近年, 我国过敏性疾病的患病率逐年增高, 各地医院纷纷设立变态反应科或过敏性疾病诊治中心. 全国各过敏中心希望开展气传花粉调查和监测工作的愿望非常强烈. 花粉症是我国最常见的过敏性疾病. 早在上世纪 80 ～90 年代, 北京协和医院带领全国 79 个城市的 85 家医院进行了我国首次,也是唯一一次全国气传花粉调查和真菌调查; 并首次出版了中国气传花粉调查、中国气传花粉和植物彩色图谱、中国气传真菌彩色图谱等工具书, 为我国花粉症患者特异性精准诊断和治疗及后续花粉过敏原特异性诊断制剂和脱敏治疗制剂的研发奠定了基础.

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 (u-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.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are heterogenetic diseases and exhibit many similarities. Dutch hypothesis proposed that these two diseases may have common genetic origins. This study aims to investigate whether asthma and COPD share a common genetic background in Chinese patients. Methods: In this case-control study, single nucleotide polymorphisms (SNPs) were genotyped using SNaPshot. Haplotype disease analysis and haplotype phenotype analysis were applied to assess the relationship between three polymorphisms of the FCER2 gene and the risk of COPD/asthma. Additionally, associations between polymorphisms of the FCER2 gene and phenotypes were analyzed. Results: We detected ten SNPs of seven genes (FCER1A, FCGR2A, FCGR2B, CHI3L1, ADRB2, STAT6, and FCER2) expressed by airway epithelial cells. We detected genotypes and allele distributions in 251 COPD patients, 597 asthma patients, and 632 healthy controls. A significant difference was found in the FCER2 gene (rs28364072) between COPD patients and controls (P=0.009). Significant differences were observed in the genotype and allele distributions of rs1801274 (FCGR2A), rs12368672 (STAT6), and rs2228137 (FCER2) between asthma patients and controls (P=0.004, 0.007 and 0.010, respectively). Notably, polymorphisms of FCER2 gene were associated with the risk of both COPD (P=0.009 for rs28364072) and asthma (P=0.01 for rs2228137). Haplotype analysis revealed that haplotype T-G-T (alleles of rs28364072, rs2228137, and rs3760687, respectively) was significantly associated with a higher risk of asthma [odds ratios (OR) =2.25, 95% confidence interval (CI): 1.26-4.01, P=0.006]. Further analysis showed that the C-A-C haplotype and C-G-T haplotype were associated with increased blood eosinophils in either COPD or asthma patients (P=0.034, and P<0.001, respectively). Moreover, haplotypes C-A-C, C-G-C, and T-G-C showed significant associations with serum IgE levels in asthma patients (P=0.002, 0.041, and 0.004, respectively). Conclusions: Our data suggest that the FCER2 gene might associate with predisposition to asthma and COPD, while FCER2 haplotypes were associated with pulmonary function measurements and blood eosinophils counts in both diseases. Our findings support the common genetic basis for asthma and COPD, suggesting a potential therapeutic target for the two diseases.

目的 评价猫皮屑、屋尘螨2种常年性变应原制剂集群免疫治疗剂量递增期的安全性.方法 对确诊为猫皮屑(10例)和屋尘螨(21例)过敏的变应性鼻炎伴或不伴哮喘患者进行集群免疫治疗.观察并记录剂量递增期不良反应发生率,并分析可能的危险因素.结果 在5周剂量递增期中,猫皮屑和屋尘螨集群免疫治疗分别注射共计126剂次和248剂次.其速发型局部反应发生率分别为11.1％和3.6％,迟发型局部反应发生率分别为1.6％和4.0％.特异性IgE/总IgE占比在速发型局部反应发生组[14.54％(4.81％,24.17％)]显著高于未发生组[4.65％(0.76％,10.86％)](P=0.043).结论 猫皮屑、屋尘螨集群免疫治疗方案可显著缩短剂量递增期时间,不良反应发生率低.特异性IgE/总IgE占比较高的患者需警惕速发型局部反应发生.

Background Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China. Methods We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes. Results Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years ( P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%). Conclusion The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors.

