Uncovering the true burden of hereditary angioedema due to C1-inhibitor deficiency: A focus on the Asia-Pacific region.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency or dysfunction is a rare genetic disorder that causes recurrent episodes of swelling in various parts of the body. Treatment goals of HAE aim to "normalize" life for all patients; however, lack of diagnostic facilities and limited access to effective treatment options in developing nations cause delays in diagnosis and place a significant burden on patients. In this review, we aim to highlight the burden of disease caused by C1-inhibitor HAE across the Asia-Pacific region, considering its epidemiology, morbidity and mortality, and socioeconomic and psychological impact. We also review the availability of guideline-recommended diagnostic facilities and treatments, and how patients are currently managed. Data were collected from published literature and HAE experts in the region, who provided information regarding diagnosis and management in their countries. Current practice was reviewed against international guidelines, as well as local guidelines/consensus used in Australia, Japan, and China. Suggestions are provided for improving the time to diagnosis in the region, increasing access to guideline-recommended treatments, and providing support to reduce the burden on patients and caregivers. There is an urgent need to improve HAE services and provide access to life-saving treatment in developing countries, and efforts should be made to increase awareness of guideline recommendations in high-income economies that do not currently provide long-term prophylactic treatments.

Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

Gut microbiome alterations in hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease with wide intra- and interindividual clinical variation. There are no reliable indicators available in clinical practice to predict the onset and severity of HAE. Uncovering the changes in the gut microbiota in HAE patients may offer insight into a missing piece of the pathogenesis and help explain the clinical heterogeneity. OBJECTIVE: Explore whether dysbiosis exists in patients with HAE and whether there are biomarkers to indicate the episodes. METHODS: Fecal samples and clinical data were collected from patients with C1-inhibitor-related HAE and their healthy family members. Patients were grouped on the basis of the most recent conditions of HAE episodes and major clinical manifestations. The gut microbiota was evaluated by sequencing the 16S ribosomal RNA gene and analyzed for diversity. RESULTS: Microbial richness and diversity were significantly reduced among patients who had recent HAE attacks, especially for those presenting with abdominal symptoms (P = .003 and P = .048 compared with healthy controls and patients with no recent episodes, respectively). Decreased Firmicutes and increased Proteobacteria were found among the individuals with a recent episode, along with a marked increase of pathogenic bacteria on the basis of the predictive functional profiling. Dysbiosis was restored after regular use of danazol or tranexamic acid. A combined biomarker composed of Bifidobacterium, Lachnospira, Paraprevotella, Desulfovibrio, and Staphylococcus was proposed to detect the recent edema episodes. CONCLUSION: We reported alterations of the gut microbiome in patients with HAE and explored the possible role of bacteria in the etiology of edema episodes, which may provide new clues for the prediction of disease course, clinical treatment, and therapeutic evaluation.

Mutation update of SERPING1 related to hereditary angioedema in the Chinese population.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by recurrent attacks of severe swellings of the skin and submucosa. More than 900 variants of the SERPING1 gene associated with HAE have been identified. However, only approximately 50 variants have been identified in the Chinese population. This study aimed to update the mutational spectrum in Chinese HAE patients and provide evidence for the accurate diagnosis of HAE. METHODS: A total of 97 unrelated HAE patients were enrolled in the study. Sanger sequencing and multiple ligation-dependent probe amplification analysis were used to identify the variants in the SERPING1 gene. The variants were reviewed in a number of databases, including the Human Gene Mutation Database (HGMD) ( http://www.hgmd.cf.ac.uk/ ) and the Leiden Open Variation Database (LOVD, https://databases.lovd.nl/shared/variants/SERPING1 ). The American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) criteria was used to determine the pathogenicity of the variants. RESULTS: Of the 97 patients, 76 different variants were identified in 90 of them and no disease-causing variants were identified in the remaining 7 patients. Among the 76 variants, 35 variants were novel and submitted to ClinVar. Missense and in-frame variants were the most common variants (36.8%), followed by frameshift (28.9%), nonsense (14.5%), splice site (13.2%) variants, and gross deletions/duplications (6.6%). CONCLUSIONS: Our findings broaden the mutational spectrum of SERPING1 and provide evidence for accurate diagnosis and predictive genetic counseling.

