group-B (n=77), who received Ketamine 50mg in 5ml saline, respectively. The effects of nebulized Ketamine versus nebulized Magnesium Sulfate to prevent post-operative sore throat, were observed in both the Groups. Results: Both drugs were effective in the prevention of sore throat after extubation. Our study showed that Ketamine nebulization was more effective than Magnesium Sulfate nebulization in preventing sore throat. The frequency of sore throat in Group-A was 54.5% (42 out of 77 patients) as compared to 31.2% (24 out of 77 patients) in Group-B, which was statistically significant (p=0.003). Conclusion: Post-operative sore throat is more effectively controlled with Ketamine as compared to Magnesium Sulfate

The objective of this study was to determine the extent that nebulized glycosylated caffeic acid phenylether ester-4-O-alpha-D-glucopyranoside (G-CAPE) attenuates particulate-induced airway inflammation in healthy horses. Our hypothesis was that nebulization with G-CAPE would result in improved respiratory scores, higher arterial oxygen partial pressure, and less inflammatory airway infiltrates in horses with induced airway inflammation, compared with untreated controls. Five healthy adult horses were housed inside a climate controlled, closed barn on straw bedding and fed ad lib moldy grass hay for 16 days to induce airway inflammation. An experimental crossover study was performed in which animals were treated with 200 mg G-CAPE dissolved in 45 mL of 10% triethanolamine (G-CAPE group) or 45 mL of 10% triethanolamine (CONTROL group), and clinical respiratory scoring, arterial blood gases, and bronchoalveolar lavages (BALs) were collected at predetermined time points up to 24 h post nebulization. While the mean neutrophil percentage decreased in treated horses compared to controls (9.3 ± 2.0 and 16.9 ± 2.4, respectively) at 6 hours post treatment (t = 6 h), the difference did not achieve statistical significance (p = 0.1154). Blood gas analysis did not differ significantly between groups. There was a significant difference in the mean respiratory scores of G-CAPE-treated horses between baseline and at 1-h post treatment (from 3.2 ± 0.7 to 1.6 ± 0.7, p = 0.0013). This study demonstrates that a single nebulized dose of G-CAPE decreased clinical respiratory scores 1 h post administration and decreased BAL percentage of neutrophils 6 h post administration in horses with particulate induced airway inflammation. This compound shows promise as an anti-inflammatory and warrants further investigation.

Objective: To compare the outcome of Salbutamol nebulization with normal saline (placebo) in transient tachypnea of the newborn. Study Design: Comparative prospective study. Place and Duration of Study: Department of Neonatal Medicine, Military Hospital Rawalpindi, from Jan 2017 to Mar 2018. Methodology: Sixty term neonates with respiratory rate >60 breaths/min and transient tachypnea of newborn score of ≥4 were enrolled. They were randomly allocated to two equal groups. Group-1 received Salbutamol nebulization (0.15 mg/kg) while Group-2 received normal Saline (placebo) nebulization. Results: The mean gestational age was 38.31±1.28 weeks, while the average birth weight was 2.97±0.27 kg. The mean change in transient tachypnea of newborn score with Salbutamol nebulization was 5.63±1.22, while 0.63±1.54 with normal Saline nebulization. Likewise, the mean change in respiratory rate with Salbutamol was 9.80±2.05, while -3.73±2.57 with normal saline. Conclusion: This study demonstrated nebulized Salbutamol as an effective tool in reversing transient tachypnea of newborns with decreasing respiratory rate compared to normal saline nebulization (placebo).

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.

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]

Background: Bronchiolitis is the most common lower respiratory tract infection in children. The management guidelines recommend only supportive measures; however, there is an increasing burden for bronchiolitis especially in developing countries. The use of nebulized hypertonic saline may aid in decreasing hospital stay and decrease the global burden of the disease.Objective: To compare between the efficacy of hypertonic saline versus normal saline in reducing duration of hospital admission and improving symptoms of acute bronchiolitis.Patients and methods: A randomized comparative clinical trial included 90 children with acute bronchiolitis, conducted at Al-Azhar University Hospital (New Damietta) during the period from October 2019 till June 2020. Patients were randomly assigned into 2 groups; 45 patients received 3% hypertonic saline nebulization (group 1), and 45 patients received 0.9% normal saline nebulization (group 2). Efficacy of treatment was assessed through duration of hospitalization and oxygen supplementation, and severity of respiratory distress.Results: there was no significant difference between both groups as regard to age, sex, baseline clinical severity score and O2 saturation. After treatment, patients who received nebulized hypertonic saline showed less duration of hospitalization (62.3±20.8 hours vs 76.8± 26.1 hours; p=0.001), less duration of O2 therapy (16.2±6.0 hours vs 25.3±5.4 hours; p=0.01). As regard to severity clinical score, patients received nebulized hypertonic saline showed significant improvement started within 24 hours from admission (P=

