Obstructive Sleep Apnea in WTC Responders: Role of Nasal Pathology

描述（由申请人提供）：在世界贸易中心（WTC）灾难之后，估计有40，000人在救援，恢复和碎片清除工作中暴露于大量灰尘。在2004年检查时，这些应答者中有相当数量的人报告了至少一种新的或恶化的上呼吸道呼吸道症状，其中50%的应答者在2007年继续有慢性鼻-鼻窦炎或上呼吸道疾病（UAD）的症状。此外，约50%的UAD患者在我们的睡眠中心报告了他们暴露后立即在问卷中报告的新发打鼾，并且阻塞性睡眠呼吸暂停（OSA）的患病率异常高，似乎与肥胖无关，这是OSA的常见风险因素。这提示我们肥胖以外的机制可能在这些受试者的OSA发病机制中起重要作用。考虑到他们的慢性鼻部症状，他们还提供了一个独特的机会来检查鼻部病理学和OSA之间的关系，并测试受试者在WTC健康计划（WTCHP）中报告的鼻部症状是否是由于暴露于WTC灰尘导致的鼻部炎症而导致的鼻阻力增加的指标。气道正压通气（CPAP）是OSA的标准治疗方法，但尽管其有效，依从性较差。具有高鼻阻力的受试者（例如患有UAD和OSA的应答者）可能在呼气期间在上气道处经历额外的压力，导致比不具有高鼻阻力的受试者更难耐受CPAP治疗。在CPAP治疗过程中，通过称为CflexTM（CPAPFlex）的方式减少过量呼气正压，可以改善这些受试者的舒适度和依从性，而不会影响CPAP疗效。在本提案中，我们将研究在罗伯特·伍德约翰逊医学院环境与职业健康科学研究所（RWJMS）和贝尔维尤医院纽约大学医学院临床卓越中心注册的应答者，以及：（一）审查9/11事件后的业务支助服务与（使用家庭睡眠监测）和上呼吸道疾病之间的关系，在1000名没有911前OSA证据的受试者中（ii）确定911后OSA、上呼吸道疾病、鼻炎症（白细胞计数和可溶性IL-8、IL-6、TNF）和鼻阻力（鼻测压法）（iii）将OSA患者的鼻阻力与CPAP依从性相关联，以表明使用CPAPFlex降低呼气压将改善CPAP依从性。OSA患者将以双盲交叉设计随机接受CPAP或CPAPFlex治疗，并测量依从性。总之，该提案将产生关于WTC暴露个体常见状况的新知识，包括鼻部病理学和OSA。通过使用成本较低但同样有效的睡眠呼吸障碍评估（有限通道便携式监测）和自动CPAP启动，它将改善暴露于WTC粉尘的个人获得护理的机会。将评估不同疗法的依从性和疗效，为护理这些患者的医生提供指导。

DESCRIPTION (provided by applicant): Following the World Trade Center (WTC) disaster, an estimated 40,000 individuals were exposed to significant amounts of dust while working in rescue, recovery and debris removal. A significant number of these responders have reported least one new or worsened upper airway respiratory symptom when examined in 2004 with 50% of responders continuing to have symptoms of chronic rhino-sinusitis or upper airway disease (UAD) in 2007. In addition, about 50% of those with UAD referred to our sleep center reported new onset snoring on their questionnaires immediately following their exposure and had unusually high prevalence of obstructive sleep apnea (OSA) that did not appear to be related to obesity, which is the usual risk factor for OSA. This suggests to us that mechanisms other than obesity may be important in the pathogenesis of OSA in these subjects. Given their chronic nasal symptoms they also provide a unique opportunity to examine the relationship between nasal pathology and OSA and test if nasal symptoms reported by the subjects in the WTC Health Program (WTCHP) are an indicator of increased nasal resistance due to nasal inflammation resulting from exposure to the WTC dust. Positive Airway Pressure (CPAP) is the standard therapy for OSA but despite its efficacy has poor adherence. Subjects with high nasal resistance (such as responders with UAD and OSA) may experience additional pressure during expiration at the upper airway resulting in greater difficulty in tolerating CPAP therapy than those who do not have high nasal resistance. Reduction of excess expiratory positive pressure by the modality known as CflexTM during CPAP therapy (CPAPFlex) may improve comfort and adherence in these subjects without compromising CPAP efficacy. In the present proposal we will study responders enrolled at the Environmental and Occupational Health Sciences Institute of Robert Wood Johnson Medical School (RWJMS) and the NYU School of Medicine Clinical Center of Excellence at Bellevue Hospital and: (i) Examine the relationships between post-9/11 OSA (using home sleep monitoring) and upper airway disease, in 1000 subjects without evidence of pre-9/11OSA (ii) Determine the relationship between post-911 OSA, upper airway disease, nasal inflammation (leukocyte counts and soluble IL-8, IL-6, TNF) and nasal resistance (rhinomanometry) (iii) Relate nasal resistance to CPAP adherence in patients with OSA to show that reduction of expiratory pressure using CPAPFlex will improve CPAP adherence. Patients with OSA will be randomized in a double blind cross over design to receive CPAP or CPAPFlex and adherence will be measured. In summary, this proposal will generate new knowledge about conditions common in WTC exposed individuals, including nasal pathology and OSA. By using a less costly but equally effective evaluation of sleep disordered breathing (limited channel portable monitoring) and automated CPAP initiation it will improve access to care for individuals exposed to WTC dust. Adherence and efficacy of different therapies will be evaluated providing guidelines to physicians caring for these patients.