Search

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

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

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

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

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

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

BackgroundPharmacological 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.MethodsDecision 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.ResultsThe 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.ConclusionThe 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.

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

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

Mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) turn out to be a promising source of cell‐free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose‐derived MSC‐EVs (haMSC‐EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC‐EVs in healthy volunteers. DiR‐labelled haMSC‐EVs were used to explore the distribution of nebulized haMSC‐EVs in the murine model. Pseudomonas aeruginosa‐induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL‐6, TNF‐α and IL‐10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC‐EVs through the nebulized route. Twenty‐four healthy volunteers were involved and received the haMSC‐EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, {"type":"clinical-trial","attrs":{"text":"NCT04313647","term_id":"NCT04313647"}}NCT04313647). Nebulizing haMSC‐EVs improved survival rate to 80% at 96 h in P. aeruginosa‐induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC‐EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC‐EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC‐EVs in lung injury diseases.

Background In recent years, nasal intermittent positive pressure ventilation (NIPPV) has been growing in popularity as a form of noninvasive ventilation for respiratory support in the initial treatment of neonates with surfactant (SF) deficiency. The combination of this type of ventilation with noninvasive SF administration (by nebulization) is an attractive treatment option for respiratory distress syndrome (RDS)-associated pathophysiology of the neonatal lungs. In this study, we aimed to test the tolerability and efficacy of SF nebulization during NIPPV for the treatment of neonatal RDS. Methods Spontaneously-breathing newborn piglets (n = 6/group) with bronchoalveolar lavage (BAL)-induced RDS were assigned to receive during NIPPV (180 min): poractant alfa (400 mg/kg) via an investigational customized vibrating-membrane nebulizer (eFlow-Neos) or poractant alfa (200 mg/kg) as a bolus using the Insure method or no surfactant (controls). Measurement and results We assessed pulmonary, hemodynamic and cerebral effects and performed histological analysis of lung and brain tissue. After repeated BAL, newborn piglets developed severe RDS (FiO2: 1, pH 70 mmHg, PaO2

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

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

One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.

La nébulisation est un mode d’administration des traitements inhalés dont la prescription et la mise en place restent délicates. Ces bonnes pratiques, réalisées par le GAT (groupe aérosolthérapie de la SPLF), étaient nécessaires, les dernières datant de 2007. Plus encore qu’une actualisation des données sur le sujet, ces recommandations d’experts se veulent une vraie aide pour le prescripteur. [Good practice for aerosol therapy by nebulization in 2020] Nebulization is a drug delivery mode whose prescription and application remain uncertain. A guide to good practice has been proposed by the work group on aerosol therapy of the French Society for Respiratory Diseases, so-called GAT. The previous recommendations date from 2007. In addition to an update of data on nebulization, these expert recommendations aim to be of real help to the prescriber.

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

Copyright © 2021 The Authors. Water transport and local (airway) hydration are critical for the normal functioning of lungs and airways. Currently, there is uncertainty regarding the effects of systemic dehydration on pulmonary function. Our aims were 1) to clarify the impact of exercise- or fluid restriction-induced dehydration on pulmonary function in healthy adults; and 2) to establish whether systemic or local rehydration can reverse dehydration-induced alterations in pulmonary function. Ten healthy participants performed four experimental trials in a randomized order (2 h exercise in the heat twice and 28 h fluid restriction twice). Pulmonary function was assessed using spirometry and whole body plethysmography in the euhydrated, dehydrated, and rehydrated states. Oral fluid consumption was used for systemic rehydration and nebulized isotonic saline inhalation for local rehydration. Both exercise and fluid restriction induced mild dehydration (2.7 ± 0.7% and 2.5 ± 0.4% body mass loss, respectively; P < 0.001) and elevated plasma osmolality (P < 0.001). Dehydration across all four trials was accompanied by a reduction in forced vital capacity (152 ± 143 mL, P < 0.01) and concomitant increases in residual volume (216 ± 177 mL, P < 0.01) and functional residual capacity (130 ± 144 mL, P < 0.01), with no statistical differences between modes of dehydration. These changes were normalized by fluid consumption but not nebulization. Our results suggest that, in healthy adults: 1) mild systemic dehydration induced by exercise or fluid restriction leads to pulmonary function impairment, primarily localized to small airways; and 2) systemic, but not local, rehydration reverses these potentially deleterious alterations.

