World Allergy Organization Journal最新文献

Background

Allergic rhinitis (AR) is a typical type 2 inflammatory disease and eosinophils play a critical role of cardinal effectors in type 2 inflammation. However, the distribution of eosinophils in patients with different subtypes of rhinitis and the effect of allergen exposure on them remain understudied. The aim of this study was to investigate the characteristics and factors influencing the distribution of systemic and local eosinophils in patients with non-AR (NAR), perennial AR (PAR), and seasonal AR (SAR), as well as the effect of seasonal allergen exposure levels on eosinophils.

Methods

This was a population-based, cross-sectional observational study of consecutive chronic rhinitis (CR) outpatients who volunteered to participate in the survey during the spring pollen season and non-pollen season of 2023 in Beijing. All participants underwent serum allergen testing, blood routine examination, and nasal secretion smear cytology, and completed questionnaires mainly involving basic information, history review, and symptom assessment. Spring pollen dispersal concentration were considered.

Results

A total of 558 CR patients eligible for enrollment were collected, including 198 NAR, 204 PAR, and 156 SAR patients. PAR had the highest blood eosinophil levels and the most severe overall nasal and ocular symptoms of SAR. Compared with subjects with blood eosinophil counts <0.3 × 10⁹/L, those with ≥0.3 × 10⁹/L had significantly more severe nasal and ocular symptoms and a significantly higher rate of comorbid asthma and allergic conjunctivitis. Blood eosinophil levels were significantly higher in SAR patients during the pollen season compared to the non-pollen season, and pollen concentrations were positively correlated with systemic and local eosinophil levels.

Conclusions

Blood eosinophil levels varied in patients with different subtypes of rhinitis. Patients with high blood eosinophil levels had more severe overall nasal and ocular symptoms, and that blood eosinophils levels were significantly higher in patients with asthma or allergic conjunctivitis than patients without comorbidities. There was a positive trend between allergen exposure and systemic and local eosinophil levels. Further longitudinal cohort studies are still needed to better analyze the influence of eosinophil levels on the clinical traits of AR.

Background and objective

Currently, there are no guideline recommendations for the duration of intranasal corticosteroid (INCS) treatment for allergic rhinitis (AR). We aimed to catalogue real-world AR-INCS prescription patterns.

Materials and methods

This multicenter, non-interventional, cross-sectional study used online general practitioner (GP) and patient surveys from 4 countries. Eligible GPs had 3–35 years of practical experience, regularly prescribed INCSs for AR treatment, and had managed ≥5 patients with AR per month according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in the previous year. Eligible patients with AR were non-pregnant females or males, aged 18–65 years, previous AR-INCS users (≥12 months), and receiving GP-prescribed AR therapy. Survey participants were from countries with 15–50% AR prevalence and mostly prescription-only INCS use of ≥100 million units annually (Brazil, Mexico, Spain, Thailand). GP surveys and GP-completed patient record forms (PRFs) gathered AR-care and INCS-use data over 10 months; each GP completed patient record forms (PRFs) for 3 patients with AR under their care. The patient survey reflected actual AR-INCS experience, treatment duration, and adherence factors from patient perspectives. The target sample size was 75 GPs, 75 patients, and ≥30 respondents per country.

Results

From 900 GP-PRFs, the mean GP-recommended AR-INCS durations reported were 8.4 (Brazil), 8.3 (Mexico), 5.4 (Spain), and 6.4 (Thailand) weeks. From 300 patient surveys, mean reported INCS recommended durations were 6.4 (Brazil), 5.1 (Mexico), 4.0 (Spain), and 4.9 (Thailand) weeks; reported actual use durations were 6.2, 4.8, 3.6, and 6.4 weeks, respectively. The most frequent GP-PRF-reported factors influencing AR-INCS treatment duration were symptom severity (76–85%), symptom recurrence (49–73%), and existing comorbidities (33–57%). The most frequent GP-PRF-reported obstacles to adherence included forgetting to take medication regularly (54–100%), subsiding symptoms (42–91%), and being unable to continue activities (33–51%). Subsiding symptoms (36–53%) and reaching the prescription duration end (20–51%) were most frequent obstacles reported by the patient survey. Patients from all surveyed countries indicated that they visited the GP, a different physician, or a pharmacy for assistance with symptom recurrence; some patients also self-medicated.

Conclusions

Real-world AR-INCS prescription durations vary between countries and actual use tends to be shorter than prescribed. Understanding underlying factors may support appropriate AR-INCS use. The study was not powered to statistically compare intercountry differences; hence, comparisons have not been drawn, and the small sample may not reflect a complete picture of clinical practice and patients with AR in each country.

