Mulberry Diels-Alder-type adducts (MDAAs), isolated from Morus alba root bark, exhibit dual activity against viral and bacterial pathogens but show sobering efficacy following oral administration. Inhalation administration may overcome issues with oral bioavailability and improve efficacy for the treatment of respiratory infections. To assess the suitability of MDAAs for inhalation administration, physicochemical (e.g. pH, pKa, logP, pH-dependent solubility) and biopharmaceutical (epithelial cytotoxicity, permeability, and uptake) properties of two bioactive MDAA stereoisomers sanggenon C (SGC) and sanggenon D (SGD) were evaluated as isolated natural compounds and within parent extracts (MA21, MA60). Despite their structural similarity, SGD exhibited a 10-fold higher solubility than SGC across pH 1.2-7.4, with slight increases at neutral pH. Both compounds were more soluble in isolated form than in the parent extracts. The more lipophilic SGC was found to be more cytotoxic when compared to SGD, indicating a better cellular penetration, which was confirmed by uptake studies. Nonetheless, SGC and SGD exhibited no measurable permeability across intact Calu-3 monolayers, highlighting their potential for increased lung retention and improved local anti-infective activity following inhalation administration. Results suggest that SGC and SGD in isolated form, rather than as extracts, are promising candidates for pulmonary drug delivery to treat lung infections.

Lung carcinoma, particularly non-small-cell lung cancer (NSCLC), accounts for a significant portion of cancer-related deaths, with a fatality rate of approximately 19 %. Niclosamide (NIC), originally an anthelmintic drug, has attracted attention for its potential in disrupting cancer cells through various intracellular signaling pathways. However, its effectiveness is hampered by limited solubility, reducing its bioavailability. This study investigates the efficacy of NIC against lung cancer using inhalable hybrid nano-assemblies with chitosan-functionalized Poly (ε-caprolactone) (PCL) as a carrier for pulmonary delivery. The evaluation encompasses various aspects such as aerodynamic and physicochemical properties, drug release kinetics, cellular uptake, biocompatibility, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells. Increasing NIC dosage correlates with enhanced inhibition of cell proliferation, showing a dose-dependent profile (approximately 75 % inhibition efficiency at 20 μg/ml of NIC). Optimization of inhaled dosage and efficacy is conducted in a murine model of NNK-induced tumor-bearing lung cancer. Following inhalation, NIC-CS-PCL-NA demonstrates significant lung deposition, retention, and metabolic stability. Inhalable nano-assemblies promote autophagy flux and induce apoptotic cell death. Preclinical trials reveal substantial tumor regression with minimal adverse effects, underscoring the potential of inhalable NIC-based nano-formulation as a potent therapeutic approach for NSCLC, offering effective tumor targeting and killing capabilities.

Inhalation systems, mostly metered dose inhalers (MDIs) and dry powder inhalers (DPIs), are currently submitted to a critical assessment for their carbon footprint (CF) and environmental impact. They are related to greenhouse gas (GHG) emissions and they produce waste of used devices with withheld drug residues and unused doses. However, with estimated contributions to anthropogenic GHG-emissions of 0.03% for MDIs and 0.0012% for DPIs globally, it may not be expected that mitigating the GHG emissions from inhalers will have a meaningful effect on the current climate change and global warming, notwithstanding that nationally these percentages may be somewhat higher, depending on the ratio of MDIs to DPIs and the total national CF. MDIs are particularly the preferred type of inhalers over DPIs in the USA and UK with ratios of 9: 1 and 7: 3 respectively. In such countries, a partial switch from MDIs to DPIs is to be recommended, providing that such a switch does not jeopardize the therapy. Using renewable energy only for the production and waste management of DPIs will make this type of inhaler almost climate neutral. A greater concern exists about inhaler waste, more particularly about the residual drug and unused doses in discarded devices. Inhalers contribute less than 0.02% to global plastic waste annually and most plastic inhalers end in the domestic waste bin and not as litter polluting the environment with plastic. However, they do contain retained drug and unused doses, whereas even full inhalers are disposed. Because globally most municipal waste (70%) ends up in dumps and landfills, leakage of the drugs into the soil and surface waters is a serious problem. It pollutes drinking water and endangers species and biodiversity. Therefore, a good collection system and an adequate waste management program for used inhalers seems to be the most meaningful measure to take for the environment, as this will stop inhalers and drugs from putting ecosystems at risk.

