Pathobiologic profile and outcomes of critically ill children and adolescents exposed to vaping and e-cigarettes

项目摘要 电子烟或吸管相关性肺损伤(EVALI)是一种严重的、危及生命的肺部疾病，占16% 病例发生在18岁以下的患者中。不幸的是，超过10%的高中生 尼古丁或THC每天，近30%的青少年在上个月吸过烟。考虑到最近的 尽管发现了这种疾病，但我们缺乏关于损伤的机制、生理途径的关键信息 EVALI的长期健康影响，特别是在青少年中。目前也不清楚是否 青少年EVALI患者的病理生物学或预后与触发肺损伤的患者不同 更常见的原因，如肺炎或败血症。 虽然EVALI是与电子烟有关的最严重的伤害形式，但其他重要的健康 初次或二次接触电子烟或电子烟可能会产生后果。接触电子烟 与哮喘和其他呼吸系统疾病、呼吸道阻力增加和肺部改变有关 功能。尼古丁是可燃香烟和电子烟的一种成分，对肺和大脑有直接影响。 儿童和青少年的发展。关于二次接触电子产品的数据有限 香烟，尽管它们暗示着有害的健康后果。因此，有很强的生物学合理性 接触过初级或次级电子烟的儿童和青少年更容易患上 严重的肺损伤和不利的健康后果，当他们因其他原因而发生肺损伤时，例如 肺炎或败血症。没有研究具体评估这一点，或者是否存在不同的影响 初次或二次接触蒸气是年龄或先前存在的心肺疾病的一种功能。 我们目前正在招募一批住进重症监护病房(ICU)的儿童(19岁)。 与肺损伤和测试呼吸机管理策略是否改善结果。我们已经开始 从所有参与者那里收集详细的电子烟和香烟接触史，并发现了几个 EVALI病例。此外，我们预计近20%的儿童有明显的二次接触电子- 香烟。我们将利用正在收集的现有生理和结果数据作为这一过程的一部分 随机对照试验，并结合生物标记物和RNA测序数据，以及连续2年的随访- 所有存活到ICU的患者的肺、神经认知、情绪健康和生活质量的改善 出院。这将提供一个前所未有的机会：(A)了解 可能在EVALI的发病机制中很重要，(B)衡量EVALI对儿童的长期健康影响 和青少年，(C)发现二次接触电子烟是否会增加患更严重电子烟的易感性 当儿童因肺炎或败血症等其他原因而出现肺损伤时，疾病或预后不良，以及 (D)确定持续接触电子烟是否会影响康复的轨迹。

Project Summary E-cigarette or Vaping Associated Lung Injury (EVALI) is a severe, life-threatening lung disease with16% of cases occurring in patients less than 18 year of age. Unfortunately, over 10% of high school students vape nicotine or THC daily, and nearly 30% of adolescents have vaped in the last month. Given the recent discovery of this disease, we lack crucial information regarding mechanistic pathways of injury, physiologic characteristics, or the long-term health effects of EVALI, particularly in adolescents. It is also unclear if the pathobiology or outcomes of adolescents with EVALI are different than patients who have lung injury triggered by more common causes, such as pneumonia or sepsis. While EVALI represents the most severe form of injury related to e-cigarettes, other significant health consequences from primary or secondary exposure to e-cigarettes or vaping likely exist. E-cigarette exposure is associated with asthma and other respiratory disease, increased airway resistance, and changes in lung function. Nicotine, a component of both combustible and e-cigarettes, has a direct effect on lung and brain development for children and adolescents. There are limited data regarding secondary exposure to e- cigarettes, although they suggest adverse health outcomes. Therefore, there is strong biological plausibility that children and adolescents with primary or secondary e-cigarette exposure will be more susceptible to severe lung injury and adverse health outcomes when they develop lung injury from other causes, such as pneumonia or sepsis. No studies have evaluated this specifically, or whether there is a differential impact of primary or secondary exposure to vaping as a function of age or pre-existing cardio-respiratory comorbidities. We are currently enrolling a cohort of children (< 19 years) admitted to the intensive care unit (ICU) with lung injury and testing whether a ventilator management strategy improves outcomes. We have begun to collect detailed e-cigarette and cigarette exposure history from all participants and have discovered several cases of EVALI. Furthermore, we anticipate nearly 20% of children have significant secondary exposure to e- cigarettes. We will leverage the existing physiologic and outcome data being collected as part of this randomized controlled trial, and combine it with biomarker and RNA sequencing data, and serial 2-year follow- up of pulmonary, neurocognitive, emotional health, and quality of life of all patients who survive to ICU discharge. This will provide an unprecedented opportunity to: (a) understand mechanistic pathways which may be important in the pathogenesis of EVALI, (b) measure the long-term health effects of EVALI in children and adolescents, (c) discover if secondary exposure to e-cigarettes increases susceptibility to more severe disease or poor outcome when children develop lung injury from other causes like pneumonia or sepsis, and (d) determine if continued exposure to e-cigarettes influences the trajectory of recovery.