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Background & aims: Gold nanoparticles (AuNPs) are useful tools for noninvasive drug delivery. AuNP nebulization has shown poor deposition results, and AuNP tracking postadministration has involved methods inapplicable to clinical settings. The authors propose an intratracheal delivery method for minimal AuNP loss and computed tomography scans for noninvasive tracking. Materials & methods: Through high-frequency and directed nebulization postendotracheal intubation, the authors treated rats with AuNPs. Results & conclusion: The study showed a dose-dependent and bilateral distribution of AuNPs causing no short-term distress to the animal or risk of airway inflammation. The study demonstrated that AuNPs do not deposit in abdominal organs and show targeted delivery to human lung fibroblasts, offering a specific and noninvasive strategy for respiratory diseases requiring long-term therapies.

Introduction SARS-COV2 infection represents a therapeutic challenge due to the limited number of effective therapies available and due to the fact that it is not clear which host response in terms of inflammation pattern is the most predictive for an optimal (and rapid) recovery. Interferon β pathway is impaired in SARS-COV2 infection and this is associated with a bigger disease burden. Exogenous inhaled interferon might be beneficial in this setting. Areas covered Nebulized interferon-β is currently investigated as a potential therapy for SARS-COV2 because the available data from a phase II study demonstrate that this medication is able to accelerate the recovery from disease. Expert opinion Further clinical studies are needed in order to better document the efficacy of this therapy especially in severe forms of COVID-19, the optimal duration of therapy and if such a medication is appropriate for domiciliary use. Also combined regimens with antivirals or with compounds which are able to enhance the endogenous production of interferon might be of promise.

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

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 hours, 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.

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

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.

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.

The coronavirus disease (COVID-19) pandemic has affected nearly all nations globally. The highly contagious nature of the disease puts the healthcare workers at high risk of acquiring infection, especially while handling airway and performing aerosol-generating procedures. The Indian Society of Critical Care Medicine, through this position paper, aims to provide guidance for safe airway management to all healthcare workers dealing with airway in COVID-19 patients. How to cite this article Praveen Kumar G, Kulkarni AP, Govil D, Dixit SB, Chaudhry D, Samavedam S, et al. Airway Management and Related Procedures in Critically Ill COVID-19 Patients: Position Statement of the Indian Society of Critical Care Medicine. Indian J Crit Care Med 2020;24(8):630–642.

Nebulization with saline solution, although commonly used to alleviate respiratory symptoms, particularly in children, is often questioned concerning its effectiveness. In this study, we investigated the effects of isotonic saline nebulization on lung function in 40 children (mean age of 14±1 years) suffering from different types of airway disorders. Measurements were carried out directly before and up to 15 min after nebulization, for six days in a row, always on the same day time in the morning. The children were divided into two study groups according to the baseline ratio of forced expired volume in one second/forced vital capacity (FEV1/FVC), below and above 80 %. We found significant improvements after saline nebulization in FEV1, mid-expiratory flow at 50 % and 75 % of FVC (MEF50 and MEF75), and peak expiratory flow (PEF) in the group with the baseline FEV1/FVC less than 80 %. In contradistinction, children with an index greater than 80 % displayed no appreciable changes in the lung function variables when compared with the baseline level before saline nebulization. We conclude that isotonic saline nebulization might mitigate the functional signs of threatening pulmonary obstruction and as such may be clinically useful in pediatric patients with mild respiratory problems.

Supplemental Digital Content is available in the text., Objectives: The current clinical treatment of neonates with respiratory distress syndrome includes endotracheal intubation and intratracheal instillation of exogenous surfactant. Nebulization of surfactant offers an attractive alternative. The aims of this study were to test nebulization as a noninvasive method of administering surfactant and determine the optimal dose for the treatment of respiratory distress syndrome–associated pathophysiology of the neonatal lungs. Design: Prospective, randomized, animal model study. Setting: An experimental laboratory. Subjects: Thirty-six newborn piglets. Interventions: Different doses (100, 200, 400, and 600 mg/kg) of poractant alfa were administered via a vibrating membrane nebulizer (eFlow-Neos; Pari Pharma GmbH, Starnberg, Germany) or a bolus administration using the intubation–surfactant–extubation (Insure) technique (200 mg/kg) to spontaneously breathing newborn piglets (n = 6/group) with bronchoalveolar lavage–induced respiratory distress syndrome during nasal continuous positive airway pressure (180 min). Measurements and Main Results: Pulmonary, hemodynamic, and cerebral effects were assessed. Histologic analysis of lung and brain tissue was also performed. After repeated bronchoalveolar lavage, newborn piglets developed severe respiratory distress syndrome. Rapid improvement in pulmonary status was observed in the Insure group, whereas a dose-response effect was observed in nebulized surfactant groups. Nebulized poractant alfa was more effective at doses higher than 100 mg/kg and was associated with similar pulmonary, hemodynamic, and cerebral behavior to that in the Insure group, but improved lung injury scores. Conclusions: In newborn piglets with severe bronchoalveolar lavage–induced respiratory distress syndrome, our results demonstrate that the administration of nebulized poractant alfa using an investigational customized eFlow-Neos nebulizer is an effective and safe noninvasive surfactant administration technique.

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.

