Obstructive Sleep Apnea in WTC Responders: Role of Nasal Pathology

描述(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暴露在大量粉尘中。这些应答者中有相当数量的人在2004年检查时报告了至少一种新的或恶化的上呼吸道症状，其中50%的应答者在2007年继续有慢性鼻窦炎或上呼吸道疾病的症状。此外，在我们睡眠中心提到的UAD患者中，约有50%在暴露后立即在他们的问卷中报告了新的鼾声发作，并有异常高的阻塞性睡眠呼吸暂停(OSA)患病率，似乎与肥胖无关，肥胖是OSA的常见风险因素。这向我们表明，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和OSA之间的关系，并测试WTC健康计划(WTCHP)中的受试者报告的鼻部症状是否是由于接触WTC粉尘导致鼻部炎症而导致鼻阻力增加的指标。呼吸道正压(CPAP)是阻塞性睡眠呼吸暂停综合征(OSA)的标准治疗方法，但尽管它有效，但依从性差。鼻腔阻力高的受试者(如UAD和OSA的应答者)在上呼吸道呼气时可能会感受到额外的压力，导致比那些没有鼻腔阻力的受试者更难耐受CPAP治疗。在CPAP治疗期间，通过称为CfleTM的模式(CPAPFlex)减少多余的呼气正压可能会在不影响CPAP疗效的情况下改善这些受试者的舒适性和依从性。在目前的提案中，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)和纽约大学医学院贝尔维尤医院临床卓越中心登记的应答者，并：(I)在1000名没有9/11OSA之前证据的受试者中，检查911后OSA(使用家庭睡眠监测)与上呼吸道疾病的关系(Ii)确定911后OSA、上呼吸道疾病、鼻炎(白细胞计数和可溶性IL-8、IL-6、鼻腔阻力(肿瘤坏死因子)和鼻腔阻力(鼻压计)(Iii)与阻塞性睡眠呼吸暂停患者的鼻腔阻力有关，表明使用CPAPFlex降低呼气压力将改善CPAP的粘附性。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。总而言之，这项建议将产生关于WTC接触者常见疾病的新知识，包括鼻部病理和OSA。通过使用成本更低但同样有效的睡眠障碍呼吸评估(有限渠道便携式监测)和自动CPAP启动，它将改善接触WTC粉尘的个人的护理机会。将对不同疗法的依从性和有效性进行评估，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.