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

Nowadays, due to a higher resistance to drugs, antibiotics, and antiviral medicaments, new ways of fighting pathogens are intensively studied. The alternatives for synthesized compositions are natural products, most of which have been known in natural medicine for a long time. One of the best-known and intensively investigated groups are essential oils (EOs) and their compositions. However, it is worth noting that the method of application can play a second crucial part in the effectiveness of the antimicrobial activity. EOs possess various natural compounds which exhibit antimicrobial activity. One of the compositions which is based on the five main ingredients of eucalyptus, cinnamon, clove, rosemary, and lemon is named “five thieves’ oil” (Polish name: olejek pięciu złodziei) (5TO) and is used in natural medicine. In this study, we focused on the droplet size distribution of 5TO during the nebulization process, evaluated by the microscopic droplet size analysis (MDSA) method. Furthermore, viscosity studies, as well as UV-Vis of the 5TO suspensions in medical solvents such as physiological salt and hyaluronic acid, were presented, along with measurements of refractive index, turbidity, pH, contact angle, and surface tension. Additional studies on the biological activity of 5TO solutions were made on the P. aeruginosa strain NFT3. This study opens a way for the possible use of 5TO solutions or emulsion systems for active antimicrobial applications, i.e., for surface spraying.

The styrene oxide to styrene carbonate conversion performed in CO2 atmosphere, herein selected as a case study, was implemented in microdroplets (aerosol) reactions at the preparative scale (3.5 mmol of the starting material) and mild conditions (1 atm CO2 pressure), within a custom-made ultrasonic nebulization reactor. Upon opti-mization of the promoter stoichiometry (1 eq of 4.3 TEG/KI ratio) and methanol (MeOH) dilution (7.5 mL of 2.5 v/v MeOH/TEG), performances under mass transfer-limited conditions of this novel methodological paradigm have been compared at 25 degrees C and 50 degrees C with those implemented as: a) no-stirred, b) stirred, and c) sonicated bulk reactions. Complete selectivity and an apparent acceleration factor (AAF) of 1.9 was registered at both temperature for microdroplets reactions in respect with the sonicated counterparts, these latter performing better than the other bulk reactions. These significative efficiency improvements, candidate aerosol reactions as a preferred process intensification approach in the realm of effective CO2-utilization strategies and, in general, in the development and exploitation of gas-liquid two-phase reactions. The present work was supported by the NATO Science for Peace and Security Programme (NATO SPS, Grant No. MYP G5885, project acronym: TANGO). The authors are grateful to the funding agency.

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

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

Peritoneal metastasis is an advanced cancer type which can be treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Here, chemotherapeutics are nebulized under high pressure in the intraperitoneal (IP) cavity to obtain a better biodistribution and tumor penetration. To prevent the fast leakage of chemotherapeutics from the IP cavity, however, nebulization of controlled release formulations is of interest. In this study, the potential of the thermosensitive hydrogel Pluronic F127 to be applied by high pressure nebulization is evaluated. Therefore, aerosol formation is experimentally examined by laser diffraction and theoretically simulated by computational fluid dynamics (CFD) modelling. Furthermore, Pluronic F127 hydrogels are subjected to rheological characterization after which the release of fluorescent model nanoparticles from the hydrogels is determined. A delicate equilibrium is observed between controlled release properties and suitability for aerosolization, where denser hydrogels (20% and 25% w/v Pluronic F127) are able to sustain nanoparticle release up to 30 hours, but cannot effectively be nebulized and vice versa. This is demonstrated by a growing aerosol droplet size and exponentially decreasing aerosol cone angle when Pluronic F127 concentration and viscosity increase. Novel nozzle designs or alternative controlled release formulations could move intraperitoneal drug delivery by high pressure nebulization forward.

