Allergy Asthma and Clinical Immunology最新文献

Background: Circular RNA (circRNA) has the potential to serve as a crucial regulator in the progression of bronchial asthma. The objective of this investigation was to elucidate the functional dynamics of the circ_0070934/miR-199a-5p/Mannoside acetylglucosaminyltransferase 3 (MGAT3) axis in the development of asthma.

Methods: Circ_0070934, miR-199a-5p and MGAT3 in peripheral venous blood of 38 asthmatic patients and 43 healthy controls were detected by qRT-PCR, and the expression of MGAT3 protein was examined by ELISA. The GSE148000 dataset was analyzed for differences in MGAT3. The BEAS-2B cells were transfected with circ_0070934 plasmid and small interfering RNA, miR-199a-5p mimics and inhibitors. The apoptosis level was detected by flow cytometry and MGAT3 was detected by qRT-PCR and Western blot. The expression of E-cadherin, N-cadherin, Vimentin was examined by Western blot. Interleukin-4 (IL-4) and IL-13 were used to co-stimulate BEAS-2B cells as an asthmatic airway epithelial cell model. BEAS-2B cells exposed to type 2 cytokines (IL-4 and IL-13) were treated with circ_0070934 plasmid, and the expression of E-cadherin, N-cadherin, and Vimentin was detected by Western blot. The binding relationships were verified using dual-luciferase reporter assay and miRNA pull-down assay.

Results: The expression of circ_0070934 and MGAT3 in peripheral venous blood of asthmatic patients was down-regulated, and the expression of miR-199a-5p was up-regulated. And the expression of MGAT3 was reduced in sputum of asthma patients. Down-regulating the expression of circ_0070934 could promote apoptosis of BEAS-2B cells and increase epithelial-mesenchymal transition (EMT), and this effect can be partially reversed by down-regulating miR-199a-5p. Circ_0070934 could inhibit the process of epithelial mesenchymal transition induced by IL-4 and IL-13 in BEAS-2B cells. In addition, miR-199a-5p could respectively bind to circ_0070934 and MGAT3.

Conclusion: The findings of this study indicate that circ_0070934 may function as a competitive endogenous RNA (ceRNA) of miR-199a-5p, thereby modulating the expression of MGAT3 and impacting the process of EMT in bronchial epithelial cells. These results contribute to the establishment of a theoretical framework for advancing the prevention and treatment strategies for asthma.

Background: The poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients' costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests.

Methods: Thirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP.

Results: Twenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX. Api m 1+/Api m 2-/Api m 10- and Ves v 1+/Ves v 5+ demonstrated the most prevalent sensitizations patterns in our patients.

Conclusions: The molecular diagnosis of IgE-sensitization to Hymenoptera venoms can be valuable, especially in patients who show dual or triple-sensitization in skin tests, as the ALEX results revealed mono and double-sensitization to Hymenoptera venoms in 22 and 6 patients, respectively. Regarding the high cost and adverse reactions of venom immunotherapy, especially for two or three venoms, incorporating the molecular diagnosis alongside skin tests for accurate diagnosis of the culprit venom could help decrease costs for patients.

Background: While the impacts of atopic dermatitis (AD) on maternal and child sleep outcomes have been previously explored, less is known about the associations between infantile AD and sleep quality and quantity.

Objective: To describe the perceived causes of AD-associated maternal sleep disturbances and the association between AD severity and infant sleep outcomes.

Methods: Mothers with infants aged < 19 months old with a diagnosis of AD were recruited from social media and medical clinics in Winnipeg, Canada between October 2021 and May 2022. Infant AD severity was classified using maternal-reported data on the Patient-Oriented Scoring Atopic Dermatitis tool (PO-SCORAD). Quantitative data were collected via a series of questionnaires with a subset of mothers subsequently completing semi-structured interviews. Quantitative and qualitative data were integrated in the discussion.

Results: Mothers of infants with moderate/severe AD (6/12) were more likely to report their infant suffering from a higher degree of sleeplessness (i.e., ≥ 5 on a scale of 0-10) over the past 48 h compared to mothers of infants with mild AD (0/18). This was supported by qualitative findings where mothers described how their infant's sleep quality and quantity worsened with AD severity. Additionally, 7/32 mothers reported that their child's AD, regardless of severity, disturbed their sleep. Maternal sleep loss was most commonly attributed to infant itching (6/7), followed by worry (4/7).

Conclusion: Infantile AD severity was associated with worse sleep outcomes for both mothers and infants. We propose that maternal and infantile sleep quality and quantity can be improved by reducing AD severity through adherence to topical treatments.

Background: Correlations between mitochondrial DNA (mtDNA) and allergic rhinitis (AR) have not been reported before. This study aimed to better understand the mitochondrial genome profile with AR and to investigate the associations between AR in China and the mitochondrial genome at a single variant and gene level.

Methods: Mitochondrial sequencing was conducted on a total of 134 unrelated individual subjects (68 patients with AR, 66 healthy controls) at discovery stage. Heteroplasmy was analyzed using the Mann-Whitney U test. Sequence kernel association tests (SKAT) were conducted to study the association between mitochondrial genes and AR. Single-variant analysis was performed using logistic regression analysis and further validated in 120 subjects (69 patients with AR, 51 healthy controls). Candidate genes were further explored based on differences in mRNA and protein abundance in nasal mucosal tissue.