This consensus document addresses the reduction of the environmental impact of inhalers in Portugal. It was prepared by the Portuguese Council for Health and the Environment and the societies representing the specialties that account for these drugs\' largest volume of prescriptions, namely the Portuguese Society of Pulmonology, the Portuguese Society of Allergology and Clinical Immunology, the Portuguese Society of Pediatrics, the Portuguese Society of Internal Medicine, the Portuguese Association of General and Family Medicine and also a patient association, the Respira Association. The document acknowledges the significant impact of pressurized metered-dose inhalers on greenhouse gas emissions and highlights the need to transition to more sustainable alternatives. The carbon footprint of pressurized metered-dose inhalers and dry powder inhalers in Portugal was calculated, and the level of awareness among prescribing physicians on this topic was also estimated. Finally, recommendations were developed to accelerate the reduction of the ecological footprint of inhalers.
Este documento de consenso aborda a redução do impacto ambiental dos inaladores em Portugal. Foi elaborado pelo Conselho Português para a Saúde e Ambiente e pelas sociedades que representam as especialidades com maior volume de prescrição destes medicamentos, nomeadamente a Sociedade Portuguesa de Pneumologia, a Sociedade Portuguesa de Alergologia e Imunologia Clínica, a Sociedade Portuguesa de Pediatria, a Sociedade Portuguesa de Medicina Interna e a Associação Portuguesa de Medicina Geral e Familiar em conjunto com uma associação de doentes, a Associação Respira. Reconhece-se o impacto significativo dos inaladores pressurizados doseáveis nas emissões de gases com efeito de estufa e a necessidade de transição para alternativas mais sustentáveis. Calculou-se a pegada de carbono dos inaladores pressurizados doseáveis e dos inaladores de pó seco em Portugal e estimou-se o nível de literacia dos médicos prescritores relativamente a este tema. Finalmente, foram elaboradas recomendações com o objetivo de acelerar a redução da pegada ecológica dos inaladores.

OBJECTIVE: Inspiratory muscle training is used in rehabilitation to exercise respiratory muscles in various conditions associated with limited ventilatory reserve. In this review, we investigated inspiratory muscle training in lung transplant candidates and recipients.
METHODS: We searched 5 primary databases from inception through April 2024. Two key word entries, \"lung transplantation\" and \"inspiratory muscle training,\" were matched using the Boolean operator AND. No filters were applied for document type, age, sex, publication date, language, and subject.
CONCLUSIONS: The searched databases returned 119 citations. Seven articles that considered 64 patients (47% female) were included in the final analysis, with 1 study involving a pediatric patient. Lung transplant recipients used a threshold trainer at 15% to 60% of maximal inspiratory pressure and mostly exercised twice daily for 10 to 15 minutes per session. Lung transplant candidates exercised at 30% to >50% of maximal inspiratory pressure twice daily, performing 30 to 60 inspirations or for 15 minutes. The highest inspiratory muscle strength was observed in a series of adult lung transplant recipients whose mean value improved by 31.8 ± 14.6 cmH2O versus baseline after treatment. To the same extent, the highest value of maximal inspiratory pressure was detected in a pediatric patient who scored 180 cmH2O after training. Overall, participants obtained improvements in lung function (forced expiratory volume in 1 second, forced vital capacity), functional performance, dyspnea intensity, and exercise tolerance. Inspiratory muscle training is easy to perform and can be done at home without specific supervision (in adults) before or after a lung transplant. Nevertheless, additional rigorous investigations should aim to replicate the positive effects reported in the present review.

Of the total carbon footprint of Australia, 7% is attributed to healthcare. In the UK, inhalational agents make up 5% of the healthcare carbon footprint. This systematic review aims to determine which methods of education about the environmental impact of inhalational anaesthetic agents can be utilised to promote behaviour change, reducing the anaesthetic-related carbon footprint. This systematic review sourced records from CINAHL, EMBASE, ERIC, JBI and MEDLINE from 1970 to March 2022. The search identified 589 records, 13 of which met eligibility criteria after the screening process, in which 10 of these records were conference abstracts. Education curricula focused on inhalational agent choice (69%), lowering the fresh gas flow during maintenance anaesthesia (69%), encouraging alternatives such as total intravenous anaesthesia (23%) and/or switching off the gas on transfer (8%). The most common teaching techniques utilised in education curricula were didactic lectures (85%), visual prompts (54%), emails (46%), and conversation forums (31%). All but one study reported a positive relationship between teaching sessions and behavioural change resulting in lower inhalational anaesthetic use by participants and their organisations, reducing healthcare-associated emissions. This systematic review has demonstrated that single education sessions as well as multi-focused, multimodal education curricula on the topic of greener anaesthesia can be beneficial in promoting behavioural change.

