Search Results (3,648)

Eosinophilic esophagitis (EoE) is a chronic, food-driven inflammatory disorder of the esophagus in which repeated exposure to dietary antigens plays a central role, yet identification of clinically relevant food triggers remains largely empirical. In this retrospective, single-center study, molecular IgE sensitization profiles were descriptively characterized in adult patients with EoE (n = 22) and compared with an allergic control group with chronic urticaria (CU; n = 29) using component-resolved diagnostics. IgE sensitization was common in both cohorts and predominantly reflected inhalant-related, cross-reactive components, particularly PR-10 proteins (63.6% in EoE vs. 37.9% in CU). In contrast, sensitization to structurally stable food allergen components, including lipid transfer proteins and plant storage proteins, was observed in a subset of patients with EoE (31.8%) and was not detected in the control group (0%; p = 0.0015). These food-derived components are characterized by resistance to thermal processing and gastrointestinal digestion and may reflect patterns of sustained dietary exposure rather than acute IgE-mediated reactions. Consistent with previous observations, component-resolved diagnostics showed limited utility for the direct identification of trigger foods in eosinophilic esophagitis. Accordingly, the observed molecular sensitization patterns should be interpreted as descriptive and hypothesis-generating signals rather than as indicators of pathogenic mechanisms or clinical decision-making tools. The findings highlight the importance of considering molecular properties of food allergen components when interpreting sensitization profiles in chronic, non-IgE-mediated inflammatory diseases and underscore the need for prospective studies integrating standardized clinical and dietary outcomes. Full article

Urban cyclists experience elevated traffic-related air pollutant (TRAP) exposures due to proximity to emissions and increased breathing rates during exercise. Conventional assessments rely on concentration summaries, which may misrepresent actual inhaled doses and misclassify individuals in health studies. Street-level concentrations exhibit high temporal variability, producing non-normal distributions that challenge conventional averaging approaches. This study compares concentration- and dose-based methods to characterize cyclist exposure during urban commuting. Fifty-seven healthy adults completed cycling trips on two 9-km routes (high- and low-traffic) using conventional or electrically assisted bicycles. Real-time monitoring measured black carbon, ultrafine particles, PM_2.5, and PM₁₀. Heart rate-derived breathing rates enabled individualized inhaled dose calculations using three temporal integration methods. Mean concentrations correlated strongly with time-integrated concentrations (r = 0.988–0.998). Simplified dose calculations closely approximated full temporal integration (r > 0.999), with median dose ratios of 0.99–1.01. However, correlations between mean concentrations and inhaled doses were weaker (r = 0.72–0.78). Between 29% and 50% of participants changed exposure quartiles when comparing concentration- and dose-based classifications, with the highest reclassification for ultrafine particles (46–50%). These findings demonstrate that physiological variability substantially influences exposure classification during active commuting, supporting the integration of inhaled dose metrics in cyclist exposure assessment and epidemiological studies. Full article

Background: Pulmonary neuroendocrine cells (PNECs) are rare airway sensory cells implicated in amplifying allergic inflammation, yet due to their scarcity, the contribution of PNECs to the metabolic programs and responses of the airway epithelium remains poorly defined. Using a newly developed PNEC-enriched human airway epithelial model (ePNEC), we investigated the influence of PNECs on neuroendocrine and immune-modulatory metabolite production in response to the common aeroallergen of the house dust mite (HDM). Methods: Human bronchial epithelial cells (HBECs) and ePNEC cultures were differentiated at the air–liquid interface. Global untargeted metabolomics was performed to quantify metabolite abundance at baseline and following stimulation with HDMs. Differential expression, overlap significance, metabolite class enrichment, and pathway analyses were used to define PNEC-specific metabolic programs. Results: Principal component analysis (PCA) demonstrated strong baseline separation between ePNECs and HBECs, with HDMs inducing additional within-cell-type shifts. ePNECs displayed broader and more pronounced metabolite changes than HBECs. Baseline differences were largely preserved following allergen exposure, with significant overlap in both up- and down-regulated metabolites. ePNECs exhibited enriched neurotransmitter-linked metabolites—including serotonin, L-noradrenaline, dopamine, and histamine—at baseline and after HDM exposure. Amino acid–centered metabolism dominated the dataset, with enhanced histidine and tryptophan pathway activity in ePNECs. Pathway analysis revealed significant enrichment of phenylalanine, tyrosine, tryptophan, glutathione, and arginine–proline metabolism in ePNECs, whereas HBECs showed no significant pathway-level enrichment after HDM exposure. Conclusions: Human ePNECs engage a distinct, neuroactive metabolic program that is amplified upon HDM exposure. These findings provide a metabolic framework for how PNECs shape epithelial and neuroimmune responses to inhaled allergens. Full article

