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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.

Sustainability has emerged as a key concept in the modern techniques of washing and treating denim. The clothing industry, specifically the denim washing sector, confronts substantial sustainability issues due to its impact on water pollution and the generation of large quantities of chemical waste. This research aims to investigate the long-term sustainability of the nebulization process in the context of denim finishing. The goal is to assess the dependability of the technology as a feasible option by demonstrating its effectiveness using environmental impact measuring software. The environmental impact assessment assesses the ecological consequences of clothing across four fundamental areas: water usage, chemical utilisation, energy consumption in the production process, and labour implications. The aforementioned methods proved to have low energy and water demands, resulting in less waste and pollution. This study evaluated several aspects of nebulization on denim and concluded that nebulization is a beneficial method for applying eco-friendly finishing.

Abstract 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. Graphical Abstract

Abstract Background The purpose of the study is to analyse the effects of different inhaled asthma medications (IAMs) on the color change of dental restorative materials (DRMs). Methods In total, 192 samples were taken from six different DRMs: [Filtek Z550 (nanohybrid composite), Fusio Liquid Dentin (Self-adhering flowable composite), Filtek Ultimate (nanofilled flowable composite), Dyract XP (compomer), Fuji II LC (resin-modified glass ionomer), Fuji IX Fast (self-cured-packable glass ionomer), (n = 32)]. After the initial color values (CIELab) of DRMs were measured by using a spectrophotometer, each sample was exposed to the same IAMs via nebulizer according to the four different inhaled therapies and measurements were repeated on the 7th & 21st days. Results In all IAM groups, DRM with the least amount of ΔE was nanohybrid composite, while the highest ΔE was found in Fuji II LC. Among all experimental groups, only Fuji II LC which was administered the combined medication, exceeded the clinically unacceptable threshold (ΔE = 3.3) on 7th & 21st days. Conclusions Consequently, important factors affecting the susceptibility to color stability are the type of IAMs, the administration time-dosage, and the type of DRMs.

Particulate matter (PM) present in the air pollution increases morbidity and mortality due to several reasons. The dataset presents a comparative analysis of nebulization process of Fe2O3 and SiO2 nanoparticles or crude PM (NIST1648a) and that with reduced content of organic matter (LAp120). Nebulization tests were carried out to determine concentrations of nanoparticle and PM suspensions, in order to create an atmosphere with a concentration of PM particles about 1000 µg/m3 of air in the exposure chambers. It is important to properly recreate environmental conditions during further research on animals. The absorbance spectrum of the suspensions of the tested materials was measured in the range of 300–700 nm. The changes in the absorbance of these suspensions depending on the concentration after their passage through the nebulizers were examined. Based on the absorbance, it was determined to what extent the suspensions are passed out and dispersed by the nebulizers. The operating mode of the nebulizers and the concentration of suspensions were determined in order to establish the optimal exposure conditions and the microclimate of the chambers for further studies with mice. The dataset can help in optimization of nebulization process for all researchers exploring the further issue of the influence of the air pollution on the broadly understood animal functions, behavioral parameters and biochemical aspects.

Abstract 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).

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 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.

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.

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.

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.

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.

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.

The interaction of surface acoustic waves (SAWs) with liquids enables the production of aerosols with adjustable droplet sizes in the micrometer range expelled from a very compact source. Understanding the nonlinear acousto-hydrodynamics of SAWs with a regulated micro-scale liquid film is essential for acousto-microfluidics platforms, particularly aerosol generators. In this study, we demonstrate the presence of micro-cavitation in a MHz-frequency SAW aerosol generation platform, which is touted as a leap in aerosol technology with versatile application fields including biomolecule inhalation therapy, micro-chromatography and spectroscopy, olfactory displays, and material deposition. Using analysis methods with high temporal and spatial resolution, we demonstrate that SAWs stabilize spatially arranged liquid micro-domes atop the generator's surface. Our experiments show that these liquid domes become acoustic resonators with highly fluctuating pressure amplitudes that can even nucleate cavitation bubbles, as supported by analytical modeling. The observed fragmentation of liquid domes indicates the participation of three droplet generation mechanisms, including cavitation and capillary-wave instabilities. During aerosol generation, the cavitation bubbles contribute to the ejection of droplets from the liquid domes and also explain observed microstructural damage patterns on the chip surface eventually caused by cavitation-based erosion.

