Allergy Asthma and Clinical Immunology最新文献

Background: Despite significant advances in understanding the epigenetic landscape of chronic rhinosinusitis (CRS), the specific microRNAs (miRNAs) with a causal role in CRS pathogenesis remain unclear.

Objective: This study aims to identify miRNAs that causally contribute to CRS and to elucidate their clinical relevance and underlying molecular mechanisms.

Methods: We employed Mendelian randomization (MR) analysis, leveraging mirQTLs as exposure variables and two independent CRS datasets as outcomes, to identify miRNAs causally linked to CRS. Robustness of the findings was ensured through multiple sensitivity analyses. The expression levels of identified CRS-associated miRNAs were validated using qRT-PCR, and their diagnostic potential was assessed through ROC curve analysis. Target genes and potential pathways regulated by the causal miRNAs were predicted via MiRNet and enrichment analyses, followed by experimental validation using western blotting and immunohistochemistry.

Results: MiR-130a-3p and miR-196b-5p were significantly associated with an increased risk of CRS, while miR-339-3p was associated with a decreased risk. These associations were confirmed by qRT-PCR, and no evidence of pleiotropy or heterogeneity was observed. ROC analysis revealed diagnostic potential for these miRNAs in CRS. Enrichment and experimental analyses suggested that the MAPK and PI3K-AKT pathways are predominantly activated by the target genes of the positively and negatively associated miRNAs, respectively.

Conclusions: MiR-130a-3p and miR-196b-5p are positively associated with CRS risk, whereas miR-339-3p is protective. These miRNAs represent promising diagnostic biomarkers and therapeutic targets for CRS. The MAPK and PI3K-AKT pathways likely mediate the effects of these causal miRNAs, offering further insight into the molecular mechanisms underlying CRS.

Background: Severe asthma and moderate-to-severe atopic dermatitis can significantly impact the lives of children and adolescents. However, real-world data on pediatric patients' perceptions of their medication are limited.

Methods: This non-interventional cross-sectional study at a university hospital explored patients' perceptions. We included patients aged between 6 and 17 with severe asthma and/or moderate-to-severe atopic dermatitis. For patients treated with dupilumab, a minimum dupilumab treatment duration of 16 weeks was required. We conducted one structured interview per patient, based on a questionnaire consisting of open questions and ratings on 6-point Likert scales (response scale range: "0: not at all" to "5: very strongly").

Results: The study included 57 participants (severe asthma: n = 31; moderate-to-severe atopic dermatitis: n = 21; both: n = 5) who reported a "rather moderate" burden of asthma (median: 2; Q25/Q75: 0.3/2.8) or atopic dermatitis (3; 1.5/3.5). They experienced their current medications as "rather helpful" (asthma: 4; 3/5; atopic dermatitis: 4; 3/5). Twelve of the participants (21%) reported refusing to take their medication because of reluctance, but all resumed treatment. All participants receiving dupilumab therapy (n = 16) reported an improvement in their disease within a maximum of 2.5 months after starting treatment. The median fear of injection decreased from 3 (0/5) before the first injection to 0.5 (0/1) at the time of the survey.

Conclusions: In this real-world, interview-based study, we found that pediatric patients perceived treatment as highly beneficial for asthma and atopic dermatitis. Furthermore, pediatric patients seemed to respond well to dupilumab therapy in terms of both disease improvement and less fear of injection.

Trial registration: DRKSID DRKS00028092.

Food insecurity is a growing concern, that is currently estimated to affect 1 in 4 Canadian children. Due to the additional effort required for management and the disproportionate cost of allergy friendly foods, households with food allergy may be at increased risk of experiencing food insecurity. With this in mind, we aimed to describe and compare the prevalence of food insecurity amongst children in households managing pediatric food allergy between 2019, 2020 and 2022 using a repeated cross-sectional design. A total of 117 participants were recruited via social media between these three distinct timepoints, referred to as waves. All participants completed an anonymous online survey consisting of demographic questions and the Household Food Security Module from the Canadian Community Health Survey. Rates of child food insecurity were comparable between Waves 1 and 2 (34% and 35%, respectively; p=0.75), but, increased significantly between Waves 2 and 3 (35% and 56%, respectively; p=0.005). Amongst children identified as food insecure, the proportion who were marginally food insecure remained relatively stable, whereas, levels of moderate food insecurity appeared to increase, although not significantly. Conversely, the proportion classified as severely food insecure decreased across the waves, but again, this difference was not statistically significant. Our findings demonstrate an upward trend in child food insecurity levels, showcasing the need for a larger scale, longitudinal evaluation of the intersection between food allergy and food insecurity. We call on researchers and policy makers to attend to this important issue.

Background: Hereditary angioedema (HAE) is a rare, potentially life-threatening condition that requires accessible and reliable information. YouTube has emerged as a significant source of health-related content, offering valuable insights while posing the risk of misinformation that warrants caution among users. The aim of this study was to evaluate the popularity, reliability, understandability, actionability, and overall quality of YouTube videos related to HAE.

Method: A search was conducted on YouTube using the term "hereditary angioedema." Videos were categorized based on their origin (health or nonhealth) and content type (medical professional education (MPE), patient education (PE), patient experience, or awareness). The quality, reliability, understandability, and actionability of the videos were assessed via the Global Quality Scale (GQS), the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V), and the Quality Criteria for Consumer Health Information (DISCERN) tool. Three independent allergists evaluated the videos.