Results: In the discovery stage, 886 variants, including 836 SNV and 50 indels, were identified with mitochondrial sequencing. No statistically significant differences were identified for the mitochondrial heteroplasmy or SKAT analysis between these two groups after applying a Boferroni correction. One nonsynonymous variants, rs3135028 (MT8584.G/A) in ATP6, was related to a reduced risk of AR in both the discovery and validation cohorts. Furthermore, mRNA levels of MT-ATP6 in nasal mucosal tissue were significantly lower in AR individuals than in controls (P < 0.05).

Conclusions: In a two-stage analysis of associations between AR and mtDNA variations, mitochondrial gene maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.

Background: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP.

Material and method: In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1β, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov-Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant.

Results: The mean ± SD age of the studied groups was 37 ± 8.7 years old (21-50) for the AERD, and 40.4 ± 7.7 years old (31-52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups.

Conclusion: Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

Background: Asthma is a common respiratory illness affecting 2.8 million Canadians, including 9.7% of Albertans. Prior studies showed a substantial decrease in ED visits for asthma in the decade preceding 2010, followed by a stabilization. This was attributed to improvements in the pharmacologic and non-pharmacologic treatments for asthma during that period followed by a balance between epidemiologic drivers and protective factors in the population.

Methods: We assessed whether this trend continued in Alberta from 2010 to 2022 using population level data for the volume of daily ED visits, acuity of asthma exacerbations in the ED, and hospitalization rate.

Results: The mean number of ED visits decreased from 4.5 to 2.2 per million persons per day, but the acuity of exacerbations and the proportion requiring hospitalization increased. The number of patients presenting with the highest level of acuity increased by over 300%, and the percentage of patients requiring hospitalization increased from 6.8 to 11.3%.

Conclusion: Total ED visits for asthma exacerbations continues to decline in Alberta. The reasons for an increase in more severe exacerbations requires further attention.

Background: According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases.

Objective: The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association.

Methods: A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: "What is the prevalence of asthma in people with T1DM?" After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review.

Results: Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles.

Conclusion: The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren't as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist.

Background: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.

Case presentation: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.

Conclusions: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Background: The diagnosis of Alpha-gal Syndrome (AGS) is based on the presence of symptoms after being exposed to potential sources of alpha-gal together with values ​​of specific IgE (sIgE) to alpha-gal ≥ 0.1 kUA/L or ≥ 0.35 kUA/L. The aim of this study was to evaluate the diagnostic validity of sIgE levels to alpha-gal ≥ 0.1 kUA/L for identifying AGS.

Methods: This was a cross-sectional analysis of adult patients with available data on sIgE levels to alpha-gal, classified into two groups according to the presence (Group 1) or absence (Group 2) of symptoms after being exposed to potential sources of alpha-gal. Values of sIgE to alpha-gal ≥ 0.1 kUA/l were considered a positive result. A descriptive analysis of internal and external validity parameters was performed in the entire population and adjusted by sex.

Results: The study included 33 individuals in Group 1 and 65 in Group 2, with a mean age of around 47 years. The analysis of internal validity parameters revealed a high sensitivity, specificity, and positive probability ratio, with higher sensitivity in men and higher specificity in women. The analysis of external validity parameters showed a high negative predictive value and global value in all populations and both sexes. However, the positive predictive value was relatively high in men, but low in women.

Conclusions: Our results suggest that sIgE levels ≥ 0.1 kUA/L may be a useful tool for the diagnosis of AGS, although other factors and diagnostic techniques should also be considered.

Purpose: Determine whether variable extrathoracic airflow limitation (VEAL) is observed in patients with negative methacholine challenge tests (MCT).

Methods: Electronic medical records of patients undergoing MCT at Jesse Brown VA Medical Center between January 2017 and December 2019 were reviewed. Only patients with negative MCT were selected. Pertinent demographic, clinical, and pulmonary function tests (PFT) and MCT data were abstracted from each record. Spirometric flow-volume loops recorded during each test were inspected by one co-author to determine the first inhaled methacholine concentration at which FEF₅₀/FIF₅₀ was either > 1 or further increased if baseline FEF₅₀/FIF₅₀ after nebulized saline (vehicle) already exceeded 1. Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant.

Results: One hundred and twenty-seven consecutive patients with normal baseline PFT and negative MCT were identified. Thirteen patients (10.2%) had negative MCT and FEF₅₀/FIF₅₀ > 1 after testing. They were predominately obese (BMI, 31.3 ± 6.6), non-smoking (10), White (8) males (9) aged 51.3 ± 14.1 years (mean ± SD) referred for symptoms suggestive of asthma (n = 7) or for chronic cough (n = 6). Five had obstructive sleep apnea, three gastroesophageal reflux disease, and two chronic rhinosinusitis. FEF₅₀/FIF₅₀ increased significantly from 0.72 ± 0.21 after nebulized saline (vehicle) to 1.21 ± 0.13 after inhaled methacholine (p < 0.001). Median inhaled methacholine concentration eliciting these responses was 1.0 mg/mL (range, 0.25-16 mg/mL).

Conclusions: VEAL is observed in a subset of patients with a negative MCT. This phenomenon should be recognized and reported to the referring healthcare providers and its clinical significance addressed as indicated.