Background/Objectives: Carrier-based dry powder inhaler (DPI) formulations remain the predominant platform for respiratory drug delivery. However, integrated development frameworks that align upstream particle engineering with downstream manufacturing are underdeveloped. This study aimed to develop a comprehensive Quality-by-Design (QbD) strategy that systematically connects jet milling, formulation design, and blending scale-up for carrier-based DPI products containing micronized crystalline active pharmaceutical ingredient (API). Methods: Phenytoin was selected as a model API to investigate process–formulation–performance relationships. Jet milling parameters were optimized to generate three distinct API particle size distributions while monitoring solid-state integrity. A design of experiments (DoE) evaluated the impact of API particle size and lactose fines level on aerodynamic performance (fine particle fraction, FPF) and powder processability (flowability, compressibility). High-shear and low-shear blending techniques were compared, and a novel V-shell blending scale-up methodology was developed based on maintaining particle fall velocity and total strain across multiple scales (one-, two-, and eight-quart). Results: Optimized jet milling produced inhalation grade API particles with controlled amorphous content localized to high-energy processes. DoE analysis identified a design space in which API Dv90 of 2.9–4.5 µm and coarse lactose <96% maximized both aerosolization and blend flowability. Low-shear blending achieved superior lung delivery (FPF 62.6 ± 1.7%) compared with high-shear micing (50.1 ± 1.5%). The particle-velocity-based scale up strategy produced statistically equivalent FPF and ED across all scales (p < 0.01), with content uniformity (RSD ≤ 5%) and variability comparable to commercial DPIs. Conclusions: This integrated QbD framework demonstrates that the co-optimization of particle size engineering, formulation composition, and blending dynamics is essential for achieving robust and scalable DPI products. The approach offers a material-sparing, efficient pathway from API characterization through commercial scale manufacturing and is broadly applicable to respiratory drug development. Full article

Diacetyl has been a known key volatile compound for almost one century, a metabolite naturally produced by different microorganisms during fermentation processes, with traditional applications in food products preparations. Since its discovery, diacetyl has been recognized and actively explored regarding its buttery aroma, which is beneficial for a variety of fermented dairy foods. It is primarily synthesized by lactic acid bacteria (LAB) and other microbial groups through citrate metabolism, a pathway that is strain-dependent and strongly influenced by environmental conditions. Moreover, beyond its sensory relevance, diacetyl has attracted increasing scientific attention because of its antimicrobial activity, including synergistic interactions with bacteriocins and other microbial metabolites, which may enhance food preservation and biotechnological strategies. In contrast, its presence merits attention and needs to be carefully monitored in alcoholic beverages such as beer and wine, where excessive accumulation may compromise product quality. Some studies suggested that diacetyl may have negative health influences and presents safety concerns, as inhalation exposure was associated with pulmonary toxicity and occupational diseases, and was even suggested as one of the risk factors in electronic cigarettes. Emerging studies suggest that diacetyl may exhibit pharmacological potential, including antioxidant, antifungal, and even neuroprotective properties, although research is still in early stages and merits deeper scientific evaluation. Considering its dual nature, beneficial and harmful, this review provides an overview of diacetyl’s properties, safety considerations, and promising applications in biotechnology, biomedicine, and fermented food systems, but with a focus on potential industrial and health hazards. In the current review, we have presented evidence for diacetyl’s beneficial properties and discussed its hazards. Full article

