Evaluation of the effectiveness and safety of sequential vaccination with inactivated SARS-CoV-2 vaccine and Ad5-nCoV booster in pediatric liver transplant recipients.

Amidst the COVID-19 pandemic, uncertainty persists among caregivers regarding the vaccination of pediatric liver transplant recipients (PLTRs). This study evaluates the immunogenicity and safety of COVID-19 vaccination in this vulnerable population. A cohort of 30 PLTRs underwent sequential vaccinations with an inactivated SARS-CoV-2 vaccine followed by an Ad5-nCoV booster. We collected and analyzed blood samples pre-vaccination and four weeks post-vaccination to quantify antibody and IGRA (IFN-γ Release Assay) levels. We also documented any adverse reactions occurring within seven days post-vaccination and monitored participants for infections over six months post-vaccination, culminating in a comprehensive statistical analysis. The Ad5-nCoV booster substantially elevated IgG (T1: 18.01, 20%; T2: 66.61, 55%) and nAb (T1: 119.29, 8%; T2: 3799.75, 80%) levels, as well as T-cell responses, in comparison to the initial dose. The first dose was associated with some common adverse reactions, such as injection site pain (13.3%) and fever (16.6%), but a low rate of systemic reactions (16.0%). There was no significant difference in Omicron infection rates or RTPCR conversion times between vaccinated and unvaccinated groups. Notably, following Omicron infection, vaccinated individuals exhibited significantly higher SARS-CoV-2 IgG and nAb titers (average IgG: 231.21 vs. 62.09 S/CO, p = 0.0003; nAb: 5246.11 vs. 2592.07 IU/mL, p = 0.0002). The use of inactivated vaccines followed by an Ad5-nCoV booster in PLTRs is generally safe and elicits a robust humoral response, albeit with limited T-cell responses.

Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Atomized inhalation of Icaritin reduces airway inflammation and remodeling in asthmatic mice.

BACKGROUND: Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice. METHOD: Different groups of ovalbumin (OVA)-induced asthma mice with acute and chronic airway inflammation received ICT. Asthmatic mice received budesonide (BDND) aerosol inhalation as a positive control, while normal control and asthma model mice received the same volume of saline. Following finishing of the study, analyses were conducted on behavioral tests, biochemical indices, and histological structures of lung tissues. RESULTS: Aerosol inhalation of ICT can notably reduce inflammatory cells infiltration around the airways and pulmonary vessels, and suppressed goblet cell hyperplasia in asthmatic mice. Long-term inhalation of ICT can decrease airway collagen deposition and airway smooth muscle hyperplasia, and alleviate airway hyperresponsiveness, mirroring the effects observed with hormone employed in clinical practice. CONCLUSION: Nebulized inhalation of ICT can effectively inhibit airway inflammation in asthmatic mice, improve airway remodeling, and reduce airway hyperresponsiveness, with effects similar to those of hormones. It may serve as a potential candidate used as a hormone replacement asthma treatment.

Expert panel consensus recommendations on the utilization of nebulized budesonide for managing asthma and COPD in both stable and exacerbation stages in Thailand.

OBJECTIVE: This study investigated the utilization of nebulized budesonide for acute asthma and COPD exacerbations as well as for maintenance therapy in adults. DATA SOURCES: We conducted a search on PubMed for nebulized budesonide treatment. SELECTED STUDIES: Selecting all English-language papers that utilize Mesh phrases "asthma," "COPD," "budesonide," "nebulized," "adult," "exacerbation," and "maintenance" without temporal restrictions, and narrowing down to clinical research such as RCTs, observational studies, and real-world studies. RESULTS: Analysis of 25 studies was conducted to assess the effectiveness of nebulized budesonide in asthma (n = 10) and COPD (n = 15). The panel in Thailand recommended incorporating nebulized budesonide as an additional or alternative treatment option to the standard of care and systemic corticosteroids (SCS) based on the findings. CONCLUSION: Nebulized budesonide is effective and well-tolerated in treating asthma and COPD, with less systemic adverse effects compared to systemic corticosteroids. High-dose nebulized budesonide can enhance clinical outcomes for severe and mild exacerbations with slow systemic corticosteroid response. Nebulized budesonide can substitute systemic corticosteroids in some situations.

A non-inferiority randomized controlled trial comparing nebulized ketamine to intravenous morphine for older adults in the emergency department with acute musculoskeletal pain.

