The global prevalence of allergic diseases, such as allergic rhinitis (AR) and asthma, has gradually increased since 1960s. AR prevalence has surged by 5%–25% across various regions in the past few decades.¹ Similarly, the prevalence of asthma has progressively increased over the last 65 years in industrialized countries and 30–40 years in urbanized areas of low- and middle-level income countries, correlating with the ongoing processes of urbanization and industrialization.² After the industrial revolution and particularly after 1950s when common usage of fossil fuels had started, increased energy consumption and increased waste discharge have led to global warming and climate change, causing air pollution, and chemical hazards—significant contributors to the escalating prevalence of allergic diseases.^{3, 4}

Allergic diseases are triggered by environmental allergens and influenced by climate changes. Studies on the relationship between outpatient visits for AR, airborne pollen concentration, and meteorological factors indicate a robust connection between outpatient visits and seasonal airborne pollen concentration.⁵ In northern China, springtime temperatures are low and dry, causing allergic symptoms and increasing the number of patients with AR, whereas increased humidity reduces outpatient visits. Meanwhile, climate changes, such as thunderstorms, increased temperature and humidity, impact environmental allergen exposure. Global warming contributes to changes in local vegetation patterns, prolonging vegetation periods for allergenic plants. This increases airborne pollen concentrations and prolongs the allergy season. Studies indicate that global warming has caused pollen belts to expand in size and migrate northward over the past 30 years.⁶ In the current issue, Yin et al. investigated the changes in sensitization profiles to aeroallergens among Chinese patients with AR from 2009 to 2021.⁷ Their findings provide comprehensive insights into prevalent aeroallergens crucial for AR diagnosis in China. They identify the most common aeroallergens, and reveal rapidly increasing sensitization rates to cat, dog, and humulus pollen over the last decade. Nonetheless, there still exist undefined allergens that are different from what is already known. Song et al. identified fructose-bisphosphate aldolase as new pollen allergens in two Artemisia species, and report their molecular characterization which is necessary to prompt the clinical application.⁸

Air pollutants serve as irritants and toxins, amplifying the allergenicity of allergens. The “epithelial barrier theory” posits that increased environmental exposure to toxic and inflammatory substances linked to industrialization and modernization disrupts the epithelial barriers, causes microbial dysbiosis and impairs immune homeostasis. This facilitates the presentation of allergens, initiating allergic responses.⁹ Tight junction (TJ) proteins serve as a pivotal constituent of the epithelial barrier, acting as the primary defense against external stimuli. Abnormal expression of TJs plays an essential role in the development and progression of inflammatory airway diseases. In the current issue, Huang et al. give a detailed review and discussion on potential factors contributing to impair and repair of TJs in the nasal epithelium based on their structure, function, and formation process.¹⁰ Substantial evidence demonstrate the association between exposure to air pollutants and an increased risk of allergic disorders.¹¹ Notably, children and adolescents exhibit higher sensitivity to air pollution compared to adults.¹² Additionally, a synergistic effect between air pollutants and pollens may heighten allergenicity and sensitisation, exacerbating symptoms of AR and even nonallergic rhinitis.¹³ Air pollutants can directly influence the characteristics of aeroallergens. Oak pollen exposed to elevated levels of SO₂ or NO₂ significantly increased fragility and disruption of the pollen, subsequently leading to increased release of pollen cytoplasmic granules.¹⁴ Reducing risk exposure, such as air pollution is crucial for prevention and treatment of allergic diseases. In the current issue, Chen et al. highlight that improved ambient air quality is associated with a decreased prevalence of childhood asthma.¹⁵ Preschool children in Shanghai exhibited a significantly lower prevalence of doctor-diagnosed asthma and wheezing in 2019 than in 2011, independently associated with exposure to particulate matter (PM)_2.5, PM_2.5–10, and PM₁₀. Moreover, establishing monitoring and early warning systems for weather-related events can mitigate the impact of air pollution and aeroallergens on atopic diseases. Collaborating with the Beijing Tongren Hospital, Weather China has established a pollen monitoring system containing numerous observation stations that forecast daily airborne pollen concentrations. Utilising these daily pollen deposition values, Yin et al. constructed a prediction grading model of Artemisia pollen allergy based on a 5-grade optimized pollen deposition-level scale in the Beijing area. This model offers early warnings for patient protection and treatment, providing a scientific basis for allergen-specific immunotherapy in the clinical setting.¹⁶

