Frontiers in allergy最新文献

Microplastics (MPs) and Nanoplastics (NPs) have emerged as pervasive environmental contaminants with growing implications for respiratory health. Increasing evidence demonstrates that inhaled MPs can deposit throughout the airways, interact with epithelial surfaces, and trigger a cascade of inflammatory, oxidative, and structural alterations that may contribute to the onset or progression of airway diseases. Their pathogenicity is influenced by physicochemical properties, including size, shape, density, and surface charge, which determine their aerodynamic behavior, epithelial penetration, and cellular uptake. Once deposited, MPs are associated with epithelial stress responses, including oxidative stress, activation of inflammatory signaling pathways, and alterations in junction-related proteins, which may impair mucociliary function. Smaller particles and NPs are internalized through endocytosis, leading to mitochondrial dysfunction, reactive oxygen species (ROS) generation, and activation of key inflammatory pathways such as NF-κB, PI3K/Akt/mTOR, and Wnt/β-catenin. These mechanisms promote cytokine release, epithelial-mesenchymal transition, and dysregulated repair responses. Experimental and clinical evidence indicate that MPs exacerbate epithelial fragility in asthma and COPD by amplifying oxidative stress, enhancing barrier dysfunction, and intensifying maladaptive crosstalk between epithelial and immune cells. In fibrotic pathways, persistent epithelial injury activates the NLRP3 inflammasome and drives TGF-β1-mediated fibroblast activation and extracellular matrix deposition, establishing a self-perpetuating cycle of inflammation and remodeling. Emerging data suggest a potential role for MPs in lung carcinogenesis through chronic inflammation, indirect genotoxic effects mediated by oxidative stress, and altered cellular homeostasis. Overall, MPs represent an underrecognized but increasingly relevant environmental factor capable of inducing epithelial damage, promoting chronic airway inflammation, and contributing to the pathophysiology of asthma, COPD, pulmonary fibrosis, and possibly lung cancer. Understanding these mechanisms is crucial to guide preventive strategies, regulatory policies, and future clinical research. This review critically evaluates current experimental evidence on microplastic-epithelium interactions, highlighting mechanistic insights, methodological limitations, and key gaps that must be addressed to clarify their role in airway diseases.

Introduction: Salmon processing workers are exposed to bioaerosols and are at risk of developing respiratory diseases and other hypersensitivity reactions. The aim of this study was to investigate the prevalence of allergic sensitization to salmon in a study population of Norwegian salmon processing workers and to investigate salmon proteins involved in IgE-binding.

Method: A total of 977 salmon processing workers were tested with skin prick test (SPT) using both in-house salmon extracts, commercial extracts from cod and salmon, and specific IgE (sIgE) to Atlantic salmon (Salmo salar). They were also invited to answer a general questionnaire, including questions on asthma, work-related symptoms, and food-allergy to salmon. Serum from 71 sensitized workers with either a positive SPT and/or elevated sIgE to salmon, were further analyzed by immunoblot, with in-house and commercial protein extracts. Salmon proteins which were most frequently involved in IgE-binding were identified using mass spectrometric analyses of SDS-PAGE protein bands.

Results: We determined a prevalence of allergic sensitization to salmon of 7.3% (n = 71) in the present study population. Fifty-six workers had at least one positive SPT, with most having a reaction to the in-house raw muscle extract (61%), followed by in-house mucus (42%), in-house cooked muscle (17%), commercial cod (11%), commercial salmon (8%), and in-house skin (3%). All sensitized workers had IgE-binding to proteins in at least one of the protein extracts, with immunoblot protocols: mucus (100%), raw muscle (79%), cooked muscle (20%), skin (6%), and commercial cod (24%). Most frequent IgE-binding was seen in the 60-70 and >131 kDa area for mucus, and 60-70 kDa for raw muscle. Work-related symptoms were reported by 43 workers. Only three workers had self-reported allergy to salmon related to food intake, whereas 10 workers had self-reported doctor-diagnosed asthma. With mass spectrometry, known allergens were identified, as well as potentially novel allergens with possible clinical relevance.

Conclusion: Norwegian salmon processing workers are exposed to various salmon tissues at work, containing proteins which might cause allergic sensitization. Allergens other than the major fish allergen parvalbumin, including allergens not previously identified as salmon allergens, seem to play an important role in the occupational setting.

Introduction: Using machine learning to identify clinical biomarkers for determining optimal response to mepolizumab in chronic rhinosinusitis with nasal polyps.