OBJECTIVE: Our study aimed to investigate the analgesic efficacy of nebulized ketamine in managing acute moderate-to-severe musculoskeletal pain in older emergency department (ED) patients compared with intravenous (IV) morphine. METHODS: This was a non-inferiority, double-blind, randomized controlled trial conducted at a single medical centre. The patients aged 65 and older, who presented at the ED musculoskeletal pain within 7 days and had a pain score of 5 or more on an 11-point numeric rating scale (NRS), were included in the study. The outcomes were a comparison of the NRS reduction between nebulized ketamine and IV morphine 30 minutes after treatment, incidence of adverse events and rate of rescue therapy. RESULTS: The final study included 92 individuals, divided equally into two groups. At 30 minutes, the difference in mean NRS between the nebulized ketamine and IV morphine groups was insignificant (5.2 versus 5.7). The comparative mean difference in the NRS change from baseline between nebulized ketamine and IV morphine [-1.96 (95% confidence interval-CI: -2.45 to -1.46) and -2.15 (95% CI: -2.64 to -1.66) = 0.2 (95% CI: -0.49 to 0.89)] did not exceed the non-inferiority margin of 1.3. The rate of rescue therapy did not differ between the groups. The morphine group had considerably higher incidence of nausea than the control group (zero patients in the ketamine group versus eight patients (17.4%) in the morphine group; P = 0.006). CONCLUSIONS: Nebulized ketamine has non-inferior analgesic efficacy compared with IV morphine for acute musculoskeletal pain in older persons, with fewer adverse effects.

Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin B and amphotericin B deoxycholate for antifungal prophylaxis after lung transplantation.

INTRODUCTION: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB. PATIENTS AND METHODS: Patients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB. RESULTS: Both regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05). DISCUSSION: These results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy.

Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials).

Rationale: Ensifentrine is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory effects. Replicate phase III trials of nebulized ensifentrine were conducted (ENHANCE-1 and ENHANCE-2) to assess these effects in patients with chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of ensifentrine compared with placebo for lung function, symptoms, quality of life, and exacerbations in patients with COPD. Methods: These phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled trials were conducted between September 2020 and December 2022 at 250 research centers and pulmonology practices in 17 countries. Patients aged 40-80 years with moderate to severe symptomatic COPD were enrolled. Measurements and Main Results: Totals of 760 (ENHANCE-1) and 789 (ENHANCE-2) patients were randomized and treated, with 69% and 55% receiving concomitant long-acting muscarinic antagonists or long-acting ß2-agonists, respectively. Post-bronchodilator FEV1 percentage predicted values were 52% and 51% of predicted normal. Ensifentrine treatment significantly improved average FEV1 area under the curve at 0-12 hours versus placebo (ENHANCE-1, 87 ml [95% confidence interval, 55, 119]; ENHANCE-2, 94 ml [65, 124]; both P < 0.001). Ensifentrine treatment significantly improved symptoms (Evaluating Respiratory Symptoms) and quality of life (St. George's Respiratory Questionnaire) versus placebo at Week 24 in ENHANCE-1 but not in ENHANCE-2. Ensifentrine treatment reduced the rate of moderate or severe exacerbations versus placebo over 24 weeks (ENHANCE-1, rate ratio, 0.64 [0.40, 1.00]; P = 0.050; ENHANCE-2, rate ratio, 0.57 [0.38, 0.87]; P = 0.009) and increased time to first exacerbation (ENHANCE-1, hazard ratio, 0.62 [0.39, 0.97]; P = 0.038; ENHANCE-2, hazard ratio, 0.58 [0.38, 0.87]; P = 0.009). Adverse event rates were similar to those for placebo. Conclusions: Ensifentrine significantly improved lung function in both trials, with results supporting exacerbation rate and risk reduction in a broad COPD population and in addition to other classes of maintenance therapies. Clinical trial registered with www. CLINICALTRIALS: gov and EudraCT (ENHANCE-1, www. CLINICALTRIALS: gov identifier NCT04535986, EudraCT identifier 2020-002086-34; ENHANCE-2, www. CLINICALTRIALS: gov identifier NCT04542057, EudraCT identifier 2020-002069-32).