Background

The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data.

Methods

Subjects (5–65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed.

Results

Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised.

Conclusion

Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status.

Clinical trial registrations

NCT00674700; Retrospectively registered 06 May 2008.

NCT01199133; Retrospectively registered 09 September 2010.

NCT01527188; Retrospectively registered 01 February 2012.

NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.

jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.

jRCT2080222929/JapicCTI-15298; Registered 04 August 2015.

In patients with moderate to severe atopic dermatitis (AD) showing an inadequate response to dupilumab 300mg/2weeks, few real-life studies reported the response to alternative regimen maintaining dupilumab.

To assess and analyze the response to an increased dose of dupilumab or its combination with cyclosporin A (CsA), methotrexate (MTX), or itraconazole (ITRA), all adult AD patients from 7 French University Hospitals were retrospectively included if they achieved an inadequate response to dupilumab 300mg/2weeks and were subsequently treated with an increased dose of dupilumab (300mg every 7 or 10 days), or a combination of dupilumab 300mg/2weeks with CsA, MTX or ITRA. The response after 3 months, along with epidemiological, clinical, and therapeutic baseline characteristics, were collected.

Overall, 68.75% of the 48 included patients achieved an improved response, including 45.8% of complete response (CR). No strategy proved significantly better. Patients showing an initial no response never achieved a further CR versus 52.4% of patients with an initial partial response (p = 0.025). Digestive intolerance and tachycardia led to MTX and ITRA discontinuation in 3 patients.

Increasing the dose of dupilumab or combining it with CsA, MTX, or ITRA could be alternative and safe options, to be evaluated in further medico-economic studies.

Background

Allergic rhinitis (AR) is a pervasive global health issue, and currently, there is a scarcity of targeted drug therapies available. This study aims to identify potential druggable target genes for AR using Mendelian randomization (MR) analysis.

Methods

MR analysis was conducted to assess the causal effect of expression quantitative trait loci (eQTL) in the blood on AR. Data on AR were collected from 2 datasets: FinnGen(R9) (11,009 cases and 359,149 controls) and UK Biobank (25,486 cases and 87,097 controls). Colocalization analysis was utilized to assess the common causal genetic variations between the identified drug target genes and AR. We also employed available genome-wide association studies (GWAS) data to gauge the impact of druggable genes on AR biomarkers and other allergic diseases.

Results

This study employs MR to analyze the relationship between 3410 druggable genes and AR. After Bonferroni correction, 10 genes were found to be significantly associated with AR risk (P < 0.05/3410). Colocalization analysis revealed a significant causal relationship between the expression variation of CFL1 and EFEMP2 genes and AR, sharing direct causal variants (colocalization probability PP.H3 + PP.H4 > 0.8), highlighting their importance as potential therapeutic targets for AR. The CFL1 gene showed a causal link with levels of thymic stromal lymphopoietin (TSLP), eosinophil count, and interleukin-13 (IL-13) (P = 0.016, 7.45E-16, 0.00091, respectively). EFEMP2 was also causally related to eosinophil count, IL-13, and interleukin-17 (IL-17) (P = 0.00012, 0.00091, 0.032, respectively). PheWAS analysis revealed significant associations of CFL1 with asthma, whereas EFEMP2 showed associations with both asthma and eczema. Protein-Protein Interaction (PPI) network analysis further unveiled the direct interactions of EFEMP2 and CFL1 with proteins related to immune regulation and inflammatory responses, with 77.64% of the network consisting of direct bindings, indicating their key roles in modulating AR-related immune and inflammatory responses. Notably, there was an 8.01% significant correlation between immune-related pathways and genes involved in inflammatory responses.

Conclusion

These genes present notable associations with AR biomarkers and other autoimmune diseases, offering valuable targets for developing new AR therapies.

Background

Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics.

Methods

This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Science, and Scopus and assessed the risk of bias using the Cochrane tool. The outcomes of interest were the annual asthma exacerbation rate (AER), forced expiratory volume per second before bronchodilator use (preBD FEV1), the asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ) results. A frequentist network meta-analysis was conducted, and a random effects model was used to draw pooled incidence rate ratio or standardized mean differences.

Results

Twenty-three RCTs with 8376 participants were retrieved. All biologics included in this study were associated with significantly better effects than placebo in AER, preBD FEV1, and ACQ outcomes. Although there were no significant differences between the biologics in the overall study population, patients with eosinophil levels ≥300 cells/μL or eosinophilic asthma showed that dupilumab and tezepelumab were significantly better than anti-IL-5 biologics in improving preBD FEV1. Additionally, in patients with eosinophil levels ≥300 cells/μL, benralizumab, unlike reslizumab, performed significantly better than placebo in improving ACQ and AQLQ outcomes.