Chinese scholars have consistently advanced findings on the connections and mechanisms linking allergic diseases to environmental exposure. Sun et al. demonstrate the impact of air pollutants and meteorological factors on AR outpatient visits in Shanghai, China. Elevated levels of NO₂ and O₃ were strongly associated with increased hospital visits of AR patients.¹⁷ In addition, He et al. detail an association between daily 1-km resolution levels of ambient air pollution and hospital visits for allergic diseases.¹⁸ By utilizing a 1 × 1 km grid-based level of ambient pollution as a proxy for individual exposure, they revealed significant adverse impacts of individual exposure to PM_2.5 and O₃, resulting in immediate and next-day outpatient visits for allergic diseases. Moreover, the population-average exposure to ambient SO₂ and PM₁₀ was linked to an increased risk of allergic diseases. Climate changes, particularly temperature fluctuations may play a pivotal role in asthma development. Lu et al. reported that extreme temperatures promote the development of allergic asthma in mice.¹⁹ Exposure to extreme temperatures, particularly high temperatures, enhances the expression of inflammatory cytokines, induces oxidative stress in tissues, worsens airway hyperresponsiveness, and exacerbates allergic asthma.

Advancing research on asthma pathogenesis could be accelerated by reconstructing humanized mice equipped with the human immune system. Zhang et al. established a humanized asthma mouse model through intranasal administration of human IL-33 to huHSC-NOG-EXL mouse that possess the human immune system.²⁰ These humanized asthmatic mice exhibited significant eosinophilic inflammation, collagen deposition, and mucous secretion in lung tissue, offering a potential merit in clinical strategies for asthma studies. Neutrophils are recognized as key drivers of severe asthma; however, the regulation of neutrophil lung trafficking, a crucial step in neutrophilic asthma, remains unclear. Jia et al. combined data from human clinical samples with in vitro and in vivo models of neutrophilic asthma and neutrophil migration, and revealed potential roles of reduced developmental endothelial locus-1 (DEL-1) in mediating severe neutrophilic asthma. The downregulation of DEL-1 and subsequent increase in neutrophil migration into the airways of patients with severe asthma suggest that targeting this pathway may be beneficial for treating those patients.²¹

Allergen immunotherapy (AIT) is one of the most important therapies for AR. Tang et al. evaluated the safety and efficacy of Artemisia annua Allergens Sublingual Immunotherapy (SLIT) Drops in Chinese children with seasonal AR. The results indicate that 28-week SLIT treatment was effective and safe for children with Artemisia pollen-induced seasonal AR, with no major safety concerns.²² However, some patients do not response well to AIT. Identifying predictive biomarkers for AIT response is crucial for enhancing clinical efficacy. In the current issue, researchers identified allergen-specific IgE/total IgE ratio, follicular regulatory T/type 2 follicular helper T cell ratio, and CD23+ nonswitched B cell frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort comprised 72 AR patients who completed one-year SCIT follow-up.²³

The atopic march's progression, starting with AD in infancy, followed by the development of allergic asthma and AR, remains a complex phenomenon. Understanding why some children only develop AD, while others proceed with the atopic march is not well-established. In a comprehensive long-term prospective cohort study involving primarily urban, low-income, minority populations at high risk, Wang et al. revealed shared and differential risk factors for AD-only and the progression from AD to atopic march. These findings hold promise for early risk assessment and the identification of children at high risk of atopic march.²⁴ Considering the involvement of skin microbiome in AD pathogenesis, Xu et al. investigated the effects of the skin microbial metabolite propionate on acute and chronic pruritus. Their research demonstrated that propionate treatment significantly alleviated various itches and allokinesis while improving skin inflammation in an AD mouse model. The protective effect of propionate against persistent itch is mediated by direct modulation of sensory TRP channels and neuropeptide production in neurons.²⁵ Exploring itch regulation through the skin microbiome presents a novel strategy for the treatment of AD.

