RÉSUMÉ
BACKGROUND: Dry powder inhalers (DPIs) rely on both internal resistance and patients' inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. METHODS: The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland-Altman graphical analysis. RESULTS: PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland-Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients. CONCLUSIONS: In-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.
Sujet(s)
Inhalateurs à poudre sèche , Capacité inspiratoire , Broncho-pneumopathie chronique obstructive , Humains , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Mâle , Femelle , Adulte d'âge moyen , Adulte , Sujet âgé , Reproductibilité des résultats , Conception d'appareillage , Jeune adulte , Administration par inhalation , Capacité vitale , Volontaires sainsRÉSUMÉ
BACKGROUND: One of the challenges to using some flavor chemicals in aerosol products is the lack of route of administration specific toxicology data. METHODS: Flavor chemicals (88) were divided into four different flavor mixtures based upon chemical compatibility and evaluated in 2-week dose-range-finding and subsequent 90-day nose-only rodent inhalation studies (OECD 413 and GLP compliant). Sprague-Dawley rats were exposed to vehicle control or one of three increasing concentrations of each flavor mixture. RESULTS: In the dose-range-range-finding studies, exposure to flavor mixture four resulted in adverse nasal histopathology in female rats at the high dose, resulting in this flavor mixture not being evaluated in a 90-day study. In the 90-day studies daily exposures to the three flavor mixtures did not induce biologically meaningful adverse effects (food consumption, body weights, respiratory physiology, serum chemistry, hematology, coagulation, urinalysis, bronchoalveolar lavage fluid analysis and terminal organ weights). All histopathology findings were observed in both vehicle control and flavor mixture exposed animals, with similar incidences and/or severities, and therefore were not considered flavor mixture related. CONCLUSION: Based on the absence of adverse effects, the no-observed-adverse-effect concentration for each 90-day inhalation study was the highest dose tested, 2.5 mg/L of the aerosolized high dose of the three flavor mixtures.
Sujet(s)
Aromatisants , Dose sans effet nocif observé , Rat Sprague-Dawley , Animaux , Femelle , Aromatisants/toxicité , Mâle , Exposition par inhalation , Rats , Relation dose-effet des médicaments , Administration par inhalation , Consommation alimentaire/effets des médicaments et des substances chimiquesRÉSUMÉ
BACKGROUND: After suffering from COVID-19, a large number of patients need respiratory rehabilitation. One of the methods of rehabilitation is inhalation with salt aerosols. OBJECTIVE: Our work aimed to study the effectiveness of inhalations of a dry aerosol of salt precipitated from the mineral water of the "Teplitsa multidisciplinary sanatorium", Transcarpathian region of Ukraine. MATERIAL AND METHODS: 30 male patients were examined after suffering from COVID-19. We formed two groups of patients, control and main, 15 people each. Patients in the control group received inhalation with a dry aerosol of table salt of the "Aero-M-sol". In contrast, patients in the main group received a course of inhalations with a dry aerosol of salt precipitated from the mineral water. RESULTS AND DISCUSSION: Under the influence of the rehabilitation complex in both groups, there is a performance improvement but significant changes are observed only in patients of the main group. The indicator Forced Vital Сapacity1 increased to the greatest extent, which after rehabilitation is significantly higher than in the control group (p<0.05). As a result, the Tiffeneau index significantly increases in the main group compared to the control group, reaching normal values. The main effect is associated with a decrease in obstructive complications of the respiratory tract as a result of a decrease in inflammation. The use of iodine-bromine brines (as in our case) for inhalation in the treatment of respiratory diseases has been proven to be effective, with systemic effects in the form of decreased IgE and increased IgA in the blood serum having been noticed. CONCLUSIONS: The use of haloinhalations with MW salts in the rehabilitation of patients after suffering from COVID-19 disease significantly improves the clinical condition of convalescents.
