International Archives of Allergy and Immunology最新文献

Introduction: Allergic rhinitis (AR) is a chronic condition caused by an immunoglobulin E-mediated response to environmental allergens, which affects 10-40% of the global population. AR symptoms, such as nasal congestion and rhinorrhea, significantly reduce quality of life and are associated with sleep disturbances, further exacerbating the condition's burden. Despite the known impact of AR on sleep, the effects of intranasal corticosteroids on sleep quality have not been comprehensively reviewed. Therefore, this systematic review and meta-analysis aimed to investigate the efficacy of intranasal corticosteroids in improving sleep quality among patients with AR.

Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO (CRD42023460698). A comprehensive search was conducted on PubMed, Cochrane Central Register of Controlled Trials, and Ichushi-Web. Randomized controlled trials (RCTs) comparing intranasal corticosteroids with placebos in patients with AR were included. Data extraction and risk of bias assessment were independently performed by two authors. The primary outcome was the improvement in sleep quality measured by standardized questionnaires. Meta-analyses were performed using a random-effects model. The risk of bias was assessed using the RoB2 tool.

Results: Eighteen RCTs involving 6,019 participants were included. The meta-analysis of 12 comparisons from eight studies for the Rhinoconjunctivitis Quality of Life Questionnaire sleep domain showed significant improvement in sleep quality with a standardized mean difference (SMD) of 0.292 (95% confidence interval [CI]: 0.235-0.350, p < 0.0001, I2 = 0.0%). The Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire also showed improvement with an SMD of 0.284 (95% CI: 0.164-0.404, p < 0.0001) based on two comparisons from one study. However, the Epworth Sleepiness Scale did not show significant results (SMD: 0.027, 95% CI: -0.429 to 0.483, p = 0.907) based on two comparisons from two studies. Sensitivity analysis, excluding two studies with high risk of bias according to RoB2, confirmed the robustness of these results. Subgroup analyses for patients with seasonal or perennial AR showed significant improvements in both groups.

Conclusion: This study demonstrates that intranasal corticosteroids significantly improve sleep quality in patients with AR. These findings support the use of intranasal corticosteroids as a first-line treatment for AR, not only for managing daytime symptoms but also for enhancing sleep quality. Future research should focus on sleep quality changes as a primary outcome and incorporate both subjective and objective measures to better understand the relationship between sleep and AR symptoms.

Introduction: Immunotherapy has demonstrated encouraging outcomes in tackling lung adenocarcinoma (LUAD), but immune escape may bring negative impacts. Only a single study has demonstrated the function of AIM2 in LUAD and reported that NF-κB and STAT1 are the chief transcription factors, this study is designed to analyze the role of AIM2 and examine the transcription factor, BATF in LUAD immunotherapy.

Methods: Bioinformatics methods to analyze the expression and binding sites of AIM2 and BATF in LUAD, as well as the correlation between AIM2 and PD-L1. Dual-luciferase and chromatin immunoprecipitation assays were used to verify the binding of AIM2 and BATF. qRT-PCR and Western blot assayed expression of AIM2, BATF, and PD-L1 in LUAD. MTT measured cell viability, flow cytometry detected cell apoptosis, cytotoxicity assays measured the toxicity of CD8+ T cells to cancer cells, and enzyme-linked immunosorbent assay measured the expression of related cytokines. Immunohistochemistry detected the protein expression levels of AIM2, BATF, PD-L1, and CD8 in tumor tissue.

Results: AIM2 and BATF were both highly expressed in LUAD, and there was a targeted binding relationship. BATF promoted LUAD cell proliferation and inhibited apoptosis by affecting AIM2 expression. The downregulation of AIM2 and PD-L1 expression inhibited PD-L1 and activated CD8+ T cells. The rescue experiment manifested that increased BATF weakened repression of AIM2 silencing on LUAD tumor immune escape in vitro and in vivo.

