Search Results (38)

Algal and cyanobacterial blooms are anticipated to increase in frequency, duration, and geographic extent as a result of environmental changes, including climate warming, elevated nutrient concentrations, and increased runoff in both marine and freshwater ecosystems. The eutrophication of aquatic environments represents a substantial threat to human health. As eutrophication progresses, airborne algae and cyanobacteria, particularly harmful genera originating from aquatic environments, are released into the atmosphere and may pose potential risks to human health. Furthermore, respiratory distress has been documented in individuals exposed to aerosols containing harmful algal bloom (HAB) toxins. This review investigates the generation of aerosolised harmful algal blooms, their responses to environmental factors, and their associated health risks. Evidence suggests that airborne algae, cyanobacteria, and their toxins are widespread. When these are aerosolised into micrometre-sized particles, they become susceptible to atmospheric processing, which may degrade the HAB toxins and produce byproducts with differing potencies compared to the parent compounds. Inhalation of aerosolised HAB toxins, especially when combined with co-morbid factors such as exposure to air pollutants, could present a significant health risk to a considerable proportion of the global population. A more comprehensive understanding of the chemical transformations of these toxins and the composition of harmful algal and cyanobacterial communities can improve public safety. Full article

Inorganic nanoparticles (NPs) have been synthesised via mixing and coalescence of droplets containing precursors and entrained by gaseous streams. The droplets have been generated by ultrasonic aerosolisation of two different liquid phases, each containing the respective reagent. The as-produced NPs are trapped by mixing with a liquid phase in a Venturi nozzle, acting simultaneously as a collector and concentrator of the solid nanosized phase produced. Commercial electrically powered ultrasonic aerosolising devices have been adapted to atomise salt solutions characterised by high electrical conductivity. This process allowed the synthesis of calcium carbonate NPs with an average diameter in the range of (34–52) nm, according to the concentration of precursors in the aerosolised phases. This closed-loop method of synthesis, where neither capping agents were used nor demanding operating conditions were adopted, can represent a safe and viable eco-friendly technique for NP production free of undesirable compounds, as required for pharmaceutical preparations and theranostic uses. Full article

Background: Inhalational antibiotics have been used effectively to treat chronic diseases such as Pseudomonas aeruginosa infections associated with cystic fibrosis. This approach may enhance treatment options for difficult-to-treat, acute pneumonic diseases. Liposomal encapsulated ciprofloxacin (Lipoquin and/or Apulmiq) has provided protection in murine models of plague, anthrax, Q fever and tularemia. Development of the ability to deliver these drugs to nonhuman primates (NHPs) would enable further extrapolation of the data observed in small animal models of infection to humans. Methods: In this study, the methodology was established to deliver Apulmiq to common marmosets (Callithrix jacchus). Marmosets were anaesthetised with a novel, reversible anaesthetic comprising fentanyl, medetomidine and midazolam (FMM). They were placed into plethysmography tubes with their heads in an exposure chamber. The LC Sprint jet nebuliser or Pari eFlow Rapid nebuliser were used to aerosolise Apulmiq into the exposure chamber. Animals were euthanised after dosing and the concentration of ciprofloxacin was assessed in the plasma and lungs of the animals. Results: Non-compartmental pharmacokinetic analysis determined that a 30 min exposure of drug was required to reach a human-equivalent target dose of 0.8 mg/kg body weight in the lungs. Conclusions: This approach can now be used to assess the efficacy of inhalational liposomal ciprofloxacin in NHP infection models. Full article