Type 2 inflammation is a characteristic of allergic diseases and various other inflammatory disorders, including chronic rhinosinusitis with nasal polyps (CRSwNP). In their recent study, Wang et al. identified a likely significant role of tenascin C in the formation of type 2 inflammation-related edema, ultimately exacerbating disease severity in CRSwNP. Tenascin C induces the production of matrix metalloproteinase, enhancing collagen degradation, advancing our comprehension of the mechanisms underlying edema in CRSwNP.²⁶ T helper 2 (Th2) cell activation and T regulatory cell (Treg) deficiency are key features of allergic disease. Li et al. comment on the important findings published in Immunity, which identified an isoform of retinoic acid receptor alpha (RARα) that plays decisive roles in the control of T cell activation.^{27, 28} In contrast to RA-dependent transcriptional activation of nuclear RARs, RA negatively influences RARα at the plasma membrane, which results in suboptimal activation and enhanced Treg differentiation. Advances in the underlying mechanisms have driven the discovery of biologics targeting key molecules in the pathogenesis of type 2 inflammation. Dupilumab, as a humanized IgG4 monoclonal antibody targeting IL-4Rα, has shown positive feedback in treating AD patients with different ethnic backgrounds. However, there still lack real-world data for Chinese patients with big sample size. Yang et al. conducted a retrospective, single-center, noncomparative study of all patients diagnosed with moderate-to-severe AD treated with dupilumab, and report similar effectiveness of dupilumab in both quick response and steady control in Chinese AD patients of all ages.²⁹ Furthermore, an upregulation of type 2 related genes has also been observed in skin samples from patients with palmoplantar pustulosis (PPP). In a targeted treatment approach, Zheng et al. administered dupilumab to patients with PPP. Those patients exhibited a robust positive response to dupilumab, offering new insights into the treatment and pathogenesis of PPP.³⁰

In retrospect, Allergy and Chinese researchers has established greater international cooperation and communication, extending their focus beyond allergic diseases to address global health challenges. Notably, Allergy published its initial COVID-19 article by Chinese scholars on 19 February 2020, preceding the first COVID-19 case in Europe.³¹ This ground-breaking study, suggesting that asthma and allergy are not susceptibility factors for SARS-CoV-2 infection,³² marked a significant contribution. In addition, they demonstrated that human to human contact is essential for the spread of the disease and described detailed clinical, laboratory and radiology characteristics of 140 hospitalized COVID-19 patients in Wuhan, China. High levels of D-dimer, C-reactive protein, and procalcitonin were associated with severe patients as biomarkers for prediction and follow up. Eosinopenia, together with lymphopenia, were proposed as an important biomarker for severe COVID-19 and worse outcomes. In the past 4 years, these studies published in Allergy during the early stages of the COVID-19 pandemic comprehensively addressed a spectrum of relevant questions within the context of allergy and asthma.³¹ Amid the swift evolution of artificial intelligence and natural language processing, Shu et al. proposed the implementation of the “human-in-the-loop” strategy, asserting its profound potential to enhance the capabilities of large language models in medical enquiry, as highlighted in this issue.³³ The findings presented by Chinese scholars in this publication aim to further advance our understanding of the environmental influences and immune mechanisms underlying allergic diseases. The editors of Allergy acknowledge the continuous efforts of Chinese scholars in the field of allergies, and look forward to increased international cooperation and contributions.

