Allergy, Asthma & Immunology Research最新文献

Purpose: In the 'Itch-Scratch cycle', scratching manifests in various ways and further provokes skin inflammation and alteration of the skin microbiota. However, there is an unmet demand for classifying and interpreting scratching behavior. We analyze patterns of scratching behavior expressed by patients with chronic pruritus.

Methods: A survey was conducted on 206 adult patients with chronic pruritus for more than six weeks. Participants responded to a questionnaire about pruritus, including standard unidimensional-scale questions, as well as individualistic questions about sensory expression and quality of life. For scratching behavior, all patients answered questions about patterns, tools, situations, time spent, and scratched areas. Exploratory factor analysis was conducted to classify scratching behavior. Descriptive and exploratory factor analyses were used to identify the structure of the underlying factors measured by the questionnaire items.

Results: Among pruritic descriptors, 'unbearable' was the most common (84.5%). Of 206 participants, 190 (92.2%) responded that they scratched. The most common itch resolution methods were 'applying moisturizer', 'rubbing', and 'applying ointment'. The fingernails (89.3%) were the most frequently reported tool used for scratching. Participants reported most frequent scratching during sleep or rest. Among the pruritus-specific quality-of-life indicators, 'Lifelong' was the most stressful item related to all scratching behaviors. Regarding scratching differences by disease, patients with prurigo showed shorter scratching time with abnormal and aggressive behavior.

Conclusions: We analyzed scratching behavior patterns in patients with chronic pruritus. Our findings support the need for education on the importance of applying moisturizer before sleep. The results are also important for helping patients with prurigo correct their abnormal and aggressive scratching behavior patterns, which can reduce quality of life and worsen symptoms.

Purpose: Immunoglobulin E (IgE) induces mast cell/basophil activation by binding with FcεRIα and contributes to the development of allergic disease, in which targeting IgE has been considered an effective therapeutic strategy. YH35324 (YH) is a new hybrid protein with an extracellular domain consisting of FcεRIα, and its pharmacodynamic effect and safety were validated. This study aimed to evaluate the therapeutic potential of YH as an anti-IgE immunomodulator compared with omalizumab (Oma).

Methods: To evaluate the in vitro efficacy of YH in human mast cells, YH was treated with various methods, and the changes were confirmed through flow cytometry, immunoblot analysis, and immunocytochemistry. To evaluate the ex vivo efficacy of YH, the expression of FcεRIα on the surface of blood basophils was measured in 64 subjects with allergic diseases by flow cytometry. Serum soluble FcεRIα, CD23, and Mas-Related G-Protein Coupled Receptor Member X2 levels were measured by enzyme-linked immunosorbent assay.

Results: The YH-administered group exhibited significantly lower expression of FcεRIα on peripheral basophils compared to the Oma-administered group up to 14 days post-administration. YH directly suppressed FcεRIα expression on the surface of LAD2 cells, as it was bound to IgE-unbound FcεRIα and migrated into the cells by actin-dependent endocytosis, then was recycled by FcRn binding in the lysosome in vitro. Serum soluble FcεRIα levels were increased in the YH-administered group compared to the other groups and showed a positive correlation with serum-free IgE.

Conclusions: YH represents a new therapeutic agent for IgE-mediated allergic disease. Further studies are needed to evaluate its additional effects on the FcεRIα-mediated autoimmune mechanism.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting both children and adults, characterized by pruritus, eczematous lesions, and compromised skin barrier function. A key feature of AD is dysbiosis of the skin microbiome, marked by reduced microbial diversity and the overgrowth of Staphylococcus aureus in lesional skin. S. aureus exacerbates skin barrier dysfunction and immune dysregulation, leading to recurrent infections and disease flares. In contrast, commensal bacteria such as Staphylococcus epidermidis and Roseomonas mucosa may exert protective effects by inhibiting S. aureus colonization and modulating immune responses. Beyond microbial composition, microbial metabolites play a crucial role in AD pathophysiology. Short-chain fatty acids, indole derivatives, and other bacterial metabolites influence cutaneous immune responses, lipid metabolism, and skin barrier integrity. Altered metabolite profiles, including reduced levels of beneficial microbial metabolites, are associated with AD severity and disease progression. Notably, S. aureus overabundance correlates with disruption in lipid metabolism, further compromising the skin barrier. This review explores recent advances in understanding the relationship between microbial metabolites and AD pathogenesis and examines the therapeutic potential of microbiome-targeted interventions. Strategies such as probiotics, prebiotics, and topical microbiome transplantation aim to restore microbial diversity and rebalance metabolite production, ultimately improving clinical outcomes in AD patients. Future therapeutic approaches focusing on commensal-derived metabolites offer promising avenues for alleviating symptoms and modulating disease severity in AD.

Purpose: This study aimed to delve into the bidirectional and temporal relationship between depression, allergic rhinitis (AR) and chronic rhinosinusitis (CRS).

Methods: A total of 17,028 participants from the Korean National Health and Nutritional Examination Survey, surveyed in 2016, 2018, and 2020, were included in this study. Participants' medical histories were used to determine their depression, AR and CRS status, as well as the age at diagnosis. Logistic regression analyses were conducted to reveal the associations between AR/CRS and depression. Subgroup analysis was performed considering various clinical characteristics.

