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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.

Dysphagia and aspiration risk are common sequelae of stroke, leading to increased risk of stroke-associated pneumonia. This is often aggravated by stroke-related impairment of cough, the most immediate mechanical defense mechanism against aspiration. In humans, reflex cough can be repeatedly and safely elicited by inhalation of nebulized capsaicin, a compound contained in chili peppers. Could this cough-eliciting property of capsaicin support the recovery of stroke survivors who present with dysphagia and aspiration risk? We present a clinical case report of a 73-year-old man, admitted to inpatient stroke rehabilitation following a right middle cerebral artery infarct with subsequent dysphagia and hospital-acquired pneumonia. A course of daily inhalation therapy with nebulized capsaicin was initiated, triggering reflex coughs to support secretion clearance and prevent recurrence of pneumonia. Clinical observations in each inhalation therapy session demonstrate good patient response, safety and tolerability of nebulized capsaicin in this mode of application. Repeated Fiberoptic Endoscopic Evaluation of Swallowing (FEES) assessments show concurrent improvement in the patient’s swallowing status. Inhalation therapy with nebulized capsaicin may offer a viable treatment to facilitate coughing and clearing of secretions, and to minimize aspiration and risk of aspiration-related pneumonia post stroke. Further investigation in a randomized controlled trial design is warranted.

The delivery of RNA across biological barriers can be achieved by encapsulation in lipid nanoparticles (LNPs). Cationic amphiphilic drugs (CADs) are pharmacologically diverse compounds with ionizable lipid-like features. In this work, we applied CADs as a fifth component of state-of-the-art LNPs via microfluidic mixing. Improved cytosolic delivery of both siRNA and mRNA was achieved by partly replacing the cholesterol fraction of LNPs with CADs. The LNPs could cross the mucus layer in a mucus-producing air-liquid interface model of human primary bronchial epithelial cells following nebulization. Moreover, CAD-LNPs demonstrated improved epithelial and endothelial targeting following intranasal administration in mice, without a marked pro-inflammatory signature. Importantly, quantification of the CAD-LNP molar composition, as demonstrated for nortriptyline, revealed a gradual leakage of the CAD from the formulation during LNP dialysis. Altogether, these data suggest that the addition of a CAD prior to the rapid mixing process might have an impact on the composition, structure, and performance of LNPs.

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 Fe 2 O 3 and SiO 2 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/m 3 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., (© 2024 The Author(s).)

Introduction Intravenous dexmedetomidine is known to cause major adverse effects such as bradycardia, hypotension, cardiac arrhythmias, and heart block when used as premedication for attenuation of the laryngoscopy and intubation response, limiting its routine use. Thus, it is important to study other routes of administration of dexmedetomidine. Objectives To compare the hemodynamic response and sedation score between intravenous and nebulized dexmedetomidine as premedication for the attenuation of the laryngoscopy and intubation response. Materials and methods In this study, 60 patients fulfilling inclusion criteria undergoing surgeries under general anesthesia (ASA Grade I and II) were randomly allocated into two groups of 30 patients each. Group IV received intravenous 1 mcg/kg dexmedetomidine in 100 mL normal saline, and Group IN received nebulization with 1 mcg/kg dexmedetomidine diluted to a total volume of 5 cc of normal saline, 30 minutes prior to the induction of general anesthesia. Sedation scores were calculated using the Ramsay sedation score at 20 minutes after the administration of the drug; patients were induced by the standard protocol, and laryngoscopy was performed. Vitals were recorded before the administration of the drug and after intubation at stipulated time intervals. Results The median heart rate becomes significantly lower at 15 minutes (70 vs. 76.5) and 20 minutes (66 vs. 76) after induction among Group IV as compared to Group IN. The median systolic blood pressure was significantly lower at 20 minutes in Group IV (110 mmHg) than in Group IN (119 mmHg). The median diastolic blood pressure was significantly lower at 10 minutes (76 vs. 79), 15 minutes (70 vs. 77), and 20 minutes (69 vs. 78.5) in Group IV than in Group IN. The median of mean arterial pressure was significantly lower at 15 minutes (84.8 vs. 91.5) and 20 minutes (83 vs. 92) in Group IV than in Group IN. A comparison of vitals after induction shows that the median heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were significantly lower statistically among Group IV as compared to Group IN at 0, 1, 3, 5, 10, 15, and 30 minutes after induction (except for systolic blood pressure at 3 minutes). The median sedation score was lower in Group IN (0) than in Group IV (1); this difference is statistically significant. Conclusion The obtundation of hemodynamic responses following laryngoscopy and maintaining hemodynamics intraoperatively is statistically better with nebulized dexmedetomidine compared to intravenous dexmedetomidine., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Singla et al.)