Targeting LINC070974 inhibits lung adenocarcinoma cell proliferation and progression by interacting with Y-box binding protein 1.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Increasing evidence suggests that long noncoding RNAs play crucial roles in lung cancer pathogenesis. We previously identified a novel lncRNA, LINC070974, which is associated with tumor cell proliferation. In the present study, we find that knockdown of LINC070974 inhibits cell proliferation, migration and invasion as well as tumor formation both in vitro and in nude mice. LINC070974 silencing also improves cisplatin efficacy in A549/DDP cells. The function of LINC070974 may depend on its interaction with YBX1. Knockdown of LINC070974 reduces the recruitment of YBX1 to the CCND1 promoter and delays tumor progression through its coregulatory genes, which are mainly involved in the p53 signaling pathway. We utilize nebulized inhalation to deliver siRNAs targeting LINC070974 and find that LINC070974 significantly prevents tumor metastasis and growth in lung tissues. These findings reveal the role of LINC070974 in lung cancer and suggest a promising therapeutic approach involving siRNA inhalation.

Sedative and behavioral effects of atomized intranasal midazolam in comparison with nebulized midazolam for children undergoing dental treatment: A randomized clinical trial.

BACKGROUND: Fear and anxiet are significant barriers of dental care in children. Sedation emerged as a valuable behaviour guidance technique to manage uncooperative children. AIM: To evaluate the sedative and behavioral effectiveness of midazolam administered via nebulizer in comparison with intranasal atomizer in the behavior management of anxious children during dental treatment. STUDY DESIGN: Two-arm randomized clinical trial with 68 children (3-5 years) assigned to receive nebulized midazolam (NEB MDZ) and atomized intranasal midazolam (AIN MDZ) during dental treatment. The onset time, sedation levels, and behavior of children were documented. The data were analyzed using the Wilcoxon signed-rank test and Mann-Whitney U tests. RESULTS: Significant differences between the two groups in terms of onset time, sedation level, and behavior of children during the dental treatment. AIN MDZ was associated with a significantly faster onset time compared with NEB MD, (p < .001). Children who received NEB MDZ exhibited deeper levels of sedation compared with AIN MDZ group (p = .02). During the administration of local anesthesia, notable statistical differences were observed between the behavior of the two groups (p = .02). CONCLUSIONS: Midazolam administered via either nebulizer or intranasal atomizer was the effective route of administration and proved effective in the management of anxious children undergoing dental treatment. AIN MDZ, however, exhibited a faster onset time, whereas children receiving NEB MDZ demonstrated superior behavior compared with those receiving AIN MDZ.

Comparison of doses of Nebulized Magnesium sulphate as an adjuvant treatment with salbutamol in children with Status Asthmaticus.

Objectives: To compare the response between different doses of nebulized magnesium sulphate along with Salbutamol in children between two to 12 years of age with status asthmaticus. Methods: This single blinded, randomized clinical trial was carried out at the Department of Pediatrics, Dr. Ziauddin University Hospital, Karachi, Pakistan during October 2021 to September 2022. A total of 104 children aged between 2-12 years, with the diagnosis of asthma having "Pediatric Rapid Assessment Measure (PRAM)" score>4 and with reactive airways were included. Children either received three back-to-back nebulization with salbutamol solution only (n=50) or salbutamol and MgSO4 with three different doses (250mg, 500mg or 750mg) after every 20 minutes for 60 minutes. The PRAM score was used as an assessment tool to clinically score asthma. Results: In a total of 104 children, 53 (51.0%) were girls. The mean age was 5.25±2.86 years. No statistically significant difference was found in PRAM scores at baseline (p=0.448) and at 20-minutes (p=0.072) but significant differences were observed at 40-minutes (p=0.009), 60-minutes (p=0.011), 120-minutes (p=0.010), 6-hours (=0.034), 12-hours (p=0.018), 18-hours (p=0.033) and at 24-hours (p=0.029). The reduction in PRAM scores from baseline to 24-hours following treatment among Salbutamol, Salbutamol+ MgSo4 250mg, Salbutamol+ MgSo4 500mg and Salbutamol+ MgSo4 750mg group were 6.53±1.09, 7.22±1.09, 6.85±1.43 and 7.57±1.06 respectively (p=0.007). Conclusion: While children with status asthmaticus managed using salbutamol, with or without nebulized MgSO4, showed improved clinical outcomes, combining salbutamol with higher dosages of nebulized MgSO4 resulted in even greater clinical improvement.Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT04929626.

Efficacy of lignocaine nebulization in patients with COVID-19 respiratory infection: An exploratory randomized double-blinded controlled trial.