自20世纪60年代以来，过敏性疾病，如过敏性鼻炎（AR）和哮喘的全球患病率逐渐上升。过去几十年来，不同地区的 AR 患病率激增了 5%–25%。¹同样，过去 65 年来，工业化国家的哮喘患病率逐渐上升，中低收入国家的城市化地区的哮喘患病率在 30-40 年间逐渐上升，这与持续的城市化和工业化进程相关。²工业革命后，特别是 20 世纪 50 年代开始普遍使用化石燃料后，能源消耗增加和废物排放增加导致全球变暖和气候变化，造成空气污染和化学危害——这是导致过敏性疾病流行率不断上升的重要因素。疾病。^{3, 4}

过敏性疾病是由环境过敏原引发并受到气候变化的影响。对 AR 门诊就诊次数、空气花粉浓度和气象因素之间关系的研究表明，门诊就诊次数与季节性空气花粉浓度之间存在密切联系。⁵在中国北方，春季气温较低且干燥，会引起过敏症状并增加 AR 患者的数量，而湿度的增加会减少门诊就诊量。同时，雷暴、温度和湿度升高等气候变化会影响环境过敏原的暴露。全球变暖导致当地植被格局发生变化，延长了过敏植物的植被周期。这会增加空气中花粉的浓度并延长过敏季节。研究表明，过去30年来，全球变暖导致花粉带面积扩大并向北迁移。⁶在本期中，Yin 等人。研究了 2009 年至 2021 年中国 AR 患者对空气过敏原致敏情况的变化^。7他们的研究结果提供了对中国 AR 诊断至关重要的流行空气过敏原的全面见解。他们确定了最常见的空气过敏原，并揭示了过去十年对猫、狗和葎草花粉的过敏率迅速增加。尽管如此，仍然存在与已知不同的未定义的过敏原。宋等人。鉴定出果糖二磷酸醛缩酶是两种蒿属植物中新的花粉过敏原，并报告了它们的分子特征，这对于促进临床应用是必要的。⁸

空气污染物充当刺激物和毒素，放大过敏原的致敏性。 “上皮屏障理论”认为，与工业化和现代化相关的有毒和炎症物质的环境暴露增加会破坏上皮屏障，导致微生物失调并损害免疫稳态。这有利于过敏原的出现，引发过敏反应。⁹紧密连接 (TJ) 蛋白是上皮屏障的关键组成部分，是抵御外部刺激的主要防御手段。 TJs 的异常表达在炎症性气道疾病的发生和进展中起着重要作用。在本期中，黄等人。根据鼻上皮 TJ 的结构、功能和形成过程，对导致鼻上皮 TJ 损伤和修复的潜在因素进行了详细的回顾和讨论。¹⁰大量证据表明，接触空气污染物与过敏性疾病风险增加之间存在关联。¹¹值得注意的是，与成人相比，儿童和青少年对空气污染表现出更高的敏感性。¹²此外，空气污染物和花粉之间的协同效应可能会加剧过敏性和致敏性，从而加剧 AR 甚至非过敏性鼻炎的症状。¹³空气污染物可以直接影响空气过敏原的特性。橡树花粉暴露于高水平的SO ₂或NO ₂显着增加了花粉的脆性和破坏，随后导致花粉细胞质颗粒的释放增加。¹⁴减少空气污染等风险暴露对于预防和治疗过敏性疾病至关重要。在本期中，陈等人。强调环境空气质量的改善与儿童哮喘患病率的降低有关。¹⁵ 2019 年，上海学龄前儿童经医生诊断的哮喘和喘息患病率显着低于 2011 年，且与颗粒物 (PM) _2.5、PM _2.5–10和 PM ₁₀暴露独立相关。此外，建立天气相关事件的监测和预警系统可以减轻空气污染和空气过敏原对特应性疾病的影响。中国天气与北京同仁医院合作建立了一个花粉监测系统，其中包含多个观测站，可以预测每日空气中花粉浓度。 Yin 等人利用这些每日花粉沉积值。构建了蒿属的预测分级模型基于北京地区5级优化花粉沉积水平尺度的花粉过敏研究该模型为患者保护和治疗提供早期预警，为临床过敏原特异性免疫治疗提供科学依据。¹⁶

