Nebulization and In Vitro Upper Airway Deposition of Liposomal Carrier Systems.

Liposomal carrier systems have emerged as a promising technology for pulmonary drug delivery. This study focuses on two selected liposomal systems, namely, dipalmitoylphosphatidylcholine stabilized by phosphatidic acid and cholesterol (DPPC-PA-Chol) and dipalmitoylphosphatidylcholine stabilized by polyethylene glycol and cholesterol (DPPC-PEG-Chol). First, the research investigates the stability of these liposomal systems during the atomization process using different kinds of nebulizers (air-jet, vibrating mesh, and ultrasonic). The study further explores the aerodynamic particle size distribution of the aerosol generated by the nebulizers. The nebulizer that demonstrated optimal stability and particle size was selected for more detailed investigation, including Andersen cascade impactor measurements, an assessment of the influence of flow rate and breathing profiles on aerosol particle size, and an in vitro deposition study on a realistic replica of the upper airways. The most suitable combination of a nebulizer and liposomal system was DPPC-PA-Chol nebulized by a Pari LC Sprint Star in terms of stability and particle size. The influence of the inspiration flow rate on the particle size was not very strong but was not negligible either (decrease of Dv50 by 1.34 µm with the flow rate increase from 8 to 60 L/min). A similar effect was observed for realistic transient inhalation. According to the in vitro deposition measurement, approximately 90% and 70% of the aerosol penetrated downstream of the trachea using the stationary flow rate and the realistic breathing profile, respectively. These data provide an image of the potential applicability of liposomal carrier systems for nebulizer therapy. Regional lung drug deposition is patient-specific; therefore, deposition results might vary for different airway geometries. However, deposition measurement with realistic boundary conditions (airway geometry, breathing profile) brings a more realistic image of the drug delivery by the selected technology. Our results show how much data from cascade impactor testing or estimates from the fine fraction concept differ from those of a more realistic case.

Pharmacokinetics of vancomycin in sputum of intubated patients: Optimized intravenous delivery vs. inhaled therapy.

AIMS: Intubated patients with methicillin-resistant Staphylococcus aureus pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15-20 µg/mL) in 38-79% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit. METHODS: Airway pharmacokinetics of optimized IV and inhaled vancomycin in infected clinically stable prolonged mechanically ventilated patients were measured. First, IV vancomycin was given until optimized concentrations were achieved (15-20 µg/mL), and, at the same time point, sputum vancomycin concentrations were measured. Then, sputum concentrations were re-assessed after 4 treatments of inhaled vancomycin (120 mg/2 mL) via a previously characterized nebulizing system that deposited 18 ± 2 mg in the lungs. Vancomycin post-distribution phase serum peak and trough concentrations were also obtained. Serum albumin was measured to assess binding to vancomycin. RESULTS: Mean serum trough concentration was 18.4 ± 6.5 µg/mL. Sputum concentrations were affected by serum albumin. Only patients with severe hypoalbuminaemia had penetration of drug leading to therapeutic (15.7-17 µg/mL) sputum concentrations. Following inhaled vancomycin, sputum concentrations increased significantly to 199 ± 37.0 µg/mL (P = .002) exceeding minimum inhibitory concentration by 2 orders of magnitude. CONCLUSION: Despite optimized serum concentrations, patients with albumin near normal had suboptimal concentrations of vancomycin in their sputum. Inhaled therapy may be clinically important for successful treatment of ventilator-associated methicillin-resistant Staphylococcus aureus infection. Further studies of inhaled therapy are needed to define their role as adjunctive therapy in ventilator-associated pneumonia and as single therapy in tracheobronchitis.

Comparative study of the vibrating capillary nebulizer (VCN) and commercially available interfaces for on-line coupling of capillary electrophoresis with ICP-MS.