Background and Aims: Coronavirus disease (COVID-19)-related pneumonia is proposed to be an inflammatory process. The treatment currently includes supportive therapy and low-dose steroids. Anti-inflammatory drugs have been proposed to prevent cytokine storms and improve oxygenation in such cases. The study aimed to assess the efficacy of nebulized lignocaine in COVID-19 patients with pneumonia. Material and Methods: This was an exploratory randomized double-blinded control trial conducted in COVID-19 patients with respiratory failure requiring oxygen therapy either by face mask or non-invasive mechanical ventilation. Patients included were of the age of more than 18 years of either gender. The patients were randomized to receive either lignocaine or distilled water nebulization. The outcomes assessed were PaO2/FiO2 ratio, hemodynamics, respiratory parameters, and sequential organ failure score (SOFA). Results: The two groups were comparable concerning demographic variables. The PaO2/FiO2 were significantly higher in the lignocaine group from day 2 onward. The SPO2 was significantly higher on day 3 in the lignocaine group and thereafter there was no significant difference. Other hemodynamic, respiratory parameters, and SOFA scores showed no difference in both the groups. Conclusion: Lignocaine nebulization improved oxygenation in COVID-19 patients and can be used as adjunctive therapy along with other supportive medications.

A multicentre neonatal interventional randomised controlled trial of nebulized surfactant for preterm infants with respiratory distress: Neo-INSPIRe trial protocol.

INTRODUCTION: Respiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce. Recent trials from high-resourced countries utilising aerosolized surfactant have had a low quality of evidence and varying outcomes. METHODS AND ANALYSIS: The Neo-INSPIRe trial is an unblinded, multicentre, randomised trial of a novel aerosolized surfactant drug/device combination. Inclusion criteria include preterm infants of 27-34+6 weeks' gestational age who weigh 900-1999g and who require CPAP with a fraction of inspired oxygen (FiO2) of 0.25-0.35 in the first 2-24 h of age. Infants are randomised 1:1 to control (CPAP alone) or intervention (CPAP with aerosolized surfactant). The primary outcome is the need for intratracheal bolus surfactant instillation within 72 h of age. Secondary outcomes include the incidence of reaching failure criteria (persistent FiO2 of > 0.40, severe apnoea or severe work of breathing), the need for and duration of ventilation and respiratory support, bronchopulmonary dysplasia and selected co-morbidities of prematurity. Assuming a 40% relative risk reduction to reduce the proportion of infants requiring intratracheal bolus surfactant from 45 to 27%, the study will aim to enrol 232 infants for the study to have a power of 80% to detect a significant difference with a type 1 error of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been granted by the relevant human research ethics committees at University of Cape Town (HREC 681/2022), University of the Witwatersrand HREC (221112) and Stellenbosch University (M23/02/004). TRIAL REGISTRATION: PACTR202307490670785.

Nebulized Heparin to Reduce COVID-19-induced Acute Lung Injury: A Prospective Observational Study.

Background: High mortality due to COVID-19 disease has been a serious concern, a few of the causes being disseminated intravascular coagulation (DIC) and venous thromboembolism. Considering this, some experts have used heparin. However, its role still needs to be validated. Materials and methods: This study predicts the role of nebulized heparin in decreasing the severity of lung injury caused by COVID-19. Thirty patients admitted with COVID-19 acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) of All India Institute of Medical Sciences, Rishikesh, were included in this study, which was conducted over a period of 3 months. Patients were nebulized with 2 mL of heparin 5,000 units/mL IV formulation diluted with 3 mL of 0.9% sodium chloride, every 6 hours for a total duration of 7 days. Improvement in oxygenation (ratio of partial pressure of oxygen in blood and fraction of inspired oxygen delivered, pO2/FiO2 ratio) was calculated as the primary outcome. Other parameters like effect on inflammatory markers (neutrophil-lymphocyte ratio, total leukocyte count, interleukin (IL-6), and D-dimer values), time to liberate from mechanical ventilation, and hospital stay were calculated as secondary outcomes. Results: In our study population, the mean age was 54.5 years and the majority of patients were males (79.0%). All patients received prone ventilation and none of them required tracheostomy. However, 5 patients (16.6%) succumbed to illness. After nebulization with unfractionated heparin, no statistically significant difference was seen in the neutrophil-lymphocyte ratio (mean = 6.87, p = 0.318) and interleukin (IL-6) levels (mean = 62.85, p = 0.6) over 7 days. Similarly, the D-dimer level also had no statistically significant change (mean = 1853.73 p = 0.570). However, there was a statistically significant improvement in oxygenation (pO2/FiO2 ratio) over 7 days (mean = 184.96, p = 0.00). Similarly, there was a significant improvement in PaO2 (84.17 ± 33.82) and SO2 (92.30 ± 3.49). Although, no significant changes were seen in the partial pressure of carbon dioxide on nebulized heparin administration. Conclusion: Administration of nebulized heparin in COVID-19 pneumonia with mild ARDS may improve oxygenation and result in the improvement of inflammatory markers with variable sensitivity and specificity. How to cite this article: Gupta B, Chandrakar S, Gupta N, Jain G. Nebulized Heparin to Reduce COVID-19-induced Acute Lung Injury: A Prospective Observational Study. Indian J Crit Care Med 2023;27(3): 222-224.

Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review.

Coronavirus disease-2019 (COVID-19) is an extremely contagious illness caused by the SARS-CoV-2 virus and has been declared a pandemic by the World Health Organization (WHO). There are currently no particular treatments, however, nebulized heparin has been offered as a viable therapy. The purpose of this systematic review is to assess the efficacy of nebulized heparin in COVID-19 patients with respiratory symptoms. Methods: Relevant studies were identified through a systematic search of the PubMed, Medline, Embase, Cochrane Library and Web of Science, and Scopus databases. The search terms included "nebulized heparin," "COVID-19," and "SARS-CoV-2." Studies that evaluated the use of nebulized heparin in COVID-19 patients with respiratory symptoms were included. The rest of the studies along with those that were not published in English were excluded. The systematic review was registered under PROSPERO-CRD42023413927. Observations: Five studies have been included in this systematic review. Case reports, case series, observational studies, and randomized controlled trial (RCT) comprised the studies. The patient sample sizes ranged from 2 to 98. The studies assessed the efficacy of nebulized heparin in COVID-19 patients with variable disease severity. The evaluated outcomes included mortality, hospital stay duration, oxygen requirements, and laboratory parameters. Conclusion: Based on the clinical studies included in this systematic review, nebulized heparin may be useful in the management of COVID-19. Oxygen saturation was greater, inflammatory indicators were lower, and hospital stays were shorter in these patients. However, the studies had limitations, including inconsistent sample sizes, varying dosages of nebulized heparin, and no control groups. Nebulized heparin in patients with COVID-19 needs to be studied further to determine its safety and effectiveness. How to cite this article: Gupta B, Ahluwalia P, Gupta N, Gupta A. Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review. Indian J Crit Care Med 2023;27(8):572-579.

A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome.

OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.

Nebulized Salbutamol with or without Magnesium Sulphate in the Management of Acute Asthma in Children in India: A Randomized Controlled Trial.

BACKGROUND: There is inconclusive evidence on the role of nebulized magnesium sulphate (MgSO4) in the management of acute asthma in paediatric population. OBJECTIVES: Whether the use of nebulized salbutamol with or without MgSO4 in the management of acute asthma results in clinically significant improvement in lung function in Indian children? The primary outcome measure was to assess improvements in peak expiratory flow rate (PEFR), heart rate, respiratory rate and SpO2. METHODS: This was a single centre; prospective double-blind randomized control trial conducted in paediatric intensive care unit of a tertiary care centre. Ninety children of 6-14 years with acute exacerbations of bronchial asthma were enrolled to receive either inhaled magnesium sulphate (95 mg) with salbutamol (5 mg) or inhaled salbutamol (5 mg) alone. All patients got three nebulizations done during the first hour at 20 min intervals, two nebulizations during the second hour at 30 min intervals, hourly for the next 2 h and then at 24 and 48 h. RESULTS: Eighty-five patients were finally analysed as per protocol analysis. The trial showed that PEFR increased gradually in both groups over the study duration, but it was statistically not significant. Heart rate decreased significantly in both groups over the study duration. Respiratory rate decreased significantly between the groups at 24 and 48 h only. SpO2 improved too in both groups but was not significant statistically. CONCLUSION: The addition of nebulized MgSO4 to salbutamol does not seem to result in improvement in lung function in the management of acute asthma in Indian children.

Nebulized budesonide combined with systemic corticosteroid vs systemic corticosteroid alone in acute severe asthma managed in the emergency department: a randomized controlled trial.