Measles virus is one of the most contagious airborne human viruses which keeps causing outbreaks in numerous countries over the world despite the existence of an efficient vaccine. Fusion inhibitory lipopeptides were shown to inhibit viral entry into target cells, and their adequate administration into the respiratory tract may provide a novel preventive approach against airborne infections. Aerosol delivery presents the best administration route to deliver such preventive compounds to the upper and lower respiratory tract. This approach offers a conceptually new strategy to protect the population at risk against infection by respiratory viruses, including measles. It is a noninvasive needle-free approach, which may be used when antiviral protection is required, without any medical assistance. In this chapter, we describe the nebulization approach of lipopeptide compounds in nonhuman primates and the subsequent measles virus challenge., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

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 [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) enables highly specific silencing of potential target genes for treatment of pulmonary pathologies. The intracellular RNAi pathway can be activated by cytosolic delivery of small interfering RNA (siRNA), inducing sequence-specific gene knockdown on the post-transcriptional level. Although siRNA drugs hold many advantages over currently applied therapies, their clinical translation is hampered by inefficient delivery across cellular membranes. We previously developed hybrid nanoparticles consisting of an siRNA-loaded nanosized hydrogel core (nanogel) coated with Curosurf®, a clinically used pulmonary surfactant (PS). The latter enhances both particle stability as well as intracellular siRNA delivery, which was shown to be governed by the PS-associated surfactant protein B (SP-B). Despite having a proven in vitro and in vivo siRNA delivery potential when prepared ex novo , clinical translation of this liquid nanoparticle suspension requires the identification of a long-term preservation strategy that maintains nanoparticle stability and potency. In addition, to achieve optimal pulmonary deposition of the nanocomposite, its compatibility with state-of-the-art pulmonary administration techniques should be evaluated. Here, we demonstrate that PS-coated nanogels can be lyophilized, reconstituted and subsequently nebulized via a vibrating mesh nebulizer. The particles retain their physicochemical integrity and their ability to deliver siRNA in a human lung epithelial cell line. The latter result suggests that the functional integrity of SP-B in the PS coat towards siRNA delivery might be preserved as well. Of note, successful lyophilization was achieved without the need for stabilizing lyo- or cryoprotectants. Our results demonstrate that PS-coated siRNA-loaded nanogels can be lyophilized, which offers the prospect of long-term storage. In addition, the formulation was demonstrated to be suitable for local administration with a state-of-the-art nebulizer for human use upon reconstitution. Hence, the data presented in this study represent an important step towards clinical application of such nanocomposites for treatment of pulmonary disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To evaluate the role of nebulized N-acetyl cysteine (NAC) in liquefying the airway secretions and improving the outcome of patients of esophageal atresia with tracheoesophageal fistula (EA + TEF). It was a non-randomized interventional study. Two milliliters of 10% NAC was given in a nebulized form (2:5 dilution, every six hourly) to patients of ET + TEF, along with regular suction of upper esophageal pouch. The group was compared with control, which comprised patients of EA + TEF receiving only saline nebulization. The consistency of the secretions was compared by hand held consistometer in unit of time (seconds) required to cross a predetermined distance along with gravity. Sixty patients were assessed. Of these, 30 patients were present in both groups. The study group showed significant (p = 0.01–0.0001) decrease in consistency of secretions from the control group after day 2 of NAC nebulization. Patients' discharge was significantly (p = 0.01) earlier in cases. There was no significant (p = 0.41) difference in mortality between the groups. No specific adverse effects were observed in the study group. It appears that nebulized NAC decreases the consistency of secretions in EA + TEF patients. It is interesting to note that the group of patients that received NAC was discharged earlier than the control group and had a higher survival rate than the control group. Whether this is directly attributable to the use of NAC is unknown. A prospective double-blinded randomized clinical trial is warranted to confirm these results. Level II, prospective comparative study (non-randomized). • Nebulized N-acetyl cysteine (NAC) has not been assessed in a prospective study for liquefying secretions in patients of esophageal atresia with trachea-esophageal fistula (EA + TEF). • NAC appears to liquefy thick secretions in these patients. • When used nebulized NAC appears to decrease the hospital study of patients of EA + TEF. • It may also be having effect on deceasing mortality; however, it needs more evidence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Pharmacological treatment for bronchiolitis is primarily supportive because bronchodilators, steroids, and antibiotics, show little benefit. Clinical studies have suggested that nebulized 3% hypertonic solution is useful for infants with bronchiolitis. This study aims to evaluate the cost-effectiveness of the HS inhalations in infant bronchiolitis in a tropical country.Methods: Decision tree analysis was used to calculate the expected costs and QALYs. All cost and use of resources were collected directly from medical invoices of 193 patient hospitalized with diagnosis of bronchiolitis in tertiary centers, of Rionegro, Colombia. The utility values applied to QALYs calculations were collected from the literature. The economic analysis was carried out from a societal perspective.Results: The model showed that nebulized 3% hypertonic solution, was associated with lower total cost than controls (US $200vs US $240 average cost per patient), and higher QALYs (0.92 vs 0.91 average per patient); showing dominance. A position of dominance negates the need to calculate an incremental cost-effectiveness ratio.Conclusion: The nebulized 3% hypertonic solution was cost-effective in the inpatient treatment of infant bronchiolitis. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other tropical countries. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection is the most common cause of acute lower respiratory tract infection in children, leading to their death. Currently, no effective prevention and treatment methods for RSV infection are available. RSV and many other unknown viruses pose a serious threat to human health. Our previous study demonstrated that Mycobacterium vaccae nebulization can protect against allergic asthma. As RSV infection and asthma are closely related, we hypothesized that M. vaccae could protect against pulmonary RSV infection. Therefore, we evaluated the effect of M. vaccae on RSV infection in Balb/c mice. Methods: The mice were randomized into three groups: normal, RSV, and M. vaccae. One week before the RSV infection model was established, the mice in the M. vaccae group were nebulized with M. vaccae. On the fourth day after RSV infection, airway responsiveness, airway inflammation, pulmonary RSV infection, mRNA levels of pulmonary toll-like receptor (TLR) 7 and TLR8, and pulmonary NF09, acetylcholine, and epidermal growth factor regulator (EGFR) expression levels in all mice were measured. Results: The airway inflammation in the M. vaccae group was alleviated compared with that in the RSV group. In the M. vaccae group, the pulmonary mRNA level of RSV and the pulmonary expression levels of NF09, acetylcholine, and EGFR were decreased considerably, whereas the mRNA levels of TLR7 and TLR8 were increased significantly. Conclusions: One-week nebulization of M. vaccae can protect against RSV infection in Balb/c mice. The mechanism involves the regulation of neurotransmitters and expression of TLR7, TLR8, and EGFR. [ABSTRACT FROM AUTHOR]