[no abstract available]

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

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=

The SARS-CoV-2 pandemic, which suddenly appeared at the beginning of 2020, revealed our knowledge deficits in terms of ventilation and air pollution control. It took many weeks to realize that aerosols are the main route of transmission. The initial attempt to hold back these aerosols through textile masks seemed almost helpless, although there is sufficient knowledge about the retention capacity of fabric filters for aerosols. In the absence of a sufficient number of permanently installed heating, ventilation, and air conditioning systems, three main approaches are pursued: (a) increasing the air exchange rate by supplying fresh air, (b) using mobile air purifiers, and (c) disinfection by introducing active substances into the room air. This article discusses the feasibility of these different approaches critically. It also provides experimental results of air exchange measurements in a school classroom that is equipped with a built-in fan for supplying fresh air. With such a fan and a window tilted at the appropriate distance, an air exchange rate of 5/h can be set at a low power level and without any significant noise pollution. Heat balance calculations show that no additional heat exchanger is necessary in a normal classroom with outside temperatures above 10°C. Furthermore, a commercial mobile air purifier is studied in a chamber and a test room setup in order to examine and evaluate the efficiency of such devices against viable viruses under controlled and realistic conditions. For this purpose, bacteriophages of the type MS2 are used. Both window ventilation and air purifiers were found to be suitable to reduce the concentration of phages in the room.

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 μm as measured by cascade impaction, and a volumetric median diameter of 4.09 μm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

International audience; Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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

Background: Foreign body aspiration in pediatrics is usually managed by rigid bronchoscopy, which is associated with plenty of adverse events. Objective: We tried to compare the effect of nebulized saline, lidocaine or combined lidocaine with epinephrine on postoperative respiratory complications.Patients and methods: This prospective study included 90 children, who were divided into three groups according to the nebulized solution; NS group (normal saline 0.9%), L group (lidocaine 1% 4 mg.kg- 1) and LA group [4 mg.kg- 1 lidocaine 1% and adrenaline (1:1000) 3 mg). Our primary outcome was the incidence of post-operative respiratory complications, while the secondary ones included hemodynamic changes and the incidence of intraoperative cough or desaturation. Results: All pre-procedural data were insignificant among the three groups. The LA group expressed higher heart rates, while the L group showed a significant reduction when compared to NS group. Propofol consumption showed a significant decline in two studied groups compared to the NS group. Intraoperative cough was higher in NS group in comparison to L and LA groups. Although, intraoperative desaturation per case along with post-operative sedation showed no significant difference among the three groups, post-operative cough frequency attacks and severity were higher in NS group when compared to L and LA group and when L group were compared to LA group. Post-operative stridor was insignificant among the three groups.Conclusion: Nebulized lidocaine/adrenaline combination is appropriate option to achieve proper intraoperative sedation and upper airway conditions with reduction of post-operative negative respiratory outcomes together with minor hemodynamic changes.

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 efficiency of lung drug delivery of nebulized drugs is governed by aerosol quality, which depends both on the aerosolization process itself but also on the properties of aerosol precursors. This paper determines physicochemical properties of four analogous micro-suspensions of a micronized steroid (budesonide, BUD) and seeks relationships between these properties and the quality of the aerosol emitted from a vibrating mesh nebulizer (VMN). Despite the same BUD content in all tested pharmaceutical products, their physicochemical characteristics (liquid surface tension, viscosity, electric conductivity, BUD crystal size, suspension stability, etc.) are not identical. The differences have a weak influence on droplet size distribution in the mists emitted from the VMN and on theoretical (calculated) regional aerosol deposition in the respiratory system but, simultaneously, there is an influence on the amount of BUD converted by the nebulizer to aerosol available for inhalation. It is demonstrated that the maximum inhaled BUD dose is below 80–90% of the label dose, depending on the nebulized formulation. It shows that nebulization of BUD suspensions in VMN is sensitive to minor dissimilarities among analogous (generic) pharmaceutics. The potential clinical relevance of these findings is discussed.

Bacteriophages have been identified as a potential treatment option to treat lung infection in the context of antibiotic resistance. We performed a preclinical study to predict the efficacy of delivery of bacteriophages against Pseudomonas aeruginosa (PA) when administered via nebulization during mechanical ventilation (MV). We selected a mix of four anti-PA phages containing two Podoviridae and two Myoviridae, with a coverage of 87.8% (36/41) on an international PA reference panel. When administered via nebulization, a loss of 0.30–0.65 log of infective phage titers was measured. No difference between jet, ultrasonic and mesh nebulizers was observed in terms of loss of phage viability, but a higher output was measured with the mesh nebulizer. Interestingly, Myoviridae are significantly more sensitive to nebulization than Podoviridae since their long tail is much more prone to damage. Phage nebulization has been measured as compatible with humidified ventilation. Based on in vitro measurement, the lung deposition prediction of viable phage particles ranges from 6% to 26% of the phages loaded in the nebulizer. Further, 8% to 15% of lung deposition was measured by scintigraphy in three macaques. A phage dose of 1 × 109 PFU/mL nebulized by the mesh nebulizer during MV predicts an efficient dose in the lung against PA, comparable with the dose chosen to define the susceptibility of the strain.