Abstract 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.

Background Sedation is crucial part of the management of cochlear implant surgery. Preoperative anxiety is more aggravated in deaf children due to limited communication. The aim of the present study was to investigate the efficacy and safety of two different doses of nebulized dexmedetomidine in deaf children undergoing cochlear implantation.Patients and Methods Fifty patients undergoing cochlear implantation were randomly allocated into two equal groups, D3 and D4, and were premedicated by nebulized three and four μg/kg dexmedetomidine, respectively, 30 min before induction of anesthesia.Results The depth of sedation in D4 group was comparable with that of D3 group. The onset of sedation and the time to maximum sedative effect were significantly earlier in D4 than in D3 group. BIS score at admission to operating theater was significantly lower in D4 than in D3 group. The level of parental separation anxiety, the degree of ease of venipuncture, and the severity level of emergence agitation were comparable in both groups. The quality of surgical field was significantly better, and the recovery time was significantly shorter in D4 group than in D3 group. The level of heart rate and mean blood pressure were significantly lower, and the rate of bradycardia and hypotension were significantly higher in D4 group than in D3 group.Conclusions Premedication by each of three and four μg/kg of nebulized dexmedetomidine provides a satisfactory sedation level that facilitate parental separation and intravenous cannulation, but three μg/kg was superior because it was associated with lower frequency of side effects.

Harjit Dumra,1 Arjun Khanna,2 Sujeet K Madhukar,3 Meena Lopez,4 Jaideep Gogtay4 1Sparsh, Chest Disease Centre, Navrangpura, Ahmedabad, India; 2Pulmonary Medicine, Amrita Hospital and Research Institute, Faridabad, Haryana, India; 3Madhukar’s Clinic and Lung Hospital, Patna, Bihar, India; 4Medical Affairs Department, Cipla Ltd, Mumbai, Maharashtra, IndiaCorrespondence: Meena Lopez, Cipla Ltd, Mumbai, Maharashtra, India, Tel +91-22-23082891, Email meena@cipla.comPurpose: The aim of the survey was to evaluate attitudes and perceptions toward nebulization therapy for the management of chronic obstructive pulmonary disease (COPD) in Indian population.Patients and methods: A cross-sectional, multicenter, quantitative survey was conducted from July to August 2019 among 103 COPD patients [> 40 years, either gender, belonging to socio-economic class (SEC) A or SEC B] and their family caregivers. One-on-one interviews were conducted telephonically via an online survey platform (KoBo data collection tool) using a structured questionnaire. Patients receiving home nebulization were included, and the usage of nebulizers, satisfaction, and benefits and concerns with nebulizers were assessed.Results: Overall, 47% patients were on handheld inhalers + nebulizer, 54% used nebulizer for > 8 weeks, and 27% used nebulizers daily for home maintenance. Majority of the patients (77%) were satisfied with nebulization therapy. Around 70% family caregivers opined that the quality of life of COPD patients improved post-nebulization therapy. The benefits of nebulizers perceived by patients were easier breathing (89%), feeling of well-being (86%), and ease of use (86%), while family caregivers reported reduced hospitalization (76%) and easier breathing (75%). Among those with prior experience with inhalers, 72% felt nebulizers gave long-term relief, while 65% perceived having immediate relief compared to inhaler. Overall, 61% opined that benefits with nebulizers outweighed the inconvenience associated with its use. Key concerns regarding nebulizers cited by patients were time-consuming procedure (50%), feeling of dependency (49%), and social embarrassment (48%), while family caregivers highlighted social embarrassment (45%) and multiple daily use (45%) as major concerns. Majority of the patients (73%) were compliant with their recommended frequency of the nebulizer.Conclusion: This first-of-its-kind survey highlights that the majority of patients and family caregivers were satisfied with nebulizers and reported improvements in symptoms and reduced hospitalizations with nebulizer therapy. The patients preferred nebulized therapy to inhalers.Keywords: nebulization, quality of life, home nebulization, nebulizer device, quantitative survey, satisfaction, patient perception, patient attitude

