Search Results (88)

Background/Objectives: Asthma, a chronic airway inflammatory disease characterized by bronchial narrowing and caused by an inflammatory response, results in airway obstruction and hyperresponsiveness. Stachydrine (STA), an abundant metabolite found in plants and humans, is recognized for its bioactivity in treating fibrosis, cancer, and inflammation. However, its effects on asthma have not been fully elucidated. We aimed to investigate the ameliorating effects of STA on chronic airway inflammation caused by Dermatophagoides pteronyssinus (house dust mite, HDM). Methods: We used a murine model of HDM-induced airway inflammation to assess the change in metabolite profile by chronic airway inflammation. The mice were challenged with HDM (35 challenges in total) for up to 12 weeks. Serum metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Results: HDM exposure increased airway hypersensitivity, immune cell infiltration, cytokine production, goblet cell hyperplasia, collagen deposition, and alpha smooth muscle actin and fibronectin expression. Serum metabolite analysis revealed that STA levels were lower in the mice with HDM-induced chronic inflammation than in the controls. In vitro analyses demonstrated that HDM sensitization increased cytokine production (interleukin [IL]-6 and IL-8) and extracellular signal-regulated kinase (ERK) activity. However, STA treatment reduced HDM-induced IL-6 and IL-8 production and ERK activity. Co-treatment with a mitogen-activated protein kinase (MAPK) inhibitor and STA resulted in a more pronounced reduction in cytokine production and MAPK activity. Conclusions: These findings suggest that STA, particularly when used in combination with a MAPK inhibitor, effectively suppresses airway inflammation through ERK pathway inhibition, making it a potential therapeutic agent for asthma treatment. Full article

House dust mites (HDMs) are a major source of indoor allergens, significantly contributing to allergic rhinitis, asthma and atopic dermatitis. This review examines the epidemiology, microbiological classification and pathophysiology of HDM allergy, highlighting key allergens such as Der p 1, Der p 2 and Der p 23. Furthermore, we discuss the pivotal role of allergen-specific immunotherapy (AIT), the only disease-modifying treatment for immunoglobulin (Ig)-E disease. Recent studies have identified predictive biomarkers for allergen-specific immunotherapy (AIT) efficacy, including the specific IgE to total IgE (sIgE/tIgE) ratio and regulatory follicular T cell profiles, supporting a more personalized approach to therapy. Additionally, emerging immunotherapy strategies, such as recombinant allergens and peptide-based formulations, aim to improve safety and clinical outcomes. As HDM allergy prevalence rises globally, further research into optimizing diagnostics and treatment strategies remains crucial for enhancing patient care. Full article

(1) Background: Respiratory allergens, particularly ragweed (RW) pollen and house dust mites (HDMs), are major triggers of respiratory inflammation and allergic diseases. This study investigated the impact of single- versus combined-allergen exposure on the barrier function of normal human bronchial epithelial (NHBE) cells cultured at the air–liquid interface (ALI). (2) Methods: NHBE cells were exposed to RW pollen extract (200 µg/mL), HDM extract (200 µg/mL) and their combination at varying concentrations (200 µg/mL, 100 µg/mL, 50 µg/mL, 25 µg/mL). Additional groups included a mixture of Amb a 1, Amb a 11 and Amb a 12 (100 mg/mL) and combinations of Der p 1 with the ragweed allergens (50 mg/mL, 100 µg/mL). Transepithelial electrical resistance (TEER) was recorded over 72 hours to assess barrier integrity, and immunofluorescence (IF) staining for zonula occludens-1 (ZO-1) was performed to evaluate tight junction alterations. (3) Results: TEER measurements showed a significant reduction in epithelial barrier integrity following allergen exposure, with the most pronounced disruption observed with the combined exposure to RW and HDM groups. IF staining confirmed extensive tight junction damage, highlighting their synergistic impact. (4) Conclusions: These findings emphasize the importance of assessing cumulative allergen effects, as combined exposure may exacerbate epithelial dysfunction and represent a key aspect in the management of allergic rhinitis and asthma. Full article