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

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

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

International audience

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

International audience; Mucormycosis are life-threatening fungal infections especially affecting immunocompromised or diabetic patients. Despite treatment, mortality remains high (from 32 to 70% according to organ involvement). This review provides an update on mucormycosis management. The latest recommendations strongly recommend as first-line therapy the use of liposomal amphotericin B (≥5mg/kg) combined with surgery whenever possible. Isavuconazole and intravenous or delayed-release tablet forms of posaconazole have remained second-line. Many molecules are currently in development to fight against invasive fungal diseases but few have demonstrated efficacy against Mucorales. Despite in vitro efficacy, combinations of treatment have failed to demonstrate superiority versus monotherapy. Adjuvant therapies are particularly complex to evaluate without prospective randomized controlled studies, which are complex to perform due to low incidence rate and high mortality of mucormycosis. Perspectives are nonetheless encouraging. New approaches assessing relationships between host, fungi, and antifungal drugs, and new routes of administration such as aerosols could improve mucormycosis treatment.

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

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

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

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

Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform recommendations on their best use. This systematic review aimed to clarify the role of NebCSs in children 5 years or younger for the management of acute asthma exacerbations, asthma maintenance therapy, and the treatment of VIW. Electronic databases were used to identify relevant English language articles with no date restrictions. Studies reporting efficacy data in children 5 years or younger, with a double-blind, placebo- or open-controlled, randomized design, and inclusion of 40 or more participants (no lower patient limit for VIW) were included. Ten articles on asthma exacerbation, 9 on asthma maintenance, and 7 on VIW were identified. Results showed NebCSs to be at least as efficacious as oral corticosteroids in the emergency room for the management of mild to moderate asthma exacerbations. In asthma maintenance, nebulized budesonide, the agent of focus in all trials analyzed, significantly reduced the risk of further asthma exacerbations compared with placebo, cromolyn sodium, and montelukast. Intermittent NebCS treatment of VIW was as effective as continuous daily treatment. In summary, NebCSs are effective and well tolerated in patients 5 years or younger for the management of acute and chronic asthma.

International audience

Aerosol therapy is a key modality for drug delivery to the lungs of respiratory disease patients. Aerosol therapy improves therapeutic effects by directly targeting diseased lung regions for rapid onset of action, requiring smaller doses than oral or intravenous delivery and minimizing systemic side effects. In order to optimize treatment of critically ill patients, the efficacy of aerosol therapy depends on lung morphology, breathing patterns, aerosol droplet characteristics, disease, mechanical ventilation, pharmacokinetics, and the pharmacodynamics of cell-drug interactions. While aerosol characteristics are influenced by drug formulations and device mechanisms, most other factors are reliant on individual patient variables. This has led to increased efforts towards more personalized therapeutic approaches to optimize pulmonary drug delivery and improve selection of effective drug types for individual patients. Vibrating mesh nebulizers (VMN) are the dominant device in clinical trials involving mechanical ventilation and emerging drugs. In this review, we consider the use of VMN during mechanical ventilation in intensive care units. We aim to link VMN fundamentals to applications in mechanically ventilated patients and look to the future use of VMN in emerging personalized therapeutic drugs.

BACKGROUND: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. METHODS: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. RESULTS: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. CONCLUSION: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients. ispartof: Journal of Clinical Medicine vol:9 issue:4 ispartof: location:Switzerland status: published

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

Introduction: Pulmonary drug delivery is a complex field of research combining physics which drive aerosol transport and deposition and biology which underpins efficacy and toxicity of inhaled drugs. A myriad of preclinical methods, ranging from in- silico to in-vitro, ex–vivo and in-vivo, can be implemented.Areas covered: The present review covers in-silico mathematical and computational fluid dynamics modelization of aerosol deposition, cascade impactor technology to estimated drug delivery and deposition, advanced in-vitro cell culture methods and associated aerosol exposure, lung-on-chip technology, ex–vivo modeling, in-vivo inhaled drug delivery, lung imaging, and longitudinal pharmacokinetic analysis.Expert opinion: No single preclinical model can be advocated; all methods are fundamentally complementary and should be implemented based on benefits and drawbacks to answer specific scientific questions. The overall best scientific strategy depends, among others, on the product under investigations, inhalation device design, disease of interest, clinical patient population, previous knowledge. Preclinical testing is not to be separated from clinical evaluation, as small proof-of-concept clinical studies or conversely large-scale clinical big data may inform preclinical testing. The extend of expertise required for such translational research is unlikely to be found in one single laboratory calling for the setup of multinational large-scale research consortiums.