Background: Targeting drugs to the olfactory region in the nasal cavity can bypass the restrictive blood–brain barrier and enhance their direct delivery to the brain. However, complex nasal geometry and its demographical variations can pose challenges for targeted drug deposition in the olfactory region. Deposition of particles in the nasal cavity is influenced by particle size, airflow rate, and nasal geometry. Therefore, this study investigated the effect of these parameters on regional microparticle deposition with the view to provide insights into the nose-to-brain delivery of drugs. Methods: In this study, three anatomically accurate human nasal cavities were reconstructed in silico and deposition of microparticles under nebulization and bi-directional airflow conditions was simulated. Microparticle deposition data were analyzed to gain insight into the effect of particle size and nasal geometry. Results: Maximum olfactory deposition was observed with particles in the size range of 8 to 12 μm under nebulization and 14 to 18 μm under bi-directional airflow condition. Geometric differences between subjects were shown to significantly impact overall and regional particle deposition and introduced inter-subject variability. Significant intra-subject variability in microparticle deposition was also observed in the bi-directional delivery cases. Conclusions: The data from this study suggest that tailoring particle size, combined with a delivery protocol, may provide a unique and pragmatic way to target drugs to the olfactory region. Differences in nasal anatomy among humans can cause variability in particle deposition and need to be considered in any future applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: High-flow nasal cannula (HFNC) is commonly used to provide respiratory support to pediatric patients with respiratory failure. Although the use of bronchodilators via HFNC has been described, the feasibility and safety of aerosolized bronchodilator delivery via HFNC are controversial. In this study, we sought to evaluate whether the HFNC system can be used to deliver nebulized bronchodilators at lower gas flow of 2-4 L/min, increase patient comfort, and minimize respiratory therapist (RT) bedside time when compared to traditional interfaces. METHODS: A retrospective chart review of all pediatric subjects who were admitted to the pediatric ICU in a tertiary care children's hospital and required nebulized bronchodilators between December 2017 and June 2018. RESULTS: A total of 205 nebulizations were administered to 28 children; 31% of nebulized bronchodilators were given using a nebulization system integrated into the HFNC. Nebulized treatments resulted in an average increase in heart rate of 9.98 (95% CI 3.72-16.2) beats/min when HFNC was used and 0.64 (95% CI -1.65 to 2.93) beats/min when traditional interfaces were used, a difference of 9.34 (95% CI 2.30-16.4) beats/min (P < .001). RT bedside time was significantly longer for HFNC nebulized treatments (P = .031). Subjective level of comfort was not statically different when nebulized bronchodilators were delivered via HFNC or via traditional interfaces. Length of pediatric ICU stay was not statistically different between subjects who received some aerosol nebulized bronchodilators via HFNC versus those who received all bronchodilators through traditional interfaces (P = .11). CONCLUSIONS: Aerosol bronchodilator delivery using HFNC is feasible at low gas flow (ie, 2-4 L/min). However, the use of HFNC did not improve subjects' comfort, and it increased RT bedside time. Further prospective randomized studies are needed to determine the efficacy and efficiency of aerosol therapy delivered through HFNC and potential patient-oriented outcomes. [ABSTRACT FROM AUTHOR]

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.

ObjectiveCurrent 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.DesignProspective animal study.SettingBiosecurity Control Level 2-designated large animal research facility at the Murdoch Children’s Research Institute, Melbourne, Australia.SubjectsFour weaned Border-Leicester/Suffolk lambs at 5 months of age.InterventionsFour 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 ResultsBoth 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.ConclusionsAerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.

Abstract Particle‐based pulmonary delivery has great potential for delivering inhalable therapeutics for local or systemic applications. The design of particles with enhanced aerodynamic properties can improve lung distribution and deposition, and hence the efficacy of encapsulated inhaled drugs. This study describes the nanoengineering and nebulization of metal–phenolic capsules as pulmonary carriers of small molecule drugs and macromolecular drugs in lung cell lines, a human lung model, and mice. Tuning the aerodynamic diameter by increasing the capsule shell thickness (from ≈100 to 200 nm in increments of ≈50 nm) through repeated film deposition on a sacrificial template allows precise control of capsule deposition in a human lung model, corresponding to a shift from the alveolar region to the bronchi as aerodynamic diameter increases. The capsules are biocompatible and biodegradable, as assessed following intratracheal administration in mice, showing >85% of the capsules in the lung after 20 h, but 90% of capsules remaining nonassociated with cells. The amenability to nebulization, capacity for loading, tunable aerodynamic properties, high biocompatibility, and biodegradability make these capsules attractive for controlled pulmonary delivery.