Asthma, a chronic airway disease, is marked by allergic inflammation, hyperresponsiveness, and tissue remodeling. Influenza infections in asthma patients can cause severe exacerbations, though the underlying mechanisms remain unclear. This study investigated how pre-existing allergic inflammation affects immune responses to influenza infection in mice exposed to house dust mite (HDM). Mice were repeatedly exposed to HDM, followed by infection with the influenza A virus, and were sacrificed three days post-infection. Plasma was analyzed for HDM-specific immunoglobulins, while lung tissue was used for immune cell flow cytometry and RNA sequencing analysis. HDM exposure induced allergic inflammation, evidenced by more HDM-specific IgE, IgG1, IgG2, eosinophils, neutrophils, Th1, and Th17 cells compared to controls. Upon influenza infection, the effects of HDM and influenza co-infection interacted, showing fewer Th1 cells and regulatory T cells and more Th2 cells compared to mice exposed to the influenza virus alone. Interestingly, RNA-seq analysis revealed less upregulation of Th1-related genes and antiviral pathways in co-exposed mice, suggesting impaired Th1 immunity and antiviral responses. Pre-existing allergic inflammation significantly altered immune responses in mice co-infected with influenza, revealing underdeveloped antiviral responses as early as three days post-infection. These findings may explain the increased susceptibility of patients with asthma to severe viral diseases. Full article

Asthma, a chronic inflammatory airway disease, leads to airflow obstruction and exhibits sex differences in prevalence and severity. Immunomodulatory diets, such as the ketogenic diet (high fat, low carbohydrate, moderate protein), may offer complementary benefits in managing airway inflammation. While anti-inflammatory effects of ketogenic diets are documented in cardiovascular diseases, their impact on asthma, especially regarding sex-specific differences, remains unexplored. Few studies on diet and asthma have considered sex as a biological factor. To test the hypothesis that a ketogenic diet affects airway inflammation in a sex-specific manner, we used a mouse allergic airway inflammation model. Male and female C57BL/6J mice (3–4 weeks old, n = 5–6/group) were fed a ketogenic diet or normal chow for 12 weeks. From weeks 7 to 12, mice were challenged intranasally with house dust mite allergens (HDM) 5 days/week to induce airway inflammation. Lung tissue was analyzed 72 h post-exposure using flow cytometry to assess immune cell populations, and data were analyzed with two-way ANOVA. The ketogenic diet increased body weight in allergen-exposed mice, with a greater effect in males than females (p = 0.0512). Significant sex–diet interactions were noted for alveolar macrophages, CD103⁺, CD11B⁺, and plasmacytoid dendritic cells (p < 0.05). Eosinophil reductions were observed in males but not females on the ketogenic diet. The diet also increased NKT cells and decreased NK cells in males but not females (p < 0.001). These findings highlight sex-specific effects of ketogenic diets on lung immune responses, with stronger impacts in males. Full article

Chronic Rhinosinusitis (CR) is a common inflammatory condition with complex pathophysiology involving multiple interleukins. In times of precision medicine, it is mandatory to cluster our patients to offer the best tailored treatment with the lowest cost possible. Therefore, some triage markers can be used towards this goal, without raising much financial burden. The aim of this study was to identify the association of staphylococcal enterotoxin (SE)-specific IgE of types A, B, C, and TSST-1 (toxic shock syndrome toxin-1); and total IgE (tIgE) and specific IgE for Dermatophagoides pteronyssinus (DP), Dermatophagoides farinae (DF), and Blomia tropicalis (BT) in Brazilian patients with CRSwNP. Thirty-six patients with CSRwNP were analyzed for serum IgE levels: tIgE and specific IgE for: DP, DF, BT, and SE types A, B, C, TSST-1 by ImmunoCAP^®. The mean value of tIgE in SE-specific IgE-positive patients was 767 IU/mL and in house-dust-mite (HDM)-positive patients, the mean tIgE was 319 IU/mL (p < 0.005). A total of 86% of patients who had high tIgE levels but were SE-specific IgE-negative had positive specific IgE for at least one of the HDMs tested. The Fisher exact test statistic value for this association was significant (p < 0.05/p = 0.014). We found an association between high levels of tIgE and SE-specific IgE in patients with CRSwNP, possibly related to local and peripheric polyclonal IgE production. The mean value of tIgE—with a suggested cutoff point of tIgE levels of 767 IU/mL—can be used as a triage biomarker for positive SE-specific IgE in CRSwNP patients. Full article