There is lack of standardization of practices and limited evidence on efficacy and safety of nebulization of antimicrobials. We sought to determine inhalation practices in one tertiary care hospital by performing a cross-sectional survey. Eleven adult ICUs were included in the analysis. Three units followed established protocols. Ventilation circuit filters were exchanged at least daily in all but one units. Dosages of aminoglycosides and CMS depended on indication and unit. Nebulization of antimicrobials was generally regarded as safe and efficacious. Our data indicate that approach to nebulization of antimicrobials may be heterogeneous even in a single center. Electronic supplementary material The online version of this article (10.1007/s10096-020-04017-0) contains supplementary material, which is available to authorized users.

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

This article contains information on the experimental design and methods on how the safety and tolerability data concerning patients with moderate to very severe chronic obstructive pulmonary disease (COPD) were obtained. This is in addition to our original research article. [1] We have also provided information on the clinical laboratory tests that were conducted.Further interpretation and discussion of the data are demonstrated in the article “Revefenacin, a Once-daily, Lung-selective, Long-acting Muscarinic Antagonist for Nebulized Therapy: Safety and Tolerability Results of a 52-week Phase 3 Trial in Moderate to Very Severe Chronic Obstructive Pulmonary Disease.” [1] Keywords: Chronic obstructive pulmonary disease, COPD, Long-acting muscarinic antagonist, Nebulization, Revefenacin

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.

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

Jiarui Yang,1,* Yushi Liu,1,* Yanhui Xu,1,* Xiaodan Li,1,* Jiayu Fu,1 Xiaodan Jiang,1 Yilin Chou,1 Jiahui Ma,1 Ran Hao,1 Rong Zhang,2 Weiqiang Qiu,1 Xuemin Li11Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Neurobiology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China*These authors contributed equally to this workPurpose: To present a new ocular nebulization therapy for the treatment of dry eye disease (DED) and investigate the efficacy of vitamin B12 (VB12) and oxytocin (OXT) nebulization with clinical parameters and in vivo confocal microscopy (IVCM).Patients and methods: Thirty-eight patients with DED were enrolled, with 19 receiving VB12 nebulization and 19 receiving OXT nebulization twice weekly for 3 months. Clinical signs and symptoms including Ocular Surface Disease Index, self-assessment of light sensitivity and dryness, tear meniscus height, tear break-up time (BUT), and corneal staining, along with IVCM data of basal epithelial cell density, sub-basal dendritic cell (DC) density, nerve density, and nerve tortuosity were acquired at baseline, 1 month, and 3 months after starting treatment.Results: Patients treated with VB12 improved significantly in all signs and symptoms except for nerve tortuosity during the three-month treatment, while OXT demonstrated similar effects apart from BUT and nerve tortuosity. VB12 group revealed a higher BUT at 1 month and 3 months with a higher basal epithelial cell density at 3 months compared with OXT group, and a lower DC density was observed in OXT group at 1 month. Change of basal epithelial cell density was more significant at 3 months in VB12 group, with OXT group showing a significantly higher DC reduction at 1 month.Conclusion: The nebulization therapy delivering VB12 and OXT appears to be effective in improving the symptoms and signs of dry eye, with a relatively stronger effect of BUT elevation and epithelial repair in VB12 and anti-inflammation in OXT nebulization.Keywords: dry eye, in vivo confocal microscopy, nebulization, oxytocin, vitamin B12

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

International audience; Mycobacterium abscessus is responsible for difficult-to-treat chronic pulmonary infections in humans. Current regimens, including parenteral administrations of cefoxitin (FOX) in combination with amikacin and clarithromycin, raise compliance problems and are frequently associated with high failure and development of resistance. Aerosol delivery of FOX could be an interesting alternative. FOX was administered to healthy rats by intravenous bolus or intratracheal nebulization, and concentrations were determined in plasma and epithelial lining fluid (ELF) by liquid chromatography-tandem mass spectrometry. After intrapulmonary administration, the FOX area under the curve within ELF was 1,147 times higher than that in plasma, indicating that this route of administration offers a biopharmaceutical advantage over intravenous administration. FOX antimicrobial activity was investigated using time-kill curves combined with a pharmacokinetic/pharmacodynamic (PK/PD) type modeling approach in order to account for its in vitro instability that precludes precise determination of MIC. Time-kill data were adequately described by a model including in vitro degradation, a sensitive (S) and a resistant (R) bacteria subpopulation, logistic growth, and a maximal inhibition-type growth inhibition effect of FOX. Median inhibitory concentrations were estimated at 16.2 and 252 mg/liter for the S and R subpopulations, respectively. These findings suggest that parenteral FOX dosing regimens used in patients for the treatment of M. abscessus are not sufficient to reduce the bacterial burden and that FOX nebulization offers a potential advantage that needs to be further investigated.