由中国医师协会、中国医师协会变态反应医师分会(以下简称分会)主办的"中国医师协会第五届变态反应医师分会年会(CCAA2021)"于2021年12月17日至19日以线上线下相结合形式召开.目前疫情虽尚未结束,但分会推广变态反应专科建设、过敏专科医生培训体系建设的脚步没有停下,在尹佳会长的领导下,分会为全国同道精心准备了一场学术盛宴,同时创造了安全而高效的学习、交流渠道.

教育部、国家卫生健康委员会第三轮全国高等学校医学专业研究生国家级规划教材《临床变态反应学》暨《中华医学百科全书·变态反应学》编写会议于2022年4月29日以线上形式召开.北京协和医院变态(过敏)反应科主任医师、北京协和医学院变态反应学系主任、中国医师协会变态反应医师分会会长尹佳教授,向所有与会者表达了热烈的欢迎和诚挚的感谢(图1).

食物过敏是一种由食物变应原引起的异常免疫反应.食物过敏的发生和发展是遗传因素与环境因素的共同作用,其中环境因素发挥重要作用,但其发病机制尚不明确.多项研究表明,肠道菌群与食物过敏的发生和发展密切相关,肠道菌群失衡可通过增强Th2型免疫应答,干扰免疫成熟,减少Treg细胞,破坏肠道黏膜屏障等机制导致机体出现食物过敏.本文针对肠道菌群紊乱与食物过敏的关系及其潜在机制进行综述,为食物过敏的早期预防及病因治疗提供依据.

Background Efficient therapy and potential prophylaxis are confounded by current ignorance of the pathogenesis of airway remodelling and blockade in COPD. Objective To explore the role of the IL-33/ST2 axis in cigarette smoke (CS) exposure-induced airways remodelling. Methods C57BL/6, BALB/c and IL-1RL1 -/- mice exposed to CS were used to establish an animal surrogate of COPD (air-exposed=5~8, CS-exposed=6~12). Hallmarks of remodelling were measured in mice. Cigarette smoke extract (CSE)-induced proliferation and protein production in vitro by fibroblasts in the presence of anti-interleukin-33 (anti-IL-33) or hST2 antibodies were measured. Expression of IL-33 and ST2 and other remodelling hallmarks were measured, respectively, in bronchoalveolar lavage fluid (BALF) (controls=20, COPD=20), serum (controls=59, COPD=90) and lung tissue sections (controls=11, COPD=7) from patients with COPD and controls. Results Wild-type mice exposed to CS elevated expression of hallmarks of tissue remodelling in the lungs and also in the heart, spleen and kidneys, which were significantly abrogated in the IL-1RL1 -/- mice. Fibroblasts exposed to CSE, compared with control, exhibited early cellular translocation of IL-33, accompanied by proliferation and elevated protein synthesis, all inhabitable by blockade of IL-33/ST2 signalling. Expression of IL-33 and ST2 and hallmarks of tissue remodelling were significantly and proportionally elevated in BALF, serum and tissue samples from patients with COPD. Conclusions Exposure to CS induces remodelling changes in multiple organs. The data support the hypothesis that CS-induced lung collagen deposition is at least partly a result of CS-induced IL-33 translocation and release from local fibroblasts.

