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BACKGROUND: Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25µg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. METHODS: The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). RESULTS: A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. CONCLUSION: Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.
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Analgésicos Opioides , Dolor Irruptivo , Dolor en Cáncer , Fentanilo , Humanos , Fentanilo/uso terapéutico , Fentanilo/farmacología , Fentanilo/administración & dosificación , Método Doble Ciego , Masculino , Persona de Mediana Edad , Femenino , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Dolor Irruptivo/tratamiento farmacológico , Dolor Irruptivo/etiología , Anciano , Dolor en Cáncer/tratamiento farmacológico , Adulto , Administración por Inhalación , Estudios Cruzados , Dimensión del Dolor/métodos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: Both physicians and patients are increasingly aware of the environmental impacts of medication. The shift of treatment paradigm towards MART-treatment (Maintenance and Reliever Therapy) in asthma affects the treatment-related emissions. The carbon footprint of inhaled medication is also tied to the type of the device used. Today the most commonly used propellant-containing pressurised metered-dose inhalers (pMDIs) have a carbon footprint typically 20-40-fold higher than propellant-free dry powder inhalers (DPIs) and soft mist inhalers. METHODS: We analysed the carbon footprint of inhaled medications in Europe using published life cycle analyses of marketed inhalers and comprehensive 2020 European sales data. In addition, we give an estimate on treatment-related emissions of different treatment regimens on Global Initiative for Asthma (GINA) step 2. RESULTS: There is potential to reduce the carbon footprint of inhaled medications by 85% if DPIs are preferred over pMDIs. Emissions from pMDIs in the EU were estimated to be 4.0 megatons of carbon dioxide equivalent (MT CO2e) and this could be reduced to 0.6 MT CO2e if DPIs were used instead. In the treatment of moderate asthma with DPI, an as-needed combination of inhaled corticosteroid and long-acting beta-agonist in a single inhaler had a substantially lower annual carbon footprint (0.8 kg CO2e) than the more traditional maintenance therapy with an inhaled corticosteroid alone with as-needed short-acting beta-agonist (2.9 kg CO2e). DISCUSSION: There has been an urgent call for healthcare to reduce its carbon footprint for appropriate patients with asthma and chronic obstructive pulmonary disease (COPD), changing to non-propellant inhalers can reduce the carbon footprint of their treatment by almost 20-fold.
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Asma , Huella de Carbono , Inhaladores de Polvo Seco , Gases de Efecto Invernadero , Inhaladores de Dosis Medida , Humanos , Asma/tratamiento farmacológico , Administración por Inhalación , Gases de Efecto Invernadero/análisis , Europa (Continente) , Antiasmáticos/administración & dosificaciónRESUMEN
Purpose: COPD affects more than 300 million people worldwide, requiring inhalation treatment. Novel triple formulations of ICS, LABAs and LAMAs are becoming the mainstay of treatment, however there is still a lack of clinical evidence for personalized therapy. Patients and Methods: RATIONALE was a non-interventional, prospective, 52 week study, assessing the effectiveness of beclometasone/formoterol/glycopyrronium-bromide (BDP/FF/G), in symptomatic COPD patients, with moderate airflow obstruction. The study included 4 visits, where data on demographic parameters, exacerbations, symptoms, quality of life (based on the EQ-5D-3L questionnaire) and lung function were collected. Data on adherence to treatment, based on prescriptions filled was collected from the database of the National Health Insurance Fund, with the patients' consent. The primary objective was the change of adherence to treatment during the study, compared to baseline. Results: Altogether 613 patients had been enrolled. Their average age was 64.56 years and 50.5% were female. The average CAT score was 20.86, and most patients had suffered minimum one exacerbation (82.2%). Average FEV1 was 59.6%. Most patients had some limitation in one or more dimensions of EQ-5D-3L, with an average visual analogue scale score (VAS) of 60.31. After 12 months of treatment, adherence improved significantly - proportion of patients in the highest adherence group increased from 29.8% to 69.7% (p<0.001). The average CAT score improved by 7.02 points (95% CI 5.82-8.21, p<0.001). There was a significant improvement in all dimensions of EQ-5D-3L, with an average increase of 17.91 (95% CI 16.51-19.31, p< 0.001) points in the VAS score. Exacerbation frequency also decreased significantly. Conclusion: Although limitations of observational studies are present, we observed that early introduction of fixed triple combination results in a marked improvement in adherence to treatment, symptom scores, exacerbation frequency and quality of life. The optimal choice of treatment is crucial for reaching the highest possible adherence.
