Crosslink augmentation to resist snoring and obstructive sleep apnea syndrome

交联增强可抵抗打鼾和阻塞性睡眠呼吸暂停综合症

• 批准号: 8452036
• 负责人: THOMAS P HEDMAN
• 金额: $ 24.49万
• 依托单位: ORTHOPEUTICS, LP
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-05 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8452036
• 关键词: Address; Affect; Age; Air; Animals; Apnea; Architecture; Beds; Biomechanics; Breathing; Cicatrix; Connective Tissue; Crosslinker; Data; Diagnosis; Dorsal; Environmental Wind; Equus caballus; Euthanasia; Exhibits; Failure; Family; Fatigue; Feasibility Studies; Fibrosis; Flaccid Muscle Tone; Frequencies; Human; In Vitro; Incidence; Individual; Inferior; Injectable; Injection of therapeutic agent; Investigation; Lead; Life; Measures; Mechanics; Modeling; Muscle Fibers; Nerve Fibers; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Oral; Palate; Peripheral Nerves; Phase; Physiological; Pilot Projects; Plastics; Play; Prevalence; Prevention; Procedures; Property; Reporting; Resistance; Role; Safety; Schedule; Severities; Sleep; Sleep Deprivation; Small Business Innovation Research Grant; Snoring; Soft Palate; Specimen; System; Techniques; Technology; Testing; Tissues; Trauma; United States; Woman; aged; airway obstruction; awake; base; crosslink; improved; in vivo; men; minimally invasive; phase 1 study; phase 2 study; programs; protein crosslink; public health relevance; resilience; success; treatment effect; vibration

DESCRIPTION (provided by applicant): Snoring is a condition that affects people of all ages, with a reported prevalence of up to 48% of men and 34% of women. Snoring poses not only an inconvenience with regard to sleep-cycle disruption of the sufferer's bed partner and family, but it can also lead to sleep-deprivation in the sufferer and to a more serious and sometimes life-threatening condition, obstructive sleep apnea syndrome (OSAS), where breathing is interrupted during sleep by physical obstruction of the airway. Prevalence of OSAS in the United States has been estimated at 4.2% for those aged 16 and older, or approximately 10 million individuals. Both snoring and OSAS are in most cases the result of obstructed airflow due to abnormalities in the geometry of the air passages and the propensity for aberrant deformation of the soft palate. Repeated trauma to the soft palate due to snoring can be expected to increase its passive deformability and damage muscle fibers and peripheral nerve fibers, increasing the tendency for obstruction. Thus, treatment of snoring can play an important role in reducing the incidence of OSAS. Current treatments include surgery, the use of oral appliances, and more recently, minimally invasive procedures targeted at stiffening the soft palate. All of the newer procedures rely to some extent on the formation of fibrotic scar tissue to stiffen the soft palate. This fibrotic tissue can be expected to exhibit inferior mechanical properties and loss of structural integrity, leading to the eventual loss of some initial treatment-related benefits. This Phase I study aims to determine feasibility of injecting non-toxic protein crosslinking agents to stiffen the soft palate without producing scar tissue. Previous testing suggests that this technique can augment the soft palate's mechanical properties, reduce vibration, and concomitantly increase resistance to mechanical degradation. The overall aim of this program will be to commercialize a less expensive, faster (same-day benefit), and superior injectable treatment for the reduction of snoring, prevention of OSAS, and reduction of airway collapse. Feasibility will be evaluated in four parts: 1) the ability of crosslinking agents to improve the mechanical properties and increase the resistance to mechanical degradation of soft palate tissue will be tested; 2) a wind tunnel test system will be developed to measure the vibration magnitude and oscillation frequency of horse soft palates; 3) the wind tunnel will be used to quantify reduction of vibration in horse soft palates following preferred crosslinker injections; ad 4) safety and treatment effect will be evaluated in pilot studies involving treatment of soft palats in normal horses and horses diagnosed with dorsal displacement of the soft palate (DDSP) which involves a form of awake snoring and apnea.

描述（由申请人提供）：打鼾是一种影响所有年龄段人群的疾病，据报道，男性患病率高达48%，女性患病率高达34%。打鼾不仅给患者的床伴和家人的睡眠周期中断带来不便，而且还会导致患者睡眠不足，并导致更严重的，有时甚至危及生命的情况，即阻塞性睡眠呼吸暂停综合征（OSAS），即睡眠期间呼吸因呼吸道的物理阻塞而中断。据估计，美国16岁及以上人群的OSAS患病率为4.2%，即约1000万人。在大多数情况下，打鼾和OSAS都是由于气流通道几何形状异常和软腭异常变形的倾向而导致气流受阻的结果。因打鼾而反复损伤软腭，可预期其被动变形性增加，损伤肌纤维和周围神经纤维，增加阻塞的倾向。因此，治疗打鼾对减少阻塞性睡眠呼吸暂停的发病率起着重要作用。目前的治疗方法包括手术，使用口腔器械，以及最近针对软腭硬化的微创手术。所有的新手术都在一定程度上依赖于纤维化瘢痕组织的形成来硬化软腭。

项目成果

Soft Palate Modification Using a Collagen Crosslinking Reagent for Equine Dorsal Displacement of the Soft Palate and Other Upper Airway Breathing Disorders.

使用胶原交联试剂对马软腭背侧移位和其他上呼吸道呼吸疾病进行软腭修饰。

• DOI: 10.1155/2019/9310890
• 发表时间: 2019
• 期刊: International journal of biomaterials
• 影响因子: 3.1
• 作者: Hunt,Stephanie;Kuo,Jonathan;Aristizabal,FabioA;Brown,Matt;Patwardhan,Abhijit;Hedman,Thomas
• 通讯作者: Hedman,Thomas