Methods: Single center retrospective observational study with 84 CRSwNP patients treated with mepolizumab. We evaluated 4 machine learning algorithms: Decision Tree, Logistic Regression, K-Nearest Neighbors and Extreme Gradient Boosting. K-Fold cross-validation incorporating hyperparameter optimization in the process was used to ensure robustness and prevent overfitting.

Results: After 6, 12 and 24 months, SNOT-22, VAS overall symptom score, VAS-smell, asthma control test (ACT) and nasal polyp score (NPS) significantly improved (p < 0.001). 44.1% of patients were classified as "super-responders" after 2-year of Mepolizumab treatment based on EPOS/Euforea criteria. XGBoost emerged as the most accurate for predicting super-response to mepolizumab, achieving an ROC- AUC of 0.766. In contrast, Logistic Regression was the least effective for predicting sustained super-response at 24 months, with an ROC-AUC of 0.628. Significant predictors included Blood Neutrophilia and Blood Eosinophilia where higher baseline scores were linked to higher probabilities of super-response at 24 months. Shapley Additive Explanations were employed to identify the most critical baseline features and to visualize their directional impacts on treatment responses.

Conclusions: Machine learning models, particularly XGBoost, can predict real-world super-response to mepolizumab in severe CRSwNP by identifying key predictors like high baseline BEC, high baseline BNC and AERD comorbidity. These insights have the potential to refine CRSwNP treatment strategies and support clinical decision-making, ultimately enhancing patient outcomes by predicting treatment response prior to starting medication.

Introduction: Respiratory oscillometry is a sensitive tool for assessing small airways dysfunction. However, limited evidence on cutoff values for interpretation remains a barrier to its clinical use. The aim of this study was to determine whether the presence and severity of abnormalities, defined by Z-scores for oscillometric parameters, are associated with asthma symptoms and exacerbation risk.

Methods: We retrospectively reviewed the medical records of all patients with asthma managed in a severe asthma clinic between 2019 and 2022 who underwent routine oscillometry. Z-scores for oscillometric parameters were analyzed as continuous and categorical variables to assess their associations with asthma control and exacerbation risk.

Results: When analyzed as categorical variables, Z-score-defined severity thresholds for resistance (R₅), reactance (X₅), and the area under the reactance curve (A_X) were associated with levels of asthma control (as measured by the ACQ5). When analyzed as continuous variables, Z-scores were also correlated with worst asthma control (as assessed by both ACQ5 and the asthma control test) (P < 0.005). These correlations remained significant after adjustment for spirometric indices, FeNO, and treatment changes. Elevated Z-scores (>1.64) for R₅ were associated with a higher risk of exacerbations (OR 2.70, 95% CI 1.27-5.17, P = 0.009). The risk of exacerbation increased with the severity of airway obstruction. Similar trends were observed for A_X and X₅; however, these associations did not reach statistical significance.

Discussion: The presence and severity of airway obstruction, as defined by R₅ Z-scores, predict poorer asthma control and an increased risk of exacerbations. Similar associations with asthma control were also observed for X₅ and A_X Z-scores. Clinicians should use Z-scores over other cutoffs to aid interpretation.

Tic disorders are childhood-onset neuropsychiatric conditions that frequently co-occur with allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. This narrative review maps the current clinical and mechanistic evidence linking allergic conditions to tic disorders and evaluates whether allergy focused interventions may modify tic severity. Across multiple epidemiological studies, allergic diseases are reported more often in children with tic disorders than in controls. However, direct clinical evidence supporting a canonical "central allergic response" within the brain (e.g., IgE-driven allergic effector mechanisms in the CNS) in primary tic disorders remains limited. The available literature instead more strongly supports indirect, peripheral, brain directed pathways. Peripheral inflammatory mediators may modulate the neurovascular unit and glial reactivity, thereby influencing cortico-striato-thalamo-cortical circuit excitability. Histamine, acting as both an immune mediator and a neuromodulator, may further intersect with dopaminergic signalling relevant to tic expression. In parallel, allergy related symptom burden, particularly sleep disruption and psychological stress, may contribute to tic exacerbation. Observational studies suggest that controlling allergic symptoms can be associated with reduced tic severity in some individuals, although certain anti allergic agents have been reported to coincide with tic worsening in selected cases. Overall, current findings support a model in which allergic conditions influence tic disorders primarily via immune signalling and symptom burden rather than through a direct central allergic mechanism. Allergy assessment and management may be considered in selected patients, but mechanistic studies and controlled trials are needed to clarify causality and guide evidence-based care.