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

COVID-19 is caused by the infection of the lungs by SARS-CoV-2. Monoclonal antibodies, such as sotrovimab, showed great efficiency in neutralizing the virus before its internalization by lung epithelial cells. However, parenteral routes are still the preferred route of administration, even for local infections, which requires injection of high doses of antibody to reach efficacious concentrations in the lungs. Lung administration of antibodies would be more relevant requiring lower doses, thus reducing the costs and the side effects. But aerosolization of therapeutic proteins is very challenging, as the different processes available are harsh and trigger protein aggregation and conformational changes. This decreases the efficiency of the treatment, and can increase its immunogenicity. To address those issues, we developed a series of new excipients composed of a trehalose core, a succinyl side chain and a hydrophobic carbon chain (from 8 to 16 carbons). Succinylation increased the solubility of the excipients, allowing their use at relevant concentrations for protein stabilization. In particular, the excipient with 16 carbons (C16TreSuc) used at 5.6 mM was able to preserve colloidal stability and antigen-binding ability of sotrovimab during the nebulization process. It could also be used as a cryoprotectant, allowing storage of sotrovimab in a lyophilized form during weeks. Finally, we demonstrated that C16TreSuc could be used as an excipient to stabilize antibodies for the treatment against COVID-19, by in vitro and in vivo assays. The presence of C16TreSuc during nebulization preserved the neutralization capacity of sotrovimab against SARS-CoV-2 in vitro; an increase of its efficacy was even observed, compared to the non-nebulized control. The in vivo study also showed the wide distribution of sotrovimab in mice lungs, after nebulization with 5.6 mM of excipient. This work brings a solution to stabilize therapeutic proteins during storage and nebulization, making pulmonary immunotherapy possible in the treatment of COVID-19 and other lung diseases.

Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane. RMs were prepared by the solvent evaporation method. Four weeks after infection, guinea pigs (GPs) were assigned to groups treated with a combination of RM-RLs or RLs alone. RLs were nebulized after extrusion whereas RMs were suspended in saline and nebulized to GPs in a nose-only inhalation chamber. Necropsy was performed after the treatment, the lungs and spleen were resected for bacteriology. RLs had mean diameters of 137.1 ± 33.7 nm whereas RMs had a projected area diameter of 2.48 µm. The volume diameter of RMs was 64 ± 1 µm, indicating that RMs were aggregated. The treatment of TB-infected GPs with RLs significantly reduced their lung bacterial burden and wet spleen weight compared with those treated with blank liposomes. The treatment of TB-infected animals with RM-RLs also reduced their lung bacterial burden and wet spleen weight even though these reductions were not statistically different. Based on these results, the permeation of RIF into granulomas appears to be enhanced when encapsulated into liposomes delivered by the pulmonary route.

Objective Tachycardia is a potential side effect of salbutamol inhalation. We aimed to study the short-term effect of salbutamol nebulization on the heart rate of healthy volunteers. Material and methods A randomized, single-blinded, placebo-controlled, cross-over study was conducted with 30 healthy volunteers divided into two groups of 15 each. One group was nebulized with salbutamol (2.5 mg/2 ml dilution) while the other group was given normal saline (2 ml). Each arm underwent administration of the opposite drug the following week. Baseline readings of heart rate and blood pressure were taken at zero (T0), seven (T7), 15 (T15), and 30 (T30) minutes. Results Thirty volunteers between the ages of 20 and 25 years were studied. The mean heart rate value was higher for nebulized salbutamol at each point as compared to saline. When nebulized with salbutamol, the heart rate had a significant rise (p= < 0.00001) at 15 minutes as compared to saline nebulization. Conclusion Salbutamol nebulization, even at a low dose, can lead to a significant increase in heart rate when compared to nebulization with normal saline in healthy individuals.

Evidence-based management of bronchial asthma and wheezing in children and adults recommends the employment of inhaled corticosteroids (ICSs). Difficulty in using some inhalation devices for ICS delivery, such as pressurized metered-dose and dry-powder inhalers, is common among young children and in the elderly, and for that reason, they are replaced with nebulizers. We reviewed comparative studies that evaluated funisolide with other ICSs currently available on the market, including beclomethasone dipropionate, fluticasone propionate, and budesonide. Moreover, we assessed the physicochemical properties of these ICSs in determining drug fate in the lung. Data indicate that the flunisolide output in respirable particles by any type of pneumatic nebulizer (traditional, open breath or breath-enhanced) is superior to the output of other ICSs. This is principally attributed to the higher water solubility of flunisolide. Furthermore, in vivo simulation studies demonstrate that the intersubject variability of the inhaled dose among asthmatic children was much greater for suspensions of fluticasone propionate and beclomethasone dipropionate than for those of flunisolide. The physicochemical properties and pharmacokinetic profile of flunisolide favor its employment in nebulization.

Mass spectrometry coupled to low-temperature plasma ionization (LTPI) allows for immediate and easy analysis of compounds from the surface of a sample at ambient conditions. The efficiency of this process, however, strongly depends on the successful desorption of the analyte from the surface to the gas phase. Whilst conventional sample heating can improve analyte desorption, heating is not desirable with respect to the stability of thermally labile analytes. In this study using aromatic amines as model compounds, we demonstrate that (1) surface acoustic wave nebulization (SAWN) can significantly improve compound desorption for LTPI without heating the sample. Furthermore, (2) SAWN-assisted LTPI shows a response enhancement up to a factor of 8 for polar compounds such as aminophenols and phenylenediamines suggesting a paradigm shift in the ionization mechanism. Additional assets of the new technique demonstrated here are (3) a reduced analyte selectivity (the interquartile range of the response decreased by a factor of 7)-a significant benefit in non-targeted analysis of complex samples-and (4) the possibility for automated online monitoring using an autosampler. Finally, (5) the small size of the microfluidic SAWN-chip enables the implementation of the method into miniaturized, mobile LTPI probes.

