Search Results (3,752)

Background/Objectives: Innovative intranasal delivery systems have emerged as a strategy to overcome the limitations of conventional COVID-19 vaccines, including suboptimal mucosal immunity, limited antigen retention, and vaccine hesitancy. This study aimed to evaluate physicochemical properties and murine safety of a novel COVID-19 intranasal vaccine candidate based on CHIVAX 2.1 (CVX)-loaded chitosan nanoparticles (CNPs). Methods: The CVX recombinant protein was encapsulated into CNPs using the ionic gelation method. The nanoparticles were characterized by their physicochemical properties (mean size, zeta potential, morphology, and encapsulation efficiency) and spectroscopic profiles. Mucin adsorption and in vitro release profiles in simulated nasal fluid were also assessed. In vivo compatibility was evaluated through histopathological analysis of tissues in male C-57BL/6J mice following intranasal administration. Results: CNPs exhibited controlled size distribution (38.5–542.5 nm) and high encapsulation efficiency (65.4–92.2%). Zeta potential values supported colloidal stability. TEM analysis confirmed spherical morphology and successful CVX encapsulation, and immunogenic integrity was also demonstrated. Mucin adsorption analysis demonstrated effective nasal retention, particularly in particles ≈90 nm. In vitro release studies revealed a biphasic protein profile, where ≈80% of the recombinant protein was released within 2 h. Importantly, histopathological analyses and weight monitoring of intranasally immunized mice revealed no signs of adverse effects related to toxicity. Conclusions: The ionic gelation encapsulation process preserved the physical and immunological integrity of CVX antigen. Furthermore, the intranasal administration of the CVX-loaded CNPs demonstrated a favorable safety profile in vivo. These findings support the potential of the CVX intranasal vaccine formulation for further immunogenicity studies, with no apparent biosafety concerns. Full article

Background and Objectives: a “vicious vortex” model was proposed to explain the pathophysiology of bronchiectasis, incorporating abnormal mucus, altered mucociliary clearance and chronic inflammation. Evidently, airway clearance needs to be implemented in the patient’s daily routine for a protracted period in order to ameliorate the clinical outcomes. High Flow therapy (HFT) has several physiologic effects and represents a valid therapy for various respiratory diseases. The aim of this study is to assess clinical and radiologic effects of long-term HFT in adult non-CF bronchiectasis. Materials and Methods: This is a retrospective observational cohort study including adult patients affected by bronchiectasis and frequent exacerbations and hospitalizations. A chest HRCT was performed, and a quantitative evaluation of the scans was conducted applying a modified Bhalla score of five items. A total of 44 patients completed the follow up, 23 in the HF-group and 21 in the controls (No-HF group). Results: The median follow up was 41 months (range 36–48 months). The mean age was 65 years, 45% were females. After treatment the annual rate of exacerbations was significantly lower in the HF group (1.2 ± 0.95 versus 3.5 ± 1.0 per year, p < 0.0001). The annual rate of hospitalizations was significantly lower in the HF group (0.4 ± 0.52 versus 1 ± 0.93 per year, p = 0.01). The total score of the modified Bhalla improved after treatment in the HF group with a mean score of 5.32 versus 8.38, p = 0.034. The difference was substantially due to the lower score of mucoid impactions in the HF group. Conclusions: Bronchiectasis is an evolutive disease. Long-term HFT reduces the annual rate of exacerbation and hospitalization. In addition, HFT prevents mucoid impaction and potentially influences the radiological evolution of the disease. Full article

Bovine respiratory disease complex (BRDC) is a leading cause of morbidity and mortality in pre-weaned calves, yet the role of commensal nasal microbiota in outbreak severity remains poorly understood. This study characterized nasal bacterial communities during two BRDC outbreaks of differing severity (moderate vs. severe) and at ~30 days post-treatment. Nasal swabs were collected from calves and analyzed using 16S rRNA gene sequencing (V1–V3 regions, Illumina MiSeq) and quantitative PCR targeting three major BRDC pathogens. Microbial community profiles differed between outbreak groups and across timepoints. Calves in the severe outbreak group exhibited lower microbial diversity compared to those in the moderate outbreak. In both groups, diversity significantly increased from outbreak to post-treatment. At the time of disease, nasal communities were dominated by the genera Mycoplasmopsis, Mesomycoplasma, and Caviibacter, with qPCR confirming Mycoplasma bovirhinis as the predominant species. These findings indicate that BRDC outbreaks in pre-weaned calves are associated with reduced microbial diversity and the dominance of pathogenic Mycoplasma species, with recovery characterized by greater bacterial diversity. Shifts in nasal microbiome composition between outbreak and post-treatment may reflect pathogen-driven disruption during disease and subsequent microbial community rebalancing. Full article