Consensus on treatment goals in hereditary angioedema: A global Delphi initiative.

BACKGROUND: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. OBJECTIVES: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. METHODS: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. RESULTS: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients' lives. CONCLUSIONS: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients.

Recurrent and acute abdominal pain as the main clinical manifestation in patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease that often leads to misdiagnosis. The delay of diagnosis is > 10 years in China. Recurrent and acute abdominal pain is one of the common symptoms of HAE. Because of the high misdiagnosis rate, it usually results in unnecessary surgical procedures. This study focused on the clinical symptoms and management of HAE-related abdominal attacks in Chinese patients to provide some new insight for the emergency department (ED) physicians and gastroenterologists. Methods: A Web-based survey was conducted among 107 patients with HAE from 94 unrelated families. Detailed questions with respect to the abdominal attacks were asked, including the frequency, symptoms, and duration before and after confirmed diagnosis. The demographic characteristics, diagnosis process, and treatment outcomes were also included. Results: Approximately 70% of the patients with HAE presented with abdominal symptoms during the onset of edema, mostly characterized by pain (94.8%), nausea (83.1%), vomiting (83.1%), diarrhea (59.7%), and constipation (23.4%). The patients were easily misdiagnosed as having gastroenteritis (35.1%) and appendicitis (10.4%), and 24.7% of them received unnecessary appendectomy or laparotomy. Danazol, a widely used drug for long-term prophylaxis of HAE in China, can reduce the attack frequency and alleviate the abdominal symptoms, but the adverse effects are also significant and more severe in women. Conclusions: Abdominal symptoms are common and important clinical features of HAE but are easily confused with other gastrointestinal diseases. ED physicians and gastroenterologists should consider HAE when patients experience recurrent and unexplained abdominal pain. Proper medical treatment should be administered in a timely manner if an HAE diagnosis is confirmed and efforts are required to increase access in China to medications both for on-demand treatment and long-term prophylaxis.

[Advances in the Pathogenesis of Hereditary Angioedema].

Hereditary angioedema(HAE)is a rare,hereditary disease characterized by recurrent subcutaneous and submucosal edema.Known genes associated with the pathogenesis of HAE include C1 esterase inhibitor gene,FⅫ gene,plasminogen gene,and angiopoietin 1 gene.Based on the known gene mutations,this review analyzes the effects of these mutations on the functions of protein products to figure out the possible pathogenic mechanism,so as to provide references for further investigations on the pathogenesis of HAE and seeking new prevention and treatment approaches.

Risk factors for diagnostic delay in Chinese patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is still underdiagnosed or diagnosed after a serious delay. This study aimed to evaluate the diagnostic delay (DD) and misdiagnosis of HAE, and to explore the risk factors associated with a longer DD. Methods: An Internet-based survey was sent to 129 patients with type 1 and 2 HAE who presented to the Allergy Department, Peking Union Medical College Hospital between 1983 and 2017; 107 patients (82.9%) responded, among whom, a total of 96 patients provided complete information about medical visits. DD was divided into two subperiods according to the lower quartile, i.e., DD ≤ 6 years and DD > 6 years. Results: The median DD of all 96 patients with HAE was 11.04 years (interquartile range [IQR], 6.06-18.27 years). A significant difference (p < 0.001) in the median DD was found between different decades of onset, i.e., before 1999 (19.75 years [IQR, 13.58-29.50 years]), between 2000 and 2009 (8.67 years [IQR, 5.67-11.04 years]), and between 2010 and 2017 (3.79 years [IQR, 2.29-5.71 years]). Patients with a previous misdiagnosis experienced a longer median delay to complement 1 inhibitor HAE diagnosis (13.17 years [IQR, 7.40-20.50 years]) compared with patients without a previous misdiagnosis (median 6.96 years [IQR, 2.83-10.65 years]; p ≤ 0.001). According to the logistic regression analysis, a younger age of onset and earlier decade of onset were significant predictors of a DD of >6 years. The most frequently visited departments and most frequently misdiagnosed diseases were summarized. Conclusion: The median DD of patients with HAE was 11.04 years (IQR, 6.06-18.27 years). A younger age of onset and earlier decade of onset were predictors of a DD of >6 years. Seventy-five percent of the patients reported receiving more than one previous misdiagnosis. The patients with a previous misdiagnosis had longer DDs compared with patients without a misdiagnosis.

