International Archives of Allergy and Immunology最新文献

Introduction: Allergic diseases are common clinical diseases. Although allergen-specific immunotherapy (AIT) and biologics have been widely recognized, the clinical efficacy, safety, advantages and disadvantages of the combined application have not yet been sufficiently recognized. We aimed to investigate the efficacy and safety of AIT combined with biologics in patients with allergic rhinitis and asthma.

Methods: PubMed, EMBASE, the Cochrane Library, and Web of Science were systematically searched to identify RCTs investigating AIT combined with biologics for treating allergic rhinitis and asthma. The relevant outcome indicators, including incidences of emergency drugs use, severe nasal symptoms, severe adverse effects (AEs), local reactions at the site of administration, headache, and general AEs, were collected and extracted. Routine and network meta-analyses were conducted using RevMan-5.4 and STATA-MP-14 to assess efficacy and safety.

Results: Eight RCTs and a retrospective study involving 1494 patients aged 5 to 65 years with allergic rhinitis and asthma were included in this review. ① Routine meta-analysis revealed that AIT combined with biologics was significantly better than control treatment (placebo, AIT or biologics) in terms of the incidence of emergency drugs use, severe nasal symptoms, and severe AEs (P=0.0002; P=0.01; P=0.02). However, the differences in the incidence of local reactions at the site of administration, headache and general AEs were not significant. ② In the network meta-analysis, compared with AIT or placebo alone, AIT combined with biologics observably reduced the incidence of emergency drugs use and severe nasal symptoms (OR=0.32, 95% CI 0.14-0.73; OR=0.41, 95% CI 0.26-0.63). Furthermore, AIT combined with biologics yielded an evidently lower incidence of serious adverse reactions than AIT alone (OR=0.42, 95% CI 0.23-0.74).

Conclusion: The combined application of AIT and biologics has promising prospects in the clinical treatment of allergic rhinitis and asthma due to the improvement of both clinical efficacy and safety.

Trial registration: SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42024496277).

Introduction: Osthole, a naturally occurring coumarin derivative, has been isolated from the traditional Chinese medicinal herb Cnidium monnieri. This compound exhibits a range of pharmacological properties, including anticancer, antioxidant, anti-inflammatory, and immunomodulatory effects. The objective of this study was to investigate the role of osthole in tissue remodeling in chronic rhinosinusitis with nasal polyp (CRSwNP).

Methods: The effects of osthole on nasal polyp (NP) formation were examined within a mouse model of NPs induced by cigarette smoke (CS). The detection of polypoid changes and goblet cell metaplasia was achieved through the use of haematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining, respectively. The levels of TGF-β1, matrix metalloproteinases 2, 7, 9, and 12 (MMP2, MMP7, MMP9, MMP12), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) in nasal lavage fluid were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was employed to ascertain the expression of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, ZO-1, α-SMA and vimentin), as well as the activity of the PI3K/AKT/NF-κB pathway. The expression of E-cadherin in nasal epithelium was determined through immunohistochemistry.

Results: In the OVA+SEB or CS-exposed NP mouse model, osthole was observed to reduce the incidence of polypoid changes and goblet cells, while simultaneously increasing the expression of E-cadherin in the epithelium when compared to the CS-treated group. After treatment with osthole, the levels of TGF-β1, MMP2, MMP7, MMP9 and MMP12 in nasal lavage fluid were observed to decrease, while the levels of TIMP-1 were found to increase. In vitro, cigarette smoke extract (CSE) was observed to down-regulate the expression of E-cadherin and ZO-1, while simultaneously up-regulating the expression of α-SMA and vimentin. Moreover, osthole up-regulated the expression of E-cadherin and ZO-1 while down-regulating the expression of α-SMA and vimentin. This effect of osthole was reversed by PI3K/AKT/NF-κB pathway agonists.

Conclusion: Osthole attenuates CS exposure-induced EMT via the PI3K/AKT/NF-κB pathway, providing a theoretical and experimental basis for its clinical application in the treatment of CRSwNP.

Introduction: Seasonal allergic rhinitis (SAR) is a common health condition that is associated with an increased risk for bronchial asthma. Besides conventional medicine, treatments from traditional, complementary and integrative medicine are widely used by individuals with SAR. This review aims to systematically summarize evidence on the efficacy, effectiveness, and safety of European/Western phytotherapy (PT) and medications from anthroposophic medicine (AM) in individuals with SAR.

Methods: Four electronic databases were screened for clinical studies published between January 1990 and March 2023. The results were qualitatively synthesized and the study quality was assessed.

Results: In total, 14 studies were included, 11 from European/Western PT and three from AM. About half of the studies were rated as being of sufficient quality. The most frequently studied plant was Petasites hybridus (butterbur), showing beneficial effects on immunological parameters, subjective symptoms, and nasal airflow. Beneficial immunological and clinical effects were also shown for an herbal preparation combining Citrus limonis (lemon) and Cydonia oblonga (quince). The medications examined by studies of sufficient quality were judged to be safe.