After shifting away from invasive mechanical ventilation and intratracheal instillation of surfactant toward non-invasive ventilation with nasal CPAP and less invasive surfactant administration in order to prevent bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome, fully non-invasive surfactant nebulization is the next Holy Grail in neonatology. Here we review the characteristics of animal-derived (clinical) and new advanced synthetic lung surfactants and improvements in nebulization technology required to secure optimal lung deposition and effectivity of non-invasive lung surfactant administration. Studies in surfactant-deficient animals and preterm infants have demonstrated the safety and potential of non-invasive surfactant administration, but also provide new directions for the development of synthetic lung surfactant destined for aerosol delivery, implementation of breath-actuated nebulization and optimization of nasal CPAP, nebulizer circuit and nasal interface. Surfactant nebulization may offer a truly non-invasive option for surfactant delivery to preterm infants in the near future.

Abstract The coronavirus disease 2019 (COVID‐19) pandemic has become a serious burden on global public health. Although therapeutic drugs against COVID‐19 have been used in many countries, their efficacy is still limited. We here reported nanobody (Nb) phage display libraries derived from four camels immunized with the SARS‐CoV‐2 spike receptor‐binding domain (RBD), from which 381 Nbs were identified to recognize SARS‐CoV‐2‐RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin‐converting enzyme 2 (ACE2) with SARS‐CoV‐2‐RBD variants and two Nbs blocked the interaction of human ACE2 with bat‐SL‐CoV‐WIV1‐RBD and SARS‐CoV‐1‐RBD. Among these candidates, Nb11‐59 exhibited the highest activity against authentic SARS‐CoV‐2 with 50% neutralizing dose (ND50) of 0.55 μg/ml. Nb11‐59 can be produced on large scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11‐59 might be a promising prophylactic and therapeutic molecule against COVID‐19, especially through inhalation delivery.

Abstract Background and Aims Postoperative sore throat (POST) is common after endotracheal intubation making patients uncomfortable and anxious in postoperative period. The present study was undertaken to compare efficacy of equal dose of dexamethasone in preventing POST via three different routes, i.e., intravenous, topical, and nebulization before surgery. Methods and Results The present prospective double-blind randomized parallel group trial included 190 patients of either sex above 18 years, American Society of Anesthesiologists (ASA) physical status I–II posted for laparoscopic cholecystectomy. The patients were divided into three groups. Patients in group N were nebulized with 8 mg dexamethasone prior to surgery, patients in group I received intravenous dexamethasone (8 mg) before induction of anesthesia, while patients in group C were intubated with endotracheal tube which was pretreated (cuff soaked in dexamethasone 8 mg). The severity of POST and hoarseness of voice was determined by interviewing patients after 24-h of completion of surgery. Incidence of POST decreased in all patients with maximum decrease in group N (18%), while 30.8% in group I and 30.4% in group C. This decrease was not statistically significant when compared to group I (p 0.14) as well as group C (p 0.15). Incidence of hoarseness significantly decreased in group N (15.6%) as compared to group I (40.3%) as well as group C (39.1%). This decrease was statistically significant when compared to group I (p 0.005) as well as group C (p 0.009). Conclusions Topical dexamethasone (group C) is as effective as intravenous dexamethasone in decreasing incidence of POST, while both the techniques are not effective in decreasing hoarseness of voice. Nebulization is most effective method in decreasing POST as well as hoarseness. Trial Registration CTRI/2017/08/009524 dated 29 August 2017 prospectively.

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.

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.