Upper airway edema in 43 patients with hereditary angioedema.

BACKGROUND: Upper airway edema (UAE) occurs infrequently in hereditary angioedema (HAE), but still results in significant morbidity and mortality. OBJECTIVE: To assess patients with HAE and UAE to determine whether unique features exist that can predict the risk of UAE. METHODS: Clinical, laboratory, and genetic data were compared between 43 patients with HAE and 743 UAE attacks and those without UAE and normal controls after ethics committee approval. RESULTS: Most patients had their first episode of UAE in the second (25.6%), third (27.9%), and fourth (23.3%) decades of life, and the mean age at onset was 27.3 years. Evolution of UAE from initial to maximum symptoms was 4.6 hours on average, and most cases (69.8%) progressed within 4 hours. Dyspnea was the most frequent manifestation in per-episode (92.2%) and per-patient (97.7%) analyses. Men developed more asphyxiation attacks (19 vs 2) and underwent more tracheotomies (12 vs 2) than did women. UAE was associated with facial edema in half the studied patients. Patients with a positive family history of UAE had a high risk of UAE attacks. CONCLUSION: Symptoms limited to the upper airway should be taken seriously. Dyspnea may be the only manifestation of UAE. UAE attacks most commonly start spontaneously and usually progress rapidly, as quickly as 30 minutes, from awareness of symptoms to maximum airway involvement. Patients with a positive UAE family history are predisposed to UAE attacks, and men appear to be more apt to develop asphyxiation than women.

Causal relationship between eosinophilic esophagitis and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study.

Background: Eosinophilic esophagitis (EoE) and inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are immune-mediated gastrointestinal diseases with overlapped pathogenesis and are sometimes concurrently diagnosed, but their causal relationship remains unclear. We investigated the causal relationship between EoE and IBD and its subtypes via a two-sample bidirectional Mendelian randomization (MR) approach. Methods: MR analyses were performed using summary data of a genome-wide association study (GWAS) on individuals of European ancestry. Independent single-nucleotide polymorphisms correlated with EoE (from a GWAS meta-analysis containing 1,930 cases and 13,634 controls) and IBD (from FinnGen GWASs containing 9,083 IBD, 2,033 CD, and 5,931 UC cases, and GWASs of IBD genetic consortium containing 12,882 IBD, 6,968 UC, and 5,956 CD cases) were selected as instruments. We applied the inverse variance weighted (IVW) method as the primary analysis followed by several sensitivity analyses. For the forward MR study, estimates from IVW methods were subsequently meta-analyzed using a random-effect model. Results: Our results suggested a causal effect of EoE on IBD [pooled odds ratio (OR), 1.07; 95% confidence interval (CI), 1.02-1.13] and EoE on UC (pooled OR, 1.09, 95% CI, 1.04-1.14). No causal link between EoE and CD was observed (pooled OR, 1.05; 95% CI, 0.96-1.16). The reverse MR analyses revealed no causal effect of IBD (and its subtypes) on EoE. Sensitivity analyses confirmed the robustness of primary results. Conclusions: Our findings provided evidence of a suggestive causal effect of EoE on IBD (specifically on UC) in the European population. Increased awareness of concurrent or subsequent IBD in patients with EoE is called for. Still, the present evidence is not adequate enough and ought to be validated by further investigations.

Epidemiology, economic, and humanistic burden of hereditary angioedema: a systematic review.

BACKGROUND: This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. METHODS: A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). RESULTS: In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. CONCLUSION: This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society.

Eosinophilic gastritis and gluten-sensitive enteropathy manifested as hypoproteinemia and treated with omalizumab: a case report.