Background: Respiratory viruses spread through airborne droplets and aerosols, causing highly contagious acute respiratory syndromes in humans. This study evaluated the antiviral potential of vapours of catmint-oil-based formulations against respiratory viruses. Methods: The antiviral activity of formulations with or without catmint oil (CO) in solution or in aerosolised form was determined against influenza virus H1N1 ATCC VR-1469 and mouse hepatitis virus (MHV-1) ATCC/VR261. In solution, both viruses were exposed to CO formulations for 2–3 h. In aerosolised form, H1N1 was exposed to formulations for 2 min in a closed cylinder and MHV-1 for 10 min in a booth. The antiviral effect of the formulations was evaluated by growing H1N1 in a Madin–Darby canine kidney (MDCK; ATCC-CRL-2936) and MHV-1 in A9 ATCC/CCL 1.4 cells using TCID50 and a plaque assay, respectively. Transmission electron microscopy (TEM) was conducted to investigate the mode of action of the formulations. Results: In solution, the formulation containing hydrogenated CO (HCO), bromelain, N-acetylcysteine and Tween 20 (Formulation (1)) reduced the viability of H1N1 by 2.6 ± 0.07 log₁₀ (p = 0.025) and MHV-1 by 4.5 ± 0.14 log₁₀ (p = 0.014) within 2–3 h. In vapourised form, Formulation (1) produced similar antiviral effects against H1N1, reducing it by 3.00 ± 0.07 log₁₀ (p = 0.002) within 2 min, and Formulation (1) produced a 3.00 ± 0.07 log₁₀ reduction of MHV-1 (p < 0.001) within 10 min (the minimum time needed to detect infective viral particles in the experimental set-ups). Formulation (3) (without bromelain) reduced H1N1 by 1.57 ± 0.14 log₁₀ (p = 0.008) after 2 min and MHV-1 by 1.3 ± 0.04 log₁₀ (p = 0.057) after 10 min. In the absence of catmint oil (Formulation (4)) or in the absence of catmint oil and bromelain (Formulation (5)), there were only slight reductions in the viability of aerosolised H1N1 (1.00 ± 0.14 log₁₀, p = 0.046; <1 log₁₀, p = 0.966, respectively) and MHV-1 (1.07 ± 0.02 log₁₀, p = 0.013; 0.16 ± 0.03 log₁₀, p = 0.910, respectively). The TEM analysis showed that the formulation disrupted the H1N1 envelopes and caused a reduction in size of the viral particles. Conclusions: The catmint-oil-based formulations reduced the H1N1 and MHV-1 by disrupting the vial envelopes. Full article

(1) Background. A definition of healthcare-associated infections is essential also for the attribution of the restorative burden to healthcare facilities in case of harm and for clinical risk management strategies. Regarding M. chimaera infections, there remains several issues on the ecosystem and pathogenesis. We aim to review the scientific evidence on M. chimaera beyond cardiac surgery, and thus discuss its relationship with healthcare facilities. (2) Methods. A systematic review was conducted on PubMed and Web of Science on 7 May 2024 according to PRISMA 2020 guidelines for reporting systematic reviews, including databases searches with the keyword “Mycobacterium chimaera”. Article screening was conducted by tree authors independently. The criterion for inclusion was cases that were not, or were improperly, consistent with the in-situ deposition of aerosolised M. chimaera. (3) Results. The search yielded 290 eligible articles. After screening, 34 articles (377 patients) were included. In five articles, patients had undergone cardiac surgery and showed musculoskeletal involvement or disseminated infection without cardiac manifestations. In 11 articles, respiratory specimen reanalyses showed M. chimaera. Moreover, 10 articles reported lung involvement, 1 reported meninges involvement, 1 reported skin involvement, 1 reported kidney involvement after transplantation, 1 reported tendon involvement, and 1 reported the involvement of a central venous catheter; 3 articles reported disseminated cases with one concomitant spinal osteomyelitis. (4) Conclusions. The scarce data on environmental prevalence, the recent studies on M. chimaera ecology, and the medicalised sample selection bias, as well as the infrequent use of robust ascertainment of sub-species, need to be weighed up. The in-house aerosolization, inhalation, and haematogenous spread deserve experimental study, as M. chimaera cardiac localisation could depend to transient bacteraemia. Each case deserves specific ascertainment before tracing back to the facility, even if M. chimaera represents a core area for healthcare facilities within a framework of infection prevention and control policies. Full article

Waterproofing sprays can cause acute respiratory symptoms after inhalation, including coughing and dyspnoea shortly after use. Here, we describe two cases where persons used the same brand of waterproofing spray product. In both cases the persons followed the instructions on the product and maximized the ventilation by opening windows and doors; however, they still became affected during the application of the product. Products with the same batch number as that used in one case were tested for their effect on respiration patterns of mice in whole-body plethysmographs and lung surfactant function inhibition in vitro. The product was used in spraying experiments to determine the particle size distribution of the aerosol, both using a can from one case and a can with an identical batch number. In addition, the aerosols in the mouse exposure chamber were measured. Aerosol data from a small-scale exposure chamber and data on the physical and temporal dimensions of the spraying during one case were used to estimate the deposited dose during the spraying events. All collected data point to the spraying of the waterproofing product being the reason that two people became ill, and that the inhibition of lung surfactant function was a key component of this illness. Full article