Pulmonary infection is one of the main complications occurring in patients suffering from acute respiratory distress syndrome (ARDS). Besides traditional risk factors, dysregulation of lung immune defenses and microbiota may play an important role in ARDS patients. Prone positioning does not seem to be associated with a higher risk of pulmonary infection. Although bacteria associated with ventilator-associated pneumonia (VAP) in ARDS patients are similar to those in patients without ARDS, atypical pathogens (Aspergillus, herpes simplex virus and cytomegalovirus) may also be responsible for infection in ARDS patients. Diagnosing pulmonary infection in ARDS patients is challenging, and requires a combination of clinical, biological and microbiological criteria. The role of modern tools (e.g., molecular methods, metagenomic sequencing, etc.) remains to be evaluated in this setting. One of the challenges of antimicrobial treatment is antibiotics diffusion into the lungs. Although targeted delivery of antibiotics using nebulization may be interesting, their place in ARDS patients remains to be explored. The use of extracorporeal membrane oxygenation in the most severe patients is associated with a high rate of infection and raises several challenges, diagnostic issues and pharmacokinetics/pharmacodynamics changes being at the top. Prevention of pulmonary infection is a key issue in ARDS patients, but there is no specific measure for these high-risk patients. Reinforcing preventive measures using bundles seems to be the best option. 46;12

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.

The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients. However, IFN nebulization is currently not standard in Europe and the United States. Therefore, our group has set up a project aimed to evaluate the possibility to nebulize IFN-β-1b (a drug currently used in Europe to treat multiple sclerosis via subcutaneous injections) and to assess the safety of this new mode of administration in SARS-CoV-2 infected patients. We present here literature data that allowed us to build our hypothesis and to develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to gain first pre-clinical and clinical experience of IFN-β-1b nebulization. After validation of the nebulization method and verification of droplet size compatible with nebulization, the method has been applied to four intensive care patients treated at our university hospital, for whom none of the COVID-19 therapies initially used in France led to significant clinical improvement. All patients exhibited negative viral carriage and experienced clinical improvement 7–16 days after having initiated nebulized IFN-β-1b inhalation therapy. No side effects were observed. All patients were alive within a 90-days follow-up. Although it is not possible to draw firm conclusions on treatment efficacy based on this case report, our study shows that pulmonary IFN-β-1b administration is feasible, with a good safety profile. This procedure, which presents the advantage of directly targeting the lungs and reducing the risks of systemic side effects, may represent a promising therapeutic strategy for the care of patients with severe COVID-19. However, our preliminary observation requires confirmation by randomized controlled trials.

Background: Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated the role of nebulized versus invasively delivered PS, yet the results remained inconsistent. Therefore, we aimed to conduct this meta-analysis to evaluate the effects and safety of nebulized versus invasively delivered PS in the treatment of NRDS. Methods: We searched PubMed et al databases from inception date to May 15, 2020 for RCTs that compared nebulized vs invasively delivered PS. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated for each outcome by means of fixed- or random-effects model. Results: Two RCTs with a total of 95 preterm neonates were identified, with 48 neonates received PS nebulization and 47 neonates undergone invasive PS administration. There was no significant difference in the SpO2 level (MD = −0.44, 95% CI −6.01 to 5.12) and the A/APaO2 level (MD = 0.01, 95% CI −0.02 to 0.05) 1 hour after treatment among 2 groups. But the duration of mechanical ventilation in the nebulization groups was significantly less than that of invasive group (MD = −30.70, 95% CI −41.45 to 19.95). Conclusions: Given the limited evidences, the effects and safety of nebulized versus invasively delivered PS still need further verification.

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

Objective Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs. Design Prospective animal study. Setting Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia. Subjects Four weaned Border-Leicester/Suffolk lambs at 5 months of age. Interventions Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure. Measurements and main results Both the HYDRA and AeroNeb Go® produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 μm, range = 0.54-5.41μm) and the AeroNeb Go® (3.07 ± 1.56 μm, range = 0.86-10 μm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung. Conclusions Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.

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., We 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 including several mutants. Nb11‐59 exhibited potent antiviral activity against authentic SARS‐CoV‐2 with 50% neutralizing dose (ND50) of 0.55 μg/ml, and it can be produced on large scale in Pichia pastoris with titers reached 20 g/L. Importantly, Nb11‐59 showed a good stability and could be developed as an inhaled drug to treat COVID‐19.