Introduction: Post-operative pharyngeal discomfort or sore throat is unavoidable outcome of endotracheal intubation. There are some pharmacological and non-pharmacological methods for prevention of post-operative sore throat. Nebulization is better than gargle or other methods as small volume of drug required for effect, easy way of administration, better patient compliance and most importantly no risk of aspiration as seen with gargle. Method: Fifty patients of ASA grading I and II, aged between 15-65 years undergoing general anaesthesia on elective basis were randomly divided in two groups. Twenty-five patients received pre-operative nebulization with 1cc ketamine (50mg) with 1cc normal saline while others received nebulization with 1cc Lignocaine 4% with 1cc normal saline. Then General anaesthesia was given. Number of intubation attempts, duration of laryngoscopy and duration of surgery were recorded. Patients were evaluated for post-operative sore throat, hoarseness of voice and cough up to 24hours after extubation. Results: Incidence of post-operative sore throat was reduced with ketamine nebulization while incidence of cough after extubation was less with lignocaine nebulization. Incidence of hoarseness of voice was comparable in both groups. Conclusion: Pre-operative nebulization is simple, safe and effective technique to reduce incidence of post-operative sore throat, hoarseness of voice and cough. Incidence of post-operative sore throat is reduced with pre-operative nebulization with ketamine. In addition, pre-operative nebulization attenuates stress response to laryngoscopy and intubation.

Abstract Background Experimental infection of pigs via direct intranasal or intratracheal inoculation has been mainly used to study the infectious process of influenza A viruses of swine (IAVs-S). Nebulization is known to be an alternative method for inoculating pigs with IAVs-S, because larger quantities of virus potentially can be delivered throughout the respiratory tract. However, there is very little data on the experimental infection of pigs by inhalation using nebulizer. In the current study, we used intranasal nebulization to inoculate pigs with 9 different IAVs-S—3 H1N1, 2 H1N2, and 4 H3N2 strains. We then assessed the process of infection by evaluating the clinical signs, nasal and oral viral shedding, and seroconversion rates of the pigs inoculated. Results Lethargy and sneezing were the predominant clinical signs among pigs inoculated with 7 of the 9 strains evaluated; the remaining 2 strains (1 H1N1 and 1 H1N2 isolate) failed to induce any clinical signs throughout the experiments. Significantly increased rectal temperatures were observed with an H1N1 or H3N2 strains between 1 and 3 days post-inoculation (dpi). In addition, patterns of nasal viral shedding differed among the strains: nasal viral shedding began on 1 dpi for 6 strains, with all 9 viruses being shed from 2 to 5 dpi. The detection of viral shedding was less sensitive from oral samples than nasal secretions. Viral shedding was not detected in either nasal or oral swabs after 10 dpi. According to hemagglutination–inhibition assays, all inoculated pigs had seroconverted to the inoculating virus by 14 dpi, with titers ranging from 10 to 320. Conclusions Our current findings show that intranasal nebulization successfully established IAV-S infections in pigs and demonstrate that clinical signs, viral shedding, and host immune responses varied among the strains inoculated.

Background: Endotracheal intubation is the prominent cause of airway mucosal injury which results in postoperative sore throat (POST), with an incidence of 21%–65%. Although this complication is minor, if left unresolved, it produces significant agony and annoyance to the patient. This study was conducted to evaluate the efficacy of nebulized ketamine in decreasing POST. Materials and Methods: After written informed consent, 96 patients of the American Society of Anesthesiologists physical status (PS) 1–2 between 18 and 60 years, of either sex undergoing general anesthesia (GA) with tracheal intubation were enrolled in this prospective, randomized, placebo-control, and double-blind controlled trial. Patients were randomized into two groups; Group 1 received ketamine 50 mg (1.0 ml) with 4.0 ml of saline nebulization, while Group 2 received saline nebulization 5.0 ml for 15 min. GA was administered 15 min after completing nebulization. On reaching postanesthesia care unit, POST monitoring was done at 0, 2, 4, 6, 12, and 24 h after extubation. POST was graded on a four-point scale (0–3). Results: The overall incidence of POST in this study was 25%: POST was experienced by 7 patients (14.6%) in ketamine and 17 patients (35.4%) in saline group (Fisher's exact P = 0.018). There was statistically significant reduction in the incidence of POST in ketamine group when compared to saline, at 2, 4, 6,12, and 24 h postoperatively (P < 0.05*). Severity of sore throat was also higher in saline group when compared to ketamine at 4 h (P = 0.030*) and 6 h (P = 0.016*) postextubation. Conclusion: Preoperative ketamine nebulization effectively reduced the incidence and severity of POST, with no adverse effects.

Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF.