中国学者在过敏性疾病与环境暴露之间的联系和机制方面不断取得进展。孙等人。证明空气污染物和气象因素对中国上海 AR 门诊就诊的影响。 NO ₂和O ₃水平升高与AR患者就诊次数增加密切相关。¹⁷此外，He 等人。详细说明了环境空气污染的每日 1 公里分辨率水平与过敏性疾病医院就诊之间的关联。¹⁸通过利用基于 1 × 1 公里网格的环境污染水平作为个人暴露的代理，他们揭示了个人暴露于 PM _2.5和 O ₃的显着不利影响，导致过敏性疾病立即和第二天门诊就诊。此外，人口平均暴露于环境 SO ₂和 PM ₁₀与过敏性疾病风险增加有关。气候变化，特别是温度波动可能在哮喘发展中发挥关键作用。卢等人。报道称，极端温度会促进小鼠过敏性哮喘的发生。¹⁹暴露于极端温度，特别是高温下，会增强炎症细胞因子的表达，诱发组织氧化应激，加剧气道高反应性，并加剧过敏性哮喘。

通过重建配备人类免疫系统的人源化小鼠，可以加速哮喘发病机制的研究进展。张等人。通过向具有人类免疫系统的 huHSC-NOG-EXL 小鼠鼻内施用人 IL-33，建立了人源化哮喘小鼠模型。²⁰这些人源化哮喘小鼠在肺组织中表现出明显的嗜酸性炎症、胶原蛋白沉积和粘液分泌，为哮喘研究的临床策略提供了潜在的优点。中性粒细胞被认为是严重哮喘的关键驱动因素；然而，中性粒细胞肺运输的调节是中性粒细胞哮喘的关键步骤，目前尚不清楚。贾等人。将人类临床样本的数据与中性粒细胞哮喘和中性粒细胞迁移的体外和体内模型相结合，揭示了发育性内皮基因座 1 (DEL-1) 减少在介导严重中性粒细胞哮喘中的潜在作用。 DEL-1 的下调以及随后中性粒细胞迁移到严重哮喘患者气道中的增加表明，针对该途径可能有利于治疗这些患者。²¹

过敏原免疫疗法（AIT）是 AR 最重要的疗法之一。唐等人。评估了青蒿过敏原舌下免疫治疗 (SLIT) 滴剂对患有季节性 AR 的中国儿童的安全性和有效性。结果表明，28周的SLIT治疗对于蒿花粉诱发的季节性AR儿童是有效且安全的，没有重大的安全问题。²²然而，一些患者对 AIT 反应不佳。识别 AIT 反应的预测生物标志物对于提高临床疗效至关重要。在本期中，研究人员将过敏原特异性 IgE/总 IgE 比值、滤泡调节性 T/2 型滤泡辅助 T 细胞比值和 CD23+ 非转换 B 细胞频率确定为区分同济队列中 72 名 AR 患者中应答者与非应答者的关键生物标志物完成了为期一年的 SCIT 随访。²³

从婴儿期的 AD 开始，随后发展为过敏性哮喘和 AR，特应性反应的进展仍然是一个复杂的现象。为什么有些孩子只会患 AD，而另一些孩子却会出现特应性症状，这一点尚不明确。在一项主要涉及城市、低收入、高风险少数民族人群的综合长期前瞻性队列研究中，Wang 等人。揭示了仅 AD 的共同和差异危险因素以及从 AD 到特应性进展的进展。这些发现为早期风险评估和识别特应性高风险儿童带来了希望。²⁴考虑到皮肤微生物组参与 AD 发病机制，Xu 等人。研究了皮肤微生物代谢物丙酸盐对急性和慢性瘙痒的影响。他们的研究表明，丙酸盐治疗可显着缓解 AD 小鼠模型中的各种瘙痒和异动，同时改善皮肤炎症。丙酸盐对持续性瘙痒的保护作用是通过直接调节感觉 TRP 通道和神经元中神经肽的产生来介导的。²⁵通过皮肤微生物组探索瘙痒调节为治疗 AD 提供了一种新策略。