Background: Patients with intra-oral malignancies warrants use of awake Fiberoptic assisted naso-thracheal intubation to secure an airway due to multiple risk factors leading to anticipated difficult airway. Different techniques such as airway blocks, local anesthesia (LA) gargles, spray, nebulization and mild sedation are in practice to improve the success rate of fiberoptic assisted intubation. Methods: Sixty patients of ASA I and II with Mallampatti score 3 and above, posted for Commando operations were enrolled in this study and were divided into 2 groups. Group AB (Airway Block, n=30) were given Superior laryngeal nerve block bilaterally and recurrent laryngeal nerve block transtracheally with Inj 2% Lignocaine. Second Group AN (Airway Nebulization, n=30) patients airway was nebulized with 4% Lignocaine with ultrasonic nebulizer. After confirmation of satisfactory anesthesia clinically Fiber-optic assisted naso-tracheal intubation was attempted. Hemodynamic monitoring, total time taken for intubation, patients comfort and any complications occurred were noted. Statistical Analysis– All the observed values were tabulated and analyzed using software SPSS version 17.0. Results: Demography and Hemodynamic observations were comparable in the groups. The time taken for intubation, patient comfort score, intubation conditions were excellent in AB group than in group AN. Airway complications like laryngospasm and cough were noted in AN Group. Conclusions: Judicial use of combined Airway blocks such as Bilateral Superior and trans-tracheal recurrent laryngeal nerve blocks could facilitate a successful fiber-optic assisted awake naso-tracheal intubation in anticipated difficult intubation with negligible complications.

(1) Background: It is common practice in the treatment of respiratory diseases to mix different inhalation solutions for simultaneous inhalation. At present, a small number of studies have been published that evaluate the physicochemical compatibility and aerosol characteristics of different inhalation medications. However, none of them studied Atrovent®. Our work aims to address the lack of studies on Atrovent®. (2) Methods: Portions of admixtures were withdrawn at certain time intervals after mixing and were tested by pH determination, osmolarity measurement, and high-performance liquid chromatography (HPLC) assay of each active ingredient as measures of physicochemical compatibility. The geometrical and aerosol particle size distribution, active drug delivery rate, and total active drug delivered were measured to characterize aerosol behaviors. (3) Results: During the testing time, no significant variation was found in the pH value, the osmotic pressure, or the active components of admixtures. With the increase in nebulization volume after mixing, fine particle dose (FPD) and total active drug delivered showed statistically significant improvements, while the active drug delivery rate decreased compared to the single-drug preparations. (4) Conclusions: These results endorse the physicochemical compatibility of Atrovent® over 1 h when mixed with other inhalation medications. Considering aerosol characteristics, simultaneous inhalation is more efficient.

Background Short-acting β2-agonist (SABA) nebulization is commonly prescribed for children hospitalized with severe asthma exacerbation. Either intermittent or continuous delivery has been considered safe and efficient. The comparative efficacy of these two modalities is inconclusive. We aimed to compare these two modalities as the first-line treatments. Methods An efficacy research with a retrospective cohort study design was conducted. Hospital records of children with severe asthma exacerbation admitted to Hat Yai Hospital between 2015 and 2017 were retrospectively collected. Children initially treated with continuous salbutamol 10 mg per hour or intermittent salbutamol 2.5 mg per dose over 1–4 h nebulization were matched one-to-one using the propensity score. Competing risk and risk difference regression was applied to evaluate the proportion of children who succeeded and failed the initial treatment. Restricted mean survival time regression was used to compare the length of stay (LOS) between the two groups. Results One-hundred and eighty-nine children were included. Of these children, 112 were matched for analysis (56 with continuous and 56 with intermittent nebulization). Children with continuous nebulization experienced a higher proportion of success in nebulization treatment (adjusted difference: 39.5, 95% CI 22.7, 56.3, p

In patients with fibrotic pulmonary disease such as idiopathic pulmonary fibrosis (IPF), inhaled aerosols deposit mostly in the less affected region of the lungs, resulting in suboptimal pharmacokinetics of airway-delivered treatments. Refinement of aerosol delivery technique requires new models to simulate the major alterations of lung physiology associated with IPF, i.e., heterogeneously reduced lung compliance and increased airway caliber. A novel physical model of the respiratory system was constructed to simulate aerosol drug delivery in spontaneously breathing (negative pressure ventilation) IPF patients. The model comprises upper (Alberta ideal throat) and lower airway (plastic tubing) models and branches into two compartments (Michigan lung models) which differ in compliance and caliber of conducting airway. The model was able to reproduce the heterogeneous, compliance-dependent reduction in ventilation and aerosol penetration (using NaF as a model aerosol) seen in fibrotic lung regions in IPF. Of note, intrapulmonary percussive ventilation induced a 2–3-fold increase in aerosol penetration in the low-compliance/high airway caliber compartment of the model, demonstrating the responsiveness of the model to therapeutic intervention.

Purpose Intermittent nebulization of short-acting beta-agonists (SABA) is the initial treatment of choice for children with asthma exacerbation. However, children with severe asthma exacerbation (SAE) may not show an adequate response and need aggressive stepwise therapy. We aimed to explore factors associated with a poor response to intermittent nebulized SABA in children with SAE. Methods A retrospective cohort study of children with SAE diagnosed according to the definition of the British Guidelines on the Management of Asthma, who were admitted at Hat Yai Hospital from January 1, 2015, to December 31, 2017. All children were treated with intermittent SABA nebulization. Treatment failure was defined as children needing escalated therapy. Logistic regression with confounding score adjustment was used to explore the predictors of treatment failure. Results One hundred thirty-three children were included in the analysis, 59 were in the failure group and 74 were in the success group. After adjusting for potential confounders, they were significantly associated with a previous history of intubation (adjusted OR 6.46, 95% CI 1.13 to 36.79, p=0.036), receiving