Sujet(s)
COVID-19 , Stations de cure , Humains , COVID-19/rééducation et réadaptation , Mâle , Ukraine , Adulte d'âge moyen , Administration par inhalation , Adulte , SARS-CoV-2 , Aérosols , Eau minéraleRÉSUMÉ
Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative "LOOP" platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08LOOP featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08LOOP system is also compatible with commercially available ALC0315 LNPs. Thus, the "LOOP" method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis.
Sujet(s)
Fibrose pulmonaire idiopathique , Nanoparticules , ARN messager , Anticorps à chaîne unique , Fibrose pulmonaire idiopathique/traitement médicamenteux , Fibrose pulmonaire idiopathique/immunologie , Animaux , Administration par inhalation , ARN messager/administration et posologie , ARN messager/génétique , ARN messager/métabolisme , Nanoparticules/composition chimique , Mâle , Souris , Anticorps à chaîne unique/administration et posologie , Humains , Poumon/métabolisme , Poumon/anatomopathologie , Souris de lignée C57BL , Lipides/composition chimique , Modèles animaux de maladie humaine , LiposomesRÉSUMÉ
BACKGROUND: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model. METHOD: Rats were exposed to cerium dioxide (CeO2, 28.4 ± 10.4 nm) and titanium dioxide (TiO2, 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m3 or a repeated exposure of 2 × 5 days to 5 mg/m3. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF). RESULTS: Although similar lung deposited doses were obtained for both materials, exposure to CeO2 induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO2 did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure. CONCLUSION: We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.
Sujet(s)
Liquide de lavage bronchoalvéolaire , Cérium , Exposition par inhalation , Poumon , Titane , Animaux , Titane/toxicité , Titane/pharmacocinétique , Cérium/toxicité , Cérium/pharmacocinétique , Distribution tissulaire , Mâle , Poumon/métabolisme , Poumon/effets des médicaments et des substances chimiques , Liquide de lavage bronchoalvéolaire/composition chimique , Liquide de lavage bronchoalvéolaire/cytologie , Rats , Nanostructures/toxicité , Administration par inhalation , Rat Wistar , Modèles biologiques , Taille de particule , Nanoparticules métalliques/toxicitéRÉSUMÉ
Purpose: Triple therapy (long-acting muscarinic antagonist/long-acting ß2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany. Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year's continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence. Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users. Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.
Sujet(s)
Agonistes des récepteurs béta-2 adrénergiques , Bronchodilatateurs , Association médicamenteuse , Adhésion au traitement médicamenteux , Antagonistes muscariniques , Broncho-pneumopathie chronique obstructive , Humains , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Broncho-pneumopathie chronique obstructive/diagnostic , Broncho-pneumopathie chronique obstructive/physiopathologie , Mâle , Femelle , Allemagne , Sujet âgé , Études rétrospectives , Adulte d'âge moyen , Agonistes des récepteurs béta-2 adrénergiques/administration et posologie , Administration par inhalation , Antagonistes muscariniques/administration et posologie , Bronchodilatateurs/administration et posologie , Résultat thérapeutique , Quinuclidines/administration et posologie , Facteurs temps , Bases de données factuelles , Chlorobenzènes/administration et posologie , Chlorobenzènes/usage thérapeutique , Données administratives des demandes de remboursement des soins de santé , Association de médicaments , Alcools benzyliques/administration et posologie , Alcools benzyliques/usage thérapeutique , Nébuliseurs et vaporisateurs , Glycopyrronium/administration et posologie , Poumon/effets des médicaments et des substances chimiques , Poumon/physiopathologieRÉSUMÉ
Glutathione (GSH), a tripeptide synthesized intracellularly, serves as a pivotal antioxidant, neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) while maintaining redox homeostasis and detoxifying xenobiotics. Its potent antioxidant properties, particularly attributed to the sulfhydryl group (-SH) in cysteine, are crucial for cellular health across various organelles. The glutathione-glutathione disulfide (GSH-GSSG) cycle is facilitated by enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR), thus aiding in detoxification processes and mitigating oxidative damage and inflammation. Mitochondria, being primary sources of reactive oxygen species, benefit significantly from GSH, which regulates metal homeostasis and supports autophagy, apoptosis, and ferroptosis, playing a fundamental role in neuroprotection. The vulnerability of the brain to oxidative stress underscores the importance of GSH in neurological disorders and regenerative medicine. Nebulization of glutathione presents a novel and promising approach to delivering this antioxidant directly to the central nervous system (CNS), potentially enhancing its bioavailability and therapeutic efficacy. This method may offer significant advantages in mitigating neurodegeneration by enhancing nuclear factor erythroid 2-related factor 2 (NRF2) pathway signaling and mitochondrial function, thereby providing direct neuroprotection. By addressing oxidative stress and its detrimental effects on neuronal health, nebulized GSH could play a crucial role in managing and potentially ameliorating conditions such as Parkinson's Disease (PD) and Alzheimer's Disease (AD). Further clinical research is warranted to elucidate the therapeutic potential of nebulized GSH in preserving mitochondrial health, enhancing CNS function, and combating neurodegenerative conditions, aiming to improve outcomes for individuals affected by brain diseases characterized by oxidative stress and neuroinflammation.
