Search Results (359)

Objectives: This study evaluates the efficacy of existing and new aerosol mitigation methods during nebulization (Neb) in combination with high-flow nasal cannula (HFNC) oxygen supplementation and non-invasive ventilation (NIV). Methods: We recorded fugitive aerosol particle concentrations over time and assessed the peak (P) and area (A) efficacy of active and passive mitigation methods, comparing them to a no-mitigation condition. Peak efficacy was measured by the reduction in maximum aerosol concentration, while area efficacy was quantified by the reduction of the area under the aerosol concentration–time curve. Results: For HFNC with Neb, we found that active mitigation using a mask with a biofilter and a fan (referred to as the aerosol barrier mask) significantly outperformed passive mitigation with a face mask. The peak and area efficacy for aerosol reduction were 99.0% and 96.4% for active mitigation and 35.9% and 7.6% for passive mitigation, respectively. For NIV with Neb, the active mitigation method, using a box with a biofilter and fan, also outperformed passive mitigation using only the box. The peak and area efficacy for aerosol reduction were 92.1% and 85.5% for active mitigation and 53.7.0% and 25.4% for passive mitigation, respectively. Conclusion: We concluded that active mitigation set up systems advantageous for effective reduction of airborne aerosols during aerosol generated procedures. Full article

Background: Off-label nebulization of tranexamic acid (TXA) solution is common practice for the treatment of hemoptysis. However, data regarding nebulization protocols, resulting aerodynamic parameters of the generated aerosol, and corresponding biopharmaceutical parameters are missing. The aim of this in vitro study was to investigate the aerosol characteristics of nebulized sterile, aqueous TXA solution. Methods: TXA solution 100 mg/mL was nebulized for 2 min by a multi-dose vibrating mesh nebulizer using 15 L/min and 30 L/min air flow rates. The generated aerosol was analyzed by a Next Generation Cascade Impactor. For each air flow rate, the mean Fine Particle Dose (FPD), Fine Particle Fraction (FPF), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were quantified. Results: Nebulization at 15 L/min air flow rate resulted in a MMAD of 6.68 ± 0.23 µm and GSD of 2.02 ± 0.16. The FPD < 5 µm was 16.56 ± 0.45 mg, the FPF < 5 µm 28.91 ± 3.40%. Nebulization at 30 L/min air flow rate revealed a MMAD of 5.18 ± 0.12 µm and GSD of 2.14 ± 0.10. The FPD < 5 µm was 16.30 ± 1.38 mg, the FPF < 5 µm 35.43 ± 0.59%. Conclusions: Nebulization of TXA 100 mg/mL solution by a specified vibrating mesh nebulizer generated an aerosol particle distribution and deposition pattern suitable for the treatment of hemoptysis with bronchial origin. Full article

This review explores recent advancements in inhaled nanoparticle formulations and inhalation devices, with a focus on various types of nanoparticles used for inhalation to treat inflammatory lung diseases and the types of devices used in their delivery. Medical nebulizers have been found to be the most appropriate type of inhalation devices for the pulmonary delivery of nanoparticles, since formulations can be prepared using straightforward techniques, with no need for liquefied propellants as in the case of pressurized metered dose inhalers (pMDIs), or complicated preparation procedures as in the case of dry powder inhalers (DPIs). We demonstrated examples of how formulations should be designed considering the operation mechanism of nebulizers, and how an interplay of factors can affect the aerosol characteristics of nanoparticle formulations. Overall, nanoparticle-based formulations offer promising potential for the treatment of inflammatory lung diseases due to their unique physicochemical properties and ability to provide localized drug delivery in the lung following inhalation. Full article

The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1α) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1α ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1α pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1α-mediated HPA axis. A high-calorie diet boosts HIF-1α signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection. Full article