Background: Bordetella bronchiseptica (Bb) infection commonly causes respiratory disease in dogs. Gentamicin delivered by aerosol maximizes local drug delivery without systemic absorption but clinical response to protocols remains undetermined. Objectives: To compare the clinical response to 2 protocols of aerosolized delivery of gentamicin in bordetellosis. Animals Forty‐six dogs with Bb infection confirmed by culture or quantitative polymerase chain reaction on bronchoalveolar lavage. Methods: Retrospective study. Administration of aerosolized gentamicin for ≥10 minutes q12h for ≥3 weeks using 4 mg/kg diluted with saline (group 1) or undiluted 5% solution (group 2). Clinical response firstly assessed after 3‐4 weeks and treatment pursued by 3‐weeks increments if cure not reached. Cure defined as absence of cough persisting at least a week after treatment interruption. Results: Demographic data were similar between both groups. Clinical cure at 3‐4 weeks was more frequently observed with the use of undiluted solution (19/33 vs 3/13 dogs, P =.03) in association with a shorter median duration of treatment (4 vs 6 weeks, P =.01). Dogs from group 2 having less than 1000 cells/μL in lavage were also more likely to be cured at 3‐4 weeks than dogs with more than 1000 cells/μL [9/9 vs 10/19, P =.006] and median duration of treatment in that subgroup of animals was reduced (3 vs 5 weeks, P =.02). Conclusion and Clinical Importance: Aerosolized delivery of gentamicin seems effective for inducing clinical cure in Bb infection. Clinical response appears better using undiluted 5% solution, particularly in the subgroup of dogs having less than 1000 cells/μL in lavage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present study aimed to formulate and evaluate metformin sterosomes. Sterosomes were prepared by incorporating stearylamine and cholesterol in different ratios. Sterosomes were characterized using size, zeta potential, entrapment efficiency (EE%) and in vitro release. Aerosol generated by nebulization was evaluated by a cooled Andersen cascade impactor (ACI) at 15 L/min. In vitro cytotoxicity of free and metformin-containing sterosomes was tested against human cancer cell lines. A comparative pharmacokinetic study between sterosomal formulation and free drug solution (750 mg) was performed. Spirometry was performed before and at time intervals after inhalation. The mean hydrodynamic diameter of the formulated vesicles was in the range of 288.7–578 nm. The EE% varied from 71 ± 1.4% to 89 ± 5.2%, with an optimum EE% of 89 ± 5.2at a lipid ratio of 2/1 stearylamine/cholesterol. Metformin sterosomes displayed an inhibitory effect on A549 lung cancer cell lines which significantly (p < 0.05) increased depending on dose and prolonged exposure time. Spirometric data were minimally changed before and after inhalation without a statistically significant difference in the forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or FEV1/FVC ratio (p > 0.05). Metformin-loaded sterosomes resulted in a significant increase in biological half-life (t1/2) with a mean value of 7.31 ± 1.04 h compared to 3.99 ± 0.17 h of the solution form. However, the peak plasma concentration of metformin sterosomes was lower than that achieved by metformin-free solution aerosol, and the difference was statistically significant (p < 0.05).The eligibility of sterosomes for aerosol delivery by nebulization would provide a novel strategy for delivery of metformin by inhalation as a potentially effective inhalation treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem/stromal cells (MSCs) have demonstrated promise in pathogenic acute respiratory distress syndrome models and are advancing to clinical efficacy testing. Besides immunomodulatory effects, MSC derived conditioned medium (CM) has direct antibacterial effects, possibly through LL-37 and related secreted peptide activity. We investigated MSC-CM compatibility with vibrating mesh technology, allowing direct delivery to the infected lung. Methods: MSC-CM from bone marrow (BM) and umbilical cord (UC) MSCs were passed through the commercially available Aerogen Solo nebulizer. Known colony forming units of Escherichia coli, Staphylococcus aureus, and multidrug resistant Klebsiella pneumoniae clinical isolates were added to MSC-CM in an orbital shaker and antibacterial capacity assessed through OD600 spectrophotometry. To exclude the possible effects of medium depletion on bacteria proliferation, MSC-CM was concentrated with a 3000 Da cutoff filter, diluted with fresh media, and retested against inoculum. Enzyme-linked immunosorbent assay was used to quantify levels of antimicrobial peptides (AMPs) and IL-8 present at pre- and postnebulization. Results: Both BM and UC MSC-CM inhibited proliferation of all pathogens, and this ability was retained after nebulization. Concentrating and reconstituting CM did not affect antibacterial properties. Interestingly, LL-37 protein did not appear to survive nebulization, although other secreted AMPs and an unrelated protein, IL-8, were largely intact. Conclusion: MSC-CM is a potent antimicrobial agent and is compatible with vibrating mesh nebulization delivery. The mechanism is through a secreted factor that is over 3000 Da in size, although it does not appear to rely solely on previously identified peptides such as LL-37, hepcidin, or lipocalin-2. [ABSTRACT FROM AUTHOR]