Capillary electrophoresis (CE) is a powerful and sensitive tool for speciation analysis when combined with inductively coupled plasma mass spectrometry (ICP-MS); however, the performance of this technique can be limited by the nature of pneumatic nebulizers. This study compares two commercially available pneumatic nebulizers to a newly introduced vibrating capillary nebulizer (VCN) for on-line coupling of CE with ICP-MS. The VCN is a low-cost, non-pneumatic nebulizer that is based on the design of capillary vibrating sharp-edge spray ionization. As a piezoelectrically driven nebulization source, the VCN creates an aerosol independent of gas flows and does not produce a low-pressure region at the nebulizer orifice. To compare the systems, we performed replicate analyses of sulfate in river water with each nebulizer and the same CE and ICP-MS instruments and determined the figures of merit of each setup. With the CE-VCN-ICP-MS setup, we achieved around 2-4 times lower sensitivity compared to the commercial setups. However, the VCN-based setup provided lower noise levels and better linear correlation from the analysis of calibration standards, which resulted in indistinguishable LOD and LOQ values from the in-house-built VCN-based and commercial setups for CE-ICP-MS analysis. The VCN is found to have the highest baseline stability with a standard deviation of 3500 cts s-1, corresponding to an RSD of 2.7%. High reproducibility is found with the VCN with a peak area RSD of 4.1% between 3 replicate measurements.

Emergency physicians' preferences in bronchodilator delivery for asthma exacerbations: a cross-sectional study.

OBJECTIVE: Asthma is a chronic respiratory disorder characterized by airway inflammation and narrowing often leading to acute exacerbations that necessitate a visit to the emergency department (ED). While life threatening cases usually require bronchodilator delivery by nebulizers, mild to moderate acute asthma exacerbations can be treated by bronchodilators delivered either by metered dose inhalers (MDI). Numerous studies have attempted to compare between the two modalities and have drawn similar conclusions in that both are comparable in efficacy with minimal differences. What is evident, however, is that physicians remain inclined to favor nebulizers in the majority of acute asthma exacerbations. METHODS: In this questionnaire-based study, a survey was distributed to physicians who treat asthma exacerbations to examine demographics, knowledge, beliefs, and current practice in regard to bronchodilator therapy. RESULTS: The majority (90.8%) of physicians prefer short-acting beta agonists via nebulizer, with 9.2% favoring MDI + spacer. Participants include consultants, residents, and specialists across various emergency disciplines. While 90.1% find MDI + spacer equally effective as nebulizers, advantages cited include cost-effectiveness (49.6%), shorter ED stays (63.4%), quicker administration (67.9%), and ease of use (58.8%). Challenges include availability (66.4%) and ineffectiveness in younger patients (45%). Despite this, 65.6% are willing to switch to MDI for initial asthma management in the ED, while 34.4% are resistant. CONCLUSION: Concerns about availability and effectiveness in younger patients remain barriers. However, a significant number are willing to adopt MDIs with spacers, indicating potential for broader use with better availability and training.

The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

Impact of Nebulization on the Physicochemical Properties of Polymer-Lipid Hybrid Nanoparticles for Pulmonary Drug Delivery.

Nanoparticles (NPs) have shown significant potential for pulmonary administration of therapeutics for the treatment of chronic lung diseases in a localized and sustained manner. Nebulization is a suitable method of NP delivery, particularly in patients whose ability to breathe is impaired due to lung diseases. However, there are limited studies evaluating the physicochemical properties of NPs after they are passed through a nebulizer. High shear stress generated during nebulization could potentially affect the surface properties of NPs, resulting in the loss of encapsulated drugs and alteration in the release kinetics. Herein, we thoroughly examined the physicochemical properties as well as the therapeutic effectiveness of Infasurf lung surfactant (IFS)-coated PLGA NPs previously developed by us after passing through a commercial Aeroneb® vibrating-mesh nebulizer. Nebulization did not alter the size, surface charge, IFS coating and bi-phasic release pattern exhibited by the NPs. However, there was a temporary reduction in the initial release of encapsulated therapeutics in the nebulized compared to non-nebulized NPs. This underscores the importance of evaluating the drug release kinetics of NPs using the inhalation method of choice to ensure suitability for the intended medical application. The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics.

