Identification of probable pectinesterase as a major allergen of pollen of the Asian white birch (Betula platyphylla) in northern China.

BACKGROUND: Pollen of the Asian white birch (Betula platyphylla) is a major source of allergens in spring in northern China, yet little research on its pollen allergens has been done so far. OBJECTIVE: To analyze the B. platyphylla pollen allergen profile of patients from northern China and to identify the major pollen allergens in this patient cohort. METHODS: Sera from 35 Chinese patients with birch pollinosis were collected for this study. The IgE-binding proteins in B. platyphylla pollen extract were analyzed by IgE immunoblots. A novel major allergen was purified by cation exchange chromatography and affinity chromatography. Its IgE reactivity was evaluated by ELISA. The protein was excised from a 2D electrophoresis gel and subjected to ESI-QUAD-TOF. RESULTS: In our study cohort, the prevalence of IgE specific for Bet v 1 was 68.8% (n = 22/32) as measured by ImmunoCAP. In immunoblots, two major bands at around 17 kDa and 70 kDa were detected by IgE from 68.5% (24/35) and 65.7% (23/35) of sera, respectively. The 17 kDa band was identified as Bet v 1 by a monoclonal antibody to Bet v 1 and inhibition experiments with recombinant Bet v 1. The 70 kDa band was a polymorphic glycoprotein and 7 isoforms were found. The protein was identified as probably pectinesterase with a molecular weight of 66 kDa and a PI of 5.7. CONCLUSIONS: A 66 kDa protein, probably belonging to pectinesterase family, was identified as a novel major allergen of B. platyphylla pollen in patients from northern China.

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.

Retrospective analysis of epidemic thunderstorm asthma in children in Yulin, northwest China.

BACKGROUND: An epidemic of thunderstorm asthma in pediatric patients occurred in Yulin, a northwest city of China, on 11 September 2018. We described the epidemic and retrospectively analyzed the demographic and clinical aspects of the involved children. METHODS: The caseload data of patients were collected from the hospital information system in Yulin Pediatric Hospital. The detailed document of hospitalized children with thunderstorm asthma was sourced from the medical records. RESULTS: The mean number of daily visits to emergency/outpatient department and the daily admission to hospital were 2.7 and 16 times, respectively, than on the other days of September. A gender prominence of males was observed in both emergency/outpatient and inpatient department. Among the 51 hospitalized children with detailed medical records, 56% of them had never experienced or were diagnosed with asthma and 25% had confirmed diagnosis of asthma. Sixty-seven percent had a history of allergic rhinitis during August and September. Seventy-six percent of the hospitalized children presented as moderate asthma. Ninety-four percent of the pediatric patients had positive IgE against mugwort pollen and 78% were monosensitized to pollen. CONCLUSION: Thunderstorm asthma can affect children, especially who has allergic rhinitis or asthma without preventive management. Mugwort is also an aeroallergen in thunderstorm asthma attacks. IMPACT: Thunderstorm can induce asthma attacks in children with allergic rhinitis owing to mugwort and aggravate symptoms in children with confirmed diagnosis of asthma. Children with mugwort allergy are susceptible to thunderstorm asthma and a preponderance of boys was observed. Better identification of allergic children to mugwort, giving suitable protective measures during thunderstorm and standard therapy to existing allergic situation could be a benefit for children at risk of thunderstorm asthma.

Levels of nasal exhaled hydrogen sulfide in the general population and allergic rhinitis patients.