PIPAC is a new and promising technique for the intraperitoneal administration of chemotherapy. It can be used in patients with various peritoneal cancer metastases. It is mainly a palliative treatment, but there is some neoadjuvant treatment potential. We have operated on 41 patients with various intra-abdominal cancers. PIPAC was performed every 6 weeks. The indication was extension of peritoneal carcinomatosis beyond the criteria for cytoreductive surgery and HIPEC. The effect was evaluated according to the peritoneal cancer index, the peritoneal regression grading score and the amount of ascites. Complications were classified according to the Clavien-Dindo system. We have performed 100 PIPAC procedures. There were two major complications, classified as Clavien Dindo III (2%). The number of procedures varied from 1 to 6. Five patients switched to cytoreductive surgery and HIPEC, and one was indicated for the watch and wait strategy due to total regression according to PRGS. Three patients are still continuing treatment. The others stopped treatment mainly because of progression of the disease and loss of metastases. We observed a reduction in ascites production soon after PIPAC application. PIPAC is a safe and well-tolerated treatment modality. It is mainly a palliative treatment that can improve the quality of life by reducing the production of ascites, but in about 10% of cases, it can reduce the extent of the disease and allow for further radical treatment. Full article

High-flow nasal oxygen therapy is being increasingly adopted in intensive and home care settings. The concurrent delivery of aerosolised therapeutics allows for the targeted treatment of respiratory illnesses. This study examined in-line aerosol therapy via a nasal cannula to simulated adult and paediatric models with healthy, obstructive and restrictive lung types. The Aerogen Solo vibrating mesh nebuliser was used in combination with the Inspired^TM O2FLO high-flow therapy system. Representative adult and paediatric head models were connected to a breathing simulator, which replicated several different states of lung health. The aerosol delivery was quantified at the tracheal level using UV-spectrophotometry. Testing was performed at a range of supplemental gas flow rates applicable to both models. Positive end-expiratory pressure was measured pre-, during and post-nebulisation. The increases in supplemental gas flow rates resulted in a decrease in aerosol delivery, irrespective of lung health. Large tidal volumes and extended inspiratory phases were associated with the greatest aerosol delivery. Gas flow to inspiratory flow ratios of 0.29–0.5 were found to be optimum for aerosol delivery. To enhance aerosol delivery to patients receiving high-flow nasal oxygen therapy, respiratory therapists should keep supplemental gas-flow rates below the inspiratory flow of the patient. Full article

(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the “proof-of-principle” effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings. Full article

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs–fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127–175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs–fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID. Full article

Background: Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. Results: The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Conclusions: Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection. Full article

Acute respiratory distress syndrome (ARDS) is a severe complication of lung injuries, commonly associated with bacterial, fungal and viral infections, including SARS-CoV-2 viral infections. ARDS is strongly correlated with patient mortality and its clinical management is very complex, with no effective treatment presently available. ARDS involves severe respiratory failure, fibrin deposition in both airways and lung parenchyma, with the development of an obstructing hyaline membrane drastically limiting gas exchange. Moreover, hypercoagulation is related to deep lung inflammation, and a pharmacological action toward both aspects is expected to be beneficial. Plasminogen (PLG) is a main component of the fibrinolytic system playing key roles in various inflammation regulatory processes. The inhalation of PLG has been proposed in the form of the off-label administration of an eyedrop solution, namely, a plasminogen-based orphan medicinal product (PLG-OMP), by means of jet nebulisation. Being a protein, PLG is susceptible to partial inactivation under jet nebulisation. The aim of the present work is to demonstrate the efficacy of the mesh nebulisation of PLG-OMP in an in vitro simulation of clinical off-label administration, considering both the enzymatic and immunomodulating activities of PLG. Biopharmaceutical aspects are also investigated to corroborate the feasibility of PLG-OMP administration by inhalation. The nebulisation of the solution was performed using an Aerogen^® Solo^TM vibrating-mesh nebuliser. Aerosolised PLG showed an optimal in vitro deposition profile, with 90% of the active ingredient impacting the lower portions of a glass impinger. The nebulised PLG remained in its monomeric form, with no alteration of glycoform composition and 94% of enzymatic activity maintenance. Activity loss was observed only when PLG-OMP nebulisation was performed under simulated clinical oxygen administration. In vitro investigations evidenced good penetration of aerosolised PLG through artificial airway mucus, as well as poor permeation across an Air–Liquid Interface model of pulmonary epithelium. The results suggest a good safety profile of inhalable PLG, excluding high systemic absorption but with good mucus diffusion. Most importantly, the aerosolised PLG was capable of reversing the effects of an LPS-activated macrophage RAW 264.7 cell line, demonstrating the immunomodulating activity of PLG in an already induced inflammatory state. All physical, biochemical and biopharmaceutical assessments of mesh aerosolised PLG-OMP provided evidence for its potential off-label administration as a treatment for ARDS patients. Full article