Pulmonary drug delivery has emerged as a powerful strategy for the treatment of respiratory infectious diseases, including bacterial, fungal, and viral infections such as influenza and COVID-19, by enabling high local drug concentrations while minimizing systemic exposure. However, the clinical success of inhaled anti-infective therapies critically depends on the precise engineering of particle properties that govern lung deposition, cellular targeting, and therapeutic efficacy. In this review, we provide a comprehensive and technology-driven overview of cutting-edge formulation and manufacturing strategies for pulmonary drug delivery, with particular emphasis on the key process and formulation parameters required to generate effective inhalable systems for the treatment of infectious diseases. Advanced particle-engineering approaches, including spray drying, spray freeze drying, jet milling, and supercritical fluid technologies are discussed as enabling tools to tightly control aerodynamic particle size, morphology, and solid-state properties. In parallel, emerging platforms such as nanoparticle-based delivery systems are examined for their ability to target specific lung cell populations, including epithelial cells and alveolar macrophages, thereby enhancing antimicrobial efficacy. Finally, innovative manufacturing concepts such as microfluidics and three-dimensional (3D) printing are highlighted as promising strategies to improve particle size uniformity, reproducibility, and formulation customization. By integrating formulation science with advanced manufacturing technologies, this review identifies the critical design and processing parameters that underpin effective pulmonary delivery of anti-infective therapies and outlines future directions for the development of next-generation inhaled treatments. Full article

Background/Objectives: Clinical remission (CR) is an ambitious and attainable treatment goal for asthma; however, CR definitions vary. Evidence of CR in Japanese patients with moderate-to-severe asthma on inhaled therapies is lacking and was evaluated based on three guideline definitions: the United States Workgroup consensus statement, Japanese Guidelines for adult asthma (JGL), and Practical Guidelines for Asthma Management (PGAM). Methods: Post hoc analysis of Phase III studies including Japanese participants: Japanese subpopulation of CAPTAIN (NCT02924688) and a 52-week Japanese long-term safety study (NCT03184987). CAPTAIN randomized participants to once-daily fluticasone furoate/vilanterol (FF/VI) regimens ± umeclidinium (UMEC). The long-term safety study allocated participants to once-daily FF/UMEC/VI based on asthma control status. All three CR definitions assessed systemic corticosteroid use, severe exacerbations, and asthma control (Asthma Control Questionnaire-5 <1.5 [Workgroup] or ≤0.75 [JGL/PGAM]); Workgroup and JGL also assessed lung function (change from baseline in trough forced expiratory volume in 1 s of ≥0 [stabilized] or ≥100 mL [optimized]). Results: CR attainability varied on definition and thresholds used. At Week 24 in the CAPTAIN Japanese subpopulation, 34–59% and 18–45% of participants (Workgroup; stabilized and optimized), and 21–34% and 8–24% (JGL; stabilized and optimized) met CR criteria across treatment arms. At Week 52 in the long-term safety study, equivalent figures for CR achievement were 33–60%, 22–45%, 11–28%, and 11–23%. Conclusions: This analysis demonstrates that CR, using different definitions and criteria, is an attainable treatment goal with inhaled therapy in Japanese patients with moderate-to-severe asthma not yet eligible for biologics. Full article

Environmental Health Practitioners (EHPs) play a critical regulatory role within municipal health services, yet their occupational health and safety (OHS) risks remain poorly characterised in the literature. This narrative review synthesises evidence on the physical, biological, chemical, ergonomic, and psychosocial hazards encountered by EHPs during routine municipal inspection and enforcement activities. A structured literature search across major databases was conducted, and findings were synthesised using a risk characterisation framework to examine hazard types, exposure pathways, and associated health outcomes. The review demonstrates that EHPs are exposed to simultaneous and interacting hazards through multiple routes, including inhalation, dermal contact, ingestion, traumatic incidents, and psychosocial strain. Where available, quantitative indicators of exposure magnitude from inspection-relevant environments were identified, highlighting both potential risk severity and significant gaps in direct exposure measurement. Importantly, the findings indicate that occupational risks faced by EHPs are largely systemic, shaped by organisational constraints, resource limitations, enforcement contexts, and broader governance conditions rather than isolated individual behaviours. This review contributes to safety science by providing an integrated conceptual model of EHP occupational exposure pathways and by highlighting the need for system-level OHS interventions within municipal health services. Strengthening PPE provision, organisational support, and exposure monitoring is essential to improving EHPs safety and the effectiveness of environmental health regulation. Full article