Sujet(s)
Antioxydants , Glutathion , Maladies neurodégénératives , Stress oxydatif , Humains , Stress oxydatif/effets des médicaments et des substances chimiques , Glutathion/métabolisme , Glutathion/administration et posologie , Antioxydants/administration et posologie , Antioxydants/pharmacologie , Maladies neurodégénératives/traitement médicamenteux , Nébuliseurs et vaporisateurs , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Animaux , Espèces réactives de l'oxygène/métabolisme , Administration par inhalation , Facteur-2 apparenté à NF-E2/métabolismeRÉSUMÉ
BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.
Sujet(s)
Asthme , Plaquettes , Nanoparticules , Polyphénols , Thé , Animaux , Souris , Polyphénols/administration et posologie , Polyphénols/pharmacologie , Asthme/traitement médicamenteux , Asthme/métabolisme , Nanoparticules/administration et posologie , Thé/composition chimique , Plaquettes/effets des médicaments et des substances chimiques , Plaquettes/métabolisme , Administration par inhalation , Humains , Souris de lignée BALB C , Femelle , Anti-inflammatoires/administration et posologie , Anti-inflammatoires/pharmacologieRÉSUMÉ
This research article elucidates the pivotal role of radiopharmacy in the contemporary landscape, underscoring its potential therapeutic efficacy in addressing symptoms associated with aged-related neurocognitive processes. Clinical trials, characterized by the judicious application of modest radiation doses, exemplified by low-dose radon, have yielded affirmative outcomes in the amelioration of aged, related symptoms. MATERIAL AND METHODS: The study was conducted on an animal model. The effect of low doses of radon on cognitive processes is being studied by inhalation of randomized mineral water. Changes in the clinical picture were studied using behavioral tests, namely the Barnes maze tests. At the cellular level, radon-contained water inhalation causes different changes: in the fraction of synaptic membranes (determined by Na, K-ATPase activity), aged, related changes by telomerase activity and oxidative stress level changes. RESULTS: Our studies show that age-related changes in brain tissue are less noticeable after radon inhalation, namely, the concentration of amyloid plaques decreases in a group of aged rats after radon therapy. A significant improvement in cognitive function was observed after radon inhalation in aged rats. CONCLUSION: The results show that exposure to radon-containing mineral water leads to improved spatial perception, potentially improving age-related cognitive functions not only at the level of neurocognitive tests, but also changes at the level of cellular functioning.