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: Bronchiolitis is a common cause of illness and hospitalization in infants and young children. The effectiveness of various bronchodilators remains unclear. This study was conducted to assess the efficacy of nebulized magnesium sulfate in hospitalized children with moderate bronchiolitis in the age group of 1-24 months. Subjects and Methods: This was a prospective observational study done from December 2018 to June 2020. All children with moderate bronchiolitis (clinical severity score [CSS]-4-8) meeting inclusion/exclusion criteria were enrolled. A detailed history, demographic profile, CSS and oxygen saturation in room air, and heart rate were recorded. They were given two doses of magnesium sulfate in the form of nebulization for 10 min each, at 30 min apart. The children were assessed for CSS at 0 h, 1 h, and 4 h after nebulization. The children were considered improved if CSS <4 at the end of 4 h. The children were monitored for adverse reactions of magnesium sulfate. Results: Sixty children were enrolled. The mean age was 7.5 ± 6.47 months. Most children (51.7%) were in 1-6 months. The mean CSS scores at 0 h, 1 h, and 4 h were 6 ± 1.008, 2.95 ± 1.395, and 2.40 ± 1.564, respectively (P = < 0.001). Fifty-three (88.3%) children improved and seven (11.7%) children did not improve. In nonimproved group, subanalysis was done and found hypoxia (odds ratio - 12.6) as a significant risk factor. Flushing was the most common adverse effect noticed in eight (13.3%) children. Conclusions: Children with moderate bronchiolitis were improved with nebulized magnesium sulfate. [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]

We analyze changes in circulating platelets in COVID-19 positive patients who received conventional treatment Dexamethasone and Enoxaparin (Dexa-Enoxa) compared to patients treated with conventional therapy plus nebulization with alkaline hypertonic ibuprofenate (AHI). Results show that after 24 h of nebulization with AHI, circulating platelets shows an increase about 40% at 24 h and reach 65% at 96 h. In patients with platelets content below 200,000 by microliter the increase was 49% and 79% at 24 and 96 h respectively. In patients with platelets above 200,000 by microliter the increase was 24% and 31% at 24 and 96 h, respectively. The increase of platelets via AHI was similar in both, men and women. To evaluate whether this action of AHI was related to platelets from COVID-19 positive patients or also for healthy people, two controls were included: one of them with 10 healthy volunteers and another one with COVID-19 positive patients hospitalized and treated only with Dexa-Enoxa. Results show that, in healthy volunteers, the number of circulating platelets remains unchanged even after 7 days of treatment with AHI. In COVID-19 positive patients treated only with Dexa-Enoxa for 4 days, platelets increased only 16%. [ABSTRACT FROM AUTHOR]

Background: Endotracheal intubation is the prominent cause of airway mucosal injury which results in postoperative sore throat (POST), with an incidence of 21%-65% if left unresolved, it produces significant agony and annoyance to the patient. Objective: The aim of the present study was to compare the hemodynamic effect of nebulized dexamethasone and nebulized ketamine on postoperative sore throat after thyroid surgeries. Patients and methods: This prospective controlled randomized double-blind study was carried out in Zagazig University Hospitals during the period from January to July 2021, included 72 patients of both gender in the age group 21-50 years, undergoing thyroidectomy under general anesthesia. Results: There was statistically significant increase of the severity and incidence of sore throat in the control groups immediately postoperatively, 2, 6, 12 and 24 hours postoperatively among the studied groups. While, there was significant difference between dexamethasone groups and ketamine group regarding the severity and incidence of sore throat immediatley, 2, and 6 hours (hr) postoperatively. Conclusions: We concluded that nebulized dexamethsone may be considered as a safe alternative to nebulized ketamine for decreasing POST. [ABSTRACT FROM AUTHOR]