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Agonistas de Receptores Adrenérgicos beta 2 , Beclometasona , Broncodilatadores , Combinación de Medicamentos , Fumarato de Formoterol , Glicopirrolato , Pulmón , Cumplimiento de la Medicación , Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Calidad de Vida , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Administración por Inhalación , Estudios Prospectivos , Anciano , Resultado del Tratamiento , Broncodilatadores/administración & dosificación , Glicopirrolato/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Pulmón/fisiopatología , Pulmón/efectos de los fármacos , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/efectos adversos , Beclometasona/administración & dosificación , Factores de Tiempo , Fumarato de Formoterol/administración & dosificación , Volumen Espiratorio Forzado , Índice de Severidad de la Enfermedad , Recuperación de la Función , Progresión de la Enfermedad , Glucocorticoides/administración & dosificaciónRESUMEN
The SARS-CoV-2 virus caused the 2019 COVID pandemic by infecting almost eight hundred million people worldwide. Because it was a new viral infection, there were no vaccines or small molecule medications that could prevent or treat the disease. This chapter provides some details for an obscure treatment for COVID-19, that has decades of anti-viral activity data both in vitro and in vivo in the literature. The medicinal molecules are compared to other small molecules that were identified as possible medications for COVID-19. We developed a computational method that ranks small molecules and their ability to penetrate mucus in the lungs of a COVID-19 patient. Our focus is ethanol as a COVID-19 treatment. The results discussed here are based on Lipinski Rules and QSAR computational methods as well as in vitro and in vivo data. These parameters indicate that ethanol should be a strong candidate for future evaluations.
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Tratamiento Farmacológico de COVID-19 , Etanol , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Etanol/farmacología , Humanos , SARS-CoV-2/efectos de los fármacos , Administración por Inhalación , Glicoproteína de la Espiga del Coronavirus/metabolismo , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/virología , AnimalesRESUMEN
Purpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers. Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract. Results: The nano-micelles, with a particle size of <100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h. Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.
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Péptidos de Penetración Celular , Insulina , Micelas , Polietilenglicoles , Insulina/administración & dosificación , Insulina/farmacocinética , Insulina/química , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Animales , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacocinética , Humanos , Tamaño de la Partícula , Administración por Inhalación , Masculino , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratas Sprague-Dawley , Moco/química , Moco/metabolismo , Moco/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Glucemia/efectos de los fármacos , Glucemia/análisisRESUMEN
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.
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Acetilcisteína , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Acetilcisteína/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Volumen Espiratorio Forzado/efectos de los fármacos , Administración por Inhalación , Capacidad Vital/efectos de los fármacos , Expectorantes/administración & dosificación , Expectorantes/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics. METHODS: A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy. RESULTS: Inhalation of 67% H2 improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels. CONCLUSIONS: Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.