Background: Combinations of a long-acting muscarinic receptor antagonist (LAMA), long-acting β-agonist (LABA), and inhaled corticosteroid (ICS) are used for patients with persistent chronic obstructive pulmonary disease (COPD) exacerbations on bronchodilator monotherapy. In this prespecified subgroup analysis, we assessed the efficacy and safety of the LAMA revefenacin in patients with COPD taking concomitant LABA, including ICS/LABA (LABA subgroup). Methods: Efficacy data were obtained from two 12-week, replicate, placebo-controlled trials and safety data were pooled from the 12-week and a 52-week tiotropium-controlled trial. Patients received revefenacin 175 µg or placebo in the 12-week or tiotropium 18 µg in the 52-week studies. The efficacy endpoint was least squares (LS) mean change from baseline in trough forced expiratory volume in 1 second (FEV1). Clinical health outcomes were assessed using the St. George’s Respiratory Questionnaire (SGRQ). Results: Revefenacin produced similar improvements from baseline in trough FEV1 in the non-LABA and LABA subgroups [placebo-adjusted LS mean change (95% confidence interval) in day 85 trough FEV1, 150.9 (110.3−191.6) ml and 139.2 (82.9−195.5) ml; p Conclusions: Once daily revefenacin for nebulization can be an effective and well-tolerated treatment for patients who require concomitant use of LABA with or without ICS. ClinicalTrials.gov identifiers: NCT02512510, NCT02459080, NCT02518139 The reviews of this paper are available via the supplemental material section.

Trabajo fin de grado. Defendido en julio de 2020. La bronquiolitis aguda (BA) es una enfermedad respiratoria de las vías aéreas bajas provocada por una infección viral. Es la enfermedad más común en los niños menores de 24 meses de edad y representa la principal causa de hospitalización en esta población. Actualmente, el papel de la fisioterapia respiratoria en la BA es controvertido. La última revisión sistemática que evalúa su eficacia en niños hospitalizados menores de 24 meses indica que la técnica de ELPr disminuye la severidad de la BA. Hasta ahora, no se ha publicado ningún estudio que permita valorar su efectividad en pacientes ambulatorios. Por tanto, el objetivo de este estudio experimental es evaluar efectividad de la técnica de espiración lenta prolongada en niños no hospitalizados con bronquiolitis aguda leve o moderada. Abstract: Acute bronchiolitis (BA) is a respiratory disease of the lower airways caused by a viral infection. It is the most common disease in children under 24 months of age and represents the main cause of hospitalization in this population. The role of chest physiotherapy in BA is currently controversial. The latest systematic review evaluating its efficacy in hospitalized children under 24 months indicates that the PSE technique decreases the severity of BA. So far, no studies have been published to assess their effectiveness in outpatients. Therefore, the aim of this experimental study is to evaluate the effectiveness of the prolonged slow expiration technique in non-hospitalized children with mild or moderate acute bronchiolitis. Ordenador con navegador de Internet; Adobe Acrobat Reader 61 p. (Según el contador de la aplicación)

BACKGROUND Incidence of bronchial asthma has dramatically increased in last 2 to 3 decades. Inhalation therapy is the treatment of choice in acute exacerbation of asthma. Levosalbutamol (R-salbutamol) has been shown in different studies to be superior to racemic salbutamol (mixture of equal amount of (R) - and (S)- salbutamol). Thus, the present study was conducted to compare response of reversibility of bronchoconstriction and tolerability of inhaled levosalbutamol versus salbutamol. MATERIALS AND METHODS A study was done on 274 patients from November 2016 to September 2018. All patients received either salbutamol (2.5 mg) or levosalbutamol (0.63 mg) by nebulisation for 3 times at interval of 20 minute all parameters like FEV1, FVC, HR, RR, SPO2, PEFR were recorded before starting treatment and after 1 hour of 1st nebulisation in both groups, and comparative study was done. RESULTS Both inhaled salbutamol and levosalbutamol were effective equally in bronchodilatation in acute exacerbation of Asthma. There was increase in heart rate in salbutamol inhalation but there was no significant change in HR in levosalbutamol group. CONCLUSION Both levosalbutamol and salbutamol showed significant improvement in acute exacerbation of bronchial asthma. There was increase in HR with salbutamol, but no significant change was observed in HR with levosalbutamol. Less dose of levosalbutamol produced the same effect and clinical improvement as compared to salbutamol.

Nebulization delivery of adeno-associated virus serotype 1 encoding sarcoplasmic reticulum Ca 2+ -ATPase2a (AAV1.SERCA2a) gene was examined in a Yukatan miniature swine model of chronic pulmonary hypertension (n = 13). Nebulization of AAV1.SERCA2a resulted in homogenous distribution of vectors, lower pulmonary vascular resistance, and a trend towards better long-term survival compared to control animals.