The favipiravir proliposomal is a powder formulation for pulmonary delivery by nebulization, prepared and characterized by film deposition on carrier method. The formulations have good flow properties and upon hydration, liposome vesicles were seen within 2-3 minutes. According to the results of SEM studies the surface morphology was coarse and non-porous. The DSC and XRD studies confirm that the favipiravir drug is crystalline, whereas the FPL6 is amorphous. In-vitro nebulization studies performed using a twin stage impinger (TSI) revealed that the nebulization time ranges from 12.95 to 14.3 minutes. The aerosol mass output and rate ranges from 44.31 to 54.28 %, and 0.17 to 0.22 mg/min. respectively. The respirable fraction ranges from 8.14 to 12.31%. The FPL6 formulation has a higher respirable fraction of 12.31%, which is available for therapeutic action in the lungs and stable. The results showed that the favipiravir proliposomal formulation was suitable for pulmonary drug delivery via nebulization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted clinical interest in recent years. However, both HFNC and nebulization are categorized as aerosol-generating procedures (AGPs). In vitro studies raised concerns that AGPs had high transmission risk. Very few in vivo studies examined fugitive aerosols with nebulization via HFNC, and effective methods to mitigate aerosol dispersion are unknown. METHODS: Two HFNC devices (Airvo 2 and Vapotherm) with or without a vibrating mesh nebulizer were compared; HFNC alone, surgical mask over HFNC interface, and HFNC with face tent scavenger were used in a random order for 9 healthy volunteers. Fugitive aerosol concentrations at sizes of 0.3-10.0 lm were continuously measured by particle sizers placed at 1 and 3 ft from participants. On a different day, 6 of the 9 participants received 6 additional nebulizer treatments via vibrating mesh nebulizer or small-volume nebulizer (SVN) with a face mask or a mouthpiece with/without an expiratory filter. In vitro simulation was employed to quantify inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 and Vapotherm. RESULTS: Compared to baseline, neither HFNC device generated higher aerosol concentrations. Compared to HFNC alone, vibrating mesh nebulizer via Airvo 2 generated higher 0.3-1.0 lm particles (all P < .05), but vibrating mesh nebulizer via Vapotherm did not. Concentrations of 1.0-3.0 lm particles with vibrating mesh nebulizer via Airvo 2 were similar with vibrating mesh nebulizer and a mouthpiece/face mask but less than SVN with a mouthpiece/face mask (all P < .05). Placing a surgical mask over HFNC during nebulization reduced 0.5-1.0 lm particles (all P < .05) to levels similar to the use of a nebulizer with mouthpiece and expiratory filter. In vitro the inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 was 6 6 times higher than vibrating mesh nebulizer via Vapotherm. CONCLUSIONS: During aerosol delivery via HFNC, Airvo 2 generated higher inhaled dose and consequently higher fugitive aerosols than Vapotherm. Simple measures, such as placing a surgical mask over nasal cannula during nebulization via HFNC, could effectively reduce fugitive aerosol concentrations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ribavirin is an antiviral drug that for many years has been administered to the lungs by aerosolization. Despite advancements in oral delivery routes, there has been a renewed interested in delivering ribavirin via the pulmonary system in select patients and the severely ill. The vibrating mesh nebulizer was previously demonstrated to be an effective alternative to the small-particle aerosol generator in particle size, chemical makeup, and concentrations of the ribavirin before and after nebulization. However, the antiviral activity of ribavirin has never been examined. We sought to study ribavirin's activity before and after nebulization via vibrating mesh nebulizer. METHODS: We grew and infected human epithelial type 2 cells and primary airway epithelial cells with respiratory syncytial virus (RSV). We then compared the antiviral effect of non-nebulized (control) and aerosolized ribavirin to untreated controls. We used traditional plaque assay and real-time polymerase chain reaction to determine the quantity of virus. RESULTS: Both non-nebulized (control) and nebulized ribavirin reduced the size of RSV plaques compared to untreated controls. Additionally, the non-nebulized and nebulized ribavirin equally inhibited RSV replication. There were no statistically significant differences between the non-nebulized and nebulized ribavirin across all time points. CONCLUSIONS: The vibrating mesh nebulizer did not affect the antiviral properties of nebulized ribavirin when compared to non-nebulized drug. Our findings add supporting evidence for the use of the vibrating mesh nebulizer in the administration of inhaled ribavirin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo and mitigation of aerosol dispersion into the environment with various commercially available devices are not known. METHODS: Nine healthy volunteers were given 3 mL saline with a small-volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved face mask for VMN, and a face mask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room with 2 particle counters positioned 1 and 3 ft from participants measuring aerosol concentrations at sizes of 0.3-10.0 lm at baseline, before, during, and after each treatment. RESULTS: Fugitive aerosol concentrations were higher with SVN than VMN and higher with a face mask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 lm in size for VMN and 0.3-3.0 lm for SVN (all P < .05). An Exhalo scavenger over the mask reduced 0.5-3.0 lm sized particle concentrations for SVN (all P < .05) but not VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosol concentrations regardless of the nebulizer type. CONCLUSIONS: SVN produced higher fugitive aerosol concentrations than VMN, whereas face masks generated higher aerosol concentrations than mouthpieces. Adding an exhalation filter to the mouthpiece or a scavenger to the face mask reduced aerosol concentrations for both SVN and VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosols as effectively as a mouthpiece with an exhalation filter. This study provides guidance for reducing fugitive aerosol emissions from nebulizers in clinical practice. [ABSTRACT FROM AUTHOR]