With unrelenting SARS-CoV-2 variants, additional COVID-19 mitigation strategies are needed. Oral and nasal saline irrigation (SI) is a traditional approach for respiratory infections/diseases. As a multidisciplinary network with expertise/experience with saline, we conducted a narrative review to examine mechanisms of action and clinical outcomes associated with nasal SI, gargling, spray, or nebulization in COVID-19. SI was found to reduce SARS-CoV-2 nasopharyngeal loads and hasten viral clearance. Other mechanisms may involve inhibition of viral replication, bioaerosol reduction, improved mucociliary clearance, modulation of ENaC, and neutrophil responses. Prophylaxis was documented adjunctive to personal protective equipment. COVID-19 patients experienced significant symptom relief, while overall data suggest lower hospitalization risk. We found no harm and hence recommend SI use, as safe, inexpensive, and easy-to-use hygiene measure, complementary to hand washing or mask-wearing. In view of mainly small studies, large well-controlled or surveillance studies can help to further validate the outcomes and to implement its use.

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.

Ventilator-associated pneumonia (VAP) is accompanied with serious complications. The current study assessed the impact of adjuvant nebulized colistin on the outcomes of VAP patients. The study was a prospectively randomized clinical controlled trial done at the international medical center, Cairo, Egypt on VAP. Patients presenting with infection ≥ 48 hours of mechanical-ventilation (MV) with age ≥ 18 years were included. Patients were excluded when presenting with documented bronchiectasis, cystic fibrosis, known allergy to polymyxin or with creatinine clearance less than 30ml/min. Eligible patients were randomly assigned to: Control group (20); received empiric IV antibiotic therapy or Test group (20); received an empiric IV antibiotic therapy with adjunctive nebulized colistin three times daily for 7 days. At baseline, both groups were subjected to full data collection, laboratory investigations (CBC, ABG, renal and liver function tests) severity scores (APACHE, SOFA) and chest X-rays. Vital signs, ventilatory status, PaO2/FiO2 (P/F ratio), 30- day mortality, weaning off MV and occurrence of complications were all assessed through the study. Groups were comparable at baseline. APACHE and SOFA scores, WBC count, P/F ratio, mode of MV, fraction of inspired O2 (FiO2) all significantly improved (p < 0.005) in the test versus control groups. Test group improved in weaning off MV, percentage of negative culture and number of deaths (p < 0.05) versus control. Adjunctive nebulized colistin improved the severity scores, APACHE and SOFA, ventilatory parameters and oxygenation with better weaning off MV. It resulted in improved bacteria eradication, chest X-ray finding and ICU death when compared with conventional therapy.

Nebulization is a very effective method of drug administration. This technique has been popular since ancient times when inhalation of plants rich in tropane alkaloids with spasmolytic and analgesic effects was widely used. Undoubtedly, the invention of anasthesia in the 19th century had an influence on the development of this technique. It resulted in the search for devices that facilitated anasthesia such as pulveriser or hydronium. From the second half of the 21st century, when the first DPI and MDI inhalers were launched, the constant development of aerosol therapy has been noticed. This is due to the fact that nebulization, compared with other means of medicinal substance application (such as oral and intravenous routes of administration), is safer and it exhibits a positive dose/efficacy ratio connected to the reduction of the dose. It enables drugs administration through the lung and possesses very fast onset action. Therefore, various drugs prescribed in respiratory diseases (such as corticosteroids, β-agonists, anticholinergics) are present on the market in a form of an aerosol.

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%.

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.

Purpose: Postoperative sore throat (POST) is a common complication. We compared postoperative nebulized furosemide, budesonide, and sodium chloride solution for POST in patients undergoing maxillofacial surgery. Methods: 75 patients were randomly divided into 3 groups. Anesthesia induction and intubation were routinely performed. Following emergence, the patients were randomized to one of three groups. Group F was treated with 40mg of aerosolized furosemide, group B received 2 mg of aerosolized budesonide and Group S was given aerosolized 0.9% sodium chloride solution. Patients were assessed for sore throat,hoarseness, foreign body sensation,dry mouth, cough，nausea and vomiting at 15 min, 1, 2, 4, 6, 8, 12, 24 and 48 h after extubation. Results: Patients all in three groups had comparable clinical and surgical data.Compared to Group S, POST at rest and during swallowing was significantly lower in Group F and Group B at 2, 4, 6, 8 and 12 h (P

Abstract 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 self‐dosing 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 SARS‐CoV‐2 and other respiratory pathologies.