目的 评价皮下免疫治疗(subcutaneous immunotherapy,SCIT)在过敏性鼻炎和过敏性哮喘中的疗效及安全性.方法 采用多中心、横断面调查研究方法对2020年1月至2020年12月11家医疗机构的患者进行问卷调查,比较SCIT治疗前后过敏性鼻炎患者鼻结膜炎症状及用药评分,哮喘患者用药情况、哮喘控制测试(asthma control test,ACT)评分和哮喘急性加重次数.总结分析SCIT过程中的局部及全身不良反应.结果 246例过敏性鼻炎和/或过敏性哮喘患者纳入研究,96.7％患者经SCIT治疗后自觉临床症状改善,SCIT治疗的中位起效时间为1(1,2)年.SCIT治疗前后,鼻结膜炎症状[1.8(1.3,2.5)vs.1(0.5,1.3)]、鼻结膜炎用药评分[2(1,2)vs.1(0,2)]、ACT评分[(16.0±4.6)vs.(21.4±3.3)]差异有统计学意义(P<0.001).SCIT治疗后,口服抗组胺药、抗组胺喷鼻剂、抗组胺药滴眼液、激素类喷鼻剂、激素类滴眼液、口服白三烯受体拮抗剂和口服茶碱类药物的用药时间缩短(P<0.05).哮喘患者在SCIT后停用吸入激素的比例较治疗前增加[(52例(34.2％)vs.72例(47.4％)],因急性加重急诊就诊次数减少(P<0.001).共89例患者出现注射局部不良反应;24例患者出现27例次全身不良反应,占全部总注射次数的0.035％(27次/77000次);22例次在注射30 min内发生,92.5％(25/27)与注射花粉变应原相关.结论 应用皮下注射免疫治疗可安全、有效的治疗过敏性鼻炎和过敏性哮喘.

Chronic obstructive pulmonary disease (COPD)/pulmonary emphysema is driven by the dysregulated airway inflammation and primarily influenced by the interaction between cigarette smoking (CS) and the individual’s susceptibility. The inflammation in COPD involves both innate and adaptive immunity. By binding to its specific ligands, chemokine receptor CXCR3 plays an important role in regulating tissue inflammation and damage. In acute animal model challenged with either CS or pathogens, CXCR3 knockout (KO) attenuated lung inflammation and pathology. However, the role of CXCR3 in CS-induced chronic airway inflammation and pulmonary emphysema remains unknown. In this present study, we investigated the effect of CXCR3 in CS-induced pulmonary emphysema in an animal model, and the association between CXCR3 single nucleotide polymorphisms (SNPs) and COPD susceptibility in human subjects. We found that after chronic exposure to side stream CS (SSCS) for 24 weeks, CXCR3 KO mice demonstrated significant airspace enlargement expressed by mean linear intercept (Lm) compared with the wild-type (WT) mice. Consistently, CXCR3 KO mice had significantly higher BAL fluid macrophages and neutrophils, TNFα, and lung homogenate MMP-9 and MMP-12. Through genetic analysis of CXCR3 polymorphisms in a cohort of COPD patients with Han Chinese ethnicity, one CXCR3 SNP, rs2280964, was found to be genetically related to COPD susceptibility. Furthermore, CXCR3 SNP rs2280964 was significantly associated with the levels of serum MMP-9 in COPD patients. Our data from both animal and human studies revealed a novel role of CXCR3 possibly via influencing MMP9 production in the pathogenesis and progression of CS-associated COPD/pulmonary emphysema.

Background IL-1 receptor associated-kinase (IRAK)-M, expressed by airway epithelium and macrophages, was shown to regulate acute and chronic airway inflammation exhibiting a biphasic response in an OVA-based animal model. House dust mite (HDM) is a common real-life aeroallergen highly relevant to asthma pathogenesis. The role of IRAK-M in HDM-induced asthma remains unknown. This study was aimed to investigate the effect of IRAK-M on allergic airway inflammation induced by HDM using IRAK-M knockout (KO) mice and the potential underlying mechanisms. Methods IRAK-M KO and wild-type (WT) mice were sensitized and challenged with HDM. The differences in airway inflammation were evaluated 24 hours after the last challenge between the two genotypes of mice using a number of cellular and molecular biological techniques. In vitro mechanistic investigation was also involved. Results Lung expression of IRAK-M was significantly upregulated by HDM in the WT mice. Compared with the WT controls, HDM-treated IRAK-M KO mice showed exacerbated infiltration of inflammatory cells, particularly Th2 cells, in the airways and mucus overproduction, higher epithelial mediators IL-25, IL-33 and TSLP and Th2 cytokines in bronchoalveolar lavage (BAL) fluid. Lung IRAK-M KO macrophages expressed higher percentage of costimulatory molecules OX40L and CD 80 and exhibited enhanced antigen uptake. However, IRAK-M KO didn’t impact the airway hyperreactivity (AHR) indirectly induced by HDM. Conclusions The findings indicate that IRAK-M protects allergic airway inflammation, not AHR, by modifying activation and antigen uptake of lung macrophages following HDM stimulation. Optimal regulation of IRAK-M might indicate an intriguing therapeutic avenue for allergic airway inflammation.