Background: The incidence of multiple food allergies (MFA), defined as exhibiting allergic responses to two or more distinct food groups, has been increasing. Since peanut (PN)/ tree nuts (TN) MFA causes severe reactions, it is challenging to study cross-reactivity immediately using human subjects. Development of a PN/TN cross-reactivity model may provide a useful tool to understand the immunological mechanisms underlying cross-reactivity among PN/TN, and a tool to develop therapies that prevent cross-reactivity.

Methods: Sensitization to the most common allergens, PN, walnut (WN), and cashew (CSH), were utilized for cross-reactive sensitization to eight other TNs (almond, pecan, pistachio, hazelnut, Brazil nut, pine nut, macadamia but, and coconut). C3H/ HeJ mice were intraperitoneally sensitized (primed) with a mixture of PN, WN, and CSH and specific (s)- IgE levels against the primed and cross-reactive TN antigens were determined. Intragastric challenges with each primed and eight unprimed allergens were performed and anaphylaxis symptoms measured. Correlation of primed IgE levels and symptoms scores with primed and unprimed allergen were conducted.

Results: PN, WN, and CSH sensitization induced significant cross reactivity against other TNs, with elevated sIgE levels against both primed and unprimed allergens. Cross-reactivity was confirmed clinically, with anaphylaxis upon primed and unprimed nut challenges, exhibiting strong positive correlations among sIgE levels and anaphylaxis observed.

Conclusion: Interestingly, as seen with patients, different priming nuts were capable of cross-sensitization against different groups of challenge nuts. Thus, we present a model system that can be developed to investigate the molecular basis of MFA and potential therapeutic approaches.

Introduction: Allergic asthma, often triggered by house dust mites (HDMs), is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. Among the major HDM allergens, Der pII plays a significant role in promoting inflammation. This study investigates the role of epidermal growth factor receptor (EGFR) inhibitors in modulating Der pII-induced cytokine production and inflammation in human immune cells.

Methods: Recombinant GST-Der pII protein was expressed and purified for subsequent studies. Human peripheral blood mononuclear cells (HPBMC), THP-1 monocytes, THP-1-derived macrophages, and pulmonary alveolar macrophages (NR8383) were exposed to Der pII, followed by treatment with EGFR inhibitors AZD-9291 and Tarceva. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of IL-6 and IL-8. Nitric oxide (NO) levels were determined using the Griess Reagent System.

Results: Der pII significantly induced pro-inflammatory cytokines, including IL-6, IL-8, and TNF-α in HPBMC and THP-1 cells. Both EGFR inhibitors reduced the secretion of IL-6 and IL-8 in these cell types. In THP-1 macrophages, AZD-9291 suppressed IL-6 expression and CD14/CD36 macrophage markers. Moreover, AZD-9291 significantly inhibited NO production in alveolar macrophages.

Conclusions: These findings suggest that EGFR plays a critical role in mediating Der pII-induced inflammation, and EGFR inhibitors may represent a potential therapeutic approach for controlling HDM-induced allergic inflammation.

Objective: Nasal inflammatory diseases significantly impair patients' quality of life, with global prevalence varying regionally. Nasal irrigation, endorsed by international guidelines as adjunctive therapy, lacks standardized protocols and patient education, potentially compromising efficacy. This study evaluated the knowledge, attitudes, and practice regarding nasal irrigation in patients with rhinosinusitis and identified factors influencing adherence, with the objective of informing evidence-based strategies to improve patient education and clinical management.

Methods: A cross-sectional survey was conducted at a tertiary hospital via a 40-item questionnaire assessing the knowledge, attitudes, practice and information sources related to nasal irrigation among 233 patients with nasal inflammatory diseases.

Results: The participants exhibited significant knowledge gaps in solvent/solute selection, concentration, temperature, irrigation devices, shelf life, and clinical indications of nasal irrigation (correct answer rate <60%). Younger participants (<50 years) demonstrated a better understanding of temperature, frequency, device differences and pediatric applicability. The attitudes were favorable: 88.7% perceived nasal irrigation as safe, and 92.6% acknowledged its importance; however, only 58.4% believed it could independently treat rhinosinusitis. Practice rates were high (80.4%), with 94.1% performing self-administered irrigation. Hospitals were the primary information source (75.5%), whereas younger, educated patients more frequently utilized online platforms and science/professional literature.

Conclusion: Despite high adherence and positive perceptions, critical knowledge gaps persist in solution parameters, device use, and clinical applications. Age- and education-stratified communication, which integrate multimedia resources and hospital-led guidance, are essential for addressing disparities and enhancing treatment efficacy, particularly among older, less educated and read populations.