Results: Regardless of occurring independently or coexisting, AR and CRS consistently preceded the diagnosis of depression. The prevalence of depression was higher among patients with AR and CRS, and similarly, the prevalence of AR and CRS was elevated among patients with depression (all P < 0.001). Depression was associated with increased odds of AR (odds ratio [OR], 1.646; 95% confidence interval [CI], 1.309-2.071; P < 0.001) and CRS (OR, 1.882; 95% CI, 1.427-2.416; P < 0.001). Similarly, AR (OR, 1.613; 95% CI, 1.278-2.036; P < 0.001) and CRS (OR, 1.869; 95% CI, 1.415-2.467; P < 0.001) were both associated with heightened odds of depression.

Conclusions: The study findings indicated a bidirectional and complex association between depression and AR/CRS, emphasizing the importance of early detection and intervention.

Purpose: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a phenotype of bronchial asthma that is characterized by a severe course and the presence of chronic rhinosinusitis (CRS) with nasal polyps. MicroRNAs (miRNAs) belong to a family of small, non-coding RNAs whose primary function is to regulate gene transcription. The aim of this study was to determine the miRNA profile and to validate selected miRNAs in biological material from the upper respiratory tract collected with a minimally-invasive method in patients with N-ERD.

Methods: The miRNA profile was assessed in subjects with N-ERD, CRS, and allergic asthma (AA), as well as healthy controls (HCs), using microarray technique. Following this, 6 miRNAs were validated using reverse transcription polymerase chain reaction in 77 subjects.

Results: The profiling identified 23 miRNAs whose expression significantly differed between patients with N-ERD and HCs. Based on these results, 6 miRNAs were selected for further validation. It was found that patients with N-ERD had significantly different expressions of miR-34a-5p and miR-22-5p compared to those with AA. In the whole study group, significant correlations were found between miR-7d-3p/miR-34a-5p/miR-22-5p and the presence of blood eosinophilia (r = 0.25, r = 0.28 and r = 0.26, for all P < 0.05). Forced expiratory volume in 1 second/forced vital capacity was correlated with miR-149a-5p expression (r = 0.27, P < 0.05).

Conclusions: The results indicate that the miRNA profile in nasal mucosal lining fluid of patients with N-ERD differs from patients with AA, CRS, and compared to HCs. Some of the miRNAs selected on the basis of profiling may be involved in the regulation of eosinophilic inflammation in the respiratory tract. Our findings suggest that specific miRNAs may be considered as potential biomarkers of N-ERD.

Purpose: Platelet-activating factor (PAF) mediates nasal congestion and rhinorrhea by affecting vascular permeability, but the underlying mechanisms remain unclear. Here, we sought to explore the effect of PAF on the nasal epithelial barrier in chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods: Human nasal epithelial cells (hNECs) were pre-treated with Apafant, a PAF receptor (PAFR) inhibitor, or MCC950, an NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor, before PAF stimulation. The nasal epithelial barrier function was assessed by measuring the transepithelial electrical resistance (TER) and sodium fluorescein flux. Additionally, the expression of mRNAs and proteins of tight junctions were assessed.

Results: PAF significantly decreased TER and enhanced the fluorescein flux permeability in air-liquid interface cultures of hNECs, while also downregulating the expression of ZO-1, occludin, claudin-1, and claudin-4. However, the disruptive effect of PAF on the nasal epithelial barrier was attenuated by MCC950, but not by Apafant. Furthermore, MCC950 inhibited PAF-induced NLRP3 activation and its downstream molecules, including caspase-1, ASC, interleukin (IL)-1β, and IL-18.

Conclusions: Our findings indicate that PAF has the potential to disrupt the nasal epithelial barrier in CRSwNP and may be linked to NLRP3 activation, while PAFR is not essential for this process. This discovery helps to explain why PAFR antagonists are ineffective in blocking PAF-mediated inflammation in clinical settings.

Ambient air pollution poses a significant yet manageable threat to human health. The growing consensus on the impact of ambient air pollutants on allergic rhinitis (AR) emphasizes the importance of prevention, control, and treatment strategies. A multidisciplinary consensus development group was established to further standardize management strategies for AR in the presence of exposure to ambient air pollutants. The quality of the evidence and the strength of the recommendations were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) system based on domestic and international relevant medical evidence. This consensus evaluates the effects of key air pollutants on public health in relation to AR, including the synergistic effects of air pollutants with meteorological conditions and aeroallergens. At the same time, the consensus provides recommendations for targeted therapeutic and preventive measures for AR under conditions of ambient air pollution, aiming to improve AR-related health outcomes. These recommendations aim to increase public and clinical awareness of the contribution of environmental factors to AR, and offer evidence-based insights for policymakers and regulators to establish informed ambient air quality standards.

