Frontiers in allergy最新文献

Background: The epithelial barrier serves as the body's first line of defense between the host immune system and the external environment. Evidence confirms that epithelial barrier damage is an initial event in the pathogenesis of allergic respiratory diseases, during which the barrier exhibits a dual "Janus-faced" role.

Methods: This review synthesizes current literature to explore the molecular and cellular mechanisms underlying epithelial barrier dysfunction, including dysregulation of tight junctions, aberrant immune signaling, and release of pro-inflammatory alarmins. We also evaluate contemporary diagnostic technologies for assessing the epithelial barrier and analyze current therapeutic strategies aimed at its restoration.

Results: An intact respiratory epithelial barrier effectively defends against allergens and pathogens. When compromised, it exacerbates inflammatory responses through the release of alarmins. Advances in omics-based profiling and advanced imaging now enable precise assessment of barrier integrity. Therapeutically, innovative strategies-including immunomodulators, biologics, and novel agents targeting epithelial repair pathways-offer promising avenues for restoring barrier function and controlling inflammation.

Conclusion: Real-time and effective diagnosis of epithelial barrier integrity, coupled with therapeutic strategies targeting the barrier, are pivotal for achieving long-term disease control in asthma, allergic rhinitis, and related conditions. Future research should focus on barrier-centric integrated approaches to bridge fundamental scientific discoveries with clinical applications.

Introduction: Allergic rhinitis (AR) is a systemic respiratory condition that is associated with a considerable humanistic burden and is frequently underdiagnosed. Despite the known effects of AR on individual patient well-being, the wider impact of AR on the UK healthcare system remains poorly defined. We aimed to compare healthcare resource use (HCRU) posed by this disease across different age groups between patients who were diagnosed in primary care only vs. those who have a secondary care diagnosis.

Methods: In this retrospective, observational study, patients with an AR record (AR diagnosis) and patients with a record of presenting with AR symptoms but no previous AR diagnosis (AR presentation) in the UK between 2009 and 2019 were defined from primary care and secondary care databases. Patients in the AR diagnosis cohort were further categorized based on whether they had a diagnostic code in primary care only, or any relevant diagnostic code(s) in secondary care for allergist or Ear, Nose, and Throat (ENT) services referrals. Key outcomes included specialist referrals, general practitioner (GP) visits, respiratory-related hospitalizations, GP-prescribed AR-related prescriptions, and coincident asthma.

Results: A total of 3,344,716 patients were defined as presenting signs of AR and 677,771 patients were defined as having an AR diagnosis between 2009 and 2019. Only 11.7% of the AR presentation group received ≥1 referral to an allergist or ENT, and most patients in the AR diagnosis group received a diagnosis in primary care only (89.3%). Compared to their HCRU before diagnosis, patients diagnosed with AR experienced an increase in mean GP visits [7.5-10.0 per patient per year (PPPY)], respiratory-related hospitalizations (5.5-7.1 PPPY), and AR-related medications (mean 8.8-15.0 PPPY). Patients with at least one diagnostic code in secondary care generally reported higher HCRU post-diagnosis than those in primary care. The incidence rate of asthma was lower after AR diagnosis compared to before, with a shorter interval between the onset of asthma and the diagnosis of AR.

Conclusion: Patients with AR impose a greater burden on the UK healthcare system following their diagnosis, especially those who require follow-up from respiratory specialists.

Introduction: Allergen immunotherapy (AIT) is an effective and safe treatment; however, it is not recommended in consensus guidelines for severe allergic asthma patients. As AIT has been shown to be capable of modifying the course of the disease, it should be considered a concomitant treatment for specific asthma patients. This study aimed to define the profile of patients with severe allergic asthma who are most likely to benefit from AIT.

Methods: A conjoint analysis approach was adopted to comprehensively assess the importance of clinical attributes in therapeutic decision-making. A scientific committee selected the main attributes to be considered: lung function, clinical control of allergic asthma, current main treatment and etiological confirmation of moderate to severe allergic asthma. Using the fractional factorial analysis technique, 8 eligible patient profiles for AIT were defined. Participant allergists, by means of a questionnaire, classified the profiles in order of preference, mimicking the comprehensive assessment performed in clinical practice.

Results: 91 allergists from Spain and Portugal with experience in asthma and AIT participated in the study. Allergists gave greater importance to the clinical control of allergic asthma (relative importance of 51.6%), followed by preserved lung function (relative importance of 25.0%), thus confirming that the most important criterion was good control of the underlying asthmatic condition.

Conclusions: The expert allergists endorse the use of AIT in the management of moderate to severe allergic asthma in patients with appropriate clinical characteristics. Additional studies to further investigate the safety and effectiveness of this new therapeutic approach would be of interest.

Chronic spontaneous urticaria (CSU) is a heterogeneous disease with variable responses to treatment. Identifying predictors of response to omalizumab and relapse after its discontinuation is essential for optimizing management. This narrative review aims to summarize current evidence, emphasizing clinically accessible parameters to provide a practical guide for physicians in routine care settings. Response to omalizumab appears to be influenced by the underlying pathophysiological subtype of CSU. Type IIB autoimmune CSU, associated with lower total IgE levels, higher IgG anti-thyroid peroxidase levels, basopenia, eosinopenia, elevated C-reactive protein, and greater disease activity, correlates with poorer responses. Coexisting inducible urticaria is associated with the need for longer duration of omalizumab therapy. Patients with higher body mass index may be poor responders to omalizumab at licensed doses but may benefit from dose escalation. Predictors of relapse after discontinuation include high baseline disease activity, which may be related to type IIB autoimmune CSU, and longer disease duration. Achieving complete disease control prior to tapering omalizumab may also reduce the risk of recurrence. In conclusion, clinically accessible parameters can assist in predicting response to omalizumab and relapse risk. These indicators can support individualized treatment decisions and counseling in daily practice. Further research is needed to refine relapse predictors and validate strategies such as treatment optimization.