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Hidrógeno , Dinámicas Mitocondriales , Encefalopatía Asociada a la Sepsis , Animales , Encefalopatía Asociada a la Sepsis/tratamiento farmacológico , Ratones , Hidrógeno/farmacología , Hidrógeno/administración & dosificación , Hidrógeno/uso terapéutico , Dinámicas Mitocondriales/efectos de los fármacos , Masculino , Administración por Inhalación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Ratones Endogámicos C57BL , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacosRESUMEN
Inhalable formulations with cyclodextrins (CDs) as solubility and absorption enhancers show promise for pulmonary delivery. Thiolated hydroxypropyl-ß-cyclodextrin (HP-ß-CD-SH) has mucoadhesive properties, enhancing drug absorption. Moreover, it has self-aggregation capability, which could further improve absorption and drug stability, as well as reduce irritation. This study aims to stabilize CD nanoaggregates using bifunctional cross-linkers and evaluate their benefits for lung drug delivery compared to pristine HP-ß-CD-SH. METHODS: The effectiveness of cross-linked HP-ß-CD-SH nanoparticles (HP-ß-CD-SH-NP) was compared to transient nanoaggregates in enhancing the activity of dexamethasone (DMS) and olive leaf extracts (OLE). DMS, a poorly soluble drug commonly used in lung treatments, and OLE, known for its antioxidant properties, were chosen. Drug-loaded HP-ß-CD-SH-NP were prepared and nebulized onto a lung epithelial Air-Liquid Interface (ALI) model, assessing drug permeation and activity. RESULTS: HP-ß-CD-SH with 25% thiolation was synthesized via microwave reaction, forming 150 nm nanoaggregates and stabilized 400 nm HP-ß-CD-SH-NP. All carriers showed good complexing ability with DMS and OLE and were biocompatible in the lung ALI model. HP-ß-CD-SH promoted DMS absorption, while stabilized HP-ß-CD-SH-NP protected against oxidative stress. CONCLUSION: HP-ß-CD-SH is promising for lung delivery, especially as stabilized nanoaggregates, offering versatile administration for labile molecules like natural extracts.
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2-Hidroxipropil-beta-Ciclodextrina , Dexametasona , Sistemas de Liberación de Medicamentos , 2-Hidroxipropil-beta-Ciclodextrina/química , Animales , Humanos , Dexametasona/química , Dexametasona/administración & dosificación , Dexametasona/farmacología , Dexametasona/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Compuestos de Sulfhidrilo/química , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Nanopartículas/química , Administración por Inhalación , Portadores de Fármacos/química , beta-Ciclodextrinas/química , RatasRESUMEN
BACKGROUND: Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. METHODS: This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. RESULTS: A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. CONCLUSION: This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Nebulizadores y Vaporizadores , SARS-CoV-2 , Insuficiencia del Tratamiento , Humanos , Masculino , Femenino , Persona de Mediana Edad , Proyectos Piloto , Administración por Inhalación , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Anciano , Agua , Adulto , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma can be treated with inhaled corticosteroids (ICS) delivered by low climate impact inhalers (dry powder inhalers) or high climate impact inhalers (pressurized metered-dose inhalers containing potent greenhouse gasses). ICS delivered with greenhouse gasses is prescribed ubiquitously and frequent despite limited evidence of superior effect. Our aim was to examine the beneficial and harmful events of ICS delivered by low and high climate impact inhalers in patients with asthma and COPD. METHODS: Nationwide retrospective cohort study of Danish outpatients with asthma and COPD treated with ICS delivered by low and high climate impact inhalers. Patients were propensity score matched by the following variables; age, gender, tobacco exposure, exacerbations, dyspnoea, body mass index, pulmonary function, ICS dose and entry year. The primary outcome was a composite of hospitalisation with exacerbations and all-cause mortality analysed by Cox proportional hazards regression. RESULTS: Of the 10,947 patients with asthma and COPD who collected ICS by low or high climate impact inhalers, 2,535 + 2,535 patients were propensity score matched to form the population for the primary analysis. We found no association between high climate impact inhalers and risk of exacerbations requiring hospitalization and all-cause mortality (HR 1.02, CI 0.92-1.12, p = 0.77), nor on pneumonia, exacerbations requiring hospitalization, all-cause mortality, or all-cause admissions. Delivery with high climate impact inhalers was associated with a slightly increased risk of exacerbations not requiring hospitalization (HR 1.10, CI 1.01-1.21, p = 0.03). Even with low lung function there was no sign of a superior effect of high climate impact inhalers. CONCLUSION: Low climate impact inhalers were not inferior to high climate impact inhalers for any risk analysed in patients with asthma and COPD.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/diagnóstico , Anciano , Estudios Retrospectivos , Dinamarca/epidemiología , Estudios de Cohortes , Administración por Inhalación , Adulto , Inhaladores de Polvo Seco , Clima , Inhaladores de Dosis Medida , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Resultado del TratamientoRESUMEN
Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.