Conclusion: BATF promoted AIM2 expression, upregulated PD-L1, inhibited CD8+ T cell activity, and ultimately led to immune escape in LUAD. Our research uncovered an innovative outlook on the intricate regulation of immune checkpoint molecules and proposed a new approach to target the BATF/AIM2 axis in tumor immunotherapy.

Introduction: Sporotrichosis, a prevalent deep fungal infection in clinical settings, currently lacks rapid and accurate diagnostic methodologies. This study explores a novel rapid diagnosis method for sporotrichosis by combining FTA cards and nested PCR with fungal fluorescence staining.

Methods: The study involved skin lesion tissues from 26 patients diagnosed with sporotrichosis (Experimental Group). The Positive Control Group consisted of fungal suspensions from clinical strains of Sporothrix, while the Negative Control Group included fungal solutions of other fungi, namely Trichophyton rubrum, Trichophyton mentagrophyte, and Candida albicans. DNA was extracted from the slurry of skin lesions in the Experimental Group and from fungal suspensions in the Control Group using FTA cards, followed by nested PCR amplification. Subsequently, nested PCR amplification was performed. Histopathological examinations, including HE and fluorescence staining, were conducted on paraffin sections prepared from skin lesion tissues in the Experimental Group.

Results: Among the 26 clinical skin lesion tissues in the Experimental Group, 8 cases showed a specific positive band upon nested PCR amplification, resulting in a positive rate of 30.8%. In the Control Group, the fungal solution of the clinical strain of Sporothrix showed a specific positive band upon nested PCR amplification, while all other fungi Negative Control Group tested negative. Histopathological examination revealed granulomatous inflammatory changes in most samples after HE staining. Fluorescence staining detected spores in 17 cases, resulting in a detection rate of 65.4% (17/26).

Conclusion: The combination of FTA cards with nested PCR method proved to be simple and rapid but demonstrated a relatively low positive rate. Fungal fluorescence staining significantly improved the sensitivity of detecting sporotrichosis in histopathological examinations, thereby improving the speed and efficiency of diagnosis.

Introduction: Patients with immediate type allergic reactions to penicillins are at risk of anaphylaxis on reexposure. Diagnostic gold standard is drug provocation test (DPT) if allergy is not diagnosed by other means, such as skin testing or in vitro testing with measurement of specific IgE. Specific IgE testing carries low risk for the patient and blood sampling can be performed in primary care, but it is reported to have low sensitivity. The aim of this study was to evaluate if clinical characteristics of patients with suspected allergic reactions to penicillin and elevated specific IgE to penicillins, differed from patients without specific IgE, to identify predictors for elevated specific IgE to penicillins.

Methods: Levels of specific IgE to five penicillins (penicillin G, penicillin V, amoxicillin, ampicillin, and penicillin minor determinants) were available for 9,100 patients. Using multiple logistic regression, clinical data from 430 patients in this group who had elevated specific IgE to one or more penicillins were compared to data from 4,094 patients without specific IgE to penicillins, who had undergone DPT with a penicillin.

Results: In total 5.2% of patients had elevated specific IgE to one or more penicillins. Significantly more patients with elevated specific IgE had a history of immediate type reactions (<2 h) (OR = 4.34, p < 0.001); circulatory symptoms (OR = 1.63, p = 0.03) or angioedema (OR = 1.46, p = 0.005). Also, significantly more patients with elevated specific IgE had been treated with adrenaline (OR = 2.21, p = 0.005), steroids (OR = 1.76, p < 0.001), or antihistamines (OR = 1.83, p < 0.001).

Conclusion: A history of an immediate type reaction requiring treatment, combined with elevated specific IgE to one or more penicillins is suggestive of an IgE mediated penicillin allergy and further allergy investigations may not be needed. Specific IgE to penicillins may be used early in allergy investigation of patients with severe immediate type reactions to penicillins.

Introduction: Individuals with inborn errors of immunity (IEI) are at increased risk of respiratory infection and frequently receive prolonged broad-spectrum antibiotics, leading to antibiotic resistance. The aim of this study was to identify respiratory pathogens and antibiotic resistance patterns in IEI patients.