Objective To evaluate if nebulised surfactant reduces intubation requirement in preterm infants with respiratory distress treated with nasal continuous positive airway pressure (nCPAP). Design Double blind, parallel, stratified, randomised control trial. Setting Sole tertiary neonatal unit in West Australia. Patients Preterm infants (290–336 weeks’ gestational age, GA) less than 4 hours of age requiring 22%–30% supplemental oxygen, with informed parental written consent. Interventions Infants were randomised within strata (290–316 and 320–336 weeks’ GA) to bubble nCPAP or bubble nCPAP and nebulised surfactant (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation (100 mg/kg) was repeated after 12 hours for persistent supplemental oxygen requirement. Main outcome measures The primary outcomes were requirement for intubation and duration of mechanical ventilation at 72 hours. Data analysis followed the intention-to-treat principle. Results 360 of 606 assessed infants were eligible; 64 of 360 infants were enrolled and randomised (n=32/group). Surfactant nebulisation reduced the requirement for intubation within 72 hours: 11 of 32 infants were intubated after continuous positive airway pressure (CPAP) and nebulised surfactant compared with 22 of 32 infants receiving CPAP alone (relative risk (95% CI)=0.526 (0.292 to 0.950)). The reduced requirement for intubation was limited to the 320–336 weeks’ GA stratum. The median (range) duration of ventilation in the first 72 hours was not different between the intervention (0 (0–62) hours) and control (9 (0–64) hours; p=0.220) groups. There were no major adverse events. Conclusions Early postnatal nebulised surfactant may reduce the need for intubation in the first 3 days of life compared with nCPAP alone in infants born at 290–336 weeks’ GA with mild respiratory distress syndrome. Confirmation requires further adequately powered studies. Trial registration number ACTRN12610000857000.

Coenzyme Q(10) (CoQ(10)) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ(10) nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ(10) formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60 nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ(10) delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02 mu m). Stability tests showed that the most stable formulation, after 90 days, was the one containing vitamin-E TPGS, followed by the CoQ(10)-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ(10).

Ever since its emergence, the highly transmissible and debilitating coronavirus disease spread at an incredibly fast rate, causing global devastation in a matter of months. SARS-CoV-2, the novel coronavirus responsible for COVID-19, infects hosts after binding to ACE2 receptors present on cells from many structures pertaining to the respiratory, cardiac, hematological, neurological, renal and gastrointestinal systems. COVID-19, however, appears to trigger a severe cytokine storm syndrome in pulmonary structures, resulting in oxidative stress, exacerbated inflammation and alveolar injury. Due to the recent nature of this disease no treatments have shown complete efficacy and safety. More recently, however, researchers have begun to direct some attention towards GSH and NAC. These natural antioxidants play an essential role in several biological processes in the body, especially the maintenance of the redox equilibrium. In fact, many diseases appear to be strongly related to severe oxidative stress and deficiency of endogenous GSH. The high ratios of ROS over GSH, in particular, appear to reflect severity of symptoms and prolonged hospitalization of COVID-19 patients. This imbalance interferes with the body's ability to detoxify the cellular microenvironment, fold proteins, replenish antioxidant levels, maintain healthy immune responses and even modulate apoptotic events. Oral administration of GSH and NAC is convenient and safe, but they are susceptible to degradation in the digestive tract. Considering this drawback, nebulization of GSH and NAC as an adjuvant therapy may therefore be a viable alternative for the management of the early stages of COVID-19.

Made available in DSpace on 2022-04-29T08:45:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 This study applies a proof of concept for future applications in controlling the microbiota in tubes and tracheal appliances used in the respiratory tract. Therefore, the physical–chemical parameters of the plasma-activated and nebulized water (NPAW) are measured in a nebulizer tube with different lengths between 0.1 and 3.0 m. The pH values and oxidation–reduction potential (ORP) do not change during nebulization of PAW over a 1.0 m tube. However, for longer lengths, there is an increase in pH and a decrease in ORP. At 3.0 m, the pH increases approximately 16% compared with the 1.0 m position with a 20% decrease in the ORP values. Hydrogen peroxide (H2O2) measured quantitatively using test strips presents values between 0.5 and 2.0 mg/L for condensed NPAW in different tube lengths between 0.1 and 3.0 m, and maintains the approximate value of 2.0 mg/L in tubes up to 1.0 m, with a reduction proportional to the increase in the length of the tube. The antimicrobial efficacy of NPAW applied for 15 min shows the inactivation of Staphylococcus aureus and Escherichia coli but without significant inactivation of Candida albicans. Laboratório de Plasmas e Processos Instituto Tecnológico de Aeronáutica (ITA) i3N Departamento de Física Universidade de Aveiro Campus Santiago Laboratório de Genoma Instituto de Ciência e Tecnologia (ICT) UNESP Division of Thoracic Surgery Instituto do Coracao Faculdade de Medicina Hospital das Clinicas HCFMUSP Universidade de Sao Paulo Faculdade de Engenharia (FEG) UNESP Laboratório de Genoma Instituto de Ciência e Tecnologia (ICT) UNESP Faculdade de Engenharia (FEG) UNESP

A generalized formulation for coagulation of charged particles is presented in this paper. The governing equations can be solved semi-implicitly for a number of discrete size and charge bins. The computationally efficient mechanism gives volume and charge conserved solution with time. A distinct way of handling electrostatic dispersion in dynamic model has been used in this work. The scheme has been tested for charged, nebulized aerosol particles by model studies and also compared with experimental observations. The model simulated results show that charge can significantly affect the coagulation dynamics if charge level is higher than the Boltzmann equilibrium charge limit for less than 1 μm particles. It was found that for the bipolar charge case, there was a significant effect on the enhancement of the coagulation process. For the case of unipolar charge, electrostatic dispersion was seen to play a role in the depletion of number concentration. The model was then validated against results of six controlled experiments in which electrical low pressure impactor (ELPI) was used for measurement of charge and number size distribution. Our model results were found to be in reasonable agreement with observed values. The developed model is fast (independent of time step) and numerically stable. It can be used for several applications involving coagulation dynamics of charged aerosol particles.