Purpose: To investigate regional changes in tear film quality associated with orthokeratology (Ortho-K) lens wear using high-resolution spatial mapping and to evaluate the potential of artificial intelligence (AI) models in anticipating these changes. Methods: This study analysed tear film quality in 92 Ortho-K wearers divided into three groups based on lens wear duration (10–29 days, 30–90 days, and ≥91 days). Placido-based topographer measurement was used to generate regional tear film maps before and after treatment. A custom MATLAB pipeline enabled regional comparisons and statistical mapping. A feedforward neural network was trained to forecast local tear film quality using spatial data. Results: Single-value global mean metrics showed minimal changes in tear film quality across groups. However, regional mean mapping revealed significant mid-peripheral and peripheral deterioration over time, particularly in nasal and temporal corneal zones. These changes were often overlooked by global averaging and remained invisible through tear film breakup time (TBUT) measurements. The AI model predicted spatial tear quality with high accuracy (R ≥ 0.9 in testing), capturing nuanced regional variations. Conclusions: The regional analysis uncovers subtle, clinically relevant tear film disruptions caused by Ortho-K lens wear, particularly in peripheral areas. These insights challenge the adequacy of traditional single-value global mean assessments. The AI model demonstrates the potential for non-invasive, predictive evaluation of tear stability, supporting more personalised and effective Ortho-K care. Full article

SARS-CoV-2 variants have demonstrated distinct epidemiological patterns and clinical presentations throughout the COVID-19 pandemic. Understanding variant-specific differences at the respiratory epithelium is crucial for understanding their pathogenesis. Here, we utilized human nasal organoid air–liquid interface (HNO-ALI) cell cultures to compare the viral replication kinetics, innate immune response, and epithelial damage of six different strains of SARS-CoV-2 (B.1.2, WA, Alpha, Beta, Delta, and Omicron). All variants replicated efficiently in HNO-ALIs, but with distinct replication kinetic patterns. The Delta variant exhibited delayed replication kinetics, achieving a steady state at 6 days post-infection compared to 3 days for other variants. Cytokine analysis revealed robust pro-inflammatory and chemoattractant responses (IL-6, IL-8, IP-10, CXCL9, and CXCL11) in WA1, Alpha, Beta, and Omicron infections, while Delta significantly dampened the innate immune response, with no significant induction of IL-6, IP-10, CXCL9, or CXCL11. Immunofluorescence and H&E analysis showed that all variants caused significant ciliary damage, though WA1 and Delta demonstrated less destruction at early time points (3 days post-infection). Together, these data show that, in our HNO-ALI model, the Delta variant employs a distinct “stealth” strategy characterized by delayed replication kinetics and epithelial cell innate immune evasion when compared to other variants of SARS-CoV-2, potentially explaining a mechanism that the Delta variant can use for its enhanced transmissibility and virulence observed clinically. Our findings demonstrate that variant-specific differences at the respiratory epithelium could explain some of the distinct clinical presentations and highlight the utility of the HNO-ALI system for the rapid assessment of emerging variants. Full article

Introduction: Occupational allergic rhinitis (OAR) is a common respiratory condition that can lead to varying degrees of symptom severity, significantly impacting workers’ quality of life and productivity. While occupational risk factors are well established, the influence of nonoccupational factors, such as obesity, that contribute to OAR severity remains largely unexplored. Aims: This study aims to study the association between obesity and the severity of OAR. Methods: A cross-sectional analytical study was conducted among patients diagnosed with OAR at the Occupational Medicine Department of Farhat Hached University Hospital of Sousse. It combines a retrospective review of medical records (2013–2021) with prospective structured telephone interviews (January–March 2023). Data were collected from medical records and supplemented with telephone interviews. The severity of OAR was assessed via the PAREO score and rhinomanometry results. Results: A total of 196 patients were included. The mean age was 39.69 ± 7.92 years, with a sex ratio of 0.53. The most frequently reported symptoms were nasal obstruction (78.6%) and sneezing (88.8%). The mean PAREO score was 5.78 ± 1.61, with severe OAR reported in 59.2% of the patients. Obesity was significantly associated with increased severity of OAR symptoms (p < 0.001; OR = 5.4; 95% CI [2.6–11.1]), a finding confirmed after adjustment for variables such as age, sex, and occupational seniority. Conclusion: Obesity appears to be a modifiable risk factor influencing OAR severity. Integrating weight management strategies into the treatment of OAR patients may contribute to significant symptom relief and improved quality of life. Further longitudinal studies are needed to confirm these findings and explore the underlying mechanisms involved. Full article