The airway epithelium serves as both a physical barrier and as an active contributor in maintaining immune defense. Upon exposure to external insults such as injury and infection, the epithelium releases alarmins including interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP), which assist in initiating and amplifying the immune response. Complementing these are the collectins, particularly surfactant protein-D (SP-D), which also participate in the innate immune response. SP-D along with its closely related collectin, SP-A, bind pathogens, apoptotic cells, and allergens, promoting phagocytosis while modulating inflammation and preventing excessive Th2-driven responses. This review discusses the role of the airway epithelium in host defense mechanisms, particularly in chronic obstructive pulmonary disease (COPD) and asthma, and explores the therapeutic implications of epithelial-driven immune responses in respiratory inflammation.

We report a case of a 24-year-old man with long-standing, severe atopic dermatitis and partly controlled moderate bronchial asthma, marked type-2 inflammation and high molecular sensitization to house-dust mite and Alternaria allergens. Because the patient's disease was refractory to conventional topical and systemic therapies, we initiated dupilumab (600 mg SC loading dose, then 300 mg every 2 weeks) to rapidly suppress systemic T2 inflammation; subcutaneous allergen-specific immunotherapy (house-dust-mite and Alternaria, Clustek®) was started at week 8. Clinical scores and lung function were followed longitudinally, and serial biomarkers (total IgE, peripheral eosinophils, allergen-specific IgG4) were measured. The patient experienced notable clinical improvement in skin and respiratory symptoms by week 6, permitting stepwise reduction of inhaled therapy; a progressive rise in allergen-specific IgG4 was observed after AIT. At week 48 the patient achieved sustained clinical remission (SCORAD 1; DLQI 0; ACQ-5 0) with normalized eosinophils and reduced total IgE. While a single case cannot prove causality or isolate the independent effect of AIT from dupilumab, this well-documented example demonstrates the feasibility and tolerability of initiating dupilumab followed by targeted AIT and suggests complementary clinical and serologic dynamics consistent with early T2 suppression and later tolerance induction. These observations support further systematic evaluation of combined biologic + AIT strategies to determine their disease-modifying potential and optimal sequencing.

We present a rare case of severe IgE-mediated hypersensitivity to carboxymethylcellulose (CMC) following an intraarticular knee injection with triamcinolone acetonide (Triamcort®). The patient experienced a grade IV anaphylactic reaction shortly after administration. Diagnostic workup, including skin prick testing and basophil activation test, confirmed sensitization to CMC. Importantly, the patient tolerated medications containing crosscarmellose and microcrystalline cellulose without adverse reactions, suggesting no clinically relevant cross-reactivity. This case highlights the need to consider excipients such as CMC as potential triggers of severe allergic reactions especially in cases of unexplained anaphylaxis to injectable medication and underscores the importance of thorough allergological assessment to ensure safe future treatments.

Background: The increasing prevalence of allergic diseases, along with their diagnosis and treatment, presents a growing challenge in health care. To reduce this burden, a highly sensitive and specific point-of-care test for detecting sensitization could be implemented in a primary health care setting. The study aimed to investigate the accuracy of FastCheckPOC 20 Atopy (FCP20) in comparison with the multiplex assay Allergy Explorer 2 (ALEX²) system.

Methods: In this cross-sectional study, 215 participants were recruited from South Tyrol, Italy. Serum samples were analyzed using both FCP20 and ALEX². Dichotomous data were used to calculate sensitivity and specificity in comparison with the ALEX².

Results: The overall sensitivity of the FCP20 was 43.3% (95% CI: 40.3%-46.2%), and the specificity was 92.1% (95% CI: 91.1%-93.0%). Inhalation allergens showed a higher sensitivity than food allergens; the grass pollen (gx17) exhibited the highest sensitivity at 79.8% (95% CI: 72.6%-85.7%). Among patients with severe allergic symptoms, bronchial asthma, or eczema, sensitivity increased to over 83%.

Conclusions: FCP20 demonstrates high specificity and may be considered for the exclusion of sensitization to selected allergens, but its low sensitivity limits its utility as a general screening tool.

Even in eosinophilic granulomatosis with polyangiitis (EGPA), not all manifestations of eosinophilic inflammation respond equally to anti-interleukin-5 (IL-5) therapy. We report a case of steroid-refractory eosinophilic otitis media (EOM) in a patient with EGPA, where systemic symptoms such as asthma and chronic rhinosinusitis initially responded to high-dose mepolizumab, but relapsed upon corticosteroid tapering. Introduction of tezepelumab led to marked improvement in EOM and upper and lower airway symptoms. To sustain remission, we employed a bi-monthly alternating regimen of tezepelumab and mepolizumab, achieving long-term control without dual biologic use or systemic corticosteroid escalation. This case highlights a personalized and steroid-sparing strategy for managing complex type 2 inflammation in EGPA.