Effect of different doses of dexmedetomidine as an adjuvant to lignocaine nebulization: A comparative study during awake flexible fiberoptic bronchoscopy.

Background and Aims: Mild to moderate sedation during bronchoscopy is essential for patient safety, comfort during and after the procedure, and to facilitate the performance of the bronchoscopist. Dexmedetomidine is a highly selective, centrally acting α-2 agonist used to provide conscious sedation during various procedures. The aim of this study was to compare the efficacy of three different doses of dexmedetomidine nebulization as an adjuvant to lignocaine during bronchoscopy. Material and Methods: Ninety American Society of Anesthesiologists physical status I/II patients, aged from 18 to 60 years, scheduled for an elective bronchoscopy, were recruited. They were divided into three groups: 30 patients in each group. Group I: The patient was nebulized with a mixture of 4 ml of 4% lignocaine and dexmedetomidine 0.5 µg/kg. Group II: The patient was nebulized with a mixture of 4% lignocaine, 4 ml, and dexmedetomidine, 1 µg/kg. Group III: The patient was nebulized with 4% lignocaine 4 ml and dexmedetomidine 1.5 µg/kg. Results: The mean cough score was (1.17 ± 0.37), (1.40 ± 0.49), and (1.70 ± 0.75) in group III, group II, and group I, respectively. A significant difference was found between the groups. Patients were more comfortable with a statistically significant difference in the comfort score in group III as compared to group II and group I. Conclusion: Dexmedetomidine nebulization in a dose of 1.5 µg/kg (compared to 1 µg/kg or 0.5 µg/kg) as an adjuvant to lignocaine, provides better bronchoscopy conditions and patient satisfaction.

Inhalable Nitric Oxide Delivery Systems for Pulmonary Arterial Hypertension Treatment.

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.

Viral Preservation with Protein-Supplemented Nebulizing Media in Aerosols.

The outbreak of SARS-CoV-2 has emphasized the need for a deeper understanding of infectivity, spread, and treatment of airborne viruses. Bacteriophages (phages) serve as ideal surrogates for respiratory pathogenic viruses thanks to their high tractability and the structural similarities tailless phages bear to viral pathogens. However, the aerosolization of enveloped SARS-CoV-2 surrogate phi6 usually results in a >3-log10 reduction in viability, limiting its usefulness as a surrogate for aerosolized coronavirus in "real world" contexts, such as a sneeze or cough. Recent work has shown that saliva or artificial saliva greatly improves the stability of viruses in aerosols and microdroplets relative to standard dilution/storage buffers like suspension medium (SM) buffer. These findings led us to investigate whether we could formulate media that preserves the viability of phi6 and other phages in artificially derived aerosols. Results indicate that SM buffer supplemented with bovine serum albumin (BSA) significantly improves the recovery of airborne phi6, MS2, and 80α and outperforms commercially formulated artificial saliva. Particle sizing and acoustic particle trapping data indicate that BSA supplementation dose-dependently improves viral survivability by reducing the extent of particle evaporation. These data suggest that our viral preservation medium may facilitate a lower-cost alternative to artificial saliva for future applied aerobiology studies. IMPORTANCE We have identified common and inexpensive lab reagents that confer increased aerosol survivability on phi6 and other phages. Our results suggest that soluble protein is a key protective component in nebulizing medium. Protein supplementation likely reduces exposure of the phage to the air-water interface by reducing the extent of particle evaporation. These findings will be useful for applications in which researchers wish to improve the survivability of these (and likely other) aerosolized viruses to better approximate highly transmissible airborne viruses like SARS-CoV-2.

Patient and social factors related to nebulizer use in COPD patients at the transition of care: a qualitative study.