The Northwestern pond turtle (Actinemys marmorata) is native to Washington State, USA and has developed a grossly evident form of shell disease affecting a large percentage of the free-ranging population in this state. Emydomyces testavorans is a novel fungus in the order Onygenales that is the presumed causative agent for shell disease in the Northwestern pond turtle. Terbinafine hydrochloride is a lipophilic allylamine broad-spectrum antifungal that penetrates keratin and concentrates in the stratum corneum. This study evaluated the drug concentration in the plasma and keratin of 18 Northwestern pond turtles after nebulization with 18 mg terbinafine solution (2 mg/ml) once a day for 28 days. Blood and keratin samples were collected serially during the course of treatment, and for 14 days following the last dose. Plasma and keratin were analyzed by high-performance liquid chromatography. No significant concentrations of terbinafine were found in the plasma of the turtles. Terbinafine in turtle keratin peaked after 16 days of treatment and maintained therapeutic concentrations for 14 days posttreatment. Turtle shell lesions also showed signs of clinical improvement posttherapy. Nebulization of terbinafine is recommended for the treatment of shell disease secondary to Emydomyces testavorans; however, pulse antifungal therapy is likely needed to prevent disease from reoccurring. [ABSTRACT FROM AUTHOR]

Inhalation therapy is the cornerstone of chronic obstructive pulmonary disease (COPD) management. However, for many COPD patients who are managed at home, nebulization therapy offers an effective alternative treatment and fulfills the gap of catering to the specific population of patients who are unable to use handheld inhaler devices appropriately. The present review highlights key aspects, namely selection of the right beneficiaries for home nebulization, available drugs in nebulized formulations for the treatment of COPD, and the importance of care, cleaning, and maintenance, which are prerequisites for ensuring successful nebulization therapy.

Administration of sub-dissociative doses of ketamine is used via intranasal (IN) and intravenous routes in the pediatric emergency department for managing acute pain. Due to difficulties in both obtaining intravenous access and compliance with IN medications in children, administration of ketamine via breath-actuated nebulizer can serve as a valuable modality for timely analgesia in children where dosing titration is patient controlled. We describe five pediatric patients who received ketamine via breath-actuated nebulizer at 0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg, with all patients experiencing a decrease in pain score. This case series introduces ketamine inhalation as a modality for managing pain in children.

Intro duction: Awake fiberoptic bronchoscope-guided intubation is the preferred airway management strategy in a patient with a difficult airway and limited mouth opening. The aim is to compare the efficacy of nebulization and airway nerve block using lignocaine to provide airway anesthesia in awake patients using fiberoptic bronchoscope for nasal intubation to make the patient comfortable, cooperative, and agreeable. Methods: In this randomized, prospective, single-blinded study, sixty adult patients scheduled for oral cancer surgeries were divided into two equal groups. Nebulization with 4% lignocaine (10 ml) was performed in Group N, and superior bilateral laryngeal and trans-laryngeal recurrent laryngeal nerve blocks used 2% lignocaine (2 ml) were given in Group B. Nasotracheal intubation using fiberoptic bronchoscope were performed. Intravenous midazolam and fentanyl were used for sedation and analgesia. We recorded the ease of intubation, coughing episodes, vocal cord status, hemodynamic variables, patient recall, and lignocaine toxicity. Student's t-test and Chi-square tests were used for appropriate data. Statistical significance was considered for P < 0.05 (SPSS Version 20, IBM, USA). Results: The intubation time was shorter with better intubating conditions in Group B (120.3 ± 42.6 s) than Group N (200.4 ± 60.3 s) (P < 0.001). Cough severity and patient recall for untoward effects were lower in Group B. Intubation were done successfully in all patients. Conclusion: Airway nerve blocks provided better airway anesthesia characterized by easier fiberoptic intubation and patient comfort than lignocaine nebulization. Nebulization can be considered a suitable alternative when nerve blocks are not feasible due to distorted neck anatomy.

