Clinical Impact and Epidemiology of Nonsteroidal Anti-inflammatory Drug Allergies

项目总结/摘要 非甾体抗炎药（NSAID）适用于许多疾病的一线治疗， 从疼痛到心脏病，但据报道， 过敏虽然NSAID代表第二个最常见的药物过敏报告类别，估计 <20%报告的NSAID诱导的反应与过敏性超敏反应一致（例如，荨麻疹， 血管性水肿、过敏性反应），其余代表非过敏性副作用或不耐受（例如， 胃肠道不适、出血、肾毒性）。过敏过度报告和缺乏反应澄清， 导致不必要药物回避和二线使用的增加，更昂贵且更低效 替代药物，对患者结局产生下游不良影响。主要目的 这项建议的目的是确定报告的NSAID过敏对处方模式和临床的影响。 不同人群的结果，并确定真正的NSAID诱导的过敏性超敏反应的预测因子。的 拟议的研究有三个目的：（1）评估报告的NSAID过敏对术后阿片类药物的影响 在接受电子健康记录的大型患者队列中处方和持续使用阿片类药物， 常见外科手术;（2）评估阿司匹林给药和心血管不良反应的差异 急性冠状动脉综合征患者的结局，有或没有报告NSAID过敏;（3）使用 明确定义的受试者队列，这些受试者接受了过敏症专家观察的NSAID药物激发，以确定 NSAID诱导超敏反应的患者和药物特异性风险因素。李博士的研究计划将是 在临床和流行病学研究设计课程和培训的支持下， 大型数据集、信息学、患者招募和药物挑战方案的研究方法，以及 布里格姆妇女医院特殊的科研环境她将接受来自 博士过敏症专家、阿司匹林和非甾体类抗炎药引起的过敏症专家坦尼娅·莱德劳博士说， 卡伦·科斯坦巴德是一位在研究疾病风险因素方面具有丰富经验的风湿病学家， 使用大型国家队列和数据集研究受影响患者的长期结局。李博士将获得额外的 包括约书亚博伊斯博士在内的三名科学顾问的科学投入和职业指导， Elena Losina和Kimberly布卢门塔尔，他们投入了时间、资源和专业知识， 专业发展和研究目标。这项K23提案与NIH的倡议保持一致， 减少不必要的阿片类药物处方和NIAID对药物过敏研究的支持，并将 候选人在授予期间提交R 01申请，并确定自己是独立的 以患者为导向的研究者，专注于改善药物过敏患者的护理和健康。

PROJECT SUMMARY/ABSTRACT Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for first-line treatment of many conditions ranging from pain to heart disease, but therapeutic use of the entire medication class can be precluded by reported allergy. While NSAIDs represent the second most commonly reported class of drug allergies, it is estimated that <20% of reported NSAID-induced reactions are consistent with allergic hypersensitivity (eg, urticaria, angioedema, anaphylaxis), with the rest representing non-allergic side effects or intolerances (eg, gastrointestinal upset, bleeding, nephrotoxicity). Allergy over-reporting and lack of reaction clarification can lead to unnecessary drug avoidance, and increased use of second line, more costly, and less effective alternative medications, with resultant downstream adverse effects on patient outcomes. The primary objective of this proposal is to determine the impact of reported NSAID allergies on prescribing patterns and clinical outcomes in distinct populations and to define predictors for true NSAID-induced allergic hypersensitivity. The proposed study has three Aims: (1) to assess the impact of reported NSAID allergy on postoperative opioid prescribing and sustained opioid use in a large electronic health record-derived cohort of patients undergoing common surgical procedures; (2) to evaluate differences in aspirin administration and adverse cardiovascular outcomes in patients with acute coronary syndromes with and without reported NSAID allergy; (3) to use a well-defined cohort of subjects who have undergone allergist-observed NSAID drug challenge to determine patient- and drug-specific risk factors for NSAID-induced hypersensitivity. Dr. Li’s research plan will be supported by coursework and training in clinical and epidemiological study design, advanced biostatistical methods for research with large datasets, informatics, patient recruitment, and drug-challenge protocols, and the exceptional scientific environment at the Brigham and Women’s Hospital. She will receive mentorship from Dr. Tanya Laidlaw, an allergy specialist and expert in aspirin- and NSAID-induced hypersensitivity, and Dr. Karen Costenbader, a rheumatologist with extensive experience in investigating risk factors for disease and long-term outcomes in affected patients using large national cohorts and datasets. Dr. Li will obtain additional scientific input and career guidance from a team of three scientific advisors, including Drs. Joshua Boyce, Elena Losina, and Kimberly Blumenthal, who have committed their time, resources and expertise to facilitate her professional development and research goals. This K23 proposal is well-aligned with NIH initiatives to reduce unnecessary opioid prescribing and NIAID support of drug allergy research, and will position the candidate to submit an R01 application during the award period and to establish herself as an independent patient-oriented investigator with a focus on improving the care and health of patients with drug allergies.