Pollinosis is induced by pollen allergens, IgE-mediated and affects the respiratory system, cutaneous system, etc. Its prevalence is gradually increasing. The pollen map and calendar are acquired through pollen monitoring. Pollinosis is affected by meteorological factors and results in thunderstorm asthma. It is associated with food allergy, which can induce oral allergy syndrome and even anaphylaxis. In addition, pollinosis may progress from allergic rhinitis to asthma. Laboratory investigations for pollinosis include in vivo and in vitro tests. Pollen prevention, medication, and immunotherapy are the primary treatment modalities, and omalizumab is effective and safe.

Background: Bronchiectasis is characterized by recurrent infectious exacerbations. No existing data inform preventive strategy for exacerbations beyond chronic macrolides. OM-85 BV, an immunostimulant, has been shown to prevent recurrent respiratory infections. We initiated this 1-year, multi-centered, double-blind, and controlled trial to investigate the PReventive effect of OM-85 BV on Bronchiectasis Exacerbations in Chinese patients (iPROBE). Methods: Patients with bronchiectasis aged 18 to 75 years, having at least one exacerbation in the past year, were randomized to receive, in addition to any respiratory medications, two courses of 7 mg of OM-85 BV or matching placebo (one capsule orally per day for 10 days a month) for 3 consecutive months, followed by 3 months without treatment. The primary outcomes included the number of acute infectious exacerbations and the time to first exacerbation. Secondary endpoints included patient-reported respiratory outcomes. Safety measures were also assessed. Results: Among the 196 participants, 99 were in the OM-85 BV group and 97 in the placebo group. At week 52, the mean number of acute exacerbations per patient was equal to 0.98 and 0.75, respectively, in the two groups (P=0.14). Difference in the time to first pulmonary exacerbation was not statistically significant (P=0.11). There was no statistically significant difference in any secondary end-points. The safety profile in the two arms was good and the majority of adverse events were mild. Conclusions: OM-85 BV did not demonstrate protection in decreasing pulmonary exacerbations of bronchiectasis in this trial performed in Chinese patients. It had good safety profile.

To evaluate the efficacy and safety of subcutaneous immunotherapy (SCIT) for allergic asthma with summer and autumn pollen mixed allergen extracts. Clinical data of 25 allergic asthma patients were collected and analyzed. Self-assessment of asthma control, asthma control test (ACT), medication scores, and the percentage of forced expiratory volume in the first second to predicted value (FEV1%) were evaluated pre- and after SCIT. Adverse reactions were also recorded. Among the 25 patients with allergic asthma, 13 were prescribed with single summer and autumn pollen allergen mixed extracts, and 12 with pollen and dust mite allergen combined extracts. After SCIT, asthma symptoms improved in all patients, of which 52% (13/25) patients' asthma symptoms improved significantly. The asthma control rate increased from 52% to 92%, 36% (9/25) patients completely discontinued asthma medication, and 32% (8/25) patients' asthma medication dose was significantly reduced. The average effective time of SCIT was 20.5±9.6 months. Compared with the baseline level, the ACT score of the two groups of patients increased significantly (P <0.05), FEV1% was increased significantly (P <0.05), and the total score of asthma medication was reduced significantly (P <0.01). Twelve patients had local adverse reactions caused by injection, and 4 patients had a total of 4 systemic adverse reactions. All patients' adverse reactions relieved within a short period. The application of summer and autumn pollen allergen mixed allergen can treat summer and autumn pollen-induced allergic asthma effectively and safely.

由中国医师协会、中国医师协会变态反应医师分会主办的 "中国医师协会第四届变态反应医师分会年会 ( CCAA2020) " 于2020年12月25-26日以线上直播形式召开. 本次会议是在疫情常态化防控形势下举行的一次特殊会议. 分会以线上办会的模式, 为全国同道提供了更便捷、 更安全的交流渠道.