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

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

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

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

Prapasri Kulalert,1 Phichayut Phinyo,2,3 Jayanton Patumanond,3 Chutima Smathakanee,4 Wantida Chuenjit,4 Sira Nanthapisal5 1Department of Clinical Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 2Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 4Department of Pediatrics, Hat Yai Hospital, Songkhla, Thailand; 5Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Phichayut PhinyoDepartment of Family Medicine, Faculty of Medicine, Chiang Mai University, 110/510 Intawaroros Road, Suthep, Mueang Chiang Mai District, Chiang Mai, Chiang Mai Province 50200, ThailandTel +66 89 850 1987Email phichayutphinyo@gmail.comPurpose: Intermittent nebulization of short-acting beta-agonists (SABA) is the initial treatment of choice for children with asthma exacerbation. However, children with severe asthma exacerbation (SAE) may not show an adequate response and need aggressive stepwise therapy. We aimed to explore factors associated with a poor response to intermittent nebulized SABA in children with SAE.Methods: A retrospective cohort study of children with SAE diagnosed according to the definition of the British Guidelines on the Management of Asthma, who were admitted at Hat Yai Hospital from January 1, 2015, to December 31, 2017. All children were treated with intermittent SABA nebulization. Treatment failure was defined as children needing escalated therapy. Logistic regression with confounding score adjustment was used to explore the predictors of treatment failure.Results: One hundred thirty-three children were included in the analysis, 59 were in the failure group and 74 were in the success group. After adjusting for potential confounders, they were significantly associated with a previous history of intubation (adjusted OR 6.46, 95% CI 1.13 to 36.79, p=0.036), receiving < 3 doses of nebulized salbutamol in the emergency room (ER, aOR 3.21, 95% CI 1.15 to 9.02, p=0.027), ER measured oxygen saturation (SpO2) < 92% (adjusted OR 3.02, 95% CI 1.18 to 7.75, p=0.022), and exacerbation triggered by pneumonia (adjusted OR 2.67, 95% CI 1.19 to 6.00, p=0.017).Conclusion: We identified four prognostic factors of treatment failure in children with SAE: a previous history of intubation; receiving < 3 doses of nebulized salbutamol in the ER, SpO2 at ER < 92%; and exacerbation triggered by pneumonia. Further prospective studies are required to confirm our findings before clinical implementation.Keywords: status asthmaticus, hospitalization, nebulization, treatment failure, prognosis

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.

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

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.

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

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.

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

Patients with COVID-19 may complicate their evolution with thromboembolic events. Incidence of thromboembolic complications are high and also, patients with the critically-ill disease showed evidence of microthrombi and microangiopathy in the lung probably due to endothelial damage by directly and indirectly injured endothelial and epithelial cells. Pulmonary embolism, deep venous thrombosis and arterial embolism were reported in patients with COVID-19, and several analytical abnormal coagulation parameters have been described as well. D-dimer, longer coagulation times and lower platelet counts have been associated with poor outcomes. The use of anticoagulation or high doses of prophylactic heparin is controversial. Despite the use of anticoagulation or high prophylactic dose of heparin have been associated with better outcomes in observational studies, only in patients with non-critically ill disease benefits for anticoagulation was observed. In critically-ill patient, anticoagulation was not associated with better outcomes. Other measures such as antiplatelet therapy, fibrinolytic therapy or nebulized anticoagulants are being studied in ongoing clinical trials.

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

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.