BACKGROUND: Transition from hospital to home is a vulnerable period for patients with COPD exacerbations, with a high risk for readmission and mortality. Twenty percent of patients with an initial hospitalization for a COPD exacerbation are readmitted to a hospital within 30 days, costing the health care system over $15 billion annually. While nebulizer therapy directed at some high-risk COPD patients may improve the transition from hospital to home, patient and social factors are likely to contribute to difficulties with their use. Current literature describing the COPD patient's experience with utilizing nebulizer therapy, particularly during care transitions, is limited. Therefore, the objective of this study was to explore underlying COPD patient and social factors contributing to practical difficulties with nebulizer use at the care transition from hospital to home. METHODS: This was a qualitative study conducted between September 2020 and June 2022. Patients were included if they were ≥ 40 years old, had a current diagnosis of COPD, had an inpatient admission at a hospital, and were discharged directly to home with nebulizer therapy. Semi-structured, one-on-one interviews with patients were conducted covering a broad range of patient and social factors and their relationships with nebulizer use and readmission. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using a mixed inductive and deductive approach. RESULTS: Twenty-one interviews were conducted, and subjects had a mean age of 64 ± 8.4 years, 62% were female, and 76% were White. The predominant interview themes were health care system interactions and medication management. The interviews highlighted that discharge counseling methods and depth of counseling from hospitals were inconsistent and were not always patient-friendly. They also suggested that patients could appropriately identify, set up, and utilize their nebulizer treatment without difficulties, but additional patient education is required for nebulizer clean up and maintenance. CONCLUSIONS: Our interviews suggest that there is room for improvement within the health care system for providing consistent, effective discharge counseling. Also, COPD patients discharged from a hospital on nebulizer therapy can access and understand their treatment but require additional education for nebulizer clean up and maintenance.

Effect of therapeutic play using a toy nebulizer and toy mask on a child's fear and anxiety levels.

PURPOSE: This study aimed to examine the effect of therapeutic play using a toy nebulizer and mask before inhaler treatment on children's fear and anxiety levels in a pediatric emergency department. DESIGN AND METHOD: This randomized controlled clinical trial included 84 children aged 3-8 years who were admitted to the pediatric emergency department with respiratory system disease. This study was registered in the Clinical Trials database.Therapeutic play was applied to the children in the therapeutic play group with a toy nebulizer, toy mask, and amigurumi doll, after which the children received treatment with these devices. The children in the control group received nebular treatment using a standard nebulizer and a mask. The children were required to answer the 'Children's Fear Scale' (CFS) and 'Children's Anxiety Metre-State' (CAMS) before and after treatment. RESULTS: Fear and anxiety levels were significantly lower in the therapeutic play group than in the control group (p = 0.001). A statistically significant difference was found between the two groups regarding acceptance of the mask used during treatment and adaptation to the treatment (p = 0.001). CONCLUSIONS: Therapeutic play with a toy nebulizer and mask effectively reduced fear of hospitals and related anxiety in children. PRACTICE IMPLICATIONS: Playing therapeutic play with a toy nebulizer and toy mask during nebulization is a promising strategy to reduce children's fear and anxiety.

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study.

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O2Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O2Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

Aerosolization Performance of Immunoglobulin G by Jet and Mesh Nebulizers.

Recently, many preclinical and clinical studies have been conducted on the delivery of therapeutic antibodies to the lungs using nebulizers, but standard treatment guidelines have not yet been established. Our objective was to compare nebulization performance according to the low temperature and concentration of immunoglobulin G (IgG) solutions in different types of nebulizers, and to evaluate the stability of IgG aerosols and the amount delivered to the lungs. The output rate of the mesh nebulizers decreased according to the low temperature and high concentration of IgG solution, whereas the jet nebulizer was unaffected by the temperature and concentration of IgG. An impedance change of the piezoelectric vibrating element in the mesh nebulizers was observed because of the lower temperature and higher viscosity of IgG solution. This affected the resonance frequency of the piezoelectric element and lowered the output rate of the mesh nebulizers. Aggregation assays using a fluorescent probe revealed aggregates in IgG aerosols from all nebulizers. The delivered dose of IgG to the lungs in mice was highest at 95 ng/mL in the jet nebulizer with the smallest droplet size. Evaluation of the performance of IgG solution delivered to the lungs by three types of nebulizers could provide valuable parameter information for determination on dose of therapeutic antibody by nebulizers.