Breath-actuated nebulizers used in aerosol therapy are vital to children and patients with disabilities and stand out for their ability to accurat ely deliver medication while minimizing waste. Their performance can be measured according to the mass output and droplet size. This study aimed to analyze how the baffle impact surface geometries affect the pressure and flow streamlines inside the nebulizer using computational fluid dynamics (CFD). Computer-aided design models of conical symmetric, conical asymmetric, and arc-shaped baffle designs were analyzed using CFD simulations, with the optimal spray output validated through the differences in mass. Conical baffles exhibited superior pressure distribution and output streamlines at 0.25 cm protrusion, suggesting that the nebulizer spray performance can be enhanced by using such a conical baffle impact surface. This result serves as a valuable reference for future research. Full article

Background: Cough reflex sensitivity during cough challenge testing has been found to be modifiable with distraction in groups of healthy individuals. The purpose of this study was to examine this phenomenon in healthy controls and patients with refractory chronic cough (RCC) to advance our understanding of the role attention plays in cough modulation and shed light on avenues for therapeutic advances for RCC. Methods: Thirteen adults with RCC (mean age = 60, 12 women) and twelve healthy controls (mean age = 60, 11 women) participated in this study. The participants completed cough challenge testing with nebulized capsaicin doses tailored to their individual cough reflex sensitivity under distraction and no-distraction conditions. The distraction condition consisted of cough challenge testing while completing a cognitive (visual memory) task on a tablet. Capsaicin doses included the dose that elicited two coughs (C2), and up to three doubling doses above C2. Capsaicin doses were administered in serial order with a placebo dose randomized into the order to control for an anticipation effect during each condition. For each dose administered, the participants were instructed to cough if they needed to. Cough frequency within 15 s and maximal urge-to-cough with each dose were recorded. The order of conditions (distraction or no distraction) was alternated, and all testing was completed within one session. Results: There were no meaningful differences in the dose–response rate parameters for cough frequency or urge-to-cough, respectively, when comparing the results from the RCC group in the condition without distraction to the condition with distraction (p = 0.647, 95% CI = −2.25, 1.15; p = 0.783, 95% CI = −1.94, 0.84), and to the healthy control group without distraction (p = 0.921, 95% CI = −2.11, 2.73, p = 0.887, 95% CI = −1.40, 0.80), and with distraction (p = 0.970, 95% CI = −2.16, 3.36), p = 0.808, 95% CI = −1.49, 0.89). Conclusions: Distraction with the cognitive task chosen in this study did not influence cough reflex sensitivity in either group, which is contrary to studies on healthy volunteers and anecdotal evidence reported by RCC patients. Attentional resources may not have been sufficiently taxed, or too few capsaicin doses were administered to capture an effect as there was high individual variability in cough frequency and urge-to-cough. Additional research is needed to tailor the difficulty of the cognitive task to each participant and incorporate a real-world distraction scenario that may better reveal how attentional manipulation could be harnessed to optimize the effectiveness of behavioral cough suppression therapy for patients with refractory chronic cough. Full article

Pressurized intra-thoracic aerosol chemotherapy (PITAC) is a novel and promising strategy for the treatment of malignant pleural effusion (MPE). PITAC enables effective pleurodesis while potentially exerting an antineoplastic effect by delivering chemotherapeutic agents as a therapeutic aerosol into the thoracic cavity via a nebulizer. Our preliminary study involved nine patients with unresectable pleural mesothelioma (PM) treated with PITAC. Among them, one case was particularly emblematic for demonstrating notable oncological improvements in addition to well-known palliative benefits. This patient underwent two PITAC procedures, one year apart, without perioperative complications. Redo pleural biopsies from both previous and new sites revealed only fibrous tissue and inflammatory cells, with no evidence of malignancy. Beyond achieving pleurodesis, PITAC—by combining cytotoxic and sclerosing effects—may offer effective local antineoplastic control and represent a promising avenue for enhancing loco-regional therapy in PM. Full article