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Infecciones por Bacterias Gramnegativas , Nanopartículas , Animales , Ratones , Nanopartículas/química , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Péptidos/química , Péptidos/farmacología , Péptidos/administración & dosificación , Bacterias Gramnegativas/efectos de los fármacos , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Alveolos Pulmonares/metabolismo , Administración por Inhalación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/patologíaRESUMEN
Introduction: It is known that the use of inhaled corticosteroids increases the incidence of pneumonia in patients followed up with the diagnosis of chronic asthma and chronic obstructive pulmonary disease (COPD). This study aimed to investigate the contribution of inhaled steroid use to pneumonia severity and mortality in cases with COVID-19 pneumonia. Materials and Methods: The study is a retrospective, observational study. Among the cases admitted to the pandemic clinic, patients diagnosed with COVID-19 pneumonia were included. The plan was to compare cases who received and did not receive inhaled corticosteroids in terms of pneumonia severity and mortality. In order to define risk factors for mortality, univariate and multivariable negative binomial regression analyses were performed. Result: In our study, it was observed that n= 540 (75%) cases did not receive inhaled corticosteroids (group 1), and 180 (25%) cases used inhaled corti costeroids (group 2). Group 1 and group 2 cases were compared in terms of pneumonia severity with no significant difference between the two groups (p= 0.11). Then, risk factors affecting mortality in all cases were examined with univariate analyses. Increasing age, applying mechanical ventilation, having severe pneumonia, having interstitial lung disease, and applying prone position were found to be statistically significant factors in mortality (p < 0.05). Conclusions: In conclusion, in our study, it was observed that the use of inhaled corticosteroids did not increase the severity of pneumonia and mortality. It was thought that the treatment they received could be continued when the patients treated with inhaled corticosteroids due to asthma and COPD had COVID-19 pneumonia.
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Corticoesteroides , COVID-19 , Índice de Severidad de la Enfermedad , Humanos , Masculino , Administración por Inhalación , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , COVID-19/mortalidad , COVID-19/complicaciones , Anciano , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Factores de Riesgo , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Adulto , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Asma/tratamiento farmacológico , Asma/complicaciones , Asma/mortalidadRESUMEN
BACKGROUND: Unusually high variability in blood Δ9-tetrahydrocannabinol (THC) concentrations have been observed in subjects inhaling similar cannabis products over similar time periods when consumption is ad libitum. This makes simple gravimetric dose estimation a poor predictor of THC exposure. Population pharmacokinetic analyses of blood THC concentration versus time data are routinely used to estimate pharmacokinetic parameters. The aim of this study was to estimate the inhaled dose of THC in occasional and daily users of high potency market cannabis. METHODS: Blood THC concentrations were measured for 135 minutes from 29 participants who either smoked high concentration flower or inhaled concentrates ad libitum during a 15-minute session. Frequent blood samples were obtained over the following 135 minutes. RESULTS: The estimated central and rapidly equilibrating volumes of distribution of a 3-compartment model were 19.9 ± 1.2 and 51.6 ± 4.7 L whereas the intercompartmental clearances were 1.65 ± 0.14 and 1.75 ± 0.10 L/min, respectively. Covariate-adjusted analysis revealed that the estimated inhaled THC dose was considerably less among occasional users compared with daily users. CONCLUSIONS: Three-compartment pharmacokinetics of THC did not differ among the 3 user groups, and the early phase (first 135 minutes postinception of inhalation) kinetics were similar to those previously described after smoking low potency cannabis products. Therefore, inhaled THC dose can be estimated from pharmacokinetic data and covariate-driven adjustments can be used to estimate THC doses, based on the participant cannabis usage pattern (occasional versus daily), improving the accuracy of THC exposure estimates compared with those derived from weighed THC content alone.