Conclusion: In summary, this systematic review highlights two herbal preparations, one from European/Western PT and one from AM, that appear to be promising options in the treatment of SAR.

Introduction: Asthma is associated with upper airway diseases and allergic diseases; however, the causal effects need to be investigated further. Thus, we performed this two-sample Mendelian randomization (MR) analysis to explore and measure the causal effects of asthma on allergic rhinitis (AR), vasomotor rhinitis (VMR), allergic conjunctivitis (AC), atopic dermatitis (AD), and allergic urticaria (AU).

Methods: The data for asthma, AR, VMR, AC, AD, and AU were obtained from large-scale genome-wide association studies summarized recently. We defined single-nucleotide polymorphisms satisfying the MR assumptions as instrumental variables. Inverse-variance weighted (IVW) approach under random-effects was applied as the dominant method for causal estimation. The weighted median approach, MR-Egger regression analysis, MR pleiotropy residual sum and outlier test, and leave-one-out sensitivity analysis were performed as sensitivity analysis. Horizontal pleiotropy was measured using MR-Egger regression analysis. Significant causal effects were attempted for replication and meta-analysis.

Results: We revealed that asthma had causal effects on AR (IVW, odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.74-2.14; p < 0.001), VMR (IVW, OR = 1.40; 95% CI, 1.15-1.71; p < 0.001), AC (IVW, OR = 1.65; 95% CI, 1.49-1.82; p < 0.001), and AD (IVW, OR = 2.13; 95% CI, 1.82-2.49; p < 0.001). No causal effect of asthma on AU was observed. Sensitivity analysis further assured the robustness of these results. The evaluation of the replication stage and meta-analysis further confirmed the causal effect of asthma on AR (IVW OR = 1.81, 95% CI 1.62-2.02, p < 0.001), AC (IVW OR = 1.44, 95% CI 1.11-1.87, p < 0.001), and AD (IVW OR = 1.85, 95% CI 1.42-2.41, p < 0.001).

Conclusions: We revealed and quantified the causal effects of asthma on AR, VMR, AC, and AD. These findings can provide powerful causal evidence of asthma on upper airway diseases and allergic diseases, suggesting that the treatment of asthma should be a preventive and therapeutic strategy for AR, VMR, AC, and AD.

Introduction: FOXO1 plays an important role in regulating immune processes that contribute to allergic inflammation; however, genetic variants influencing FOXO1 expression in AR pathogenesis remains unclear. This study aimed to investigate the functional effect of FOXO1 single nucleotide polymorphisms (SNPs) on AR development by performing genetic association and functional analysis studies.

Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We assessed the associations of FOXO1 transcript expression levels in peripheral blood mononuclear cells (PBMC) with AR phenotype, total nasal symptom score (TNSS), and SNP genotype in a sub-cohort of n = 658 individuals from the SMCSGES population. Associations of FOXO1 SNPs with AR were assessed in a cohort of n = 5,072 individuals from the SMCSGES population. In vitro promoter luciferase assay was used to evaluate the effect of AR-associated SNPs on FOXO1 promoter activity.

Results: FOXO1 transcript expression in PBMC was significantly associated with the risk of AR (p < 0.05) and TNSS among AR patients (p < 0.0001). We identified a significant association between tag-SNPs rs9549246 and FOXO1 transcript expression in PBMC from the SMCSGES sub-cohort and the multiethnic eQTLGen consortium (false discovery rate-adjusted p < 0.05). The minor allele "A" of tag-SNP rs9549246 was significantly associated with a higher risk of AR (p = 0.04422, odds ratio = 1.21, 95% confidence interval = 1.01-1.45) in the SMCSGES genotyping cohort (n = 5,072). In vitro luciferase assay showed the minor allele "A" of rs35594717 (tagged by rs9549246) was significantly associated with a higher FOXO1 promoter activity (p < 0.05).

Conclusion: FOXO1 transcript expression in PBMC has a strong association with the risk and symptom severity of AR. Genetic variants tagged by rs9549246 were shown to affect the expression of FOXO1 and contribute to the development of AR in the SMCSGES population.

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions.

Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients' symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed.

Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment.

Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments.

Introduction: A particularly aggressive course of chronic sinusitis with nasal polyps is seen in patients with bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). These patients often report exacerbation associated with consumption of foods reach in salicylates. Therefore, the authors analyzed the effect of a low-salicylate diet (LSD) on the course of chronic sinusitis with polyps in patients with NSAID-exacerbated respiratory disease (N-ERD) to answer the question: which patients would obtain the best therapeutic benefit?

Methods: Adult patients with N-ERD were selected for dietary intervention with LSD. Patients were seen on two occasions: at an initial visit and a follow-up after 12 weeks of diet. At both visits, an evaluation was performed with total nasal symptom score (TNSS) and modified Lund-Kennedy (L-K) endoscopy score.