Sujet(s)
Eau minérale , Radon , Animaux , Eau minérale/usage thérapeutique , Radon/usage thérapeutique , Rats , Mâle , Comportement animal/effets des radiations , Comportement animal/effets des médicaments et des substances chimiques , Apprentissage du labyrinthe/effets des médicaments et des substances chimiques , Administration par inhalation , Stress oxydatif/effets des médicaments et des substances chimiques , Mémoire/effets des médicaments et des substances chimiques , Mémoire/effets des radiations , Vieillissement/physiologie , Encéphale/effets des radiations , Encéphale/effets des médicaments et des substances chimiques , Encéphale/métabolisme , Cognition/effets des radiations , Cognition/effets des médicaments et des substances chimiques , Rat Wistar , Sodium-Potassium-Exchanging ATPase/métabolismeRÉSUMÉ
Dry powder inhalers (DPIs) are state-of-the-art pulmonary drug delivery systems. This article explores the transformative impact of nanotechnology on DPIs, emphasizing the Quality Target Product Profile (QTPP) with a focus on aerodynamic performance and particle characteristics. It navigates global regulatory frameworks, underscoring the need for safety and efficacy standards. Additionally, it highlights the emerging field of nanoparticulate dry powder inhalers, showcasing their potential to enhance targeted drug delivery in respiratory medicine. This concise overview is a valuable resource for researchers, physicians, and pharmaceutical developers, providing insights into the development and commercialization of advanced inhalation systems.
Sujet(s)
Systèmes de délivrance de médicaments , Inhalateurs à poudre sèche , Inhalateurs à poudre sèche/méthodes , Humains , Administration par inhalation , Systèmes de délivrance de médicaments/méthodes , Nanoparticules/composition chimique , Poumon/métabolisme , Poumon/effets des médicaments et des substances chimiques , Nanomédecine/méthodes , Taille de particule , Nanotechnologie/méthodesRÉSUMÉ
OBJECTIVE: This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children. METHODS: A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point. RESULTS: (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks. CONCLUSION: ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.
Sujet(s)
Hormones corticosurrénaliennes , Antiasthmatiques , Asthme , Toux , Association de médicaments , Antagonistes des leucotriènes , Humains , Asthme/traitement médicamenteux , Toux/traitement médicamenteux , Études rétrospectives , Femelle , Mâle , Enfant , Résultat thérapeutique , Hormones corticosurrénaliennes/usage thérapeutique , Hormones corticosurrénaliennes/administration et posologie , Administration par inhalation , Antagonistes des leucotriènes/usage thérapeutique , Antagonistes des leucotriènes/administration et posologie , Enfant d'âge préscolaire , Antiasthmatiques/usage thérapeutique , Antiasthmatiques/administration et posologie , Études longitudinales , Agonistes des récepteurs béta-2 adrénergiques/usage thérapeutique , Agonistes des récepteurs béta-2 adrénergiques/administration et posologie , Adolescent ,RÉSUMÉ
BACKGROUND: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count - focusing on blood EOS count 100 to < 300 cells/mm3 - as a function of exacerbation history and COPD severity. METHODS: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12-24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses. RESULTS: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD. CONCLUSIONS: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).
Sujet(s)
Bronchodilatateurs , Budésonide , Granulocytes éosinophiles , Fumarate de formotérol , Glycopyrronium , Broncho-pneumopathie chronique obstructive , Humains , Mâle , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Broncho-pneumopathie chronique obstructive/physiopathologie , Broncho-pneumopathie chronique obstructive/sang , Broncho-pneumopathie chronique obstructive/diagnostic , Glycopyrronium/administration et posologie , Femelle , Sujet âgé , Adulte d'âge moyen , Bronchodilatateurs/administration et posologie , Budésonide/administration et posologie , Granulocytes éosinophiles/effets des médicaments et des substances chimiques , Fumarate de formotérol/administration et posologie , Méthode en double aveugle , Évolution de la maladie , Poumon/effets des médicaments et des substances chimiques , Poumon/physiopathologie , Administration par inhalation , Résultat thérapeutique , Antagonistes muscariniques/administration et posologie , Volume expiratoire maximal par seconde/effets des médicaments et des substances chimiques , Volume expiratoire maximal par seconde/physiologieRÉSUMÉ
The analysis of cardiac wall mechanics is of importance for understanding coronary heart diseases (CHD). The inhalation of ultrafine particles could deteriorate CHD. The aim of the study is to investigate the effects of cardiac wall mechanics on rats of myocardial infarction (MI) after long-term inhalation of ultrafine Zn particles. Cardiac wall stresses and strains were computed, based on echocardiographic and hemodynamic measurements. It was found that MI resulted in the significantly elevated stresses and the reduced strains. The short-term inhalation of ultrafine Zn particles decreased stresses and increased strains in MI rats, but the long-term inhalation had the opposite effects. Hence, the short-term inhalation of ultrafine Zn particles could alleviate the MI-induced LV dysfunction while the long-term inhalation impaired it.
