It appears that nonsense, frameshift, and mutations on Arg466 can cause lower level of C1 inhibitor antigen than missense and in-frame mutations; however, it does not affect severity of symptoms.
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.
The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2) and depletes ACE2, which is necessary for bradykinin metabolism. The depletion of ACE2 results in the accumulation of des-Arg (9)-bradykinin and possible bradykinin, both of which bind to bradykinin receptors and induce vasodilation, lung injury, and inflammation. It is well known that an overactivated contact system and excessive production of bradykinin comprise the key mechanisms that drive the pathogenesis of hereditary angioedema (HAE). It is reasonable to speculate that COVID-19 may increase disease activity in patients with HAE and vice versa. In this review, we explore the potential interactions between COVID-19 and HAE in terms of the contact system, the complement system, cytokine release, increased T helper 17 cells, and hematologic abnormalities. We conclude with the hypothesis that comorbidity with HAE might favor COVID-19 progression and may worsen its outcomes, while COVID-19 might in turn aggravate pre-existing HAE and prompt the onset of HAE in asymptomatic carriers of HAE-related mutations. Based on the pathophysiologic links, we suggest that long-term prophylaxis should be considered in patients with HAE at risk of SARS-CoV-2 infection, especially the prophylactic use of C1 inhibitor and lanadelumab and that HAE patients must have medications for acute attacks of angioedema. Additionally, therapeutic strategies employed in HAE should be considered for the treatment of COVID-19, and clinical trials should be performed.
Background Hereditary angioedema (HAE) is a rare but serious condition characterized by unpredictable and recurrent attacks affecting the skin and mucosa. HAE has wide-ranging impacts on the health-related quality of life (HRQoL) of patients. This study aims to assess the HRQoL of Chinese patients with HAE using the 36-item Short Form Health Survey (SF-36v2) and to explore potential risk factors for low HRQoL. Methods A total of 104 patients (47 male and 57 female) over age 18 living in China with a known diagnosis of HAE due to C1-INH deficiency completed the SF-36v2 (generic HRQoL questionnaire). The results were compared to Chinese population norms. Subgroup analysis and logistic regression were used to interpret the data. Results SF-36v2 showed a significant reduction in all dimensions of HRQoL ( p < 0.001) in patients with HAE compared with the general Chinese population. Female patients reported significantly lower bodily pain (BP) ( p = 0.039) and physical component scores (PCSs) ( p = 0.027) than male patients. Patients with mucosal edema tended to report lower role-physical (RP) limitations ( p = 0.031) than patients with only skin edema. There were no differences between the mean scores of the SF-36 in relation to disease subtype, age, disease severity and long-term prophylaxis. Among female patients on long-term prophylaxis, social functioning (SF) (r = − 0.404, p = 0.010), role-emotional (RE) (r = − 0.320, p = 0.044) and mental component scores (MCSs) (r = − 0.313, p = 0.049) were negatively correlated with danazol dosage. A correlation between decreased disease control and decreased HRQoL scores was found, although the correlation was not significant in terms of RE or mental health (MH) scores. The logistic regression model revealed uncontrolled disease to be a risk factor for a low PCS (odds ratio 10.77, 95% confidence interval [CI] 1.78–65.06; p = 0.010) and laryngeal edema to be a risk factor for a low MCS (odds ratio 4.75, 95% CI 1.09–20.69; p = 0.038). Conclusions Chinese HAE patients reported significantly lower HRQoL scores than the general population. Unsatisfactory disease control is a risk factor for decreased PCSs. Laryngeal edema is a risk factor for decreased MCSs. Electronic supplementary material The online version of this article (10.1186/s13023-019-1159-5) contains supplementary material, which is available to authorized users.
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.
Background: Patients with pollinosis are often multi-sensitized to diverse pollen allergens. However, little is known about pollen allergy types among Chinese pollinosis patients. This study is aimed to characterize clinical manifestations of food allergy among patients with different types of pollen allergy. Methods:We retrospectively analyzed 402 pollinosis patients from an outpatient allergy department of the Peking Union Medical College Hospital who had been diagnosed by experienced allergists. All included patients who answered a questionnaire regarding seasonal pollinosis and clinical symptoms after ingestion of food and underwent intradermal skin tests. Total IgE and specific IgE levels were quantified by ImmunoCAP, using 0.35 kUA/L as a threshold for positivity. Results:The patients were divided into 3 groups, based on the season during which they experienced symptoms and the 2 peaks of Chinese airborne pollen: spring-tree pollen symptoms group (SG), autumn-weed pollen symptoms group (AG), and a combined spring and autumn pollen symptoms group (CG). Birch pollen (83%) and ash pollen (74%) were common allergens among patients with spring symptoms, while mugwort pollen (87%) was a common allergen among patients with autumn symptoms. In total, 30% of the study population experienced pollenrelated food allergy. Pollen-related food allergies were more prevalent among the single-season symptom groups (68% and 50% for the SG and AG, respectively) than among the CG (20%). All patients with pollen-related food-induced anaphylaxis exhibited autumn weed pollen symptoms. Except for 2 patients, all patients with food-induced anaphylaxis were allergic to mugwort pollen. In the SG, all patients with food allergy were sensitive to birch pollen, with birch and Bet v 1specific IgE levels higher in this group than in the group without food allergy (p < 0.001). In the AG, Art v 3 was more prevalent among patients with pollen-related food allergy than without food allergy (79% vs. 33%, p < 0.001), a proportion similar to the one in the CG (67% vs. 48%, p ¼ 0.01). Meanwhile, the Art v 3-specific IgE levels among patients with pollen-related food allergy were higher than among tolerant patients in the AG (p < 0.001) and CG (p ¼ 0.02). Unexpectedly, the Art v 3-specific IgE levels were higher in patients with food-induced anaphylaxis than with oral allergy syndrome only in the CG.
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