Inhaled nanoparticle (NP) therapy poses intricate challenges in clinical and pharmacodynamic realms. Recent strides have revolutionized NP technology by enabling the incorporation of diverse molecules, thus circumventing systemic clearance mechanisms and enhancing drug effectiveness while mitigating systemic side effects. Despite the established success of systemic NP delivery in oncology and other disciplines, the exploration of inhaled NP therapies remains relatively nascent. NPs loaded with bronchodilators or anti-inflammatory agents exhibit promising potential for precise distribution throughout the bronchial tree, offering targeted treatment for respiratory diseases. This article conducts a comprehensive review of NP applications in respiratory medicine, highlighting their merits, ranging from heightened stability to exacting lung-specific delivery. It also explores cutting-edge technologies optimizing NP-loaded aerosol systems, complemented by insights gleaned from clinical trials. Furthermore, the review examines the current challenges and future prospects in NP-based therapies. By synthesizing current data and perspectives, the article underscores the transformative promise of NP-mediated drug delivery in addressing chronic conditions such as chronic obstructive pulmonary disease, a pressing global health concern ranked third in mortality rates. This overview illuminates the evolving landscape of NP inhalation therapies, presenting optimistic avenues for advancing respiratory medicine and improving patient outcomes.

Background and Objectives: The impact of anesthetic agents on memory and cognitive function following general anesthesia is of great interest, particularly regarding their effects on the developing pediatric brain. While numerous studies have examined the relationship between anesthetic drugs and brain function, research focusing on early cognitive function following sedation remains limited. Materials and Methods: This study was a prospective, randomized controlled trial involving 148 pediatric patients scheduled for hematological procedures, specifically bone marrow aspiration (BMA) and intrathecal chemotherapy (ITC). Patients were divided into two groups based on the primary anesthetic used: the inhalational sedation group (IHG), in which sevoflurane was used, and the intravenous sedation group (IVG), which received propofol infusion. Apart from the main anesthetic agent, all sedation methods were consistent across both groups. A cognitive function test administered before sedation involved memorizing four distinct images, each associated with a different number. Then, the patients were asked to identify the omitted image upon awakening in the recovery room. Herein, this pre- vs. post-sedation test is called the early recognition assessment (ERA) tool. The primary outcome was the correct response rate after sedation for the two groups. Secondary outcomes included the sedation score, the behavior response score, and the correct response rates according to the number of sedation procedures. Results: This study included 130 patients in the final analysis, with 74 originally assigned to each group. The initial cognitive assessment revealed no significant difference in performance between the anesthetic agents. In addition, no differences were observed in the rates of correct responses or post-sedation scores after repeated procedures. However, the IVG demonstrated higher behavior response scores compared to the IHG. Conclusions: There were no significant differences in the rates of correct responses using the ERA tool between the two groups, irrespective of the number of sedation procedures performed. While some differences were noted in preoperative, intraoperative, and post-anesthesia care, these did not significantly impact the cognitive outcomes measured.

UNASSIGNED: Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell-derived exosome nebulization therapy (SCENT).
UNASSIGNED: Stem cell-derived exosomes were characterized for size distribution and surface markers. C57BL/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging.
UNASSIGNED: Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of Cd36 in endothelial cells (ECs). In an EC-Cd36fl/- conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (Δ=11.66±5.12%) and fractional shortening (Δ=5.72±2.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall.
UNASSIGNED: In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC-Cd36fl/- mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets.

OBJECTIVE: Inspiratory muscle training (IMT) has emerged as a potential intervention to improve respiratory outcomes for patients undergoing cardiac surgery. However, the extent of the IMT effects on preoperative and postoperative respiratory metrics remains uncertain. Hence, we designed this study to determine the effects of IMT on various outcomes of patients undergoing cardiac surgery.
METHODS: We conducted a comprehensive meta-analysis of studies evaluating the impact of preoperative and postoperative IMT on various respiratory variables and postsurgical outcomes. We synthesized data from multiple studies, encompassing diverse patient populations and IMT protocols. The key outcomes included the maximal inspiratory pressure (MIP), forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and others.
RESULTS: Our meta-analysis results showed that preoperative IMT significantly improved the MIP values with a pooled standard mean difference (SMD) of 0.62. The hospital stay length was also reduced with a SMD of - 0.4. Other variables such as FEV1 and FVC also improved significantly. Postoperative IMT improved the MIP and peak flow rate values, but the evidence was less robust than with preoperative interventions. We observed high heterogeneity across studies for several outcomes and found evidence of publication bias for some postoperative measures.
CONCLUSIONS: Both preoperative and postoperative IMT offer benefits for patients undergoing operations, especially by enhancing respiratory muscle strength and potentially reducing hospital stays. However, the presence of heterogeneity and publication bias underscores the need for further standardized research to consolidate these findings and standardize IMT protocols for optimal patient outcomes.