BACKGROUND: Objective measures used for the differential diagnosis and severity assessment of allergic rhinitis (AR) are still lacking. The involvement of hydrogen sulfide (H2 S) in the development of AR indicates that nasal exhaled H2 S (NeH2 S) has potential as a biomarker to be used in AR patients. This study aimed to evaluate the application value of NeH2 S measurement in the diagnosis and assessment of AR. METHODS: This study was a multi-center cross-sectional survey conducted in Northwestern China. Demographic information collection and rhinitis assessment were completed through questionnaires. The level of NeH2 S and serum immunoglobulin E were measured. RESULTS: The level of NeH2 S in general population ranged from 0 to 35 ppb, with a median value of 2 ppb. The NeH2 S levels in seasonal allergic rhinitis (SAR) patients were significantly lower than those in general population (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .023), and the NeH2 S value of the SAR group tended to be lower than that of the non-allergic rhinitis (NAR) group (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .094). The subgroup of AR patients with symptoms lasting longer than 2 weeks per month had a lower NeH2 S level compared with the subgroup of patients with symptoms lasting less than 2 weeks per month (2 [1, 2] vs. 2 [2, 3] ppb; p = .015). CONCLUSION: This study described the distribution range of NeH2 S levels in the general population. Further study with larger sample size was needed to clarify the relationship between NeH2 S level and AR.

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.

The efficacy of a novel smart watch on medicine adherence and symptom control of allergic rhinitis patients: Pilot study.

Background: Allergic rhinitis (AR) is a common allergic airway disorder that is often poorly managed. There is an urgent need to enhance medication adherence in order to improve treatment outcomes in patients with AR. The efficacy of wearable smart watches in improving medication adherence is currently unclear. Objectives: This study aimed to evaluate the efficacy of a novel smart watch in improving medication adherence and symptom control in patients with AR. The reliability of self-reported medication use was also investigated. Methods: This randomized, open-label, parallel controlled, pilot study enrolled adult patients with AR caused by cypress pollen. Patients were randomized in a 1:2 ratio to an intervention group and control group. Smart watches were only distributed to patients in the intervention group. During the cypress pollen season, all patients were required to take oral antihistamines daily and use nasal corticosteroids and antihistamine eye drops as needed. Daily AR symptom scores and medication usage were recorded in both groups. The smart watch was able to identify medication-taking behaviors of patients via artificial intelligence (AI) and relay this information to physicians, who sent short message service reminders to patients who forgot to take oral antihistamines for more than 2 days. Results: During the pollen season, the adherence rate to oral antihistamines in the intervention group (n = 17) was significantly higher than that in the control group (n = 38) (63.3% ± 28.5% versus 43.2% ± 30.2%, P = 0.02). The daily symptom score of the intervention group was lower than that of the control group (2.4 ± 1.1 versus 3.9 ± 1.0, P < 0.001). There was no significant difference in the on-demand medication score between the 2 groups (1.3 ± 0.4 versus 1.5 ± 0.5, P = 0.13). The consistency rate between self-reported nasal corticosteroid usage and the gold standard (ie, human observation of medication usage in the videos recorded by the smart watch) was 20.0% (0%, 53.7%), and the consistency rate between self-reported antihistamine eye drop usage and the gold standard was 24.3% (2.1%, 67.1%). Conclusions: This pilot study showed that the application of smart watches in patients with AR was associated with improved medication adherence and symptom control. Furthermore, the reliability of self-reported medication usage was limited.

Clinical profiles of patients with wheat-induced anaphylaxis at various ages of onset.

Background: Wheat-induced anaphylaxis (WIA) is a serious and potentially life-threatening wheat allergy, more common in adults than in children. Little is known about the differences in clinical profiles in WIA among patients of various ages in China. Methods: We analyzed data retrospectively from an allergy department in a tertiary hospital that included 248 patients (208 adults and 40 children and adolescents) with a history of WIA. Results: We found that alcohol was more frequent in patients aged ≥50 years [older adults] (19.0%, 4/21) than in those aged 12-17 years [adolescents] (0%, 0/33; p = 0.019). The frequency of NSAID use in older adults (42.9%, 9/21) was significantly higher than that in adolescents (0%, 0/33; p < 0.001), and patients aged 18-49 years [young adults] (2.8%, 5/178; p < 0.001). During WIA, cardiovascular symptoms in children were less frequent than those in other age groups (children, 28.6%; adolescents, 87.9%; young adults, 93.0%; older adults, 95.2%; p < 0.001). The consciousness loss rate in adults (both age groups; p < 0.001) and the hypotension rate in older adults (p = 0.006) were higher than those in other age groups. Compared with adults (young and older adults), children had a higher rate of allergic comorbidities (p = 0.004, 0.001, respectively) and a higher rate of other food allergies (p < 0.001, <0.001, respectively). Compared with the mild-to-moderate anaphylaxis group, the severe anaphylaxis group had a higher onset age (p = 0.001), higher cofactor prevalence (p = 0.004), lower allergic comorbidity rate (p = 0.014), and higher positive rate of specific IgE to omega-5 gliadin (ω-5 gliadin) (p = 0.023). Conclusion: Clinical profiles of patients with WIA are different among various onset age/severity groups. An improved understanding of WIA symptoms in various age/severity groups could help accelerate diagnosis, suggest preventive measures, and contribute to improved patient care.