Sujet(s)
Infarctus du myocarde , Contrainte mécanique , Zinc , Infarctus du myocarde/physiopathologie , Animaux , Zinc/administration et posologie , Zinc/pharmacologie , Rats , Mâle , Facteurs temps , Administration par inhalation , Taille de particule , Rat Sprague-Dawley , Phénomènes biomécaniques , Coeur/effets des médicaments et des substances chimiques , Coeur/physiopathologie , Hémodynamique/effets des médicaments et des substances chimiquesRÉSUMÉ
Pulmonary delivery and formulation of biologics are among the more complex and growing scientific topics in drug delivery. We herein developed a dry powder formulation using disordered mesoporous silica particles (MSP) as the sole excipient and lysozyme, the most abundant antimicrobial proteins in the airways, as model protein. The MSP had the optimal size for lung deposition (2.43 ± 0.13 µm). A maximum lysozyme loading capacity (0.35 mg/mg) was achieved in 150 mM PBS, which was seven times greater than that in water. After washing and freeze-drying, we obtained a dry powder consisting of spherical, non-aggregated particles, free from residual buffer, or unabsorbed lysozyme. The presence of lysozyme was confirmed by TGA and FT-IR, while N2 adsorption/desorption and SAXS analysis indicate that the protein is confined within the internal mesoporous structure. The dry powder exhibited excellent aerodynamic performance (fine particle fraction <5 µm of 70.32%). Lysozyme was released in simulated lung fluid in a sustained kinetics and maintaining high enzymatic activity (71-91%), whereas LYS-MSP were shown to degrade into aggregated nanoparticulate microstructures, reaching almost complete dissolution (93%) within 24 h. MSPs were nontoxic to in vitro lung epithelium. The study demonstrates disordered MSP as viable carriers to successfully deliver protein to the lungs, with high deposition and retained activity.
Sujet(s)
Poumon , Lysozyme , Taille de particule , Poudres , Silice , Silice/composition chimique , Lysozyme/administration et posologie , Lysozyme/composition chimique , Poumon/métabolisme , Poumon/effets des médicaments et des substances chimiques , Porosité , Poudres/composition chimique , Vecteurs de médicaments/composition chimique , Administration par inhalation , Systèmes de délivrance de médicaments/méthodes , Nanoparticules/composition chimique , Humains , Excipients/composition chimique , Animaux , Chimie pharmaceutique/méthodes , Spectroscopie infrarouge à transformée de Fourier , LyophilisationRÉSUMÉ
Background: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation. Methods: Using the Korean National Health Insurance Service database, we enrolled COPD patients initiating treatment with LAMA or LABA/ICS between January 2005 and April 2015. Propensity score matched individuals were compared on all-cause and COPD-related medical costs and HCRU over a three-year follow-up period. Results: A total of 2444 patients were enrolled in each treatment group. LAMA group was associated with significantly lower costs than LABA/ICS group, both in all-cause (403.08 vs 474.50 USD per patient per month [PPPM], cost ratio 1.18, 95% confidence interval [CI]=1.10-1.26, p<0.0001) and COPD-related (216.37 vs 267.32 USD PPPM, cost ratio 1.24, 95% CI=1.13-1.35, p<0.0001) medical costs. All-cause HCRU was not significantly different between groups, while COPD-related HRCU was higher in LAMA group (0.66 vs 0.60 medical visits PPPM, p<0.0001). Conclusion: COPD patients initiating treatment with LAMA were associated with lower all-cause and COPD-related medical costs than those starting with LABA/ICS despite the similar all-cause HCRU and higher COPD-related HCRU. Initiation with LAMA is a cost-efficient option for the treatment of COPD.