Methods: We retrospectively studied 36 IEI patients with positive bacterial growth in sputum cultures between 2014 and 2023. Data covered hospitalizations, respiratory infections, yearly antibiotic prescriptions, past sputum cultures, and antibiotic sensitivities. Patients with primary ciliary dyskinesia (PCD) and bronchiectasis served as a control group.

Results: A total of 314 sputum cultures were analyzed from patients with IEI, alongside 585 cultures from individuals with PCD and 113 cultures from patients with bronchiectasis. Patients with IEI had a median age of 23.5 years, with 61% male participants. The study compared the differences in bacterial isolates from sputum cultures and antibiotic resistance between patients with IEI and the control groups. The most common bacterial isolates across all groups were Haemophilus influenzae (159 isolates in IEI vs. 314 in PCD and 26 in bronchiectasis), Pseudomonas aeruginosa, and Streptococcus pneumoniae. In IEI patients, 992 symptomatic respiratory exacerbations and 43 pneumonia-related hospitalizations were recorded. Notably, H. influenzae in IEI patients showed high resistance rates to cefuroxime (82%), amoxicillin/clavulanic acid (66%), trimethoprim/sulfamethoxazole (59%), and ampicillin/sulbactam (49%). P. aeruginosa in IEI patients displayed significant resistance to ciprofloxacin (85%), ceftazidime (42%), and aminoglycosides (23-33%). Additionally, all S. pneumoniae isolates in IEI patients were tetracycline resistant, with high resistance rates to penicillin, clindamycin, and erythromycin. It is essential to highlight the substantial resistance of common pathogens to oral antibiotics. In contrast, the control groups exhibited lower resistance rates across all bacterial isolates.

Conclusion: Antimicrobial resistance is a growing concern among vulnerable IEI patients. We suggest conducting similar investigations in other regions to address this issue. The findings should inform future infection management guidelines for IEIs.

Background: Obese asthma represents a unique phenotype of asthma characterized by severe symptoms, poor medication controls, increased frequency of exacerbations, and an overall diminished quality of life. Numerous factors, including the complex interactions between environment, mechanical processes, inflammatory responses, and metabolites disturbance, contribute to the onset of obese asthma.

Summary: Notably, multiple metabolomics studies in the last several years have revealed the significant abnormalities in lipid metabolism among obese asthmatic patients. Several bioactive lipid messengers participate in the development of obese asthma has also been observed. Here, we present and discuss the latest advances regarding how bioactive lipid molecules contribute to the pathogenic process and mechanisms underlying obese asthma. The key roles of potentially significant effector cells and the pathways by which they respond to diverse lipid metabolites are also described. We finally summarize current lipid-related therapeutic options for the treatment of obese asthma and discuss their application prospects.

Key messages: This review underscores the impacts of abnormal lipid metabolism in the etiopathogenesis of obese asthma and asks for further investigation to elucidate the intricate correlations among lipids, obesity, and asthma.

Introduction: Stepwise oral food challenge (OFC) tests begin with low doses of allergens and progress to full doses. We previously reported the safety and efficacy of stepwise OFC for reintroducing hen eggs. In this study, we discuss its application for cow's milk (CM) allergy.

Methods: We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When participants reacted to the low dose, they underwent a very low-dose OFC using baked milk or <1 mL of CM.

Results: Positive reactions occurred in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results (p < 0.001) and anaphylaxis (p = 0.001). The lower dose group included more children with complete elimination of CM (p < 0.001), with numerous histories of anaphylaxis induced by CM (p < 0.001), and higher levels of total IgE (p = 0.033) and CM-sIgE (p < 0.001). A multivariate analysis indicated that in the low-dose-OFC group, higher CM-sIgE levels (p = 0.034), younger age (p = 0.005), and complete elimination of CM (p = 0.002) were associated with positive OFC results.