Among conductive polymers, poly(3,4 ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) has been widely used as an electrode material for supercapacitors, solar cells, sensors, etc. Although PEDOT:PSS-based thin films have acceptable properties such as good capacitive and electrical behaviour and biocompatibility, there are still several challenges to be overcome in their use as an electrode material for supercapacitors. For this reason, the aim of this work is to fabricate and characterise ternary nanocomposites based on PEDOT:PSS and graphene oxide (GO), blended with green additives (glucose (G) or ascorbic acid (AA)), which have the benefits of being environmentally friendly, economical, and easy to use. The GO reduction process was first accurately investigated and demonstrated by UV-Vis and XRD measurements. Three-component inks have been developed, and their morphological, rheological, and surface tension properties were evaluated, showing their printability by means of Aerosol Jet^® Printing (AJ^®P), an innovative direct writing technique belonging to the Additive Manufacturing (AM) for printed electronics applications. Thin films of the ternary nanocomposites were produced by drop casting and spin coating techniques, and their capacitive behaviour and chemical structures were evaluated through Cyclic Voltammetry (CV) tests and FT-IR analyses. CV tests show an increment in the specific capacitance of AAGO-PEDOT up to 31.4 F/g and excellent overtime stability compared with pristine PEDOT:PSS, suggesting that this ink can be used to fabricate supercapacitors in printed (bio)-electronics. The inks were finally printed by AJ^®P as thin films (10 layers, 8 × 8 mm) and chemically analysed by FT-IR, demonstrating that all components of the formulation were successfully aerosolised and deposited on the substrate. Full article

This review examines the effects of particle properties on drug–carrier interactions in the preparation of a dry powder inhaler (DPI) formulation, including appropriate mixing technology. The interactive effects of carrier properties on DPI formulation performance make it difficult to establish a direct cause-and-effect relationship between any one carrier property and its effect on the performance of a DPI formulation. Alpha lactose monohydrate remains the most widely used carrier for DPI formulations. The physicochemical properties of α-lactose monohydrate particles, such as particle size, shape and solid form, are profoundly influenced by the method of production. Therefore, wide variations in these properties are inevitable. In this review, the role of surface energetics in the optimisation of dry powder inhaler formulations is considered in lactose carrier selection. Several useful lactose particle modification methods are discussed as well as the use of fine lactose and force control agents in formulation development. It is concluded that where these have been investigated, the empirical nature of the studies does not permit early formulation prediction of product performance, rather they only allow the evaluation of final formulation quality. The potential to leverage particle interaction dynamics through the use of an experimental design utilising quantifiable lactose particle properties and critical quality attributes, e.g., surface energetics, is explored, particularly with respect to when a Quality-by-Design approach has been used in optimisation. Full article

The majority of in vitro studies focusing upon particle–lung cell interactions use static models at an air–liquid interface (ALI). Advancing the physiological characteristics of such systems allows for closer resemblance of the human lung, in turn promoting 3R strategies. PATROLS (EU Horizon 2020 No. 760813) aimed to use a well-characterised in vitro model of the human alveolar epithelial barrier to determine how fluid-flow dynamics would impact the outputs of the model following particle exposure. Using the QuasiVivo^TM (Kirkstall Ltd., York, UK) system, fluid-flow conditions were applied to an A549 + dTHP-1 cell co-culture model cultured at the ALI. DQ₁₂ and TiO₂ (JRCNM01005a) were used as model particles to assess the in vitro systems’ sensitivity. Using a quasi- and aerosol (VitroCell Cloud12, VitroCell Systems, Waldkirch, Germany) exposure approach, cell cultures were exposed over 24 h at IVIVE concentrations of 1 and 10 (DQ₁₂) and 1.4 and 10.4 (TiO₂) µg/cm², respectively. We compared static and fluid flow conditions after both these exposure methods. The co-culture was subsequently assessed for its viability, membrane integrity and (pro-)inflammatory response (IL-8 and IL-6 production). The results suggested that the addition of fluid flow to this alveolar co-culture model can influence the viability, membrane integrity and inflammatory responses dependent on the particle type and exposure. Full article