In carbon monoxide (CO) therapy, CO is administered at low concentrations as a controlled solution; this approach enables the drug to achieve its cytoprotective properties, including anti-inflammatory, anti-apoptotic, and vasodilatory effects. CO therapy, initially reported to benefit cardiovascular and pulmonary conditions, is now used to treat ocular diseases in preclinical models. Carbon monoxide, a compound most famously known for its deleterious effects, is receiving more attention as a potential therapeutic candidate in ocular medicine. In a few studies, controlled low-dose CO therapy has shown anti-inflammatory and anti-apoptotic effects in various models of retinal disease (such as retinal ischemia-reperfusion injury, optic nerve crush, ocular hypertension, and autoimmune uveitis). We have summarized the clinical and preclinical findings, along with the potential therapeutic value of CO, in this review. In this context, the current and emerging CO delivery methods are also described, with a focus on exploring their safety, efficacy, and applicability in retinal disorders. Although a strong preclinical paradigm exists, clinical translation is limited at best. While some trials indicate acceptable safety levels for inhaled CO or CORM-based interventions, these results have not been robust or reproducible. Bridging this efficacy gap will rely on enhanced delivery strategies, stringent PK/PD-informed dosing, and mechanism-specific endpoint-based trials. Full article

Background: Weight extremes are linked to morbidity, yet their impact on burn outcomes remains underinvestigated. Prior studies suggest an ‘obesity paradox’, showing survival benefits and better functional outcomes in obese patients. Methods: This study used the global real-world database TriNetX to assess the association between body mass index (BMI) and clinical outcomes in adult burn patients, categorized using WHO definitions. After 1:1 propensity score matching for demographics, burn severity, and smoke inhalation injury, clinical outcomes were analyzed over a six-month period following burn injury. Outcomes included mortality, sepsis, pneumonia, acute kidney injury (AKI), cardiovascular events, graft complications, skin infections, and psychological impairment. Results: After matching, 9736 patients were included in the underweight versus normal weight comparison, 72,274 in overweight versus normal weight, 71,195 in obesity versus normal weight, and 9732 in underweight versus obesity. Underweight patients were associated with higher mortality and increased risks of sepsis, pneumonia, cardiovascular events, and psychological impairment. Overweight and obese patients showed higher survival rates and overall better clinical outcome associations. Conclusions: These findings are consistent with the previously described ‘obesity paradox’ in burn care and identify underweight burn patients as a distinct high-risk subgroup. Full article

Background: Inhaler device changes at hospital discharge should address patient capacity yet often reflect routine. We evaluated the appropriateness of these decisions and their impact on clinical outcomes. Methods: In this prospective observational study (N = 480), we assessed patient technical capacity using a composite of critical errors, inspiratory flow, adherence, and knowledge. We stratified patients into ‘Need-Positive’ and ‘Need-Negative’ cohorts to quantify patterns of clinical inertia and over-adjustment. Multivariable models identified predictors of decision-making and associations with 30-day outcomes. Results: Device changes were primarily determined by the pre-admission device class (spacers: aOR 0.52; 95% CI 0.28–0.96; p = 0.037) and by the patient’s treatment pathway rather than by clinical need. This disconnect generated two types of errors: 38.3% of Need-Positive patients (n = 214) experienced clinical inertia (no corrective action), while 36.8% of Need-Negative patients (n = 266) underwent over-adjustment (unnecessary switching). Inertia perpetuated errors in patients with need, whereas over-adjustment was associated with the emergence of new errors in patients without need. Successful mismatch resolution was associated with a significantly lower 30-day readmission rate (12.1% vs. 32.5%; OR 0.48; 95% CI 0.26–0.88; p = 0.017). Conclusions: Discharge prescribing is driven more by habit than by objective assessment, leading to widespread missed opportunities for correction. Implementing evidence-based protocols to identify and resolve patient–device mismatches may represent a high-impact strategy to reduce readmissions and associated healthcare use. Full article