Conclusion: The stepwise OFC could reintroduce small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at younger ages, specifically from infancy, with very low doses, might facilitate the safe reintroduction of CM.

Introduction: Although separate immunogenic mechanisms are involved, IgE-type sensitization to wheat and celiac disease (CD) may coexist. We observationally assessed the importance of this relationship in daily practice using CD and wheat sensitization screenings.

Methods: Celiac antibody (CA) screening and food prick tests (FPTs) were requested simultaneously from patients who presented to the Allergy Clinic between January 2022 and December 2023 and had any complaint accompanied by CD symptoms/findings (non-celiac group). Patients with positive CA (CA+) underwent endoscopy. As another group, FPT results were recorded for patients previously diagnosed with CD following a gluten-free diet (celiac group).

Results: In total, 169 patients (124 non-celiac and 45 celiac) were included in the study. Wheat prick positivity (WP+) was observed in 1 patient with CD. Among 65 WP+ patients without a CD diagnosis, 14 (20.3%) tested positive for CA+, and histopathology detected CD in 4 of these cases. Among the 59 WP- patients, 4 (8.8%) had CA+. The CA+ status of those with WP+ was significantly higher than those with WP- (p = 0.023).

Conclusion: The 4 patients unaware of their CD exhibited WP+, with a higher rate of CA+ observed in the WP+ group. The association between WP+ and CA+ suggests that an impaired intestinal barrier may lead to simultaneous T helper 1 and 2 type inflammatory responses. Although different types of sensitization to the same food would not typically be expected, growing evidence indicates that this phenomenon does occur. Further studies are necessary to confirm these findings and to explore the underlying causes.

Introduction: Hereditary angioedema (HAE) is a rare genetic disorder caused by deficiency or dysfunction of C1-esterase inhibitor that is characterized by recurrent episodes of bradykinin-mediated edema. Lanadelumab has been the only available first-line therapy for long-term prophylaxis (LTP) of HAE in China since its approval in 2020. The present study aimed to investigate the clinical efficacy and safety of lanadelumab for LTP in Chinese patients.

Methods: A retrospective clinical data were collected for the 6 patients and used to examine the frequency of attack symptoms, disease-related loss of work days, and quality of life before and after LTP with lanadelumab. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL).

Results: Lanadelumab led to reductions of 97.8% and 98.5% in the attack rate and treated attack rate, respectively. All patients exhibited significant improvements in AE-QoL and DLQI scores (100% reduction rates) during the early treatment period (4 weeks and 2 weeks, respectively) and in missed work days/year (98.9% reduction rate). The efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. No serious/severe treatment-emergent adverse events occurred during lanadelumab treatment.

Conclusion: This study is the first report that demonstrates the clinical efficacy of lanadelumab and safety of LTP in HAE patients from Chinese mainland. A reasonable dosage plan can ensure a quick and long-lasting protective role of lanadelumab against HAE attacks, during COVID-19 pandemic period.

Background: The clinical outcomes of drug treatments and surgical interventions for chronic sinusitis with nasal polyps (CRSwNPs) are suboptimal, and the high recurrence rate remains a significant challenge in clinical practice. Targeted therapies such as biologics provide new perspectives and directions for treating CRSwNP.

Summary: With the continuous investigation of signaling pathways, RAS/RAF/MEK/ERK signaling pathway and other signaling pathways including Hippo, JAK-STAT, Wnt, TGF-β, PI3K, Notch, and NF-κB were confirmed to play an important role in the progression of CRSwNP. Among them, the abnormality of RAS/RAF/MEK/ERK signaling pathway is accompanied by the abnormality of this apoptotic component, which may provide new research directions for targeting the components of signaling pathways to mediate apoptosis.

Key messages: Abnormalities in signaling pathways are particularly important in studying the pathogenesis and treatment of CRSwNP. Therefore, this review summarizes the ongoing investigation and characterization of RAS/RAF/MEK/ERK signaling pathway and other signaling pathways in CRSwNP, which provides constructive ideas and directions for improving the treatment of CRSwNP.