Abstract Background Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients. Results In this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33). Conclusion In adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube. Trial registration Clinicaltrials.gov Identifier: NCT02159196

Background: Foreign body aspiration in pediatrics is usually managed by rigid bronchoscopy, which is associated with plenty of adverse events. Objective: We tried to compare the effect of nebulized saline, lidocaine or combined lidocaine with epinephrine on postoperative respiratory complications. Patients and methods: This prospective study included 90 children, who were divided into three groups according to the nebulized solution; NS group (normal saline 0.9%), L group (lidocaine 1% 4 mg.kg-1) and LA group [4 mg.kg-1 lidocaine 1% and adrenaline (1:1000) 3 mg). Our primary outcome was the incidence of post-operative respiratory complications, while the secondary ones included hemodynamic changes and the incidence of intraoperative cough or desaturation. Results: All pre-procedural data were insignificant among the three groups. The LA group expressed higher heart rates, while the L group showed a significant reduction when compared to NS group. Propofol consumption showed a significant decline in two studied groups compared to the NS group. Intraoperative cough was higher in NS group in comparison to L and LA groups. Although, intraoperative desaturation per case along with post-operative sedation showed no significant difference among the three groups, post-operative cough frequency attacks and severity were higher in NS group when compared to L and LA group and when L group were compared to LA group. Postoperative stridor was insignificant among the three groups. Conclusion: Nebulized lidocaine/adrenaline combination is appropriate option to achieve proper intraoperative sedation and upper airway conditions with reduction of post-operative negative respiratory outcomes together with minor hemodynamic changes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whereas high-flow nasal cannula (HFNC) oxygen therapy is increasingly used in patients with exacerbation of COPD, the effectiveness of β2 agonist nebulization through HFNC has been poorly assessed. We hypothesized that salbutamol vibrating-mesh nebulization through HFNC improves pulmonary function tests in subjects with COPD. METHODS: We conducted a physiological crossover study including subjects admitted to the ICU for severe exacerbation of COPD. After subject improvement allowing a 3-h washout period without bronchodilator, pulmonary function tests were performed while breathing through HFNC alone and after salbutamol vibrating-mesh nebulization through HFNC. The primary end point consisted in the changes in FEV1 before and after salbutamol nebulization. Secondary end points included the changes in FVC, peak expiratory flow (PEF), airway resistance, and clinical parameters. RESULTS: Among the 15 subjects included, mean (SD) FEV1 significantly increased after salbutamol nebulization from 931 mL (383) to 1,019 (432), mean difference +87 mL (95% CI 30-145) (P 5 .006). Similarly, FVC and PEF significantly increased, +174 mL (95% CI 66-282) (P 5 .004) and +0.3 L/min (95% CI 0-0.6) (P 5 .037), respectively. Airway resistances and breathing frequency did not significantly differ, whereas heart rate significantly increased after nebulization. CONCLUSIONS: In subjects with severe exacerbation of COPD, salbutamol vibrating-mesh nebulization through HFNC induced a significant bronchodilator effect with volume and flow improvement. [ABSTRACT FROM AUTHOR]

[Display omitted] Peritoneal metastasis is an advanced cancer type which can be treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Here, chemotherapeutics are nebulized under high pressure in the intraperitoneal (IP) cavity to obtain a better biodistribution and tumor penetration. To prevent the fast leakage of chemotherapeutics from the IP cavity, however, nebulization of controlled release formulations is of interest. In this study, the potential of the thermosensitive hydrogel Pluronic F127 to be applied by high pressure nebulization is evaluated. Therefore, aerosol formation is experimentally examined by laser diffraction and theoretically simulated by computational fluid dynamics (CFD) modelling. Furthermore, Pluronic F127 hydrogels are subjected to rheological characterization after which the release of fluorescent model nanoparticles from the hydrogels is determined. A delicate equilibrium is observed between controlled release properties and suitability for aerosolization, where denser hydrogels (20% and 25% w/v Pluronic F127) are able to sustain nanoparticle release up to 30 h, but cannot effectively be nebulized and vice versa. This is demonstrated by a growing aerosol droplet size and exponentially decreasing aerosol cone angle when Pluronic F127 concentration and viscosity increase. Novel nozzle designs or alternative controlled release formulations could move intraperitoneal drug delivery by high pressure nebulization forward. [ABSTRACT FROM AUTHOR]