The increasing prevalence of multidrug resistant bacteria has warranted the search for new antimicrobial agents as existing antibiotics lose their potency. Among these, bacteriophage therapy, as well as the administration of specific bacteriolysis agents, i.e., lytic enzymes, have emerged as attractive alternatives. Nebulizers offer the possibility for delivering these therapeutics directly to the lung, which is particularly advantageous as a non-invasive and direct route to treat bacterial lung infections. Nevertheless, nebulizers can often result in significant degradation of the bacteriophage or protein, both structurally and functionally, due to the large stresses the aerosolization process imposes on these entities. In this work, we assess the capability of a novel low-cost and portable hybrid surface and bulk acoustic wave platform (HYDRA) to nebulize a Myoviridae bacteriophage (phage K) and lytic enzyme (lysostaphin) that specifically targets Staphylococcus aureus. Besides its efficiency in producing phage or protein-laden aerosols within the 1–5 μ m respirable range for optimum delivery to the lower respiratory tract where lung infections commonly take place, we observe that the HYDRA platform—owing to the efficiency of driving the aerosolization process at relatively low powers and high frequencies (approximately 10 MHz)—does not result in appreciable denaturation of the phages or proteins, such that the loss of antimicrobial activity following nebulization is minimized. Specifically, a low (0.1 log 10 (pfu/ml)) titer loss was obtained with the phages, resulting in a high viable respirable fraction of approximately 90%. Similarly, minimal loss of antimicrobial activity was obtained with lysostaphin upon nebulization wherein its minimum inhibitory concentration (0.5 μ g/ml) remained unaltered as compared with the non-nebulized control. These results therefore demonstrate the potential of the HYDRA nebulization platform as a promising strategy for pulmonary administration of alternative antimicrobial agents to antibiotics for the treatment of lung diseases caused by pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Many important chemical transformations proceed by way of ionic and/or neutral intermediates. Great effort has been expended to understand the mechanism, with only minimum attention given to separate associated ionic and neutral intermediates. Herein, we present a nebulization method followed by on-line ionization to isolate and characterize the ionic and neutral intermediates. The separation of nebulization and ionization and electrical deflection of ionic species guarantee that only neutrals undergo the subsequent on-line ionization. We present data that show the formation of neutral intermediates and iminium ions with short lifetime in Eschweiler-Clarke methylation of di-n-butylamine, as well as data that provide evidence for the formation of carbocation and its isomer lactone products resulting from copper-mediated oxidative cyclization of 4-phenylbutyric acid. Experiments in which dissociation behavior of these two isomers varied at the same collision energy confirmed the carbocation during the cyclization. The nature of this process, which online isolates the ionic and neutral intermediates prior to ionization, greatly advances in mechanistic studies. Image 1 • A nebulization method followed by on-line ionization was developed. • The method enables on-line separation of ionic and neutral intermediates. • Isolating ionic and neutrals intermediates in two reactions was investigated. • The carbocation and its isomer lactone products were readily isolated and identified. [ABSTRACT FROM AUTHOR]

Introduction: Inhalation therapy is a crucial part of the cystic fibrosis (CF) treatment regimen. Drugs that assist in mucociliary clearance and inhaled antibiotics are used by most patients. Methods: This is a cross-sectional study where patients with CF and their caregivers answered questionnaires regarding their adherence to inhalation therapy and QoL. Demographic, spirometric, and bacteriological data, as well as S-K scores and hospitalization frequencies were also collected. Results: We included 66 patients in this study; participants had a mean age of 12.3 years and Z-scores of -1.4 for forced expiratory volume in 1 second and 48.6 for body mass index. Patients were divided into 2 groups according to their self-reported adherence to inhalation therapy: high adherence (n = 46) and moderate/low adherence (n = 20). When comparing both groups, there was no statistically significant differences in age, sex, family income, and S-K score (p > 0.05). The high-adherence group had had shorter hospitalization periods in the previous year (p = 0.016) and presented better scores in the following domains of the QoL questionnaire: emotion (p = 0.006), eating (p = 0.041), treatment burden (p = 0.001), health perception (p = 0.001), and social (p = 0.046). Conclusions: A low self-reported adherence to inhalation therapy recommendations was associated with longer hospitalizations in the previous year and with a decrease in QoL in pediatric patients with CF. [ABSTRACT FROM AUTHOR]

Particle‐based pulmonary delivery has great potential for delivering inhalable therapeutics for local or systemic applications. The design of particles with enhanced aerodynamic properties can improve lung distribution and deposition, and hence the efficacy of encapsulated inhaled drugs. This study describes the nanoengineering and nebulization of metal–phenolic capsules as pulmonary carriers of small molecule drugs and macromolecular drugs in lung cell lines, a human lung model, and mice. Tuning the aerodynamic diameter by increasing the capsule shell thickness (from ≈100 to 200 nm in increments of ≈50 nm) through repeated film deposition on a sacrificial template allows precise control of capsule deposition in a human lung model, corresponding to a shift from the alveolar region to the bronchi as aerodynamic diameter increases. The capsules are biocompatible and biodegradable, as assessed following intratracheal administration in mice, showing >85% of the capsules in the lung after 20 h, but <4% remaining after 30 days without causing lung inflammation or toxicity. Single‐cell analysis from lung digests using mass cytometry shows association primarily with alveolar macrophages, with >90% of capsules remaining nonassociated with cells. The amenability to nebulization, capacity for loading, tunable aerodynamic properties, high biocompatibility, and biodegradability make these capsules attractive for controlled pulmonary delivery. [ABSTRACT FROM AUTHOR]

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, midexpiratory 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. [ABSTRACT FROM AUTHOR]