Good Practices for the Laboratory Performance Testing of Aqueous Oral Inhaled Products (OIPs): an Assessment from the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS).

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products.

Enhanced Optimal Parameter-Based Nebulizer Design for Flow Analysis of Fluticasone Propionate.

A jet nebulizer sprays a fine mist or aerosol directly into the lungs to reduce inflammation, expand airways, and make breathing easier for respiratory patients. Asthma, COPD, emphysema, and cystic fibrosis are treated with jet nebulizers. They are chosen over other nebulizers for their shorter treatment time and wider medication compatibility. For mechanically ventilated patients, jet nebulizers humidify oxygen to provide bronchodilators, antibiotics, and other respiratory medications. Additionally, they treat pneumonia, bronchitis, and other lung infections. Aerosol therapy requires medical jet nebulizers. However, experiment setup is time-consuming and challenging to enhance smaller droplet output. The study is aimed at enhancing the nebulizer and process parameters using numerical simulation and comparing the results to experimental data from the Malvern Spraytec™ laser diffraction system. This numerical model improves nebulization knowledge and predicts process parameters that affect output. Ansys Fluent was used to analyze a Creo-designed jet nebulizer solid model. The Spraytec™ experimental method was utilized to characterize fluticasone propionate's aerosol output and build the best nebulizer. Laser diffraction and computational fluid dynamics (CFD) analysis measured the nebulizer aerosol output. Comparing particle size data between 2 and 5 µm. The results are similar, with a difference of 4.20%. Taguchi optimization found the optimal process parameter, and a conformation test enhanced the process parameter. The nebulizer generates 8.57% more fluticasone propionate at optimal particle size. The optimized nebulizer generates aerosols reliably and speeds up patient recovery.

BRONCHIECTASIS IN ADULT PATIENTS: CLINICAL PECULIARITIES AND APPROACHES TO THE TREATMENT.

OBJECTIVE: The aim: To perform a clinical analysis of bronchiectasis in adults, to analyze the effectiveness of nebulizer therapy with hypertonic NaCl solution with hyaluronic acid. PATIENTS AND METHODS: Materials and methods: All patients were performed clinical-functional examination (MRC dyspnea index, Sp O2, 6-minute walking test, external respiration function); calculated the index BODE, analyzed the SGRQ, studied the results of sputum. Statistical data analysis was performed using the Microsoft Excel for Microsoft 365 MSO 16.0.13530.2040418 package of statistical functions. RESULTS: Results: The main symptom in 100% of cases was chronic cough with production of sputum. Patients were concerned about shortness of breath (91.7%), episodic hemoptysis (29.2%), systemic symptoms (fatigue, weight loss). Hypertonic NaCl solution has a direct mucolytic effect, osmotic and anti-edematous effect. Protection of the mucous membrane of the respiratory tract makes hyaluronic acid an ideal additional component of hypertonic saline solution. All patients showed a positive effect of treatment immediately. After 2 weeks, the respiratory rate decreased, the FEV1 index increased at 8.6 (p<0.05), SpO2 increased up to 93.75 ± 7.13%, the number of points according to the SGRQ decreased, BODE index also decreased. CONCLUSION: Conclusions: Leading clinical signs of bronchiectasis were: a chronic cough with daily sputum production (100% of patients), shortness of breath (91.7%). The use of nebulizer inhalations decreased shortness of breath at 17.6% (р<0.05), improved external respiratory function indices (FVCL increased at 9.7% (р<0.01), FEV1 at 8.6% (р<0.01)) and blood oxygen saturation increased at 4.9% (р<0.05)). The offered complex increased tolerance to physical exertion (the 6-minute walk test and 4-year survival (BODE prognostic index).