BACKGROUND: Eosinophilic gastritis (EoG) has rarely been reported in conjunction with gluten-sensitive enteropathy (GSE). When this does occur, patients typically present with gastrointestinal symptoms. To our knowledge, hypoproteinemia has not been reported as the primary manifestation. Anti-IgE therapy, such as omalizumab, lowers eosinophil counts in the blood, lungs, and gut. Its efficiency in treating active EoG remain unknown. CASE PRESENTATION: We report a 33-month-old boy with a history of food allergy and atopic dermatitis who developed recurrent edema, hypoproteinemia, and eosinophilia at the age of 14 months. The diagnoses of EoG and GSE were confirmed based on the clinical presentation and results of gastrointestinal biopsies and serological testing. Although prednisone and dietary intervention were initially effective, the boy developed prednisone-related facial swelling. After stopping prednisone, his symptoms relapsed. Subsequent treatment with omalizumab, combined with dietary intervention, showed good efficacy and safety. CONCLUSIONS: To our knowledge, this is the first case of concurrent EoG and GSE that presented primarily with hypoproteinemia. We highlight the rare manifestations of these two diseases to raise clinical suspicion and prevent missed and delayed diagnoses. The pathogenesis of EoG is heterogeneous and complex. Omalizumab showed good efficacy, indicating that IgE-mediated processes may be involved in the pathogenesis of this patient's diseases.

Influence of plasma collection tubes on N-glycome in human blood samples.

Background and aims: Quantitative analysis of plasma N-glycome is a promising method for identifying disease biomarkers. This study aimed to investigate the impact of using blood collection tubes with different anticoagulants on plasma N-glycome. Materials and methods: We used a robust mass spectrometry method to profile plasma N-glycomes in two cohorts of healthy volunteers (cohort 1, n = 16; cohort 2, n = 53). The influence of three commonly used blood collection tubes on fully characterized N-glycomic profiles were explored. Results: Principal component analysis revealed distinct clustering of blood samples based on the collection tubes. Pairwise comparisons demonstrated significant differences between EDTA and heparin plasma in 55 out of 82 quantified N-glycan traits, and between EDTA and citrate plasma in 62 out of 82 traits. These differences encompassed various N-glycan features, including glycan type, sialylation, galactosylation, fucosylation, and bisection. Trends in N-glycan variations in citrate and heparin plasma were largely consistent compared to EDTA plasma. In correlation analysis (EDTA vs. heparin; EDTA vs. citrate), Pearson's correlation coefficients were consistently higher than 0.7 for the majority of N-glycan traits. Conclusion: Sample matrix variations impact plasma N-glycome measurements. Caution is crucial when comparing samples from different plasma collection tubes in glycomics projects.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

Altered Urinary Metabolomics in Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease with heterogeneous clinical symptoms. The metabolomic profile of HAE remains unknown. Uncovering the metabolic signatures of HAE may provide inspiration for a comprehensive understanding of HAE pathogenesis and may help explore potential new metabolic biomarkers. We performed a comprehensive metabolic analysis using high-performance liquid chromatography−tandem mass spectrometry (HPLC-MS/MS). Urine samples from 34 HAE patients and 82 healthy controls (HCs) were collected to characterize the metabolic signatures associated with HAE. The metabolomes of HAE patients carrying different mutation types were also compared. A total of 795 metabolites were accurately detected and quantified. We considered 73 metabolites as differential metabolites in HAE patients (with an importance in projection (VIP) value > 1.0, q-value < 0.05, and fold change (FC) ≥ 1.2 or FC ≤ 0.8). Several metabolites associated with riboflavin metabolism, the citrate cycle, oxidative stress, and inflammation, including xanthine, oxypurinol, vitamin B2, and isocitrate, were significantly altered in HAE patients. No significantly different metabolites were found in HAE patients carrying different mutation types. The present study highlights that metabolic disturbances in the purine metabolism, riboflavin metabolism, and TCA cycle may be involved in the pathogenesis of HAE. Although biochemical significance requires further experimental verification, these findings may help to identify novel candidate metabolite biomarkers associated with HAE.