Upregulated antimicrobial immune response mediated by neutrophils in the development from allergic rhinitis to asthma.

Background: Allergic rhinitis (AR) and asthma are closely related, and AR is regarded as an important risk factor for the onset of asthma. However, the pathogenesis of the development of asthma from AR is still undefined. Objective: The aim of this study was to investigate the mechanisms underlying the development of asthma from AR by comparing the transcriptome features of patients with AR with and without asthma. Methods: Patients with AR with or without asthma caused by weed pollen who presented to the Allergy Clinic of Peking Union Medical College Hospital were recruited for this study. Peripheral blood samples of all the patients were collected during the weed pollen season (September) when the patients had allergic symptoms and outside the pollen season (November) when the patients had no symptoms. Transcriptomic analysis was conducted, and the differentially expressed genes (DEGs) and enriched immune pathways between the patients with AR with asthma (AR-asthma group) and those without asthma (AR group) were identified. In addition, the expression levels of some pivotal differentially expressed RNAs were quantified using quantitative polymerase chain reaction (PCR). Results: During the weed pollen season, the immune-related Gene Ontology (GO) terms with P value < 0.05, enriched by the upregulated genes in the AR-asthma group compared to the AR group included antifungal humoral response, neutrophil-mediated killing of bacterium, antibacterial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptides, and regulation of the T cell receptor signaling pathway. The immune-related GO terms with P values <0.05 enriched by downregulated genes were positive regulation of natural killer cell-mediated cytotoxicity, microglial cell activation, natural killer cell activation, and leukocyte-mediated cytotoxicity. The GO term of antimicrobial humoral immune response mediated by antimicrobial peptides was upregulated both during and outside the pollen season, and the upregulated expression of three DEGs (LTF, PF4, and ELANE) included in this term was verified through quantitative PCR. Conclusions: The activation of the antimicrobial immune response mediated by neutrophils and the depression of cytotoxicity mediated by natural killer cells may play roles in the progression from AR to asthma.

Allergic Reactions After the Administration of COVID-19 Vaccines.

Background: Data on allergic reactions after the administration of coronavirus disease (COVID-19) vaccines are limited. Our aim is to analyze reports of allergic reactions after COVID-19 vaccine administration. Methods: The Vaccine Adverse Event Reporting System database was searched for reported allergic reactions after the administration of any of the COVID-19 vaccines from December 2020 to June 2021. After data mapping, the demographic and clinical characteristics of the reported cases were analyzed. Potential factors associated with anaphylaxis were evaluated using multivariable logistic regression models. Results: In total, 14,611 cases were reported. Most cases of allergic reactions comprised women (84.6%) and occurred after the first dose of the vaccine (63.6%). Patients who experienced anaphylaxis were younger (mean age 45.11 ± 5.6 vs. 47.01 ± 6.3 years, P < 0.001) and had a higher prevalence of a history of allergies, allergic rhinitis, asthma, and anaphylaxis than those who did not (P < 0.05). A history of allergies (odds ratio (OR) 1.632, 95% confidence interval (CI) 1.467-1.816, P < 0.001), asthma (OR 1.908, 95%CI 1.677-2.172, P < 0.001), and anaphylaxis (OR 7.164, 95%CI 3.504-14.646, P < 0.001) were potential risk factors for anaphylaxis. Among the 8,232 patients with reported outcomes, 16 died. Conclusions: Female predominance in allergic reaction cases after the receipt of COVID-19 vaccines was observed. Previous histories of allergies, asthma, or anaphylaxis were risk factors for anaphylaxis post-vaccination. People with these risk factors should be monitored more strictly after COVID-19 vaccination.