Results: Forty patients (21 female, 52.5%, median and IQR of age 52; 43.5-61) used LSD for 12 weeks. Initial analysis of dietary intervention in the whole group revealed a significant decrease in TNSS and each symptom assessed separately, and the L-K score. The group was further divided into two subgroups based on the distance between NSAID intake and the beginning of symptoms: patients with immediate (n = 9; 22.5%) or non-immediate (n = 31; 77.5%) symptoms. The absolute change in nasal obstruction, itching, TNSS, and L-K scores were significantly higher in patients with immediate than with non-immediate symptoms.

Conclusion: Results of the study indicate that patients with N-ERD and immediate symptoms may clinically benefit more from an LSD as an additional therapeutic option than patients with non-immediate symptoms.

Background: Epithelial barriers, such as the lungs and skin, face the challenge of providing the tissues' physiological function and maintaining tolerance to the commensal microbiome and innocuous environmental factors while defending the host against infectious microbes. Asthma and allergic diseases can result from maladaptive immune responses, resulting in exaggerated and persistent type 2 immunity and tissue inflammation.

Summary: Among the diverse populations of tissue immune cells, CD4+ regulatory T cells (Treg cells) are central to controlling immune responses and inflammation and restoring tissue homeostasis. Humans and mice that are deficient in Treg cells experience extensive inflammation in their mucosal organs and skin. During past decades, major progress has been made toward understanding the immunobiology of Treg cells and the molecular and cellular mechanisms that control their differentiation and function. It is now clear that Treg cells are not a single cell type and that they demonstrate diversity and plasticity depending on their differentiation stages and tissue environment. They could also take on a proinflammatory phenotype in certain conditions.

Key messages: Treg cells perform distinct functions, including the induction of immune tolerance, suppression of inflammation, and promotion of tissue repair. Subsets of Treg cells in mucosal tissues are regulated by their differentiation stage and tissue inflammatory milieu. Treg cell dysfunction likely plays roles in persistent immune responses and tissue inflammation in asthma and allergic diseases.

Introduction: Previous studies have indicated a controversy regarding the association between dietary micronutrient concentrations and the risk of allergic diseases. In this study, we employed Mendelian randomization (MR) analysis using data from two samples to investigate the causal relationship between circulating micronutrient concentrations and three allergic diseases.

Methods: In this study, we considered 16 circulating micronutrients as exposure variables (beta carotene, calcium, copper, folate, iron, lycopene, magnesium, phosphorus, selenium, vitamin A1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and zinc); and three common allergic diseases (allergic asthma [AA], atopic dermatitis [AD], and allergic rhinitis [AR]) as outcomes. The inverse variance weighted (IVW) method was primarily applied for MR analysis, supplemented by MR-Egger and weighted-median methods to corroborate the IVW results; and sensitivity analysis was conducted to ensure the robustness of the MR assumptions.

Results: Our results revealed that an increase in serum phosphorus and zinc concentrations may diminish the risk of AA, while for AD an increase in serum zinc concentration may reduce the risk, but an increase in serum vitamin C concentration may elevate the risk. As for AR, an increase in serum phosphorus and selenium concentrations appeared to be associated with a reduced risk. We did not find evidence for an association between other micronutrients and the risk of allergic diseases.

Conclusion: Our study indicates that an increase in serum phosphorus and zinc concentrations may reduce the risk of AA, while an increase in serum zinc concentration may reduce the risk of AD, but an increase in serum vitamin C concentration may elevate the risk of AD. An increase in serum phosphorus and selenium concentrations is associated with a reduced risk of AR. This provides additional support for research on the effects of micronutrients on allergic diseases.

Introduction: Multiple antigen environmental sources have been identified as possible causes of allergies, but few studies have evaluated changes in the sensitization profiles over time. The aim of this study was to evaluate the changes in IgE sensitization and exposure to dust mites, cats, dogs, and cockroaches over a 10-year period.

Methods: During a period of 10 years among patients with asthma, rhinitis and/or atopic dermatitis, we evaluated the annual frequency of atopy to Dermatophagoides farinae, Dermatophagoides pteronyssinus, Blomia tropicalis, Canis familiaris, Felis domesticus and cockroaches (Periplaneta americana and Blatella germanica). Exposure to sources was also assessed using questionnaires (Pets) or direct counts (House dust mites and cockroaches). The association between some risk factors and the prevalence of atopy was explored.

Results: A total of 6,000 records were included. Among the patients, 82% had IgE sensitization to at least one of the six allergenic sources. Sensitization to Dermatophagoides spp. was the most frequent (>78%). Exposure and sensitization in the first decade of life to Dermatophagoides spp. seem to determine the molecular spreading to other allergenic sources. Exposure to Blomia tropical increases significantly over time (year 2015; 38% vs. year 2022; 51%, p 0.03). Exposure to dogs was higher than with cats but association between atopy and exposure was stronger with cats (OR 27.4, 95% CI: 22.3-33.6, p < 0.01).

Conclusion: Exposure and sensitization in the first decade of life to Dermatophagoides spp. determine the molecular spreading of IgE antibodies to other allergenic sources. Household exposure to dogs and cats seems to be important for the subsequent development of atopy. Sensitization to B. tropicalis and cockroach appears to be mostly from cross-reactivity rather than direct exposure.