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Dronabinol , Humanos , Dronabinol/farmacocinética , Dronabinol/sangre , Dronabinol/administración & dosificación , Masculino , Adulto , Femenino , Administración por Inhalación , Adulto Joven , Fumar Marihuana , Cannabis , Persona de Mediana Edad , Relación Dosis-Respuesta a Droga , Modelos BiológicosRESUMEN
BACKGROUND: Amikacin liposome inhalation suspension (ALIS) improved sputum culture conversion rate at 6 months for patients with refractory Mycobacterium avium complex pulmonary disease (MAC-PD) in an international phase 3 trial. Patient characteristics and chest high-resolution CT (HRCT) findings associated with ALIS effectiveness are poorly documented. OBJECTIVE: We aimed to clarify ALIS effectiveness for refractory MAC-PD at 6 months, elucidating associated patient characteristics and chest CT findings. METHODS: We reviewed medical records of 12 patients with refractory MAC-PD for whom ALIS treatment was initiated at Toho University Omori Medical Center from November 2021 through September 2022. All patients demonstrated treatment persistence for at least 3 months. They were divided into culture conversion and non-conversion groups using sputum culture conversion status after 6-month ALIS treatment initiation. Clinical and radiological characteristics were compared. RESULTS: Seven of the 12 patients (58.3%) achieved sputum culture conversion within 6 months. The culture conversion group had shorter pre-ALIS initiation treatment duration [21 months (16-25) vs. 62 months (32-69); p = 0.045]; lower cavitary lesion incidence on HRCT (28.6% vs. 100%; p = 0.028); and fewer clarithromycin (CLA)-resistant strains [0/7 (0%) vs. 3/5 (60%); p = 0.045]. Chest HRCT findings improved in 4 of 7 (57.1%) and 1 of 5 (20%) patients in the culture conversion and non-conversion groups, respectively. CONCLUSION: ALIS facilitated sputum culture conversion within 6 months in 58.3% of patients with refractory MAC-PD. Sputum culture conversion was significantly more frequent for CLA-susceptible strains and patients with fewer cavitary lesions. Improved CT findings after ALIS did not always correspond to sputum culture conversion.
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Amicacina , Antibacterianos , Liposomas , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare , Esputo , Tomografía Computarizada por Rayos X , Humanos , Amicacina/administración & dosificación , Masculino , Femenino , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Anciano , Administración por Inhalación , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Esputo/microbiología , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/microbiología , Anciano de 80 o más Años , SuspensionesRESUMEN
We conducted a two-year inhalation study of butyraldehyde using F344/DuCrlCrlj rats. The rats were exposed to 0, 300, 1,000 and 3,000 ppm (v/v) for 6 hr/day, 5 days/ week for 104 weeks using whole-body inhalation chambers. The incidence of squamous cell carcinoma of the nasal cavity was increased in the 3,000 ppm groups of both male and female rats, with Fisher's exact test and the Peto test indicating that the incidence was significant. In addition to squamous cell carcinoma in the nasal cavity, in the 3,000 ppm groups one male had an adenosquamous carcinoma, one male had a carcinosarcoma, one male had a sarcoma NOS (Not Otherwise Specified), and one female had a squamous cell papilloma in the nasal cavity. The combined incidence of squamous cell carcinoma, adenosquamous carcinoma and carcinosarcoma was significantly increased in male rats and the combined incidence of squamous cell papilloma and carcinoma was significantly increased in female. Based on these results, we conclude that there is clear evidence of butyraldehyde carcinogenicity in male and female rats.
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Carcinoma de Células Escamosas , Ratas Endogámicas F344 , Animales , Masculino , Femenino , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma Adenoescamoso/inducido químicamente , Carcinoma Adenoescamoso/patología , Administración por Inhalación , Neoplasias Nasales/inducido químicamente , Carcinosarcoma/inducido químicamente , Carcinosarcoma/patología , Carcinógenos/toxicidad , Carcinógenos/administración & dosificación , Pruebas de Carcinogenicidad , Exposición por Inhalación/efectos adversos , Ratas , Factores de Tiempo , Papiloma/inducido químicamente , Papiloma/patologíaRESUMEN
This JAMA Patient Page describes e-cigarettes and the potential health effects of vaping.