Serum IgE profiles in Chinese pollinosis patients with grass pollen sensitisation.

PURPOSE: Pollen from trees, grasses, and weeds is a common allergen source. The characteristics of pollen allergy in China are obviously different from Europe. Most studies have focused on tree and weed pollen, but there is a paucity of data on grass pollen sensitisation in China. Therefore, we used component-resolved diagnostics to investigate the serum-specific immunoglobulin E (sIgE) to grass pollen in Chinese patients with pollinosis. METHODS: We retrospectively analysed 547 patients with pollen allegy from an outpatient Allergy Department in Beijing, China. All the patients answered questionnaires about their clinical allergy histories. Total immunoglobulin E (IgE) and sIgE levels to grass pollen (Bermuda, Timothy grass) were quantified by ImmunoCAP using 0.35 kUA/L as a threshold for positivity. RESULTS: Of the 547 pollinosis patients, 389 (71.1%) showed a positive sIgE reaction to either grass pollen, or both. The prevalence of food allergy was significantly lower in patients with grass pollen sensitisation. Among the 389 patients with grass pollen sensitisation, the prevalence of sIgE to allergen extracts of bermuda, mugwort, ragweed, plane, hop, ash, birch, and timothy grass was 97%, 96%, 94%, 88%, 88%, 84%, 78%, and 78%, respectively. However, only 134/389 (34%) were positive for Cyn d 1, 29/389 (7%) for Phl p 1, and 8/389 (2%) for Phl p 5b. For pollinosis patients, 62/547 (11%) were sIgE-positive for cross-reactive carbohydrate determinants (CCDs), and their grass pollen-sIgE was also positive. CONCLUSIONS: The prevalence of in vitro IgE sensitisation to grass pollen extract is high in Chinese patients with pollinosis. But mostly spurious and characterized by IgE sensitisation to profilins and CCD, induced by other pollen. Component-resolved diagnostics is an extremely useful tool precise diagnostics of pollen allergy in China.

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.

A Case of Anaphylaxis Caused by Major Royal Jelly Protein 3 of Royal Jelly and Its Cross-Reactivity with Honeycomb.

PURPOSE: Royal jelly and honeycomb are commonly consumed in China, and anaphylaxis caused by ingestion of royal jelly is rare. To date, there is no report of anaphylaxis after ingestion of royal jelly in China. Its cross-reactivity with honeycomb is still unclear. CASE REPORT: A 56-year-old Chinese female experienced two episodes of anaphylaxis within 1 hour after ingestion of royal jelly within one month. After avoiding royal jelly and other bee products, no anaphylactic reaction occurred again. The skin prick test and basophil activation test showed positive reactivity to royal jelly and honeycomb. In immunoblotting and immunoblotting inhibition tests, a 60 kDa protein was recognized in royal jelly and cross-reactivity with honeycomb. The mass spectrometry data revealed that the 62kDa protein belongs to major royal jelly protein 3. CONCLUSION: Our data suggest that major royal jelly protein 3 of royal jelly is a main allergen that induces anaphylaxis and cross-reactivity with honeycomb. Therefore, the patient was allergic to royal jelly to avoid other bee products.

Anaphylactic risk related to omalizumab, benralizumab, reslizumab, mepolizumab, and dupilumab.