House dust mites (HDM) are the world’s most important cause of allergic asthma. It is unclear why some patients with HDM allergy develop an early asthmatic reaction (EAR) only, whereas others react with a dual asthmatic reaction—EAR plus late asthmatic reaction (LAR). In patients with LAR, the symptoms and bronchial inflammation are more severe, and the current knowledge suggests that the EAR always precedes the LAR. The aim of the present study was to investigate whether a LAR can occur separately even without a significant EAR. In a pilot study of 20 patients with asthma and HDM allergy, a bronchial allergen challenge (BAC) was performed on three separate occasions with a tapered allergen dose. Before and 24 h later, exhaled NO (eNO), eosinophils and miRNAs were measured as markers of bronchial inflammation. Compared to BAC1, at BAC2 there was a significant decrease in the EAR from mean 39.25 ± 13.37% to mean 33.55 ± 5.25% (p < 0.01), whereas the LAR remained unchanged: mean 28.10 ± 10.95% to mean 30.31 ± 7.77% (n.s.). At BAC3, both the EAR and the LAR were significantly attenuated compared to the first and second BAC. In 3 (15%) patients, even the tapered allergen dose induced a dual asthmatic reaction. In 10 (50%) patients, the allergen dose was too low to trigger a significant EAR and LAR. In 7 (35%) patients, there was no EAR, but a significant LAR (mean max fall FEV1 20.5 + 4.7%) recorded. Significant correlations (p < 0.05) were found between distinct miRNAs (miR-15a-5p, miR-15b-5p and miR-374a-p5), eNO, and the decline in lung function and the presence of a LAR (p < 0.01). We can demonstrate that a LAR is induced in some patients without an EAR to low allergen exposure. This leads to a strong inflammatory reaction with an increase in eNO and a decrease in FEV1 and distinct miRNAs. Accordingly, these individuals are at greater risk of asthmatic symptoms and remodeling with loss of lung function than patients who do not have a LAR. Full article

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV₁ > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV₁ ≥ 20% (PC₂₀) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV₁ from post-diluent baseline during 0–3 h and 3–8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV₁ and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV₁ % predicted did not differ between MR and DR at baseline, but DR had lower median PC₂₀M (0.84 (range 0.07–7.51) vs. MR (2.15 (0.53–11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV₁), the maximal % change from baseline following M and HDM challenge were correlated. PC₂₀M was inversely correlated with the % change in FEV₁ and the % change in Xrs5 during the LAR (r= −0.443; p = 0.0018 and r= −0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease. Full article

Der p1 is one of the major allergens causing house dust mite (HDM) allergy. Pathological Der p1-specific B cells play a key role in allergic inflammation as producers of allergen-specific antibodies. Crosslinking the inhibitory FcγRIIb with the B cell receptor triggers a high-affinity suppressive signal in B cells. Selective elimination of allergen-specific cells could potentially be achieved by administering chimeric molecules that combine, through protein engineering, the FcγRIIb-targeting monoclonal 2.4G2 antibody with the epitope-carrying Dp52–71 peptides from Der p1. We tested this hypothesis, in a chronic mouse model of HDM allergy induced in BalB/c mice, using FACS and ELISA assays, along with histopathological and correlational analyses. Dp52–71chimera treatment of HDM-challenged mice led to a decrease in serum anti-HDM IgG1 antibodies, a reduction in BALF β-hexosaminidase levels, a lowered number of SiglecF^high CD11c^low eosinophils, and an improved lung PAS score. Furthermore, we observed overexpression of FcγRIIb on the surface of CD19 cells in the lungs of HDM-challenged animals, which negatively correlated with the levels of lung alveolar macrophages, neutrophils, and BALF IL-13. Taken together, these results suggest that the use of FcγRIIb overexpression, combined with the expansion of chimeric protein technology to include more epitopes, could improve the outcome of inflammation. Full article

Asthma is a chronic lung disease characterized by airway inflammation, hyperresponsiveness, and narrowing, with a risk of life-threatening attacks. Most current treatments primarily consist of inhalable steroids, which are not without adverse effects. Recently, there has been growing interest in alternative approaches to asthma management. In this study, we investigated the anti-asthmatic effects of the non-steroidal compound CycloZ using acute and chronic mouse models of asthma. Allergic reactions were induced with house dust mite (HDM) extract, and CycloZ or fluticasone propionate (FP) was administered orally or intranasally, respectively. CycloZ significantly ameliorated the HDM-induced robust expression of Th2 cytokines in both models. CycloZ also decreased immune cell infiltration into the lungs and reduced IL-4 and IL-13 cytokine levels in bronchoalveolar lavage fluid (BALF). Moreover, CycloZ greatly attenuated the activation of the TLR-4 pathway, which is involved in HDM recognition and signaling. The beneficial effects of CycloZ were comparable to or even superior to the current steroid treatment, FP, suggesting that CycloZ could be a promising new option for asthma therapy. Full article

