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. PUBLIC HEALTH RELEVANCE: Obstructive sleep apnea (OSA) is a highly prevalent disorder with significant morbidity and impact on quality of life that can be improved by treatment with continuous positive airway pressure (CPAP). The present project will examine the role of nasal pathology in WTC responders in the development of OSA and its impact on their ability to use CPAP. The present study contributes to understanding the relationship of nasal /upper airway mechanisms to the development of sleep apnea in this population and explores the possibility of improving comfort and adherence to CPAP treatment by modifying how CPAP is delivered.