BACKGROUND: The additive benefit of inhaled corticosteroid when used with systemic corticosteroid in acute asthma is still unclear. The objective of this study was to assess the effect of high and repeated doses of inhaled budesonide when combined with the standard treatment of adult acute asthma. METHODS: It was a prospective double-blind randomized controlled study performed in the emergency department (ED) from May 1, 2010 to February 28, 2011 (ClinicalTrials.gov, NCT04016220). Fifty patients were included and were randomized to receive intravenous hydrocortisone hemisuccinate in association with nebulized budesonide (n = 23, budesonide group) or normal saline (n = 27, control group). Nebulization of budesonide or saline was done in combination with 5 mg of terbutaline every 20 min the first hour, then at 2 h (H2), and 3 h (H3). All patients received standard treatment. Efficacy and safety of inhaled budesonide were evaluated every 30 min for 180 min. RESULTS: A significant increase in peak expiratory flow (PEF) was observed in both treatment groups at evaluation times. The increase in PEF persisted significantly compared to the previous measurement in both groups. There was no significant difference in the PEF between the two groups at evaluation times. There was no significant difference between the two groups in the evolution in the respiratory rate and heart rate. There was also no statistically significant difference between the two groups in the rate of hospitalization, the discharge criteria before the end of the protocol. CONCLUSIONS: Considering its limited power, our study suggests that the association of nebulized budesonide with hydrocortisone hemisuccinate has no additional effect over the use of hydrocortisone alone in adults' acute asthma managed in the ED.

Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model.

Acute lung injury (ALI) as a model of acute respiratory distress syndrome is characterized by inflammation, complex coagulation, and hematologic abnormalities which result in the formation of fibrin-platelet microthrombi in the pulmonary vessels with the rapid development of progressive respiratory dysfunction. We hypothesize that a nebulized fibrinolytic agent, non-immunogenic staphylokinase (nSta), may be useful for ALI therapy. First, the effect of the nebulized nSta (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg) on the coagulogram parameters was studied in healthy rats. ALI was induced in mice by nebulized administration of lipopolysaccharide (LPS) at a dose of 10 mg/kg. nSta (0.2 mg/kg, 0.4 mg/kg or 0.6 mg/kg) was nebulized 30 min, 24 h, and 48 h after LPS administration. The level of pro-inflammatory cytokines was determined in the blood on the 8th day after LPS and nSta administration. The assessment of lung damage was based on their weighing and microscopic analysis. Fibrin/fibrinogen deposition in the lungs was determined by immunohistochemistry. After nSta nebulization in healthy rats, the fibrinogen blood level as well as activated partial thromboplastin time and prothrombin time did not change. In the nebulized ALI model, the mice showed an increase in lung weight due to their edema and rising fibrin deposition. An imbalance of proinflammatory cytokines was also found. Forty percent of mice with ALI without nSta nebulization had died. Nebulized nSta at a dose of 0.2 mg/kg reduced the severity of ALI: a decrease in interstitial edema and inflammatory infiltration was noted. At a dose of 0.4 mg/kg of nebulized nSta, the animals showed no peribronchial edema and the bronchi had an open clear lumen. At a dose of 0.6 mg/kg of nebulized nSta, the manifestations of ALI were completely eliminated. A significant dose-dependent reduction of the fibrin-positive areas in the lungs of mice with ALI was established. Nebulized nSta had a normalizing effect on the proinflammatory cytokines in blood- interleukin (IL)-1α, IL-17A, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These data showed the effectiveness of nebulized nSta and the perspectives of its clinical usage in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Home Use Guidance for Aerosol-Generating Procedures During the Coronavirus Disease 2019 Pandemic.

From the early days of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were concerns that nebulizers used for the treatment of respiratory diseases as aerosol-generating devices could enhance the transmission of SARS-CoV-2. However, given the absence of any compelling data showing that nebulized treatments increase the risk of SARS-CoV-2 infection, it is unnecessary for community-dwelling patients with respiratory diseases to alter their current therapies, including nebulized treatments, to prevent symptom exacerbations. Maintaining current inhaled therapies also minimizes the risk of hospitalization and hospital-acquired infection of SARS-CoV-2.

Long-term use of liposomal nebulized amikacin and tedizolid for the treatment of disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation.

Nocardiosis is a life-threatening opportunistic infection in immunocompromised patients. Herein, we present successful adjunctive use of liposomal nebulized amikacin and tedizolid in a recipient of allogeneic hematopoietic stem cell transplantation infected with Nocardia nova complex who presented multiple complications to conventional therapeutic options.