Background: Sublingual immunotherapy (SLIT) has shown promise in mitigating allergic asthma symptoms; nevertheless, its high dose and prolonged duration of treatment raise safety concerns. This study explored the potential of Lactobacillus paracasei (L. paracasei) to enhance the effectiveness of SLIT in a mouse model of allergic asthma. Methods: Allergic asthma was induced in Balb/c mice following sensitization and challenge with a house dust mite (HDM) allergen. Subsequently, the mice were subjected to SLIT (66 and 132 µg) either alone or in combination with L. paracasei supplementation. Asthma-associated parameters, including rubbing frequency, IgE level, cytokine profiles, and histological changes, were evaluated to assess treatment efficacy. Results: mice that received SLIT 132 µg combined with the probiotic (combined 132) demonstrated a significant reduction in allergic symptoms (rubbing). This treatment strategy led to a marked IgE and eosinophil level decrease in serum; an increase in anti-inflammatory cytokines like IFN-γ and IL-10; and a reduction in pro-inflammatory cytokines IL-17 and TNF-α. The combination therapy also mitigated lung inflammation and supported the restoration of the structural integrity of the colon, promoting the recovery of goblet cells and mucus secretion. Probiotic treatment alone also effectively reduced IgE levels, increased IFN-γ, and decreased levels of IL-17 and TNF-α. Conclusions: The adjuvant effect of L. paracasei in enhancing SLIT represents a promising approach for improving asthma treatment efficacy. Full article

Background and Objectives: Allergy to dust mites (HDMs) plays an important role in atopic dermatitis (AD). However, the role of this allergy in other dermatoses is little known. The aim of this study was to assess hypersensitivity to HDMs in patients with AD or hand disease using the basophil activation test. Material and Methods: A total of 52 patients with AD, 57 with hand eczema disease, and 68 healthy volunteers qualified for this study. Diagnosis was based on the Hanifin and Rajka criteria, dermatological assessment, and exclusion of other dermatoses. The participants underwent skin prick tests (SPTs), a basophil activation test (BAT) with D. pteronyssinus allergen extract, and the concentration of specific IgE (sIgE) for the same allergen in blood serum was determined. Results: Positive results in all tests (SPT, sIgE, and BAT) were obtained (24 (46.2%) patients with AD, 9 (15.8%) with hand disease, and none in the control group for p < 0.05). The results of the SPT, sIgE, and BAT correlated with each other in the AD and hand eczema groups (Spearmen correlation test, r = 0.72 or 0.85, p < 0.05). However, the BAT was positive more often than the SPT and sIgE for D. pteronyssinus. Conclusions: House dust mite hypersensitivity is common in patients with AD and eczema. The BAT may be more sensitive for assessing sensitization to house dust mites, especially in patients with hand eczema. Full article

The aim of this study was to optimize a basophil activation test in the detection of allergy to the house dust mite Dermatophagoides pteronyssinus in children with allergic respiratory diseases. This study involved 32 cases, 13 girls and 19 boys aged 4–17 years, with perennial asthma or allergic rhinitis caused by D. pteronyssinus. The control group consisted of 13 girls and 19 boys aged 4–17 years with seasonal allergic asthma or rhinitis provoked by Timothy or birch pollen. House dust mite (HDM) allergy was excluded in the controls based on their medical history, skin prick test (SPT) results and sIgE determination. In all patients, a basophil activation test (BAT) was performed with five dilutions of D. pteronyssinus allergen (the dilution series ranged from 22.5 to 0.00225 ng/mL). The results were analyzed by using the receiver operating characteristics (ROC) to determine the optimal allergen concentrations, outcome measures and cut-off points that would differentiate most accurately between HDM-allergic and non-allergic patients. As a “gold standard”, criteria for allergen-specific immunotherapy with D. pteronyssinus or respective pollens were applied by an experienced pediatric allergist following the guidelines of the European Academy of Allergy and Clinical Immunology. The highest diagnostic efficiency was yielded by the protocol assuming a cut-off value of 9.76% activated basophils after activation with a single allergen concentration of 2.25 ng/mL (sensitivity 90.6%, specificity 100%). This protocol yielded 3 (4.7%) misclassifications, all false negative, when compared with the “gold standard”. There was a strong correlation with the BAT results at 22.5, 2.25 and 0.225 ng/mL (respectively r = 0.90 and r = 0.78, p < 0.001), as well as between the BAT at 2.25 ng/mL and SPT (r = 0.82, p < 0.001) and between the SPT and sIgE levels (r = 0.78, p < 0.001). High cross-reactivity between D. pteronyssinus and D. farinae was confirmed based on the BAT at 22.5 ng/mL (r = 0.82, p < 0.001). In conclusion, the BAT showed very good concordance with the result of a meticulous process of decision-making that combined validated allergy tests (SPT, sIgE) with expert guidelines, specialist knowledge and experience. Facing the risk of the incorrect qualification of patients for costly, long-lasting and potentially risky allergen-specific immunotherapy, the inclusion of a basophil activation test into diagnostic process seems fully justified. Full article

As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3⁺ regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications. Full article

Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency. Full article