To examine and compare nebulizing heparin versus streptokinase for reversing alveolar collapse nonresponsive to recruitment. A clinical trial at a tertiary intensive care unit (ICU). Sixty patients with severe acute respiratory distress syndrome (ARDS) (PaO 2 /F I O 2 <100) nonresponsive to recruitment maneuver (RM), prone position, and neuromuscular block (NMB) were randomized into intervention arms or the standard-of-care arm. The ICU at Beni-Suef University Hospital. Sixty patients with severe ARDS (PaO 2 /F I O 2 <100) nonresponsive to RM, PP, and NMB. Nebulized heparin (10,000 IU/4 h), nebulized streptokinase (250,000 IU/4 h), and conservative management. The primary outcome was the change in PaO 2 /F I O 2 ; the secondary outcomes included the change in compliance, plateau pressure, coagulation, and ICU mortality. The PaO 2 /F I O 2 was significantly higher in the streptokinase group from day 1 to day 8 compared to the heparin and standard-of-care groups. Streptokinase produced PaO 2 /F I O 2 >100 at day 1, >200 at day 5, and >300 at day 7. The heparin group achieved a PaO 2 /F I O 2 >100 at day 5 but remained <200 until day 8. The standard-of-care group did not achieve a PaO 2 /F I O 2 >100 after 8 days. Streptokinase significantly reduced plateau pressure and improved compliance at day 8. Only streptokinase decreased PaCO 2 (p < 0.0001). Moreover, ICU mortality was significantly lower in streptokinase patients compared to other groups. Additionally, no heparin-induced thrombocytopenia was observed in all groups. Inhaled streptokinase serves as rescue therapy in patients with severe ARDS with improving oxygenation and lung mechanics more quickly than heparin or conventional management. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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 < 0.0001 versus placebo]. Similar improvements were observed in SGRQ scores in the non-LABA and LABA subgroups [−3.3 (−5.4 to −1.2) and −3.4 (−6.3 to −0.6)]. Improvements in lung function and health outcomes were observed regardless of airflow obstruction severity. Revefenacin was well tolerated with more adverse events reported in the LABA than the non-LABA subgroup. 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. [ABSTRACT FROM AUTHOR]

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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 <.001). Improvement was also compared between the groups. The results were not significant (P =.11). The authors concluded that, in this preliminary research, inhalation aerosol therapy composed of essential oils, saline, glucocorticoids, and antibiotics led to better subjective results than intranasal glucocorticoid therapy and saline irrigation in the treatment of CRS. Further investigations with more participants, longer periods of treatment, and different validation tools are needed to confirm our results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Clinical benefits of inhaled therapies are related to the amount of drug deposited in the targeted area of the lung. Body positions that influence the distribution of lung ventilation should impact lung deposition of the nebulized drug. The aim of this study was to analyze the immediate effect of body position while the subject lies on his side (lateral decubitus) during nebulization on 3-dimen- sional total and regional lung deposition. METHODS: A randomized crossover trial was performed on healthy male volunteers without cardiovascular or pulmonary disease. A technetium-99m diethylene- triaminepentaacetic acid (99mTc-DTPA) solution (4 mL) was nebulized using an individual-controlled inhalation system in left lateral decubitus and sitting positions with a 96-h washout period (43 inspira- tions of 4 s [ie, drug delivered until second 3] with a tidal volume of 0.8 L and a low inspiratory flow (200 mL/s). Drug deposition was followed with the use of planar images and single-photon-emission computed tomography combined with low-resolution computed tomography. Total and regional depo- sitions were the main outcomes. Penetration index was also considered. RESULTS: Six participants (26.8 ± 6.9 y old) were included. Total lung deposition tended to be higher in a sitting position than in a lateral decubitus position: 10.2 ± 0.9% of nominal dose (95% CI 9.1-11.3) vs 8.6 ± 1.4% of nominal dose (95% CI 6.8-10.4) (P = .09). The deposition was significantly reduced in the dependent (left) lung in the lateral decubitus position: 3.5 ± 0.7% of nominal dose (95% CI 2.6-4.3) vs 4.7 ± 0.3% of nominal dose (95% CI 4.3-5.0) (P = .03). Penetration index was only influenced by body position for the dependent (left) lung (P = .043). CONCLUSIONS: The total amount of drug delivered to the lungs during nebulization with an individual-controlled inhalation system tended to decrease when performed in the left lateral decubitus position. Moreover, contrary to the initial hypothesis, the deposition of particles in the dependent lung was not improved by the lateral decubitus position in this configuration. (ClinicalTrials.gov registration NCT02451501.) [ABSTRACT FROM AUTHOR]