Conclusion

The comparative effects of biologics can be considered with phenotypes and biomarkers to help clinicians select an appropriate treatment for inadequately controlled asthma.

Background

Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment.

Objective

To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance.

Methods

The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period.

Results

Of 3117 patients, 507 (16.27%) patients (ages, 5–67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24–36 months of SLIT (28.13%, 153/544), followed by 12–24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3–6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis.

Conclusions

The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

Background

Allergic rhinitis (AR) is an IgE-mediated type I allergic chronic nasal disease common among all age groups, including the pediatric population. House dust mites (HDMs) are globally ubiquitous and the most important indoor aeroallergen. However, the recent prevalence of HDM-caused AR (AR-HDM) in Japan remains unknown, especially after the COVID-19 pandemic.

Objective

The objective of this study was to investigate the current prevalence of AR-HDM, its clinical features, and the current status of medical examinations in elementary school students.

Methods

A survey of 41,000 elementary school students was conducted during July 2021 in Fukui Prefecture, Japan. Parents were asked to complete a questionnaire that examined allergic disease history and clinical background.

Results

A total of 17,974 subjects were analyzed in the study. The results showed that the current prevalence of AR-HDM in elementary school children is 18.8%. We found that AR-HDM had already developed before entrance into elementary school in 68.3% of affected subjects. Among these subjects, 82.3% had received some form of treatment, such as prescription medications, whereas 4.2% were treated by allergen immunotherapy. Multiple logistic regression analysis of the onset of AR-HDM revealed that male sex, being the first-born child, comorbidity of bronchial asthma, atopic dermatitis, food allergy, and allergic conjunctivitis are associated with development of AR-HDM.

Conclusions

The present study revealed the prevalence of AR-HDM in elementary school children. The results emphasize the importance of appropriate diagnosis and treatment from infancy through early childhood.

Background

Hereditary angioedema (HAE) due to deficiency of C1 Inhibitor (C1INH-HAE) is a rare, unpredictable and potentially fatal genetic disorder. There are relatively few systematic population prevalence studies, with reports from various countries of between 1 in 20,000 and 1 in 150,000. and no Australian data. The therapeutic landscape for HAE has changed dramatically in recent years with a focus on highly effective prophylaxis, with the aim of total suppression of angioedema and achievement of a normal life.

Objectives

Epidemiological survey of HAE in South Australia, with description of patient characteristics, quality of life and treatment, with a focus on prophylaxis.

Methods

Case ascertainment was conducted over 18 months from January 2021 to July 2022, using a range of approaches with the aim of identifying all people with C1INH-HAE in South Australia. Questionnaires were administered to consenting patients utilising established HAE-specific and general survey instruments.

Results

We identified 35 people with HAE in South Australia, yielding a population prevalence of 1 in 52,400, in line with average established international prevalence. HAE was identified in 4 patients of Indigenous Australian heritage. Seventeen of 31 adult patients completed an additional multi-questionnaire survey, revealing overall satisfactory disease control. Most common prophylactic therapies were danazol, lanadelumab, and subcutaneous C1 inhibitor. Many patients (mostly male) with milder disease had responded well to low-dose danazol with good tolerance and have continued to use it, whereas patients with higher disease burden are now using newer therapies, and overall satisfaction with current prophylaxis is high.

Conclusions

Prevalence of HAE in South Australia aligns with international reports. Our population survey indicates that current long-term prophylaxis therapies including danazol, lanadelumab and C1-inhibitor, applied to appropriate patients taking into account disease activity and drug risks and tolerance, are effective for HAE attack prevention and produce high levels of satisfaction.

The global application of the skin prick test (SPT) is attributed to the low costs, easy execution, and in vivo approach. Still, the healthcare professionals’ technique and the lancet shape may challenge the standardization of the method. Thus, we investigated the influence of the shape of the lancet and the applied weight on the wheal size of SPT. Two allergic and one non-allergic individual were tested with allergens (Dermatophagoides pteronyssinus and Phleum pratense) and histamine solution (positive control), respectively. Horizontally (HS) and diagonally (DS) shouldered lancets with the same tip length (1 mm) were tested under two different conditions: either 60 g or 120 g weight pressure. The wheal size induced by the 4 different combinations was measured. The higher-weight device (120 g) induced a significantly larger and less variable wheal response with the tested allergens and histamine. However, the shape of the lancet affected the wheal size more than the applied weight. The least variable response was measured to histamine for the horizontal-shouldered lancet combined with the higher weight, whereas the same lancet with the lower weight resulted in a significant number of false negative results.