BACKGROUND: Monoclonal antibodies (mAbs) are novel, effective therapeutics for the treatment of inadequately controlled severe asthma. Knowledge of the anaphylaxis risks related to different mAbs is essential for their appropriate and safe administration. This study aimed to evaluate the associations between different mAbs and anaphylactic reactions by applying statistical approaches to pharmacovigilance data. METHODS: This was a retrospective study using data from the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2020. A total of 2006 reports of anaphylaxis related to benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab were obtained through data mining. The clinical characteristics of the cases were analyzed, and the risk signals of anaphylactic reactions and corresponding outcomes were investigated in the five mAbs. RESULTS: The patients were mainly young and middle-aged adults, with markedly more women than men. Omalizumab, benralizumab, reslizumab, and mepolizumab showed positive signals for anaphylaxis, while only dupilumab showed a negative signal. The risk of initial or prolonged hospitalization due to anaphylaxis was significantly higher in the benralizumab group than in the omalizumab group (42.86% vs. 28.92%, p = 0.024). Further, when anaphylaxis to omalizumab occurred, patients with asthma were more likely to have life-threatening outcomes than those with chronic urticaria (18.0% vs. 12.9%, p = 0.022). CONCLUSION: In the current real-world study, the positive anaphylaxis signals related to omalizumab, benralizumab, reslizumab, and mepolizumab suggested the need for the close monitoring of patients after drug use, and dupilumab showed a negative signal for anaphylaxis.

Sensitization Profiles of Timothy Grass Pollen in Northern China.

PURPOSE: Grass pollen is an important cause of IgE-mediated allergy in countries worldwide, especially within Europe. However, there has been no research on grass pollen allergy in northern China. We aimed to determine the status of grass pollen allergy and the sensitization patterns to Phleum pratense (P. pratense) in northern China. PATIENTS AND METHODS: Pollen data were collected for three geographic areas (Beijing, Shenmu, Shizuishan) in northern China. The study enrolled 101 patients (62 men; age range, 1-64 years; median age, 10 years) who had allergic rhinoconjunctivitis and/or asthma during the grass pollen season and positive skin prick test results positive to P. pratense. Serum-specific IgE (sIgE) against Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 12 was measured by ImmunoCAP. RESULTS: The pollen season of P. pratense was from June to September in Beijing, May to September in Shenmu and July to August in Shizuishan. P. pratense pollen accounted for 2-3% of the annual pollen index of total pollen counts. Among 101 patients with positive skin prick test results to P. pratense, 72% had detectable sIgE to P. pratense. Phl p 12 was the most frequently recognized component (45%), followed by Phl p 1 (22%), Phl p 5 (14%), Phl p 6 (8%) and Phl p 7 (3%). No patients had sIgE to Phl p 2. Ten sensitization patterns to the six components were observed. High rate of sIgE to Phl p 12 was positively correlated with co-sensitization to weed or tree pollen. CONCLUSION: Considering the pollen concentration, P. pratense was a minor pollen allergen in northern China and its pollen season overlapped with that of weed pollen. IgE sensitization to P. pratense was likely to be induced by cross-reactivity between grass pollen allergy and weed/tree pollen allergy.

Anaphylaxis Associated With Allergen Specific Immunotherapy, Omalizumab, and Dupilumab: A Real World Study Based on the US Food and Drug Administration Adverse Event Reporting System.

Background: Real-world studies on the allergen specific immunotherapy (AIT), omalizumab, and dupilumab associated anaphylactic events are limited. We aimed to analyze the characteristics of drug associated anaphylaxis, and to compare the differences among different drugs. Methods: A disproportionality analysis and Bayesian analysis were used in data mining to identify suspected anaphylaxis associated with AIT, omalizumab, and dupilumab based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2004 to March 2021. Demographic information, time interval to onset, and death rates of AIT, omalizumab, and dupilumab associated anaphylaxis were also analyzed. Results: Totally 9,969 anaphylactic events were identified. Reports of AIT, omalizumab, and dupilumab associated anaphylactic events were 64, 7,784, and 2,121, respectively. AIT had a high reporting odds ratio (ROR) of 5.03 [95%confidental interval (CI) 3.69-6.85], followed by omalizumab (ROR 2.24, 95% CI 2.18-2.29), and dupilumab had a negative signal for anaphylaxis. In children, most anaphylactic reactions (68%) were reported in the 12-17-year-old group. More reports of anaphylaxis related to AIT were in boys (73%), while more reports of anaphylaxis related to omalizumab (63%) and dupilumab (58%) were in girls. Most symptoms occurred on the day of drug initiation. The death rate of AIT related anaphylaxis was the lowest (0%), the death rate of omalizumab was 0.87%, while the death rate of dupilumab was 4.76%. No significant differences were observed among these drugs. Conclusion: AIT and omalizumab had a positive signal for anaphylaxis, while dupilumab had a negative signal for anaphylaxis. Patients should be strictly monitored after administration of AIT and also biologics. It also gives us a suggestion for choosing a combined biologics with AIT when the risk of anaphylaxis was considered.