2 型炎症是过敏性疾病和各种其他炎症性疾病的特征，包括慢性鼻窦炎伴鼻息肉 (CRSwNP)。在他们最近的研究中，王等人。确定了生腱蛋白 C 在 2 型炎症相关水肿的形成中可能发挥重要作用，最终加剧了 CRSwNP 的疾病严重程度。 Tenascin C 诱导基质金属蛋白酶的产生，增强胶原蛋白降解，促进我们对 CRSwNP 水肿机制的理解。²⁶辅助 T 2 (Th2) 细胞激活和调节性 T 细胞 (Treg) 缺乏是过敏性疾病的关键特征。李等人。对《免疫》杂志上发表的重要发现发表评论，该研究发现了视黄酸受体 α (RARα) 的亚型，在控制 T 细胞激活中发挥决定性作用。^{27, 28}与核 RAR 的 RA 依赖性转录激活相反，RA 对质膜上的 RARα 产生负面影响，导致激活欠佳并增强 Treg 分化。潜在机制的进步推动了针对 2 型炎症发病机制中关键分子的生物制剂的发现。 Dupilumab作为一种靶向IL-4Rα的人源化IgG4单克隆抗体，在治疗不同种族背景的AD患者中显示出积极的反馈。然而，目前仍缺乏大样本的中国患者的真实数据。杨等人。对所有诊断为中重度 AD 的患者进行了一项回顾性、单中心、非比较性研究，并报告了 dupilumab 在所有年龄段的中国 AD 患者中的快速反应和稳定控制方面具有相似的效果。²⁹此外，在掌跖脓疱病 (PPP) 患者的皮肤样本中也观察到 2 型相关基因的上调。在有针对性的治疗方法中，Zheng 等人。给 PPP 患者施用 dupilumab。这些患者对 dupilumab 表现出强烈的积极反应，为 PPP 的治疗和发病机制提供了新的见解。³⁰

回顾过去，过敏与中国研究人员建立了更广泛的国际合作与交流，将他们的关注范围从过敏性疾病扩展到应对全球健康挑战。值得注意的是，Allergy于 2020 年 2 月 19 日发表了由中国学者撰写的首篇有关 COVID-19 的文章，早于欧洲出现首例 COVID-19 病例。³¹这项开创性的研究表明哮喘和过敏不是 SARS-CoV-2 感染的易感因素，³²标志着一项重大贡献。此外，他们证明人与人之间的接触对于该疾病的传播至关重要，并描述了中国武汉 140 名住院 COVID-19 患者的详细临床、实验室和放射学特征。高水平的 D-二聚体、C-反应蛋白和降钙素原与重症患者相关，作为预测和随访的生物标志物。嗜酸性粒细胞减少症与淋巴细胞减少症一起被认为是严重 COVID-19 和更糟糕结果的重要生物标志物。在过去 4 年中，这些在 COVID-19 大流行早期阶段发表在Allergy上的研究全面解决了过敏和哮喘背景下的一系列相关问题。³¹在人工智能和自然语言处理的迅速发展中，Shu 等人。提出实施“人在环”战略，正如本期所强调的那样，断言其在增强大型语言模型在医学查询中的能力方面具有巨大的潜力。³³中国学者在本出版物中提出的研究结果旨在进一步加深我们对过敏性疾病的环境影响和免疫机制的理解。Allergy杂志的编辑们对中国学者在过敏领域的不断努力表示认可，并期待更多的国际合作和贡献。