Hepatitis A viral outbreaks continue to occur. It can be transmitted through aerosolized droplets and thus can contaminate surfaces and the environment. Ultraviolet light emitting diode (UV-C LED) systems are used for inactivation of microbes, though research is needed to determine optimal doses for aerosolized HAV inactivation. This study evaluates the UV-C LED doses for the inactivation of aerosolized hepatitis A virus (HAV) deposited on stainless-steel and glass discs. HAV was aseptically deposited onto stainless-steel or glass discs (1.27 cm diameter) using a nebulizer within a chamber followed by treatments for up to 1.5 min with 255 nm (surface dose = 0–76.5 mJ/cm²) or 279 nm (surface dose = 0–8.1 mJ/cm²) UV-C LED. Plaque assays were used to enumerate infectious titers of recovered viruses and data from three replicates were statistically analyzed. The calculated linear D₁₀-value (UV-C dose for a 1-log reduction in aerosolized deposits) for HAV by 255 nm UV-C LED was 47.39 ± 7.40 and 40.0 ± 2.94 mJ/cm² (R² = 0.94 and 0.91) and using 279 nm UV-C LED were 6.60 ± 0.27 and 5.57 ± 0.74 mJ/cm² (R² = 0.98 and 0.94) on stainless-steel and glass discs, respectively. The non-linear Weibull model showed δ (dose needed for a 1-log reduction in aerosolized HAV deposits) values for HAV of 29.69 ± 5.49 and 35.25 ± 15.01 mJ/cm² by 255 nm UV-C LED (R² = 0.99 and 0.92) and 6.67 ± 0.63 and 5.21 ± 1.25 mJ/cm² by 279 nm UV-C LED (R² = 0.98 and 0.95) on stainless-steel and glass discs, respectively. These data indicate that 279 nm UV-C LED showed higher efficiency for HAV inactivation than 255 nm UV-C LED, and that Weibull models were a better fit when tailing was observed. This study provides the inactivation data needed to aid in designing UV-C LED systems for delivering doses required to inactivate bio-aerosolized HAV deposits on stainless-steel and glass. Full article

Background: Vibrating mesh nebulizers (VMNs) are not only used to deliver typical pulmonary drugs but are also a promising platform for novel formulations and therapeutic applications. Typically, these devices operate continuously or on demand and are directly connected to the outflow interface (mouthpiece or mask) without valving systems that could spare the drug during exhalation. This paper examines the possibility of increasing the delivery of inhaled budesonide aerosol by attaching a valved holding chamber (VHC) to selected VMNs. Methods: A laboratory in vitro study was conducted for seven budesonide (BUD) nebulization products (0.25 mg/mL). The rates of aerosol delivery from VMNs alone or VMN + VHC systems were determined gravimetrically for a simulated breathing cycle, while droplet size distributions in mists were measured by laser diffraction. Results: The VMN + VHC systems increased the amount of aerosol available for inhalation and the fraction of fine particles that could penetrate the pulmonary region. Depending on the VMN and BUD product, a relative increase of 30–300% in the total drug delivery (T) and 50–350% in the pulmonary drug availability (P) was obtained. The results are explained by the reduction in aerosol losses during exhalation (the fugitive emission) by the VHC and the simultaneous elimination of the largest droplets due to coalescence and deposition in the chamber. Both VMN and BUD affected the aerosol’s properties and discharge mass and thus the actual benefits of the VHC. Conclusions: While the results confirm the superiority of VMN + VHC over VMNs alone in nebulizing BUD suspensions, they also show that it is difficult to predict the effects quantitatively without testing the individual nebulizer–chamber–drug combination. Full article

