Pathophysiology of Voice Disorders due to Combination Inhaled Corticosteroids in Asthma

哮喘联合吸入皮质类固醇引起的声音障碍的病理生理学

• 批准号: 9918314
• 负责人: Kristine Marie Tanner
• 金额: $ 53.18万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-14 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918314
• 关键词: Address; Adrenal Cortex Hormones; Adult; Adverse effects; Allergic; Analysis of Variance; Animal Model; Animals; Antiinflammatory Effect; Asthma; Behavioral; Biological Assay; Biological Markers; Breathing; Bronchitis; Child; Chlorofluorocarbons; Chronic; Chronic Bronchitis; Clinical; Communication impairment; Control Groups; Differential Diagnosis; Disease; Domestic Animals; Early Diagnosis; Edema; Enrollment; Enzyme-Linked Immunosorbent Assay; Epithelial; Epithelium; Erythema; Face; Foundations; Functional disorder; Goals; Health; Healthcare; Human; Image; Individual; Inflammation; Inflammatory; Inflammatory Response; Inhalation; Inhalators; Injury; Interleukin-1 beta; Interleukin-6; Laryngoscopy; Larynx; Longevity; Lung; Lung diseases; Lymphocyte; Measurement; Measures; Meta-Analysis; Occupational; Onset of illness; Oryctolagus cuniculus; Participant; Pathogenesis; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Physiological; Placebos; Population; Prevalence; Prevention; Public Health; Pulmonary Emphysema; Research; Sampling; Structure; Swelling; Symptoms; TNF gene; Tetraodontidae; Visual; Voice; Voice Disorders; Withdrawal; base; cost; cytokine; disorder prevention; experimental study; flexibility; in vivo; pressure; prevent; programs; psychosocial; public health relevance; side effect; theories; treatment choice; vocal cord; wound healing

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.

项目摘要/摘要 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 支气管炎和阻塞性肺部疾病。仅哮喘就占2500万例，患病率 每十年增加10％。遗传性皮质类固醇（ICS）是选择治疗 呼吸症状的长期治疗。遗憾的是，IC也与UP中的语音障碍有关 到50％的病例。这些疾病变为长期，损害沟通，并拥有大量广告 职业，财务和社会心理后果。鉴于与语音障碍相关的流行率 自2008年禁止使用氯氟化合物的遗传因素以来，ICS的组合。 必要的证据是一项新的研究计划，以应对对公共卫生的这一关键威胁。 该研究计划的长期目标是预防和治愈与 整个生命周期的组合。放在继承者面对终生的孩子，可能永久的 沟通障碍。确定与IC相关语音疾病的病理生理学是关键 开发新的语音哮喘药物的下一步。确定病理生理学至关重要 与组合相关的语音障碍，以治疗，逆转和防止这些声音变化。这 项目以3个假设驱动的目的实现了这些目标。 AIM 1确定结构性喉 IC的生物标志物与2个最常见的儿童和成人中的语音障碍有关 哮喘的表型（高Th2过敏和低Th2原发性嗜酸性粒细胞）。目标2量化语音障碍 使用体内动物模型的IC与假手术的发作和可逆性。 AIM 3检查了 通过检查与注射（IL-1β，IL-6，TNF-α）相关的IC相关语音疾病 动物真实的声带和人类虚假的声带。这些目的共同定义了病理生理学 与IC相关的语音障碍相关，为此奠定了语音障碍的基础 人口。这个翻译项目将具有直接和重大的临床意义，使得 在沟通障碍领域的强大而持续的影响。