MICA: Identifying risks for severe life-threatening allergic reactions to foods (IRIS-Allergy)

MICA：识别严重危及生命的食物过敏反应的风险（IRIS-Allergy）

• 批准号: MR/W018616/1
• 负责人: Paul Turner
• 金额: $ 105.58万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW018616%2F1
• 关键词: MICA; Identifying; risks; severe; life

Food allergy affects up to 3% of adults and 6% of children in the UK, and causes serious reactions (anaphylaxis) which can be fatal. Key to management is dietary avoidance; despite this, accidental reactions are common. Food-allergic patients are therefore prescribed rescue medication (such as adrenaline auto-injectors) to treat anaphylaxis. Most allergic reactions are not life-threatening, and respond to rescue medication. However, very severe reactions do occur and can cause death, even if adrenaline is injected in a timely manner.Currently, we are unable to identify patients at greatest risk of severe reactions. This has a significant adverse impact on quality of life, since all food-allergic individuals must be considered as being at risk of life-threatening reactions. As a result, food-allergic patients, their family and carers, food businesses and regulatory authorities have to prioritise safety and take a maximum risk-averse approach to management - creating a major public health issue.In this project, we will address a key question: can we explain why some food-allergic individuals have near-fatal reactions or die from anaphylaxis, whereas the majority will never have a truly life-threatening reaction despite multiple food exposures and reactions during their lifetime?Our group has discovered that most food-allergic patients have a similar pattern of 'stereotypical' symptoms if exposed to the food they are allergic to on multiple occasions at in-hospital food challenges. For example, some always suffer abdominal pain, whilst others do not experience gut symptoms but present with anaphylaxis. This also seems to be the case for reactions due to accidental exposure happening in the community. Furthermore, the severity of symptoms at food challenge do not correlate well to the amount of allergen eaten. These data suggest that some patients have a predisposition towards very severe (and fatal) anaphylaxis - for example, an inability to compensate when they have an allergic reaction. This represents a new paradigm in understanding factors which contribute to severe outcomes in anaphylaxis, and suggests that fatal/near-fatal food-anaphylaxis could be considered an orphan disease.Our hypothesis is that patients with truly life-threatening anaphylaxis have a different response to food allergen, which can be identified and used to predict risk. The infrastructure of the NHS provides a unique opportunity for us to investigate this.PROJECT PLANUsing NHS datasets, and in full compliance with data protection legislation, we will identify food-allergic individuals who have experienced a previous life-threatening reaction requiring intensive care in an NHS hospital in England ("cases"). We will also recruit patients who experienced a less severe anaphylaxis reaction to the same allergen around the same time, as "controls".Both "cases" and controls will be invited to attend for a detailed assessment, which will include a thorough interview to assess the circumstances of their food allergic reaction(s), and their tendency to asthma and its severity (which could increase the risk of severe reactions). We will complete immune profiling of their allergies using novel chip-based technologies. Anaphylaxis is caused by the activation of "effector" cells such as mast cells and basophils. We will investigate whether differences in anaphylaxis severity can be linked to differences in reactivity of these "effector" cells in the skin and blood. We will also collect samples for future genetic analyses to assess for traits which might predispose towards more severe reactions.By undertaking this evaluation, we will be able to compare cases to controls, to define the circumstances of near-fatal anaphylaxis reactions to food, and identify risk factors for severe outcomes.Our longer-term aim is to develop a risk calculator which can be used by clinicians to identify those at greatest risk of potentially fatal reactions.