Mist nebulizer versus heated humidifier on endotracheal tube patency in spontaneously breathing intubated patients: A prospective, randomized controlled trial.

Background and Aims: Using a humidifier in intubated patients is now a standard of care as the humidifying effect of the upper airway is lost. We conducted this study to compare the efficacy of a heated humidifier (HH) with the more commonly used conventional mist nebulizer on overnight intubated and spontaneously breathing post-operative patients. Material and Methods: This prospective, randomized control trial included 60 post-operative overnight intubated and spontaneously breathing patients, of which 30 patients were allocated to the HH group and 30 to the mist nebulizer group. The reduction of endotracheal tube (ETT) patency was measured quantitatively by the difference between the pre-intubation and immediate post-extubation ETT volume and compared between the two groups. Also, the characteristics of secretion, the temperature of inspired gas at the Y-piece, and the frequency of refilling the humidifier chamber were recorded and compared. Results: The reduction of ETT volume was significantly more in the mist nebulizer group compared to the HH group (P-value 0.00026). The mean temperature of the inspired gas (°C) was higher in the HH group (P-value < 0.0001). More patients in the mist nebulizer group had thicker (P-value 0.057) and drier secretions (P-value 0.005) compared to the HH group. None of the patients in the HH group required refilling of the humidifier chamber while the mean frequency of the refilling was 3.5 times per patient in the mist nebulizer group. Conclusion: HH may be preferred over mist nebulizer as the latter requires more frequent refilling which may not be practically possible in a busy recovery room rendering the patient at the risk of inhaling dry gas and consequent thick and dry secretions with decreased ETT patency.

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

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

Development and technical validation of an ultrasound nebulizer to deliver intraperitoneal pressurized aerosols in a rat colon cancer peritoneal metastases model.

BACKGROUND/AIM: To develop and validate a nebulizer device for anti-cancer research on pressurized intraperitoneal aerosol supply in a preclinical peritoneal metastases (PM) rat model. MATERIAL AND METHODS: For aerosol generation, an ultrasonic nebulizer (USN) was modified. Aerosol analyses were performed ex-vivo by laser diffraction spectrometry (LDS). Intraperitoneal (IP) 99mtechnetium sodium pertechnetate (99mTc) aerosol distribution and deposition were quantified by in-vivo single photon emission computed tomography (SPECT/CT) and compared to liquid IP instillation of equivalent volume/doses of 99mTc with and without capnoperitoneum. PM was induced by IP injection of HCT116-Luc2 human colon cancer cells in immunosuppressed RNU rats. Tumor growth was monitored by bioluminescence imaging (BLI), 18F-FDG positron emission tomography (PET) and tissues examination at necropsy. RESULTS: The USN was able to establish a stable and reproducible capnoperitoneum at a pressure of 8 to 10 mmHg. LDS showed that the USN provides a polydisperse and monomodal aerosol with a volume-weighted diameter of 2.6 µm. At a CO2 flow rate of 2 L/min with an IP residence time of 3.9 s, the highest drug deposition efficiency was found to be 15 wt.-%. In comparison to liquid instillation, nebulization showed the most homogeneous IP spatial drug deposition. Compared to BLI, 18F-FDG-PET was more sensitive to detect smaller PM nodules measuring only 1-2 mm in diameter. BLI, 18F-FDG PET and necropsy analyses showed relevant PM in all animals. CONCLUSIONS: The USN together with the PM rat model are suitable for robust and species-specific preclinical pharmacological studies regarding intraperitoneal delivery of pressurized aerosolized drugs and cancer research.

Preliminary bronchodilator dose effect on aerosol-delivery through different nebulizers in noninvasively ventilated COPD patients.

Objectives: This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. Method: COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose.Results: The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens(p < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery (p < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN (p < 0.001).Conclusion: Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.