Background: Many new drugs were studied for desired action in COVID-19 disease dynamics. One such molecule is Methylene blue which is a tricyclic phenothiazine compound approved for the treatment of acquired methemoglobinemia. This molecule has shown some evidence of inhibiting the interaction of the COVID-19 virus and target cells in a dose dependent manner. There are many other proposals suggesting that the mechanisms of action of Nebulized Methylene Blue [NBM] molecule could be beneficial to the management of COVID-19. The Aim of the Work: To observe and evaluate the effect of NMB on the clinical course and outcomes of patients with COVID-19 infections.Patients and Methods: An observational study including a total of 63 COVID-19 RT-PCR positive cases divided in 3 groups.Results: Difference between mean d-dimer value and mean lactate dehydrogenase [LDH] values at day sixth of the intervention among three different groups were statically significant. A general trend of reduced hospital stays in groups getting NBE in groups 1, 2 vs. group 3 was observed [Viz. 9.17 days Vs. 12 days] though statistically non-significant. Fall in inflammatory markers and oxygen requirements in group receiving methylene blue [Groups 1 and 2] vs. control [Group 3] are noticeable.Conclusion: A general trend of fall in inflammatory markers and oxygen requirements among patients in groups receiving NMB. However, our results showed no significant differences in outcome measures for oxygen saturation and duration of hospitalisation among those receiving NMB.

Objective: To assess the effects of nebulized inhaled Mycobacterium vaccae on allergic airway inflammation, airway hyperresponsiveness, and Th1/Th2 cell imbalance in mice with ovalbumin (OVA)-induced asthma. Methods: Mice received OVA sensitization and challenge for establishment of the asthmatic model. For intervention, mice received Mycobacterium vaccae nebulization once every other day from the first day of sensitization to the day before challenge. After challenge, pulmonary histological analysis and airway responsiveness measurement were performed. In addition, Th1/Th2 cytokines and OVA-specific IgE levels in bronchoalveolar lavage fluid were measured by ELISA. Th1/Th2 subset ratios and the expression of interferon-regulatory factor 4 (IRF4), IRF8 and Toll-like receptor 4 (TLR4) in dendritic cells were evaluated by flow cytometry. Results: Severe inflammatory infiltration and airway hyperresponsiveness were observed in OVA-induced asthmatic mice. Asthmatic mice showed higher Th2 cytokine concentration and increased percentage of Th2 cells, along with lower Th1 cytokine concentration and reduced percentage of Th1 cells compared with the normal control. Moreover, an imbalance of IRF4+ and IRF8+ in dendritic cells was found in asthmatic mice. Nebulized inhaled Mycobacterium vaccae reduced airway hyperresponsiveness and inflammation in OVA-induced asthmatic mice. In addition, nebulized inhaled Mycobacterium vaccae enhanced TLR4 and IRF8 expression, and alleviated the imbalance of Th1/Th2 as well as IRF4+ and IRF8+ in dendritic cells. Conclusions: Nebulized inhaled Mycobacterium vaccae protects against asthma by alleviating the imbalance of Th1/Th2 and IRF4/ IRF8 in OVA-induced asthmatic mice.

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.

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

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.

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 2/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

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: Awake fiber-optic nasal intubation is a gold standard management of difficult airway in temporal mandibular (TM) joint ankylosis. Aims and Objectives: We compared topical lignocaine nebulization with airway nerve blocks for awake fiber-optic nasal intubation in TM joint ankylosis. Materials and Methods: Fifty patients of either gender were randomly allocated into two groups of 25 each. Group I received 10 ml of 2% lignocaine nebulization over a period for 20 min. Group II received bilateral superior laryngeal nerve block and transtracheal recurrent laryngeal nerve block (each with 2 ml of 2% lignocaine). Awake fiber-optic bronchoscopy-guided nasal intubation was done in all patients. All the patients received sedation during the procedure. The intubation time, intubating conditions, vocal cord position, cough severity, and degree of patient satisfaction were recorded. Student’s t-test was used to analyze parametric data, while the Mann–Whitney U-test was applied to non-parametric data and Fisher’s test to categorical data. P

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).

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=

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.

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.

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.

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.

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.