Objective: There are currently 39 FDA-approved metered-dose (MDI) or dry-powder inhalers (DPI) on the US market. Most are high cost with significantly more drug in the device than needed for a typical average length of stay in acute care hospitals, which leads to significant waste. The objective was to assess the financial impact and chronic obstructive pulmonary disease (COPD) outcomes of a comprehensive inhaler to nebulization protocol implemented in a large multi-state US health system. Methods: The retrospective study evaluated respiratory drug costs at 28 hospitals in the health system after a phased implementation of the automatic inhaler to nebulization protocol. Purchasing data was collected for all respiratory medications impacted by the protocol for the twelve months preceding as well as the two subsequent twelve-month periods following implementation at each facility. COPD length of stay (LOS) and 30 day readmissions were also reviewed. An attempt was made to evaluate the impact on respiratory therapy (RT) department workload. Results: Compared to pre-implementation, system-wide drug expenditures declined $1,561,011 (38.5%) and $1,646,411 (40.6%) in post-implementation year 1 (PY1) and post-implementation year 2 (PY2), respectively. COPD LOS and 30 day readmissions were not adversely affected and remained relatively stable in comparative periods. Objective impact on RT productivity and labor statistics was not ascertained due to complicated variables and multiple service lines. Conclusions: In an era of increased drug costs incurred by hospitals, a comprehensive inhaler to nebulization protocol significantly decreased costs without incurring any negative observed trends in COPD LOS or readmissions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• This manuscript describes efficacy of nebulized mesenchymal stem cell on smoke inhalation-induced acute lung injury. • The one-time nebulization of 10 million mesenchymal stem cell may be insufficient to alleviate the severity of ARDS. • Further studies are needed to improve the survival of mesenchymal stem cell in harsh airway conditions. Treatment of ARDS caused by smoke inhalation is challenging with no specific therapies available. The aim of this study was to test the efficacy of nebulized adipose-derived mesenchymal stem cells (ASCs) in a well-characterized, clinically relevant ovine model of smoke inhalation injury. Fourteen female Merino sheep were surgically instrumented 5–7 days prior to study. After induction of acute lung injury (ALI) by cooled cotton smoke insufflation into the lungs (under anesthesia and analgesia), sheep were placed on a mechanical ventilator for 48 hrs and monitored for cardiopulmonary hemodynamics in a conscious state. ASCs were isolated from ovine adipose tissue. Sheep were randomly allocated to two groups after smoke injury: 1) ASCs group (n = 6): 10 million ASCs were nebulized into the airway at 1 hr post-injury; and 2) Control group (n = 8): Nebulized with saline into the airways at 1 hr post-injury. ASCs were labeled with green fluorescent protein (GFP) to trace cells within the lung. ASCs viability was determined in bronchoalveolar lavage fluid (BALF). PaO 2 /FiO 2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO 2 /PaO 2) was significantly lower in the ASCs group at 36 hr (p = 0.003). Pulmonary shunt fraction tended to be lower in the ASCs group as compared to the control group. GFP-labelled ASCs were found on the surface of trachea epithelium 48 hrs after injury. The viability of ASCs in BALF was significantly lower than those exposed to the control vehicle solution. Nebulized ASCs moderately improved pulmonary function and delayed the onset of ARDS. [ABSTRACT FROM AUTHOR]

Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy. According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022. Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed. In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases. • The systematic scooping review summarized the current evidence of nebulized liposomal amphotericin B therapy. • Increasing evidence for patients after lung transplantation and with hemato-oncological diseases was noticed. • Further investigations, including randomized controlled studies, are warranted. [ABSTRACT FROM AUTHOR]

In vitro-transcribed (IVT) mRNA has come into focus in recent years as a potential therapeutic approach for the treatment of genetic diseases. The nebulized formulations of IVT-mRNA-encoding alpha-1-antitrypsin (A1AT-mRNA) would be a highly acceptable and tolerable remedy for the protein replacement therapy for alpha-1-antitrypsin deficiency in the future. Here we show that lipoplexes containing A1AT-mRNA prepared in optimum conditions could successfully transfect human bronchial epithelial cells without significant toxicity. A reduction in transfection efficiency was observed for aerosolized lipoplexes that can be partially overcome by increasing the initial number of components. A1AT produced from cells transfected by nebulized A1AT-mRNA lipoplexes is functional and could successfully inhibit the enzyme activity of trypsin as well as elastase. Our data indicate that aerosolization of A1AT-mRNA therapy constitutes a potentially powerful means to transfect airway epithelial cells with the purpose of producing functional A1AT, while bringing along the unique advantages of IVT-mRNA.

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.

Due to the low and erratic bioavailability of oral tacrolimus (TAC), the long-term survival rate following lung transplantation remained low compared to other solid organs. TAC was reformulated and developed as inhaled formulations by thin film freezing (TFF). Previous studies reported that inhaled TAC combined with 50% w/w lactose (LAC) was safe and effective for the treatment of lung transplant rejection in rodent models. In this study, we aimed to investigate the safety and tolerability of TFF TAC-LAC in human subjects. The formulation can be delivered to the lung as colloidal dispersions after reconstitution and as a dry powder. Healthy subjects inhaled TAC-LAC colloidal dispersions at 3 mg TAC/dose via a vibrating mesh nebulizer in the first stage of this study and TAC-LAC dry powder at 3 mg TAC/dose via a single dose dry powder inhaler in the second stage. Our results demonstrated that oral inhalation of TAC-LAC colloidal dispersions and dry powder exhibited low systemic absorption. Additionally, they were well-tolerated with no changes in CBC, liver, kidney, and lung functions. Only mild adverse side effects (e.g., cough, throat irritation, distaste) were observed. In summary, pulmonary delivery of TFF TAC-LAC would be a safe and promising therapy for lung transplant recipients.

Background Indonesian guidelines for childhood asthma recom- mend giving ipratropium bromide when there are no improvement after 2 times salbutamol nebulization. The efficacy and safety of early nebulization of ipratropium bromide combined with salbutamol as first line in moderate asthma exacerbation in children are still unknown. Objective To compare efficacy and safety between nebulized salbutamol-ipratropium bromide and salbutamol alone in children with moderate asthma exacerbation. Methods Fifty-two children (2-6 years) with acute asthma (clinical score 5-10) were enrolled into a randomized single blind controlled trial comparing 2 groups of 2.5 mg nebulized salbutamol (group 1) and 2.5 mg salbutamol combined with 0.5 mg ipratropium bromide (group 2). Nebulization was given until clinical score decreased 0.05). There were no toxic effects attributable to ipratropium bromide, and the side effects were not different between these two groups. Conclusion The combination of nebulized ipratropium bromide and salbutamol in a child with acute moderate asthma exacerba- tion was associated with higher reduction of clinical score and higher oxygen saturation, and may reduce hospitalization