Pathophysiology of Voice Disorders due to Combination Inhaled Corticosteroids in Asthma

项目总结/摘要 在美国，超过4000万儿童和成人患有慢性肺部疾病，包括哮喘、慢性呼吸道疾病、哮喘、呼吸道疾病 支气管炎和阻塞性肺病。仅哮喘就占2500万例， 每十年增长10%。联合吸入皮质类固醇（IC）是治疗 长期治疗呼吸道症状。令人遗憾的是，IC也与声音障碍有关， 50%的病例。这些疾病变成慢性的，损害沟通，并具有显著的不利影响。 职业、经济和心理社会后果。考虑到嗓音障碍的普遍性 自2008年禁止使用氯氟烃推进式吸入器以来， 有证据表明，有必要采取新的研究举措，以应对这一对公共卫生的重大威胁。 这项研究计划的长期目标是预防和治疗与之相关的嗓音障碍。 在整个生命周期中的组合IC。使用吸入器的儿童面临终身，可能是永久性的 沟通障碍确定与IC相关的语音障碍的病理生理学是关键 开发新的声音保护哮喘药物的下一步。必须确定其病理生理学 与组合IC相关的声音障碍，以治疗，逆转和预防这些声音变化。这 该项目在3个假设驱动的目标中实现这些目标。目的1确定喉结构 IC使用的生物标志物与儿童和成人的嗓音障碍相关，其中2种最常见 哮喘表型（高TH 2过敏性和低TH 2主要嗜酸性粒细胞）。目标2量化嗓音障碍 使用体内动物模型比较IC与假手术的起效和可逆性。目的3探讨 通过检查与炎症相关的细胞因子（IL-1β、IL-6、TNF-α）， 动物真声带和人类假声带。总的来说，这些目标定义了 与IC相关的嗓音障碍，为嗓音障碍的治疗和预防奠定了基础， 人口这一转化项目将具有直接和重大的临床意义， 在沟通障碍领域产生了强大而持续的影响。

PROJECT SUMMARY/ABSTRACT Over 40 million children and adults in the US suffer from chronic pulmonary diseases including asthma, chronic bronchitis and obstructive pulmonary disease. Asthma alone accounts for 25 million cases, with prevalence increasing by 10% each decade. Combination inhaled corticosteroids (ICs) are the treatment of choice for the long-term management of breathing symptoms. Regrettably, ICs are also associated with voice disorders in up to 50% of cases. These disorders become chronic, impair communication, and have significant adverse occupational, financial, and psychosocial consequences. Given the prevalence of voice disorders associated with combination ICs since chlorofluorocarbon-propelled inhalers were banned in 2008, compelling clinical evidence necessitates a new research initiative to address this critical threat to public health. The long-term goal of this research program is to prevent and cure voice disorders associated with combination ICs across the lifespan. Children placed on inhalers face lifelong, possibly permanent communication impairment. Determining the pathophysiology of IC-related voice disorders is the critical next step to developing new voice-sparing asthma drugs. It is essential to determine the pathophysiology of voice disorders associated with combination ICs, to treat, reverse, and prevent these voice changes. This project accomplishes these objectives in 3 hypothesis-driven aims. Aim 1 determines structural laryngeal biomarkers of IC use associated with voice disorders in children and adults with the 2 most common phenotypes of asthma (high TH2 allergic and low TH2 primarily eosinophilic). Aim 2 quantifies voice disorder onset and reversibility for ICs versus sham using an in vivo animal model. Aim 3 examines the pathogenesis of IC-related voice disorders via examination of cytokines associated with inflammation (IL-1β, IL-6, TNF-α) from animal true vocal folds and human false vocal folds. Collectively, these aims define the pathophysiology associated with IC-related voice disorders, laying the foundation for voice disorder cure and prevention in this population. This translational project will have immediate and significant clinical implications, making a powerful and sustained impact in the field of communication disorders.