Objectives: This study aimed to evaluate the reproducibility of artificial intelligence (AI) in identifying cephalometric landmarks, comparing its performance with manual tracing by an experienced orthodontist. Methods: A high-quality lateral cephalogram of a 26-year-old female patient, meeting strict inclusion criteria, was selected. Eighteen cephalometric landmarks were identified using the WebCeph software (version 1500) in three experimental settings: AI tracing without image modification (AInocut), AI tracing with image modification (AI-cut), and manual tracing by an orthodontic expert. Each evaluator repeated the procedure 10 times on the same image. X and Y coordinates were recorded, and reproducibility was assessed using the coefficient of variation (CV) and centroid distance analysis. Statistical comparisons were performed using one-way ANOVA and Bonferroni post hoc tests, with significance set at p < 0.05. Results: AInocut achieved the highest reproducibility, showing the lowest mean CV values. Both AI methods demonstrated greater consistency than manual tracing, particularly for landmarks such as Menton (Me) and Pogonion (Pog). Gonion (Go) showed the highest variability across all groups. Significant differences were found for the Posterior Nasal Spine (PNS) point (p = 0.001), where AI outperformed manual tracing. Variability was generally higher along the X-axis than the Y-axis. Conclusions: AI demonstrated superior reproducibility in cephalometric landmark identification compared to manual tracing by an experienced operator. While certain points showed high consistency, others—particularly PNS and Go—remained challenging. These findings support AI as a reliable adjunct in digital cephalometry, although the use of a single radiograph limits generalizability. Broader, multi-image studies are needed to confirm clinical applicability. Full article

Both allergic rhinitis and chronic rhinosinusitis with or without nasal polyps have important factors in common with asthma. They are often present simultaneously, they have similar pathogenesis processes, and they have synergistic effects on the clinical manifestations. There are also important considerations regarding the common treatment of these pathologies. Taking all these into account, it is possible to place these diseases under the “united airway disease” umbrella. However, matters such as embryologic origins, anatomy and function of the upper and lower airways, as well as cases where the aforementioned pathologies can be observed independently and have different treatment responses, make up reasonable counterarguments for the “united airway disease”. This narrative review attempts to put all these factors into perspective for a slightly better understanding of the complexity of this topic. We will take into consideration factors such as epidemiological data, pathogenesis and pathology, clinical considerations, and the benefits of a common treatment. Full article

Background/Objectives: Sarcoidosis is a granulomatous disorder of unknown etiology that can affect multiple organs, including the oral cavity. This study aimed to compare the clinical and demographic characteristics of sarcoidosis cases with and without bone involvement in the jaw. Methods: A systematic review of the case reports and case series of sarcoidosis in the oral cavity between 1943 to 2024 were analyzed. Variables assessed included age, sex, presenting symptoms, duration of symptoms, diagnosis methodology, treatment approaches, and outcomes. Results: A total of 59 studies reporting 77 patients were included, with a mean age of 43.3 yrs. Female predominance was noted in both, bone-involved (61.5%) and non-bone-involvement cases (72.5%). Patients with bone involvement often presented with localized symptoms such as loose teeth (34.6%), bone loss (69.2%), and nasal obstruction (15.4%), whereas non-bone-involvement cases frequently exhibited soft tissue manifestations, like swelling (38%) and bleeding (14%). Treatment typically involved surgical intervention and steroid therapy in both groups, with favorable outcomes achieved in most cases. Conclusions: This systematic review presents the most extensive analysis of oral sarcoidosis. Oral sarcoidosis presents as two distinct clinical entities based on bone involvement. Soft tissue lesions often serve as an early diagnostic clue for systemic disease, while bony manifestations suggest a later, more destructive complication. Recognizing this dichotomy is crucial for dentists and clinicians to ensure timely diagnosis and appropriate referral, and this underscores the oral cavity’s critical role as an indicator of systemic illness and mandates a multidisciplinary management strategy. Full article