Neuropsychiatric side reactions of leukotriene receptor antagonist, antihistamine, and inhaled corticosteroid: A real-world analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

BACKGROUND: There are limited real-world studies on the differences in leukotriene receptor antagonists (LTRA), H1-antihistamines (H1-AH), and inhaled corticosteroids (ICS) associated neuropsychiatric events. In this study, we aimed to analyze the characteristics of drug associated neuropsychiatric events, and compare the differences among different drug categories. METHODS: Disproportionality analysis and Bayesian analysis were used in data mining to identify suspected neuropsychiatric events associated with LTRA, H1-AH, and ICS based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2004 to September 2020. Demographic information, time interval to onset, and death rates of LTRA, H1-AH, and ICS-associated neuropsychiatric events were also analyzed. RESULTS: A total of 9475 neuropsychiatric events were identified. The number of neuropsychiatric events related to LTRA, H1-AH, and ICS were 5201 (54.89%), 3226 (34.05%), and 1048 (11.06%), respectively. LTRA related neuropsychiatric events were more common in patients aged 4-6 years (18.66%). H1-AH and ICS related neuropsychiatric events were more common in patients aged 18-44 years (29.92%) and older than 65 years (30.60%), respectively. Montelukast was highly associated with neuropsychiatric events, with a high reporting odds ratio (ROR). Most neuropsychiatric symptoms occurred within the first 10 days after drug initiation (78.63% for LTRA, 91.39% for H1-AH, and 84.07% for ICS). The death rate due to neuropsychiatric events of first generation H1-AH was significantly higher than that of LTRA and ICS (p < 0.001). CONCLUSIONS: LTRA associated neuropsychiatric events reported in FAERS were most frequent in 4 to 6-year-old children. Most reported cases occurred within the first 10 days after drug initiation. The second generation H1-AH was relatively safe for neuropsychiatric events compared with the first generation. The fatality rate due to first generation H1-AH associated neuropsychiatric events was higher than that of LTRA and ICS. More attention should be paid to specific patients treated with LTRA and H1-AH.

Validation of diagnostic and predictive biomarkers for hereditary angioedema via plasma N-glycomics.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease with heterogeneous clinical symptoms. It is vitally important to predict whether an HAE patient will develop severe symptoms in clinical practice, but there are currently no predictive biomarkers for HAE stratification. Plasma N-glycomes are disease-specific and have great potential for the discovery of non-invasive biomarkers. In this study, we profiled the plasma N-glycome of HAE patients from two independent cohorts to identify candidate biomarkers. METHODS: Linkage-specific sialylation derivatization combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry detection and automated data processing was employed to analyze the plasma N-glycome of two independent type-1 HAE cohorts. RESULTS: HAE patients had abnormal glycan complexity, galactosylation, and α2,3- and α2,6-linked sialylation compared to healthy controls (HC). The classification models based on dysregulated glycan traits could successfully discriminate between HAE and HC with area under the curves (AUCs) being greater than 0.9. Some of the aberrant glycans showed response to therapy. Moreover, we identified a series of glycan traits with strong associations with the occurrence of laryngeal or gastrointestinal angioedema or disease severity score. Predictive models based on these traits could be used to predict disease severity (AUC > 0.9). These results were replicated in an independent cohort. CONCLUSIONS: We reported the full plasma N-glycomic signature of HAE for the first time, and identified potential biomarkers. These findings may play a critical role in predicting disease severity and guide the treatment of HAE in clinical practice. Further protein-specific and prospective studies are needed to validate our findings.