Bronchial asthma (asthma) is such a chronic airway inflammatory disease which mediated by T helper cell type 2 (Th2).The Th2 cells secret interleukin-4 (IL-4) and IL-13,which activate the downstream signal transduction through the co-receptor interleukin-4 receptor α(IL-4Rα).Dupilumab is a fully human anti-IL-4 Rα monoclonal antibody that competitive inhibits the combination between IL-4Rα and IL-4 or IL-13,which can reduce severe exacerbation and increased lung function in patients with severe asthma.The update of the efficacy and safety of dupilumab for treating severe asthma is reviewed in this article.

云天收夏色,木叶动秋声.立秋是秋天的第一个节气, 一叶知秋, 也拉开了中国北方地区秋季花粉症的序幕, 每年8月第2周被定为"中国过敏防治周".2020年8月3日至9日是我国第五个"中国过敏防治周", 今年的主题是"精准诊断, 精准防治".作为2020年"中国过敏防治周"系列活动的核心, 由北京协和医院、北京医师协会变态反应医师分会主办的"北京医师协会变态反应医师分会第4届学术年会暨第14届协和过敏性疾病国际高峰论坛"于2020年8月8日在线上隆重召开(图1).

Background Food-borne trematodiases are an important group of neglected global diseases. Affected patients in regions with low prevalence usually experience delayed diagnosis, especially when presenting with atypical clinical symptoms. Here, we presented a rare case of a Chinese patient infected with three food-borne trematodiases. Case presentation A 42-year-old man presented with diarrhea, lower extremity edema, and symptoms of cardiac dysfunction. He had a history of intermittent consumption of raw freshwater fishes for 6–7 years. Upon evaluation, he had eosinophilia, anemia, intrahepatic bile duct dilatation and a growing space-occupying lesion in the left atrium. The patient underwent a cardiac surgery which revealed an endocardial hematoma due to mechanical injuries. Imaging investigations also revealed intracranial and pulmonary lesions. A total of three trematodiases were diagnosed based upon microscopic stool examination, from which eggs of Clonorchis sinensis , Heterophyidae and Echinostomatidae were identified. Deposition of Clonorchis sinensis eggs was also observed from ileocecal squash slides. The patient was successfully treated with three cycles of praziquantel. Conclusions Food-borne trematodiases may present with systemic involvement. Patients with dietary history of high risk or atypical ingestions should be evaluated for parasitic infection, even in non-endemic areas.

IL-1R–associated kinase (IRAK)-M regulates lung immunity during asthmatic airway inflammation. However, the regulatory effect of IRAK-M differs when airway inflammation persists. A positive association between IRAK-M polymorphisms with childhood asthma has been reported. In this study, we investigated the role of IRAK-M in the susceptibility to adult-onset asthma and in chronic airway inflammation using an animal model. Through genetic analysis of IRAK-M polymorphisms in a cohort of adult-onset asthma patients of Chinese Han ethnicity, we identified two IRAK-M single nucleotide polymorphisms, rs1624395 and rs1370128, genetically associated with adult-onset asthma. Functionally, the top-associated rs1624395, with an enhanced affinity to the transcription factor c-Jun, was associated with a higher expression of IRAK-M mRNA in blood monocytes. In contrast to the protective effect of IRAK-M in acute asthmatic inflammation, we found a provoking impact of IRAK-M on chronic asthmatic inflammation. Following chronic OVA stimulation, IRAK-M knockout (KO) mice presented with significantly less inflammatory cells, a lower Th2 cytokine level, a higher IFN-γ concentration, and increased percentage of Th1 cells in the lung tissue than wild type mice. Moreover, lung dendritic cells (DC) from OVA-treated IRAK-M KO mice expressed a higher percentage of costimulatory molecules PD-L1 and PD-L2. Mechanistically, in vitro TLR ligation led to a greater IFN-γ production by IRAK-M KO DCs than wild type DCs. These findings demonstrated a distinctive role of IRAK-M in maintaining chronic Th2 airway inflammation via inhibiting the DC-mediated Th1 activation and indicated a complex role for IRAK-M in the initiation and progression of experimental allergic asthma.