“Nontuberculous mycobacteria” (NTM) is a general term for mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. In Japan, 90% of pulmonary NTM disease cases are caused by two species, Mycobacterium avium and M. intracellulare, which are collectively referred to as Mycobacterium avium complex (MAC) due to their biochemical similarity. Pulmonary MAC disease is broadly classified into fibrocavitary and nodular/bronchiectatic types, each of which exhibits distinctive pathological features. The pulmonary NTM disease incidence has been found to be 14.7 cases per 100,000 population per year, suggesting that Japan has the highest incidence of this disease in the world, and its incidence has also been shown to have already exceeded that of pulmonary tuberculosis. In addition, many elderly people have weakened immune systems, which often causes a decline in comprehension, and many medications for this have side effects, making it difficult to continue taking them and leading to treatment difficulties. The two cases reported here were both elderly women with refractory MAC lung disease, but they had different phenotypes: a fibrocavitary type and a long-standing, progressive nodular and bronchiectatic type. Treatment was performed with a regimen using Riposomal amikacin (ALIS), which is an aminoglycoside antibiotic that works by binding to bacterial Riposomes and inhibiting protein synthesis. Using amikacin Riposomal technology and a specialized inhaler, ALIS efficiently reaches alveolar macrophages, directly killing the MAC bacteria within. However, the unique administration method requires inhaler cleaning, making continued use difficult given the characteristics of patients with refractory MAC pulmonary disease. Even when treatment is possible, frequent side effects, such as hoarseness and dysphonia, while not severe, further contribute to the difficulty of initiating treatment. In both cases reported here, continued administration of rifampicin was difficult due to side effects such as liver damage and loss of appetite, and the patients’ conditions were also resistant to treatment, so ALIS was chosen, as it is thought to be more effective than other drugs and to have fewer systemic side effects. The patient had a limited understanding of how to clean the inhaler and how to inhale, making continued treatment difficult; therefore, we explained the efficacy and safety of ALIS to the patient’s family. Inhalation therapy is an effective method for delivering medication directly to the lungs, where the disease is located, while reducing systemic side effects. Until now, no inhalation therapy has existed for pulmonary MAC disease, and inhalation therapy itself is still a groundbreaking treatment administration method. This is the first case in the world where therapeutic efficacy has been confirmed with fewer than half the number of treatments required for standard treatment. Furthermore, as a new drug delivery method, inhalation offers a novel treatment option when existing medications are unavailable or ineffective for some reason, and it may be safe for use in elderly patients. Full article

Historically, the toxicological evaluation of poorly soluble low toxicity particles (PSLTs), such as titanium dioxide nanoparticles (TiO₂ NPs), distinct from conventional pigment-grade TiO₂, has focused on carcinogenicity and lung overload, leaving their pathological function in the development of pneumoconiosis undefined. In this study, we initiated a “Pneumoconiosis Renaissance”, redefining the human “Gold Standard” of pneumoconiosis pathology as a primarily interstitial “Dust Macule (DM) to Mixed Dust Fibrosis (MDF) axis”. In contrast, rats developed a species-specific “Airspace-Dominant Phenotype” (Pulmonary Dust Foci) driven by airspace stagnation. Integrating recent continuous inhalation exposure and recovery after inhalation exposure studies, we demonstrate that this overwhelming alveolar pathology in rats acts as a “Biological Mask”, physically superimposing upon and obscuring human-relevant interstitial sequestration. Crucially, however, extended recovery periods can unmask these interstitial events, revealing the true underlying pathology. We propose that future risk assessments and Adverse Outcome Pathways (AOPs) must incorporate spatial resolution. By rigorously segregating sensitive rat-specific airspace events from human-relevant interstitial remodeling, we can accurately bridge the interspecies gap. This review argues that rather than discarding the rat model, we must learn to decode it—using spatial distinctions to filter the airspace mask and evaluate the true interstitial risk of inhaled biodurable particles. Full article

Children are vulnerable to exposure to airborne microplastics (MPs) because of their developing lungs and prolonged time spent indoors. Therefore, this study employed a computational fluid–particle dynamics framework to simulate the posture-dependent transport and deposition of MPs in a realistic airway model of a 2-year-old child extending to the 8th bronchial generation. A steady inhalation breathing flow rate of 5 L/min was used for both postures. Subsequently, a discrete-phase model was used to predict the transportation and deposition of MPs, which employed an appropriate drag coefficient model. MP configurations were selected from the field survey, identifying the diameters of 4.785, 9.797, and 15.731 µm with aspect ratios of 3, 5, and 10. The results showed that posture significantly altered the deposition patterns of small- and low-aspect-ratio MPs. Specifically, the total deposition fraction was higher in the upright position than in the supine position. Local deposition analyses revealed that hotspots of deposited MPs varied across the airways under the effects of posture, especially in the upper respiratory tract. These findings provide mechanistic insights into how posture shapes regional fiber deposition in children and highlight the need to consider body orientation in pediatric inhalation exposure assessments. Full article