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，恢复和清除碎片的工作中接触到大量的灰尘。2004年检查时，这些应答者中有相当数量的人报告至少有一种新的或恶化的上呼吸道症状，2007年50%的应答者仍有慢性鼻-鼻窦炎或上呼吸道疾病（UAD）的症状。此外，在我们睡眠中心的UAD患者中，约有50%的人在接触后立即在问卷中报告新发打鼾，并且阻塞性睡眠呼吸暂停（OSA）的患病率异常高，这似乎与肥胖无关，而肥胖是OSA的常见危险因素。这提示我们，除肥胖外的其他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腔症状，他们也提供了一个独特的机会来检查鼻腔病理和OSA之间的关系，并测试WTC健康计划（WTCHP）中受试者报告的鼻腔症状是否是由于暴露于WTC粉尘引起的鼻腔炎症而导致鼻腔阻力增加的指标。气道正压通气（CPAP）是OSA的标准治疗方法，但疗效较差。高鼻阻力的受试者（如有UAD和OSA反应者）在呼气时上呼吸道可能会遇到额外的压力，导致耐受CPAP治疗的难度大于无高鼻阻力的受试者。在CPAP治疗期间，通过CflexTM （capflex）降低过量呼气正压可能会改善这些受试者的舒适度和依从性，而不会影响CPAP的疗效。在本提案中，我们将研究罗伯特伍德约翰逊医学院环境与职业健康科学研究所（RWJMS）和纽约大学医学院贝尔维尤医院临床卓越中心招收的响应者，并：(i)在1000名没有9/11前OSA证据的受试者中，检查9/11后OSA（使用家庭睡眠监测）与上呼吸道疾病之间的关系（ii）确定911后OSA、上呼吸道疾病、鼻腔炎症（白细胞计数和可溶性IL-8、IL-6、TNF）和鼻阻力（鼻压测量）之间的关系（iii）将OSA患者的鼻阻力与CPAP依从性联系起来，表明使用capflex降低呼气压将改善CPAP依从性。OSA患者将在双盲交叉设计中随机接受CPAP或capflex治疗，并测量依从性。总之，这一建议将产生新的关于WTC暴露个体常见疾病的知识，包括鼻病理和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，它将改善接触世贸中心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，为照顾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.