Results: Out of 135 reviewed videos, 111 met the inclusion criteria. The health group presented significantly higher scores than did the nonhealth group in several metrics: PEMAT-A/V understandability (83, IQR: 56-92, p = 0.001), total DISCERN score (37, IQR: 3-45, p < 0.001), reliability (23, IQR: 19-26, p < 0.001), treatment (15, IQR: 8-21, p = 0.007), and modified DISCERN score (3, IQR: 2-4, p = 0.002). Health videos were uploaded more recently (p = 0.006), while awareness videos tended to be older than more recent MPE videos (p = 0.002). The MPE videos had the longest duration, whereas the awareness videos had the shortest duration (p < 0.001). Video quality scores, assessed via the GQS, were higher in both the MPE and PE groups (scores: 3, 4, and 5; p = 0.005). Compared with the other groups, the MPE group also had significantly higher PEMAT-A/V understandability scores (91, IQR: 70.75-92, p < 0.001), total DISCERN scores (40, IQR: 30.75-49.5, p < 0.001), reliability scores (24, IQR: 21-27.25, p < 0.001), and overall scores for moderate to high quality (83, 74.8%, p = 0.002).

Conclusion: YouTube videos on HAE uploaded by health care professionals generally offer higher-quality information, but their overall reliability remains suboptimal. There is a pressing need for higher-quality, trustworthy content, particularly from professional medical organizations, to address this gap.

Background: Evidence linking hereditary angioedema (HAE) to the potential association of developing other comorbidities, and how it is affected by HAE treatment is needed. The objective of this study is to identify comorbidities and measure the prevalence in HAE patients, compared to the prevalence in the general population using multiple Canadian sources when available.

Methods: A quantitative survey design via a self-administered anonymous online questionnaire was conducted from October 13, 2022, to January 11, 2023. Respondents were individuals with HAE, enrolled in the CSL Behring patient support program (CSL Behring PLUS+; PSP).

Results: This study included 123 patients (81% female; 60% HAE-1/HAE-2, 24% HAE Normal C1-INH (nC1-INH), 16% unsure of HAE type; 85% of patients were on long-term prophylaxis plus on-demand). Patients reported using the following HAE treatments: C1-esterase inhibitor (subcutaneous or intravenous), lanadelumab, icatibant, danazol, and tranexamic acid. Respondents (69%) reported at least one: autoimmune condition, asthma, or allergy. Reported autoimmune conditions (psoriasis, rheumatoid arthritis, inflammatory bowel disease, chronic urticaria, lupus, and psoriatic arthritis) were much higher than the general population (31% versus 5-8%). Patient-reported allergies were two times higher than the general population (54% versus 27%; i.e., aeroallergens) and asthma rates nearly two times higher than the general population (17% versus 8-11%).

Conclusion: This cohort of HAE patients, most of whom were on prophylaxis, reported an increased prevalence of certain comorbidities compared to the general Canadian population. Healthcare professionals should be aware of the potentially increased risk of autoimmune conditions, allergies, and asthma in patients with HAE.

Background: An epidemiological association among asthma, blood eosinophil level and chronic rhinosinusitis (CRS) is well established, but whether consistent genetic relationships exist, and whether this reflects a shared genetic etiology between CRS and asthma or blood eosinophil level remains unclear.

Methods: Data from CRS patients (N = 1,255) and healthy controls (N = 1,032) were reviewed retrospectively to investigate associations between clinical characteristics and CRS. Data from white blood cells in the UK biobank (N = 173,480), asthma in the Trans-National Asthma Genetic Consortium (127,669) and CRS (N = 272,922) or nasal polyps (N = 264,107) in the FinnGen consortium were used to conduct genetic study, including linkage disequilibrium score regression analysis to detect genetic associations between aforementioned variables, Mendelian randomization (MR) analysis to investigate causal relationships of asthma and blood eosinophil levels on CRS, and Bayesian co-localization to consolidate MR findings and to identify shared genetic signals.

Results: We found that blood eosinophil count, blood eosinophil percentages and asthma shared positive and causal genetic correlations with CRS (all q < 0.0001) and CRS with nasal polyps (CRSwNP) (all q < 0.0001) in both our observational and genetic study. Through colocalization analysis, 4 loci are shared among asthma, CRS and CRSwNP, 7 loci are shared among blood eosinophil count, CRS and CRSwNP, 2 loci are unique to blood eosinophil count and CRS, and 3 loci are unique to blood eosinophil count and CRSwNP.

Conclusions: These findings contribute to understanding CRS etiology, and provide insights for intervention and treatment target for CRS comorbid with asthma or high blood eosinophil levels.

Background: The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.

Methods: Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.

Results: The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.

Conclusions: This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.

Food oral immunotherapy (OIT) is an option for the treatment of immunoglobin E (IgE)-mediated food allergy that involves administering gradually increasing doses of an allergenic food over time (under medical supervision) with the goal of desensitizing an individual to the food allergen. Current Canadian clinical practice guidelines for OIT recommend this form of therapy as an option in patients with food allergy. The intervention should be prioritized in the infant and toddler population, in which it is particularly well tolerated and can lead to sustained unresponsiveness (also sometimes referred to as remission). In this article, we provide an overview of OIT and discuss the role non-allergist clinicians can play in caring for patients undergoing OIT.

Background: Contact allergens typically trigger localised reactions, but systemic Type I hypersensitivity from skin contact reactions are rare.

Case presentation: We present the case of a 69-year-old non-atopic male who developed anaphylaxis following the application of moisturizer to an area of chemical burns. Skin testing showed a strong positive result to moisturizer. Whilst not all ingredients were available for testing, phenoxyethanol was thought to be the likely culprit agent based on literature review and a weakly positive skin test result.

Conclusion: Products such as moisturizers can rarely trigger anaphylaxis, especially when applied to damaged skin which may favor systemic absorption. This case highlights the need for careful consideration of cosmetic application when discerning culprit allergens.