在英国，食物过敏影响高达 3% 的成人和 6% 的儿童，并引起严重的反应（过敏反应），甚至可能致命。管理的关键是避免饮食；尽管如此，意外反应还是很常见。因此，食物过敏患者需要服用急救药物（例如肾上腺素自动注射器）来治疗过敏反应。大多数过敏反应不会危及生命，并且对救援药物有反应。然而，即使及时注射肾上腺素，也确实会发生非常严重的反应，并可能导致死亡。目前，我们无法识别发生严重反应风险最大的患者。这对生活质量有显着的不利影响，因为所有食物过敏的人都必须被视为面临危及生命的反应的风险。因此，食物过敏患者、他们的家人和护理人员、食品企业和监管机构必须优先考虑安全，并采取最大程度规避风险的管理方法，从而造成重大公共卫生问题。在这个项目中，我们将解决一个关键问题问题：我们能否解释为什么一些食物过敏的人会出现近乎致命的反应或死于过敏反应，而大多数人尽管一生中多次接触食物和反应，却永远不会出现真正危及生命的反应？如果在院内食物挑战中多次接触他们过敏的食物，食物过敏患者也会出现类似的“刻板”症状。例如，有些人总是出现腹痛，而另一些人则没有出现肠道症状，但出现过敏反应。社区中因意外接触而产生的反应似乎也是如此。此外，食物挑战时症状的严重程度与食用过敏原的量没有很好的相关性。这些数据表明，一些患者有非常严重（且致命）过敏反应的倾向，例如，当他们出现过敏反应时无法补偿。这代表了理解导致过敏反应严重后果的因素的新范式，并表明致命/近乎致命的食物过敏反应可以被视为孤儿疾病。我们的假设是，真正危及生命的过敏反应患者对食物过敏反应有不同的反应食物过敏原，可以识别并用于预测风险。 NHS 的基础设施为我们对此进行调查提供了独特的机会。项目计划使用 NHS 数据集，并完全遵守数据保护立法，我们将识别出曾经经历过危及生命反应的食物过敏个体，需要在一个特殊的环境中进行重症监护。英国 NHS 医院（“病例”）。我们还将招募大约在同一时间对相同过敏原经历过不太严重过敏反应的患者作为“对照”。“病例”和对照都将被邀请参加详细评估，其中包括彻底的访谈以评估他们的食物过敏反应的情况，以及他们患哮喘的倾向及其严重程度（这可能会增加发生严重反应的风险）。我们将使用新型芯片技术完成他们过敏的免疫分析。过敏反应是由肥大细胞和嗜碱性粒细胞等“效应”细胞的激活引起的。我们将研究过敏反应严重程度的差异是否与皮肤和血液中这些“效应”细胞的反应性差异有关。我们还将收集样本用于未来的遗传分析，以评估可能导致更严重反应的特征。通过进行这项评估，我们将能够将病例与对照进行比较，以确定对食物产生近乎致命的过敏反应的情况，以及确定严重后果的风险因素。我们的长期目标是开发一种风险计算器，临床医生可以使用它来识别那些潜在致命反应风险最大的人。

项目成果

Optimal dose of adrenaline auto-injector for children and young people at risk of anaphylaxis: A phase IV randomized controlled crossover study.

对于有过敏反应风险的儿童和青少年来说，肾上腺素自动注射器的最佳剂量：一项 IV 期随机对照交叉研究。

• DOI: http://dx.10.1111/all.15675
• 发表时间: 2023
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Patel N

The future of food allergy: Challenging existing paradigms of clinical practice.

食物过敏的未来：挑战现有的临床实践范式。

• DOI: http://dx.10.1111/all.15757
• 发表时间: 2023
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Anagnostou A

Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists

围手术期过敏反应的紧急治疗：英国复苏委员会麻醉师算法

• DOI: http://dx.10.1111/anae.16206
• 发表时间: 2024
• 期刊: Anaesthesia
• 影响因子: 10.7
• 作者: Dodd A

WAO consensus on DEfinition of Food Allergy SEverity (DEFASE).

WAO 关于食物过敏严重程度定义 (DEFASE) 的共识。

• DOI: http://dx.10.1016/j.waojou.2023.100753
• 发表时间: 2023
• 期刊: The World Allergy Organization journal
• 作者: Arasi S

Who Needs Epinephrine? Anaphylaxis, Autoinjectors, and Parachutes.

谁需要肾上腺素？

• DOI: http://dx.10.1016/j.jaip.2023.02.002
• 发表时间: 2023
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Dribin TE