The single colorimetric signal readout mode of traditional lateral flow immunoassay (LFIA), which relies on gold nanoparticles (Au NPs), is inadequate to meet the growing demand for detection in terms of sensitivity, accuracy, and flexibility. Herein, we reported a novel colorimetric and photothermal dual-mode LFIA (dLFIA) based on MoS₂ nanoflowers for rapid detection of severe acute respiratory syndrome coronavirus 2 nucleocapsid protein (SARS-CoV-2 NP). Benefiting from the strong color-producing ability and near-infrared absorption of MoS₂ nanoflowers, the visual limits of detection in colorimetric and photothermal modes were 1 and 0.1 ng/mL, respectively. The limit of detection for quantitative analysis in photothermal mode was 48 pg/mL, with a sensitivity about 10~208 times higher than that of Au NPs-LFIA. Additionally, the dLFIA strips exhibited excellent specificity, good reproducibility, and satisfactory recovery when detected the simulated nasal swab samples, possessing good application prospect. Full article

Background: This study aimed to evaluate the clinical effectiveness of dupilumab and its impact on CRSwNP and type 2 inflammatory biomarkers in patients with severe uncontrolled asthma, with or without comorbidities, within a real-life cohort. Methods: This was a single-center, prospective, and observational real-life study conducted at the Severe Asthma Unit of Germans Trias i Pujol University Hospital. The objective of this study was to assess the real-world response to dupilumab treatment in patients with severe asthma, with or without nasal polyposis, bronchiectasis, obesity, or switching from another biologic drug for their asthma. Results: The ACT score significantly increased (13.7 vs. 20.6; p = 0.001), while the number of exacerbations decreased (3.1 vs. 0.7; p = 0.005). Patients with CRSwNP showed an increase in the ACT score (13.1 vs. 19.8; p = 0.011) and a decrease in the number of exacerbations (3.0 vs. 1.3; p = 0.217). Patients with nasal polyps showed an increase in both SNOT22 (78.3 vs. 38.3; p = 0.013) and global VAS (8 vs. 4.2; p = 0.028). Patients with bronchiectasis receiving dupilumab showed an increase in the ACT score (12.7 vs. 21.3; p = 0.039) and a marked decrease in the number of exacerbations (2.8 vs. 0; p = 0.025). Obese patients treated with dupilumab showed an improvement in the ACT score (14.1 vs. 21.3; p = 0.044) and a decrease in the rate of exacerbations (3.2 vs. 1.3; p = 0.030). Patients with rhinoconjunctivitis receiving dupilumab showed an increase in the ACT score (13.4 vs. 19.1; p = 0.017) and a decrease in the number of exacerbations (3.3 vs. 0.8; p = 0.024). Conclusions: Dupilumab is a highly effective treatment for severe asthma, showing significant improvements in lung function, reductions in exacerbations, and enhanced quality of life for patients with and without nasal polyps. The results of this real-life study support dupilumab as a valuable addition to the therapeutic armamentarium for asthma, particularly for those with type 2 inflammation despite the presence of comorbidities such as bronchiectasis or obesity, or for patients in whom a previous biologic treatment failed. Full article

Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a particular problem for the pediatric population among whom the highest mortality from the disease is recorded. Several reasons for this phenomenon can be mentioned, but what is particularly important from the microbiological point of view is the correlation of the increased number of pertussis cases with the introduction of a new form of vaccine—the acellular vaccine in place of the whole-cell vaccine. In this review, we summarized the current state of knowledge on potential factors that may contribute to the decline in immunization efficacy against the pathogen. The post-vaccination response profile, symptomatic of vaccination with vaccination-acellular, is characterized by recruitment of Th₂ and Th₁₇ lymphocytes; it has been reported that in the long term, this results in insufficient activation of B cells and low titers of antibodies to key bacterial antigens (hemagglutinin, pertactin). Moreover, the immune response proceeds by bypassing the recruitment of tissue-resident memory T cells, resulting in a lack of protection against colonization of the nasal cavity by the bacterium despite vaccination. The decline in vaccination efficacy should also be attributed to the phenotypic variability of Bordetella. The popularization of the PtxP3 strain, characterized by its ability to incompletely activate immune mechanisms, poses a real threat to public health. The growing resistance of B. pertussis to standardly used antibiotics including macrolides also remains a problem. This makes it difficult to eradicate pathogens from the nasal cavity area and increases the pool of bacterial carriers in the population area. The increasing prevalence of the disease prompts reflection on more effective methods of prevention. Particularly promising in this field seem to be new vaccines, especially mucosally implemented, e.g., intranasal, or developed on the basis of B. pertussis antigens other than those used so far. Full article