Background: Various nonpharmacological and pharmacological trials have been used for attenuating postoperative sore throat (POST) with no proven single modality. Ketamine has been used as a gargle or nebulization in the attenuation of POST by its action on peripheral N-methyl-D-aspartate receptors. Topical administration of clonidine elicits antinociception through α2-adrenoceptors without producing undesirable side effect. Aim: This study aims to compare between nebulized ketamine and ketamine with clonidine in POST. Materials and Methods: The effects of nebulized ketamine and ketamine with clonidine in POST have been compared in 100 patients. Patients were divided into two groups: Group K patients were nebulized with ketamine 1 mL (50 mg) plus normal saline 3 mL and Group KC patients were nebulized with ketamine 1 mL (50 mg) plus clonidine 1 mL (50 mg) plus normal saline 2 mL. Online statistical software was used for analysis of the data. Results: At 4 h, seven patients experienced sore throat in Group K while no incidence was reported in group KC (0%). At 8 h, 12 (85.7%) patients experienced sore throat in Group K and 2 (14.28%) patients in Group KC. At 12 h, 13 (81.25%) patients experienced sore throat in Group K and 3 (18.75%) patients of Group KC. At 24 h, 6 (85.71%) patients experienced sore throat in Group K and 1 (14.28%) patient in Group KC. Patients in both groups remained hemodynamically stable with no complaint of nausea, vomiting, sedation, laryngospasm, or any other side effect. Conclusion: Nebulization with ketamine plus clonidine preoperatively is more effective in reducing POST with no adverse effects as compared to preoperative nebulization with ketamine.

International audience; Inhaled protein therapeutics meet a growing interest for the treatment of respiratory diseases. In liquid aerosols, proteins face stresses that may generate instabilities, such as physicochemical denaturations, aggregation and loss of activity. Monitoring protein stability is thus crucial but implies collection of aerosol droplets before analysis. Many aerosol collection methods may be used, still their interference on protein stability is unknown. In this study, we compared the impact of six aerosol samplers on the stability of a model monoclonal antibody (Ig1), aerosolized with a mesh nebulizer. Ig1 stability was assessed for aggregation and biological activity. The six aerosol samplers generated distinct aggregation profiles for Ig1 at all size scales; counts of micron-sized particles varied by a factor of 100. The heterogeneity did not impact Ig1 activity, which was not significantly changed after nebulization. To extrapolate these results, we evaluated the impact of two samplers on three other proteins. Depending on the protein, samplers gave discordant aggregation and/or activity profiles, sometimes in the reverse trend as compared to Ig1. In conclusion, aerosol samplers interfere with protein stability; this impact depends both on the samplers and the protein, highlighting the importance of using the same collection device throughout the aerosol development process

The purpose of the study was to compare treatment of chronic rhinosinusitis (CRS) with topical glucocorticoids and saline irrigation versus aerosol inhalation therapy. Patients diagnosed with CRS were randomly divided into 2 groups. In the first group, patients were treated with topical glucocorticoids (mometasone furoate, 100 µg in each nostril once daily) and saline irrigation (150 mL twice a day) for 2 weeks. In the second group, patients were treated with inhalation aerosol therapy composed of essential oils, saline, glucocorticoids, and antibiotics, once daily 5 times per week (Monday through Friday), for 2 weeks. The effect of the treatments was compared between the 2 groups. In the first group there was no significant improvement in the Glasgow Health Status Inventory (GHSI) (P =.29). In the second group the improvement in GHSI score was significant (P =.037). It was shown that in the first group the Glasgow Benefit Inventory score was significantly lower than in the second group (P =.002), which means that the improvement in the health status after the therapy was better in the second group. A Lund-Kennedy score showed statistical improvement in both groups (both P

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.

The retentions of fresh strawberry individual phenolic compounds after fogging using an environmentally friendly sanitizer based on peracetic acid (PAA) (mixture of 5% peracetic acid and 20% hydrogen peroxide) were studied and modeled as a function of the concentration (3.4, 20.0, 60.0, 100.0 and 116.6 μL PAA L-1 air chamber) and the treatment time (5.7, 15.0, 37.5, 60.0 and 69.3 min), using Response Surface Methodology. Information obtained from high performance liquid chromatography with photodiode array and fluorescence detection in combination with mass spectrometry was used for analyzing and quantifying the phenolics that naturally occur in strawberries (variety 'Camarosa') and to study the effects of PAA on them. Results showed that PAA fogging at certain concentrations and times caused degradation in the phenolic profile of strawberries. Anthocyanins were the most affected of the phenolic compounds, followed by proanthocyanidins with a low degree of polymerization, hydroxycinnamic acid derivatives, and the ellagitannin Sanguiin H-6. In general, pelargonidin-based anthocyanins were more susceptible to oxidation than cyanidin-based anthocyanin under the same PAA fogging conditions. In summary, the stability of strawberry individual phenolic compounds after fogging treatments was dependent on the concentration and the exposure time of PAA treatments as well as the chemical nature of them. The models developed herein allow to predict retentions of individual phenolic compounds at different fogging PAA conditions. Fil: Van de Velde, Franco. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina Fil: Grace, Mary H.. University of North Carolina; Estados Unidos Fil: Pirovani, Maria Elida. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; Argentina Fil: Lila, Mary Ann. University of North Carolina; Estados Unidos