Sujet(s)
Agonistes des récepteurs béta-2 adrénergiques , Bronchodilatateurs , Bases de données factuelles , Coûts des médicaments , Broncho-pneumopathie chronique obstructive , Bromure de tiotropium , Humains , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Broncho-pneumopathie chronique obstructive/économie , Broncho-pneumopathie chronique obstructive/diagnostic , République de Corée/épidémiologie , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Agonistes des récepteurs béta-2 adrénergiques/économie , Agonistes des récepteurs béta-2 adrénergiques/administration et posologie , Bromure de tiotropium/administration et posologie , Bromure de tiotropium/économie , Résultat thérapeutique , Bronchodilatateurs/économie , Bronchodilatateurs/administration et posologie , Facteurs temps , Administration par inhalation , Antagonistes muscariniques/économie , Antagonistes muscariniques/administration et posologie , Antagonistes muscariniques/effets indésirables , Hormones corticosurrénaliennes/administration et posologie , Hormones corticosurrénaliennes/économie , Association médicamenteuse , Analyse coût-bénéfice , Études rétrospectives , Économies , Ressources en santé/statistiques et données numériques , Ressources en santé/économie , Poumon/physiopathologie , Poumon/effets des médicaments et des substances chimiquesSujet(s)
Toux , Humains , Toux/traitement médicamenteux , Administration par inhalation , Maladie chronique ,RÉSUMÉ
INTRODUCTION: Dry powder inhaler (DPI) formulations are gaining attention as universal formulations with applications in a diverse range of drug formulations. The practical application of DPIs to pulmonary drugs requires enhancing their delivery efficiency to the target sites for various treatment modalities. Previous reviews have not explored the relation between particle morphology and delivery to different pulmonary regions. This review introduces new approaches to improve targeted DPI delivery using novel particle design such as supraparticles and metal-organic frameworks based on cyclodextrin. AREAS COVERED: This review focuses on the design of DPI formulations using polysaccharides, promising excipients not yet approved by regulatory agencies. These excipients can be used to design various particle morphologies by controlling their physicochemical properties and manufacturing methods. EXPERT OPINION: Challenges associated with DPI formulations include poor access to the lungs and low delivery efficiency to target sites in the lung. The restricted applicability of typical excipients contributes to their limited use. However, new formulations based on polysaccharides are expected to establish a technological foundation for the development of DPIs capable of delivering modalities specific to different lung target sites, thereby enhancing drug delivery.
Sujet(s)
Systèmes de délivrance de médicaments , Inhalateurs à poudre sèche , Excipients , Poumon , Polyosides , Poudres , Humains , Polyosides/composition chimique , Administration par inhalation , Poumon/métabolisme , Excipients/composition chimique , Taille de particule , Préparations pharmaceutiques/administration et posologie , Préparations pharmaceutiques/composition chimique , Préparation de médicament/méthodes , Animaux , Chimie pharmaceutique , Réseaux organométalliques/composition chimiqueRÉSUMÉ
BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear. METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified. RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared. DISCUSSION: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants' daily lives. TRIAL REGISTRATION: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.
Sujet(s)
Adhésion au traitement médicamenteux , Nébuliseurs et vaporisateurs , Broncho-pneumopathie chronique obstructive , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Humains , Administration par inhalation , Bronchodilatateurs/administration et posologie , Essais contrôlés randomisés comme sujet , Association de médicamentsRÉSUMÉ
Purpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.
Sujet(s)
Administration par voie nasale , Systèmes de signalement des effets indésirables des médicaments , Bases de données factuelles , Pharmacovigilance , Humains , Femelle , Adulte d'âge moyen , Mâle , Administration par inhalation , États-Unis/épidémiologie , Facteurs de risque , Sujet âgé , Appréciation des risques , Adulte , Hormones corticosurrénaliennes/administration et posologie , Hormones corticosurrénaliennes/effets indésirables , Food and Drug Administration (USA) , Infections de l'appareil respiratoire/épidémiologie , Infections de l'appareil respiratoire/microbiologie , Infections de l'appareil respiratoire/diagnosticRÉSUMÉ
Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.