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Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Productos de Tabaco , Humanos , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Nicotina/efectos adversos , Nicotina/administración & dosificación , Fumar/efectos adversos , Fumar/epidemiología , Cese del Hábito de Fumar/métodos , Vapeo/efectos adversos , Vapeo/epidemiología , Vapeo/legislación & jurisprudencia , Productos de Tabaco/efectos adversos , Productos de Tabaco/legislación & jurisprudencia , Productos de Tabaco/estadística & datos numéricos , Aerosoles/administración & dosificación , Aerosoles/efectos adversos , Administración por Inhalación , Estados Unidos/epidemiología , Adulto Joven , AdultoRESUMEN
This JAMA Insights explores the adverse effects and health outcomes of e-cigarettes vs combusted cigarettes and the effectiveness of using e-cigarettes as a smoking cessation aid among US adults.
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Sistemas Electrónicos de Liberación de Nicotina , Nicotina , Cese del Hábito de Fumar , Vapeo , Adulto , Humanos , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Estados Unidos/epidemiología , Vapeo/efectos adversos , Vapeo/epidemiología , Vapeo/psicología , Cese del Hábito de Fumar/métodos , Cese del Hábito de Fumar/psicología , Cese del Hábito de Fumar/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Motivación , Nicotina/administración & dosificación , Nicotina/efectos adversos , Administración por Inhalación , Reducción del DañoRESUMEN
The delivery of mRNA into the lungs is the key to solving infectious and intractable diseases that frequently occur in the lungs. Since inhalation using a nebulizer is the most promising method for mRNA delivery into the lungs, there have been many attempts toward adapting lipid nanoparticles for mRNA inhalation. However, conventional lipid nanoparticles, which have shown great effectiveness for systemic delivery of mRNA and intramuscular vaccination, are not effective for pulmonary delivery due to their structural instability during nebulization and their inability to adapt to the pulmonary microenvironment. To address these issues, we developed an ionizable liposome-mRNA lipocomplex (iLPX). iLPX has a highly ordered lipid bilayer structure, which increases stability during nebulization, and its poly(ethylene glycol)-free composition allows it to infiltrate the low serum environment and the pulmonary surfactant layer in the lungs. We selected an inhalation-optimized iLPX (IH-iLPX) using a multistep screening procedure that mimics the pulmonary delivery process of inhaled nanoparticles. The IH-iLPX showed a higher transfection efficiency in the lungs compared to conventional lipid nanoparticles after inhalation with no observed toxicity in vivo. Furthermore, analysis of lung distribution revealed even protein expression in the deep lungs, with effective delivery to epithelial cells. This study provides insights into the challenges and solutions related to the development of inhaled mRNA pulmonary therapeutics.
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Liposomas , Pulmón , Nanopartículas , Nebulizadores y Vaporizadores , ARN Mensajero , ARN Mensajero/metabolismo , ARN Mensajero/genética , Nanopartículas/química , Pulmón/metabolismo , Animales , Administración por Inhalación , Liposomas/química , Ratones , HumanosRESUMEN
Gene delivery therapy has emerged as a popular approach for the treatment of various diseases. However, it still poses the challenges of accumulation in target sites and reducing off-target effects. Aerosol gene delivery for the treatment of pulmonary diseases has the advantages of high lung accumulation, specific targeting and fewer systemic side effects. However, the key challenge is selecting the appropriate formulation for aerosol gene delivery that can overcome physiological barriers. There are numerous existing gene carriers under study, including viral vectors and non-viral vectors. With the development of biomaterials, more biocompatible substances have applied gene delivery via inhalation. Furthermore, many types of genes can be delivered through aerosol inhalation, such as DNA, mRNA, siRNA and CRISPR/Cas9. Aerosol delivery of different types of genes has proven to be efficient in the treatment of many diseases such as SARS-CoV-2, cystic fibrosis and lung cancer. In this paper, we provide a comprehensive review of the ongoing research on aerosol gene delivery therapy, including the basic respiratory system, different types of gene carriers, different types of carried genes and clinical applications.