Inhaled therapy is the cornerstone in the management of obstructive airway diseases (OADs). Nebulization is often used for the delivery of bronchodilators and corticosteroids among the elderly and children. The present pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified, highly contagious, novel coronavirus, called severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is responsible for great morbidity and mortality globally. There is a great concern regarding person-to-person transmissibility of this virus. There is also a great concern of viral transmission of this virus to the health-care personnel and the bystanders through aerosol-generating procedures including frequently used nebulization therapy. Most of the patients with OAD, during the current pandemic, who were undergoing nebulization therapy, on getting infected with SARS-CoV-2 or on its suspicion, have been shifted to other handheld devices out of fear of transmission of infection. Presently, there exist not enough evidences either on the safety or on the risk of transmissibility of SARS-CoV-2 during nebulization in COVID-19 patients. In addition, there are concerns about nebulization in OAD cases even in the absence of COVID-19 and about the use of inhaled or systemic corticosteroids in these cases. We have made some observations based on all the current information available related to these issues, which may help provide some guidance in the use of nebulizer therapy and also discussed the measures to be taken to minimize the risk of infection, if any, during the procedure.

To compare the newborn infant parasympathetic evaluation system (NIPE) scores with a validated clinical scale using two different nebulizers in children with bronchiolitis admitted to a PICU. Comfort was evaluated using the COMFORT-behavior scale (CBS) before (T1), during (T2) and after (T3) each nebulization. In order to compare NIPE and CBS values during the whole T1 to T3 period, the variable Dif-CBS was defined as the difference between maximal and minimal CBS scores, and Dif-NIPE as the difference between 75th and 25th percentile NIPE values. Analyses were carried out, firstly for the total of nebulizations and secondly comparing two different nebulization systems: a jet nebulizer (JN) and a nebulizer integrated in high flow nasal cannulas (NHF). 84 nebulizations were recorded on 14 patients with a median [25th-75th percentile] age of 6 months (3.1-9.5). A Dif-CBS of 4 points (2-7), as well as changes in CBS scores between T1 and T2, defined the nebulization as a discomfort stimulus. The NIPE system, represented as the Dif-NIPE, showed a median variation of 9 points (7-10), and was poorly correlated to Dif-CBS [rs 0.162 (P = 0.142)]. Discomfort during nebulization, assessed by CBS was greater with the JN system compared to NHF: 17 (13-22) vs 13 (9-15) (P = 0.001). NIPE monitoring detected no significant differences between both nebulization systems (P = 0.706). NIPE monitoring showed a variation in comfort during nebulization in the patient with bronchiolitis, though correlation with CBS was poor. Further research is required before NIPE can be suggested as a comfort monitoring system for the awake infant.

The aim of this study was to identify critical steps to protein stability during spray drying using two different nozzle types: a vibrating mesh nozzle and a standard two-fluid nozzle in a Buchi B-90 spray dryer. l -Lactic dehydrogenase was used as a model protein as it is a heat and shear stress sensitive protein. Trehalose was used as excipient because of its excellent stabilizing capacities. The entire spray drying process was split up into smaller steps and after each step the enzymatic activity of the protein was measured. With the vibrating mesh nozzle in total 78% of activity was lost. About 68% was due to atomizing and heating and 10% was caused by dehydration and circulation of the liquid. With the two-fluid nozzle the total activity loss was only 23%, to which atomization, dehydration, and circulation contributed almost equally. Heating was not an issue, as the two-fluid nozzle could be cooled with water. In conclusion, the type and the configuration of the nozzle used for spray drying are important determinants for maintaining protein stability, as atomizing, heating, ultra-sonication, and recirculation of the feed solution negatively influence it. The possibility to cool the two-fluid nozzle offers an important advantage to the vibrating mesh nozzle in the spray drying process of proteins. In this study, we show that, next to the optimization of the formulation, optimization of the spray drying process should be taken into account to maintain protein stability.

Visual Abstract, The ability to sense time and anticipate events is critical for survival. Learned responses that allow anticipation of the availability of food or water have been intensively studied. While anticipatory behaviors also occur prior to availability of regularly available rewards, there has been relatively little work on anticipation of drugs of abuse, specifically methamphetamine (MA). In the present study, we used a protocol that avoided possible CNS effects of stresses of handling or surgery by testing anticipation of MA availability in animals living in their home cages, with daily voluntary access to the drug at a fixed time of day. Anticipation was operationalized as the amount of wheel running prior to MA availability. Mice were divided into four groups given access to either nebulized MA or water, in early or late day. Animals with access to MA, but not water controls, showed anticipatory activity, with more anticipation in early compared to late day and significant interaction effects. Next, we explored the neural basis of the MA anticipation, using c-FOS expression, in animals euthanized at the usual time of nebulization access. In the dorsomedial hypothalamus (DMH) and orbitofrontal cortex (OFC), the pattern of c-FOS expression paralleled that of anticipatory behavior, with significant main and interaction effects of treatment and time of day. The results for the lateral septum (LS) were significant for main effects and marginally significant for interaction effects. These studies suggest that anticipation of MA is associated with activation of brain regions important in circadian timing, emotional regulation, and decision making.