Dissertação de Mestrado Integrado em Medicina Veterinária Atualmente, não existe um protocolo terapêutico definido para o tratamento de infeções respiratórias causadas por Bordetella bronchiseptica, pertencentes ao Complexo de Doenças Respiratórias Infeciosas Caninas (CIRDC). A infeção por B. bronchiseptica é um diagnóstico clínico comum em cães, especialmente naqueles provenientes de canis ou criadores, onde a densidade populacional é maior. A terapêutica atualmente aconselhada pelas diretrizes existentes consiste, principalmente, na administração empírica de doxiciclina por via sistémica, tratamento que nem sempre se demonstra eficaz. O presente estudo teve como objetivo contribuir para a elaboração de um possível protocolo terapêutico com recurso a administração de gentamicina por via aerógena na forma de nebulização. Para tal, foi estudado o caso clínico de uma cadela de 3 meses, Cavalier King Charles Spaniel (CKCS), com doença respiratória causada por B. bronchiseptica, apresentada ao Hospital Veterinário do Porto. Foi observada uma incapacidade de alcançar a cura clínica apenas com a administração de antibióticos por via sistémica, complicado ainda pelo fato de a bactéria em questão apresentar resistência a múltiplos antibióticos. Verificou-se que a cura clínica apenas foi possível quando se iniciou a administração de gentamicina por nebulização, associada a administração de outro antibiótico, neste caso azitromicina, por via sistémica. Os resultados obtidos vêm apoiar a importância que a administração de gentamicina por via aerógena, através de nebulização, parece ter, mostrando-se muito eficaz no tratamento de infeções respiratórias caninas causadas por B. bronchiseptica. ABSTRACT - Use of Nebulized Gentamicin Associated with Respiratory Kinesiotherapy in the Treatment of the Lower Respiratory Tract Disease in Dogs - Currently, there is not a defined therapeutic protocol for the treatment of respiratory infections caused by Bordetella bronchiseptica, belonging to the Canine Infectious Respiratory Disease Complex (CIRDC). B. bronchiseptica infection is a common clinical diagnosis in dogs, especially those from kennels or breeders, where population density is higher. The therapy presently recommended by the existing guidelines consists mainly of empirical systemic administration of doxycycline, a treatment that is not always effective. The aim of this study was to contribute to the elaboration of a possible therapeutic protocol using gentamicin by nebulization. A clinical case of a 3-month-old Cavalier King Charles Spaniel (CKCS) with respiratory disease caused by B. bronchiseptica, presented to the Hospital Veterinário do Porto, was studied. An inability to achieve medical cure with only the systemic administration of antibiotics was observed, which was further complicated by the fact that the bacterium presented resistance to multiple antibiotics. It was found that the clinical cure was only possible when the administration of nebulized gentamicin was initiated, in association with the administration of another antibiotic, in this case azithromycin, via the systemic route. The results obtained support the importance that the administration of nebulized gentamicin seems have, proving to be very effective in the treatment of canine respiratory infections caused by B. bronchiseptica. N/A

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.

[ES] El presente TFG tiene como objetivo desarrollar, calcular y diseñar una instalación fotovoltaica de autoconsumo para la zona del aviario del parque zoológico de Terra Natura. Dicha instalación deberá alimentar a un sistema de nebulización, encargado del riego y mantenimiento de temperatura y humedad del aviario, para la mejora de la habitabilidad tanto de las aves como de la flora existente. Se estudiarán diferentes propuestas dentro de la legislación vigente para dicho proyecto. Estas propuestas llevarán consigo un estudio tanto económico como técnico para satisfacer las necesidades del aviario., [EN] The purpose of this document is to develop, calculate and design a self-consumption photovoltaic system for the aviary area of the Terra Natura Zoo. This installation must supply a fogging system responsible for irrigating and maintaining temperature and humidity in the avian, in order to improve the habitability of both birds and existing flora. Different proposals will be considered under existing legislation for this project. These proposals will involve both an economic and a technical study to meet the needs of the aviary.