Lithium is used as a medication in the treatment of bipolar disorder. Lithium has a narrow therapeutic index, and fatal intoxications have been described. The therapeutic drug monitoring of lithium is routinely performed in serum. Serum is commonly unavailable in forensic postmortem analysis, where whole blood is the matrix of choice. In this study, an inductively coupled plasma mass spectrometry (ICP-MS) method was developed and validated for the quantification of lithium in postmortem whole blood. Sample preparation consisted of a 100-fold dilution with acid and required only 40 µL of blood. Carry-over was deemed appropriately reduced with a rinse solution containing 5% hydrochloric acid. A nebulizer gas flow rate of 1.15 L/min showed a sufficient improvement of lithium sensitivity while simultaneously minimizing the background. Germanium was determined to be the most optimal internal standard. The method was validated in terms of linearity, accuracy, precision, and lower limit of quantification. Linearity was demonstrated within the analytical measurement range of 0.10–1.5 mmol/L. The method showed acceptable precision and accuracy, with a total coefficient of a variation ≤2.3% and accuracies ranging from 105 to 108% at all concentrations in the quality control samples. The final method was applied to postmortem blood from 103 consecutive autopsy cases and demonstrated robustness by low intermediate precision and high and consistent recovery of the internal standard. Full article

Background: Bronchiolitis accounts for a substantial number of pediatric hospitalizations and its epidemiology closely parallels that of respiratory syncytial virus (RSV), its principal etiological agent. International guidelines recommend supportive therapy based primarily on oxygen supplementation and hydration. Methods: This study aimed to assess, across three pediatric wards, the impact of internal monitoring and targeted educational interventions on adherence to bronchiolitis management guidelines. Focus was placed on evaluating the effectiveness of tailored strategies in enhancing the appropriateness of treatment practices. Each center independently developed an audit and feedback strategy aligned with local practices and available resources. In Center 1, monthly staff meetings included guideline refreshers throughout the epidemic season. Center 2 appointed two attending physicians to monitor treatment prescriptions and report deviations. Center 3 established an internal protocol through staff consensus, followed by monthly review sessions. In this retrospective analysis, all consecutive patients admitted with bronchiolitis during the winter seasons of 2022–2023 and 2023–2024 (Period 2) were compared with those admitted in 2021–2022 (Period 1). Results: A total of 623 infants under 24 months of age were included, 451 (72%) of whom tested positive for RSV. Their median length of hospital stay was 6 days; 26 infants (4%) required intensive care, and no deaths were recorded. A comparative analysis of the treatment modalities used—high-flow nasal cannula (HFNC) oxygen therapy, inhaled medications, corticosteroids, and antibiotics—revealed a reduced use of non-recommended therapies (e.g., nebulized β2-agonists, steroids, and antibiotics) in Period 2, alongside heterogeneous patterns in HFNC use. Center-specific strategies, tailored to team dynamics and resource availability, effectively promoted greater adherence to evidence-based guidelines. Conclusions: Our findings suggest that structured internal interventions can lead to more appropriate bronchiolitis management and the improved standardization of care. Full article

Background. Ventilator-associated tracheobronchitis (VAT) and pneumonia (VAP) are the most frequent nosocomial infections in the critical care setting and are associated with increased morbidity. At the same time, VAP is also associated with attributable mortality, especially when caused by difficult-to-treat (DTR) Gram-negative bacteria (GNB) that have limited treatment options. Studies have assessed the impact of nebulized aminoglycosides or colistin to improve VAT and VAP outcomes or as an adjunct to intravenous antimicrobial treatment or as a preventive approach. Objective. This overview aimed to assess systematic reviews that examine the efficacy and safety of antimicrobial nebulization for preventing and treating ventilator-associated infections in the critically ill. Methods. Systematic reviews, meta-analyses, and original randomized controlled trials and prospective observational studies were included. Searches were conducted in MEDLINE (via PubMed), the Cochrane, Epistemonikos, and PROSPERO. The methodological quality assessment was performed using standardized tools. Results. Regarding VAP treatment, the included systematic reviews presented critically low quality. The clinical response effect size to amikacin and colistin nebulization were RR 1.23 (95% CI 1.13–1.34), I² = 47% and OR 1.39 (0.87–2.20), I² = 56%. The main safety concern was bronchospasm with RR 2.55 (1.40–4.66), I² = 0% and OR 5.19 (1.05–25.52), I² = 0%. The certainty of evidence was usually very low. For VAT treatment, limited evidence showed a better clinical response and less emergence of resistant bacteria. Regarding VAP prevention, data are limited to two trials; however, only the larger one presented a low risk of bias and resulted in a reduced VAP rate. Conclusions. Delivery via nebulization might be considered in addition to IV antimicrobial treatment of GNB ventilator-associated infections. The available evidence is weak, and more studies focused on infections due to DTR-GNBs should be prioritized. Full article