Throat microbiota alterations in patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease characterized by recurrent episodes of cutaneous and submucosal edema. The clinical course of HAE is heterogeneous and unpredictable. There are no reliable indicators associated with angioedema attacks and severity. Throat microbiota plays vital roles in the maintenance of human health, while its association with HAE is barely understood. Therefore, this study aimed to investigate the alteration of throat microbiota and its correlation with attacks severity in HAE patients. Methods: Throat swab samples were collected from HAE patients and their healthy family members, and then subjected to 16S rRNA sequencing. Alpha and beta diversity were used to examine the diversity and structure of bacterial communities. The relative abundance of individual bacteria was compared between study groups to determine the discriminant taxa. Spearman's correlation and linear regression were applied to analyze the correlation between throat bacteria and attacks severity. Results: Irrespective of the study groups, the throat microbiome was predominantly occupied by Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria. The recent onset of laryngeal edema is associated with the altered composition of microbiome community in HAE patients. The relative abundance of Bacteroidetes and Prevotellaceae was significantly increased in patients with recent episodes of laryngeal edema, compared to patients without recent episodes of laryngeal edema. Additionally, HAE attack severity scores positively correlated with the relative abundance of Bacteroidetes. Conclusion: We reported alterations of the throat microbial communities in HAE patients and explored the correlation between bacteria and edema severity, which may shed light on understanding the disease course and developing new therapeutic strategies for HAE.

Association between exposure to greenness and atopic march in children and adults-A systematic review and meta-analysis.

Introduction: Allergic diseases are a global public health problem. Food allergy, atopic dermatitis (AD), allergic rhinoconjunctivitis, allergic rhinitis (AR) and asthma represent the natural course of allergic diseases, also known as the "atopic march". In recent years, a large number of studies have been published on the association between greenness exposure and allergic diseases. However, systematic reviews on the association between greenness exposure and multiple allergic diseases or atopic march are lacking. Methods: In this study, PubMed, EMBASE, ISI Web of Science, and Scopus were systematically searched. Meta-analyses were performed if at least three studies reported risk estimates for the same outcome and exposure measures. Results: Of 2355 records, 48 studies were included for qualitative review. Five birth cohort studies, five cross-sectional studies, and one case-control study were included for asthma meta-analysis, respectively. Four birth cohort studies were included for AR meta-analysis. Our results support that exposure to a greener environment at birth reduces the risk of asthma and AR in childhood. In addition, higher greenness exposure was associated with decreased odds of current asthma in children. Discussion: There was a large heterogeneity among the included studies and most of them did not specify the vegetation type and causative allergens. Therefore the study results need to be further validated. In addition, a small number of studies evaluated the association between greenness and food allergy, AD and allergic rhinoconjunctivitis. More research is needed to strengthen our understanding of the association between greenness and allergic diseases.

Diagnostic accuracy and safety of Dermatophagoides pteronyssinus extracts used for skin prick test.

BACKGROUND: Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. METHODS: A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. RESULTS: There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. CONCLUSION: The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Prevalence of Comorbid Asthma and Related Outcomes in COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: The impact of asthma on coronavirus disease 2019 (COVID-19) remains largely unknown. OBJECTIVE: To investigate the asthma prevalence among patients with COVID-19 and compare outcomes between patients with and without asthma. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, bioRxiv, and medRxiv for studies reporting asthma prevalence in general patients with COVID-19 or comparing outcomes between patients with and without asthma, and excluded duplicate publications, reviews, editorials, comments, single case reports, or small case series (<10 cases). We determined the pooled estimates of effect using random-effect model. RESULTS: On the basis of 131 studies (410,382 patients), we found great variability in the prevalence of comorbid asthma among patients with COVID-19 in different countries or regions ranging from 1.1% to 16.9%. No significant difference in asthma prevalence was found between hospitalized and nonhospitalized (risk ratio [RR], 1.15; 95% CI, 0.92-1.43), severe and nonsevere (RR, 1.21; 95% CI, 0.92-1.57), intensive care unit and non-intensive care unit (RR, 1.19; 95% CI, 0.92-1.54), dead and survived (RR, 0.90; 95% CI, 0.73-1.11), intubated/mechanically ventilated and nonintubated/mechanically ventilated (RR, 0.91; 95% CI, 0.71-1.17) patients with COVID-19. Patients with asthma have a lower risk of death compared with patients without asthma (RR, 0.65; 95% CI, 0.43-0.98). Asthma is not associated with a higher risk of intubation or mechanical ventilation (RR, 1.03; 95% CI, 0.72-1.46). CONCLUSIONS: There is great variability in asthma prevalence among patients with COVID-19 in different countries or regions. Asthma is not associated with higher COVID-19 severity or worse prognosis, and patients with asthma are found to have a lower risk of death compared with patients without asthma.