INTRODUCTION Strategies to improve nasal drug delivery include development of formulations which reduce mucociliary clearance [1] and careful selection of nasal delivery device [2]. In situ gelling nanosuspensions present combined approach to increase mucoadhesion and prolong drug retention at nasal mucosa [1]. The aim of this study is to develop an in situ gelling fluticasone propionate nanosuspension and assess its nasal deposition after spraying with jet-flow nebulizer. MATERIALS AND METHODS Fluticasone propionate nanosuspensions prepared by wet media milling, were mixed with pectin and sodium hyaluronate solutions at different ratios. Formulations were characterised in terms of particle size, zeta- potential, surface tension, rheological properties, in vitro biocompatibility using Calu-3 cells, mucoadhesiveness with porcine mucosa and nasal deposition pattern using a jet- flow nebulizer and a 3D printed nasal cast. RESULTS In situ gelling fluticasone propionate nanosuspensions were characterised by particle diameter between 140.3 to 166.8 nm, zeta-potential between –89.5 and –83.2 mV and surface tension of about 37 mN m-1 at 25 °C. Rheological studies confirmed the gelation of formulations when mixed with simulated nasal fluid. The formed gel showed appropriate strength and stability profile. All formulations were biocompatible (cell viability > 90%) and mucoadhesive. Spraying the formulations with jet-flow nebulizer resulted in targeted deposition within the 3D printed nasal cast. CONCLUSION Biocompatible in situ gelling fluticasone propionate nanosuspensions have been successfully prepared. Their rheological properties imply instant gelling in contact with nasal fluid, which, combined with mucoadhesive properties, indicate the potential for extended residence time at nasal mucosa. Nasal deposition profiles proved the suitability of jet-flow nebulizer for nasal delivery of in situ gelling nanosuspensions. Acknowledgement This work has been supported in part by Croatian Science Foundation under the project UIP-2017-05-4592 and European Social Fund under the Croatian Science Foundation project DOK- 2020-01-2473. REFERENCES 1. Alshweiat, A, et al. Int J Pharm (2020) 579:119-166 2. Xi, J, et al. Pharm Res (2016) 33:1527- 1541

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

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.

This work proposes the use of emergency ventilators and anesthesia machines as temporary replacement instruments for mechanical ventilators and their corresponding functions for respiratory therapy. The objective of this work is to increase the availability of access connections to the medical gas network and to slightly reduce the demand for mechanical ventilators in clinics and hospitals. Specifically, we want to propose the use of air compressors that have various brands of mechanical ventilators as a replacement or substitute for the air bullets that emergency ventilators must have, in the same way, with these equipment it would be possible to perform respiratory therapy in areas of the hospital that are not suitable for this procedure, such as waiting rooms and using anesthesia machines which specify their ventilatory modes as temporary mechanical ventilators. By using air compressors as an air supply for nebulization therapies, space can be freed up from the gas network in therapy rooms which could be used to connect other equipment of greater importance such as mechanical fans, in the same way with this method it would be possible to do nebulizations at the patients' homes, in addition to checking that certain anesthesia machines can be used as mechanical ventilators. The use of air compressors as a supply for respiratory therapy shows that it works in a similar way to that of the gas network in terms of pressure and flow, however, the proposed assembly generates annoying noise and vibration, in addition to not having a suitable filter for the supplied air, additionally for an anesthesia equipment to function as a mechanical ventilator, it must specify which ventilatory modes it has., El presente trabajo propone el uso de ventiladores de emergencia y máquinas de anestesia como instrumentos de reemplazo temporal de ventiladores mecánicos y sus correspondientes funciones destinadas para terapia respiratoria. El objetivo de este trabajo es aumentar la disponibilidad de las conexiones de acceso a la red de gases medicinales y reducir levemente la demanda de ventiladores mecánicos en clínicas y centros hospitalarios. En específico se quiere proponer el uso de los compresores de aire que tienen varias marcas de ventiladores mecánicos como un reemplazo o sustituto para las balas de aire que deben tener los ventiladores de urgencia, de este mismo modo, con estos equipos sería posible realizar terapia respiratoria en zonas del centro hospitalario que no estén adecuadas para dicho procedimiento, como lo son salas de espera y usar máquinas de anestesia las cuales especifiquen sus modos ventilatorios como ventiladores mecánicos temporales. Al usar compresores de aire como suministro de aire para terapias por nebulización se puede liberar espacio de la red de gases en las salas de terapia los cuales se podrían usar para conectar otros equipos de mayor importancia como los ventiladores mecánicos, de igual forma con este método sería posible hacer las nebulizaciones en casa de los pacientes, además de comprobar que ciertas máquinas de anestesia se pueden usar como ventiladores mecánicos. El uso de compresores de aire como suministro para la terapia respiratoria muestra que funciona de manera similar a la de la red de gases en lo que se refiere a presión y flujo, sin embargo, el montaje propuesto genera un ruido y vibración molestas, además de no contar con un filtro adecuado para el aire que se suministra, adicionalmente para que un equipo de anestesia funcione como ventilador mecánico, debe especificar qué modos ventilatorios tiene., Pregrado, Ingeniero(a) Biomédico(a)

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; 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.