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

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-dimensional total and regional lung deposition. METHODS: A randomized crossover trial was performed on healthy male volunteers without cardiovascular or pulmonary disease. A technetium-99m diethylenetriaminepentaacetic 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 inspirations 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 depositions 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.)

Recent advances in locoregional chemotherapy have opened the door to new approaches for the clinical management of peritoneal carcinomatosis (PC) by facilitating the delivery of anti-neoplastic agents directly to the tumor site, while mitigating adverse effects typically associated with systemic administration. In particular, an innovative intra-abdominal chemotherapeutic approach, known as Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), was recently introduced to the intraperitoneal (IP) therapy regimens as a palliative therapeutic option in patients with PC, presumably providing a better drug distribution pattern together with deeper drug penetration into tumor nodules within the peritoneal space. Furthermore, the progress of nanotechnology in the past few decades has prompted the application of different nanomaterials in IP cancer therapy, offering new possibilities in this field ranging from an extended retention time to sustained drug release in the peritoneal cavity. This review highlights the progress, challenges, and opportunities in utilizing cancer nanotherapeutics for locoregional drug delivery, with a special emphasis on the aerosolization approach for intraperitoneal therapies.

Nicola A Hanania,1 Sanjay Sethi,2 Arkady Koltun,3 Jonathan K Ward,4 Jacqui Spanton,4 Dik Ng4 1Asthma Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA; 2Pulmonary, Critical Care, and Sleep Medicine, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA; 3Global Medical Affairs, Mylan Inc., Canonsburg, PA, USA; 4Mylan Global Respiratory Group, Mylan Pharma UK Ltd., Sandwich, Kent, UK Background: Formoterol fumarate inhalation solution (FFIS; Perforomist®) is a long-acting β2-agonist (LABA) marketed in the US as a nebulized COPD maintenance treatment. Because long-term LABA use was associated with a potential increased risk of exacerbation or death in asthma patients, the US Food and Drug Administration (FDA) requested a postmarketing commitment study to evaluate long-term safety in COPD patients. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, noninferiority study. Patients (N=1,071; mean age, 62.6 years; 48.5% male; 89.7% white) with moderate-to-severe COPD on stable COPD therapy received FFIS (20 µg; n=541) or placebo (n=530) twice daily. The primary end point was the combined incidence of respiratory death, first COPD-related ER visit, or first COPD exacerbation-related hospitalization during 1 year post randomization. Noninferiority to placebo was concluded if the two-sided 90% CI of the HR of FFIS to placebo was

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

Inhalational drugs often suffer from low pulmonary deposition due to their micronized size. Aim of present study was development and evaluation of a novel submicronic L-arginine respiratory fluid formulation for treatment of cardiopulmonary complications associated with chronic obstructive pulmonary disorder (COPD). Objectives were (a) to develop and characterize submicronic L-arginine respiratory fluid formulation, (b) pre-clinical safety/toxicity study in 2-animal species, (c) in vitro and in vivo evaluation in terms of respiratory fraction, and (d) clinical study to assess safety/efficacy in healthy volunteers/COPD patients. Formulation was optimized on the basis of particle size of aerosolized medication with particle size in the range of 400–500 nm. Anderson cascade impaction (ACI) studies were performed to validate the advantage in terms of respirable fraction, which indicated a high respirable fraction (51.61 ± 3.28) for the developed formulation. In vivo pulmonary deposition pattern of optimized formulation was studied using gamma scintigraphy in human volunteers using 99mTc-arginine as radiotracer. It clearly demonstrated a significant pulmonary deposition of the submicronic formulation in various lung compartments. Efficacy of the developed formulation was further assessed in COPD patients (n = 15) by evaluating its effect on various cardiopulmonary parameters (spirometry, pulse-oxymetry, echocardiography and 6-min walk test). A marked improvement was seen in patients after inhalation of submicronic arginine in terms of their cardiopulmonary status. Results suggest that submicronic arginine respiratory fluid has the potential to be developed into an attractive therapeutic option for treating COPD associated cardiopulmonary complications. Keywords: Chronic obstructive pulmonary disease, Submicronic L-arginine, Nebulization, Gamma scintigraphy

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.