Introduction: Canine sinonasal aspergillosis (SNA) can present singular as a primary disease or secondary to concurrent sinonasal pathology. We hypothesized that treatment response and prognosis differ between both forms, particularly when sinusitis is present. Methods: In this retrospective study, 30 dogs with SNA were categorized as either group pA (primary aspergillosis) or group sA (secondary aspergillosis; with additional sinonasal pathology). History, diagnostics, endoscopic therapeutic intervention of affected nose and sinus, and follow-up data were analyzed. Results: Group pA included 19/30 dogs (63%), with 15 dogs (79%) showing concurrent sinusitis. Group sA included 11/30 dogs (37%; additional conditions: foreign bodies, dental pathologies, frontal bone fracture). Only 2/11 sA dogs (18%) had sinusitis. Follow-ups in group pA were more frequent than in group sA (p = 0.04). Need for re-treatments differed significantly between groups (p = 0.02) and in dogs with sinusitis, regardless of group (p < 0.001). In group sA, treating the underlying condition plus single endoscopic debridement ± antifungal therapy led to clinical resolution in 11 of 12 dogs (92%). Conclusions: Primary SNA is frequently associated with sinusitis, requires aggressive repeated antifungal therapy, and may not achieve a definitive cure. Secondary SNA is usually confined to the nasal cavity, responds well to underlying condition treatment, carries better prognosis, and requires fewer antifungal treatments. Full article

Background and Objectives: Boosting parasympathetic activity may enhance both physical and mental functions. In this study, we introduced the Lin Nasal Airflow Reducer (L.NAR), a silicone device designed to reduce nasal airflow. This pilot and exploratory study aimed to investigate the effect of L.NAR on parasympathetic activity in adults. Materials and Methods: The test protocol consisted of two 16 min ECG sessions. In the first session, participants did not wear the L.NAR for the initial 8 min (Test 1) but wore it for the remaining 8 min (Test 2). Following a 30 min rest, the second session reversed the sequence, with participants wearing the L.NAR for the first 8 min (Test 3) and removing it for the final 8 min (Test 4). Time- and frequency-domain analyses and non-linear analyses were used to assess heart rate variability (HRV) for every 300 s moving by 10 s. Repeated measurement ANOVA was conducted to compare the means across the four tests. Results: A total of 49 participants were enrolled in the analysis, with a mean age of 40.3 ± 10.7 years. Male participants had a higher body mass index (BMI) than female participants (24.0 ± 3.3 vs. 21.3 ± 2.9 kg/m², p = 0.014). Participants in Test 3 and Test 4 had significantly lower heart rate values than those in Test 1. Participants wearing the L.NAR (Test 2 and Test 3) had significantly higher RMSSD values compared to those not using the L.NAR. Among the participants, 33 (67.3%) who wore the L.NAR showed significantly higher RMSSD levels compared to their pre-L.NAR levels during the first practice. This improvement was achieved after an average of 2.5 ± 2.9 sessions. Conclusions: In this study, we introduced a novel approach using the L.NAR to increase RMSSD, a key indicator of parasympathetic activity. Full article

Background: The anatomical variability of the nasal cavity affects intranasal drug delivery, especially to the olfactory region for nose-to-brain treatments. While previous studies used average models or 2D measurements to account for inter-individual variability, 3D shape variation of the region crossed by drug particles that target the olfactory area, namely the region of interest (ROI), remains unexplored to our knowledge. Methods: A geometric morphometric analysis was performed on the ROI of 151 unilateral nasal cavities from the CT scans of 78 patients. Ten fixed landmarks and 200 sliding semi-landmarks were digitized, using Viewbox 4.0, and standardized via Generalized Procrustes Analysis. Shape variability was analyzed through Principal Component Analysis. Morphological clusters were identified using Hierarchical Clustering on Principal Components, and characterized with MANOVA, ANOVA, and Tukey tests. Results: Validation tests confirmed the method’s reliability. Three morphological clusters were identified. Variations were significant in the X and Y axes, and minimal in Z. Cluster 1 had a broader anterior cavity with shallower turbinate onset, likely improving olfactory accessibility. Cluster 3 was narrower with deeper turbinates, potentially limiting olfactory accessibility. Cluster 2 was intermediate. Notably, 31.5% of patients had at least one cavity in cluster 1. Conclusions: Three distinct morphotypes of the region of the nasal cavity that potentially influence accessibility were identified. These findings will guide future computational fluid dynamics studies for optimizing nasal drug targeting and represent a practical step toward tailoring nose-to-brain drug delivery strategies in alignment with the principles of personalized medicine. Full article