Background: Pseudomonas aeruginosa is one of the major pathogens that cause respiratory infections. The rise of antimicrobial resistance has prompted a need for alternatives to conventional antibiotics. Bacteriophages (phages), natural predators of bacteria, are gaining interest as an alternative therapeutic option against drug-resistant infections. However, phage viability can be lost during manufacturing and delivery. Recent studies show that phages can be taken up by lung epithelial cells, which makes fewer phages available for antibacterial action against extracellular bacteria P. aeruginosa in the airways. Methods: In this study, we encapsulated phages in liposomes using thin film hydration. The effect of processing conditions and phage loading titer on the phage encapsulation and viability was studied. The impact of nebulization on phage viability was tested using an air-jet nebulizer (PARI-LC Plus). Phage cellular uptake was evaluated using an in vitro H441 lung epithelial cell model, grown at the air–liquid interface. Results: Our results demonstrate favorable encapsulation (58 ± 6.02%) can be achieved with minimum loss in phage titer (0.64 ± 0.21 log) by using a low phage titer for hydration. The liposomal formulations exhibited controlled release of phages over 10 h. The formulation also reduced the loss of phage viability during nebulization from 1.55 ± 0.04 log (for phage suspension) to 1.08 ± 0.05 log (for phage liposomes). Encapsulation of phages in liposomes enabled a two-fold reduction in phage cellular uptake and longer extracellular phage retention in the human lung epithelial cell monolayer. Conclusions: Our results indicate that liposomal encapsulation favors phage protection and improves phage availability for antibacterial activity. These findings highlight the potential of liposomes for inhaled phage delivery. Full article

Background: Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies. Methods: A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: (“liposomal interleukin” OR “liposome-encapsulated interleukin”) AND (“gene therapy” OR “gene delivery”) AND (“cancer” OR “tumor” OR “oncology”) AND (“pre-clinical studies” OR “animal models” OR “in vitro studies”. Results: Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35–50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes. Conclusions: Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy. Full article

This study details the manufacture of vanadium-doped ZnS thin films via a cost-effective spray pyrolysis technique at varying concentrations of vanadium (4, 8, and 12 wt.%). The XRD data demonstrate the hexagonal structure of the vanadium-doped ZnS layers. The analysis of their structural properties indicates that the crystallite size (D) of the vanadium-doped ZnS films decreased as the vanadium concentration rose. The strain and dislocation density of the analyzed films were enhanced by increasing the vanadium content from 4 to 12 wt.%. The linear optical results of the vanadium-doped ZnS films revealed that the refractive index values were improved from 2.31 to 3.49 by increasing the vanadium concentration in the analyzed samples. Further, the rise in vanadium content enhanced the absorption coefficient. The energy gap (Eg) study indicates that the vanadium-doped ZnS films exhibited direct optical transitions, with the Eg values diminishing from 3.74 to 3.15 eV as the vanadium concentration increased. The optoelectrical analysis shows that the rise in vanadium concentration increases the dispersion energy from 9.48 to 12.76 eV and reduces the oscillator energy from 3.69 to 2.17 eV. The optical carrier concentration of these layers was improved from 1.49 × 1053 to 2.15 × 1053, while the plasma frequency was decreased from 4.34 × 1013 to 3.67 × 1013 by boosting the vanadium concentration from 4 to 12 wt.%. Simultaneously, the increase in vanadium content improves the nonlinear optical parameters of the vanadium-doped ZnS films. The hot probe method identifies these samples as n-type semiconductors. The findings suggest that these samples serve as an innovative window layer. Full article