This study aimed to identify recent changes of AIT treatment behaviors in real-world clinical practice using a questionnaire survey in Korea. The questionnaire on AIT prescriptions and practical experiences was distributed to all members of the Korean Academy of Asthma Allergy and Clinical Immunology in June 2022. The responses were analyzed and compared with the results from 2009 and 2017. In total, 115 responses (10.1%) were collected; 58 (50.4%) from internal medicine, 34 (29.6%) from pediatricians, and 21 (18.3%) from otolaryngologists. The prescription rate for subcutaneous immunotherapy (SCIT) was 53.8%, showing a decrease from those in 2009 and 2017; however, that for sublingual immunotherapy (SLIT) increased steadily, reaching 17.9% in 2009, 40.3% in 2017, and 46.2% in 2022. The prescription rates for asthma and atopic dermatitis increased by 4.6% and 7.9%, respectively. The most frequently prescribed allergens for SCIT in 2022 were house dust mites (32.9%), pollen (30.6%), and animal dander (28.2%), with the rate for animal dander showing a significant increase from 10.3% in 2009. Most physicians (93%) used mixed allergens for SCIT, with 42.8% using a combination of 5 or more allergens. Fifty-eight (67.4%) respondents reported cases of anaphylaxis during SCIT and 36.2% reported systemic adverse reactions during SLIT. In conclusion, SLIT prescriptions, AIT for asthma and atopic dermatitis, and AIT with animal dander increased significantly from 2009 to 2022. Serial surveys of AIT practices are helpful in identifying the changes of real-world clinical practice of AIT.

Purpose: The rising prevalence of food allergy (FA) has prompted investigations into dietary factors such as trans fatty acids (TFAs). While ruminant TFAs may protect against allergies, the role of industrial TFAs remains unclear. This study evaluated the effects of industrial TFAs on FA in a murine model.

Methods: 20 Balb/c mice were divided into 4 groups: control (standard diet), OVA (ovalbumin-sensitized, standard diet), TFAs (industrial TFA-enriched diet), and TFAs+OVA (TFA diet + OVA sensitization). After two weeks, OVA and TFAs+OVA groups underwent OVA sensitization/challenge. Symptoms (anal temperature drop, diarrhea), serum immunoglobulin E (tIgE, OVA-sIgE), cytokines, immune cell profiles, and gut microbiota were analyzed.

Results: The incidence rates of anal temperature drop and diarrhea, the serum levels of tIgE, OVA-sIgE, interleukin-4 were significantly higher in the OVA and TFAs+OVA groups compared to the control group. The TFAs+OVA group had a higher degree of anal temperature drop and diarrhea score, and higher serum levels of tIgE and OVA-sIgE compared to the OVA group. The expression of interferon-γ mRNA and the numbers of Th1 cells increased in the spleen of the TFAs and TFAs+OVA group compared to the control group, whereas the numbers of spleen Th2 cells were significantly elevated in the TFAs, OVA, and TFAs+OVA groups compared to the control group. In addition, the numbers of mast cells (MCs) in the esophagus and intestinal mucosa, and the serum concentrations of MCs protease-1 were significantly increased in TFAs, OVA, and TFAs+OVA groups compared to the control group. Cecal microflora among these groups exhibited distinct patterns of differential diversity and composition.

Conclusions: Industrial TFAs may promote OVA-induced FA, Th1 and Th2-associated inflammation in mouse model, accompanied by the activation of MCs and intestinal microbiome dysbiosis.

Background: Asthma-bronchiectasis overlap (ABO) encompasses heterogeneous manifestations, which may predict distinct clinical outcomes. We sought to identify the clinical phenotypes of ABO and compare them to asthma alone or bronchiectasis alone.

Methods: In this retrospective cohort study, we extracted electronic medical records from 292 inpatients with ABO, 901 inpatients with asthma alone, and 1,192 inpatients with bronchiectasis alone who were hospitalized between 2015 and 2020. We phenotyped ABO using 2-step unsupervised clustering analysis by using an independent cohort (n = 76).

Results: Compared to asthma or bronchiectasis alone, ABO exhibited greater disease severity and worse clinical outcomes. We identified 3 ABO phenotypes: asthma-dominant ABO (ABO-A, n = 100) with more prominent asthma symptoms; bronchiectasis-dominant ABO (ABO-B, n = 89) with more pronounced features of bronchiectasis; and co-existence of asthma and severe bronchiectasis (ABO-S, n = 103) with worse clinical outcomes. Compared to ABO-B, both ABO-A and ABO-S were associated with significantly higher blood neutrophil ratios (55.8% vs. 59.1% vs. 64.4%, P < 0.001), poorer lung function (FEV1% predicted: 79.1% vs. 67.5% vs. 50.1%, P < 0.001), longer hospital stay (6.0 vs. 7.0 vs. 7.0 days, P = 0.004), and higher risks of hospitalization within the next 2 years (ABO-A: hazards ratio [HR], 3.76, 95% confidence interval [CI], 1.12-12.62, P = 0.032; ABO-S: HR, 4.05, 95% CI, 1.14-14.36, P = 0.031).

Conclusions: The radiologic severity of bronchiectasis and the use of systemic corticosteroids can identify the clinical phenotypes of ABO. The heterogeneity of clinical manifestations may help formulate personalized management strategies and predict the prognosis of ABO.