Uncontrolled Lower Respiratory Symptoms in the WTC Survivor Program

描述（由申请人提供）：接触世界贸易中心（WTC）灾难的粉尘和烟雾导致响应者和社区成员的上呼吸道和下呼吸道症状（LRS）对健康产生不利影响。贝尔维尤医院世贸中心环境健康中心（WTC EHC）是一个于2005年启动的治疗项目，目标是社区成员，现在被称为“幸存者”，包括当地居民、当地工人和接触世贸中心粉尘和烟雾的清洁工人。下呼吸道症状（咳嗽、喘息、呼吸困难、胸闷）在这个项目的患者中很普遍。尽管接受了治疗，在世贸中心双子塔被毁11年后，许多世贸中心EHC患者报告临床反应不完全，并伴有持续的下呼吸道症状。持续不受控制的下呼吸道症状（LRS）患者仍然接受长期高剂量ICS治疗，通常还使用LABA，使他们面临长期ICS治疗的不良健康影响的风险。尽管进行了治疗干预，但症状仍持续存在，需要重新评估并寻找持续症状的原因。我们的总体假设是，尽管积极的药物治疗，但与症状控制的患者相比，未控制LRS的WTC EHC患者的气道生理异常、气道炎症和合并症的发生率增加。确定不受控制的LRS的这些机制对于指导治疗具有重要的潜力，可以减少继发性不良健康结果。我们将使用一项前瞻性研究来检验这一假设，其目的如下：具体目的1：检验假设，尽管对下呼吸道症状进行了积极治疗，但仍有一组不受控制的下呼吸道症状（ULRS）患者不同于控制的下呼吸道症状（CLRS）患者。特异性目的2：验证与CLRS相比，肺生理学的离散测量与WTC EHC合并ULRS患者相关的假设。特异性目的3：验证与CLRS相比，较高水平的炎症标志物（FeNO、外周嗜酸性粒细胞、c反应蛋白、血清骨膜蛋白）与WTC EHC合并ULRS患者相关的假设。具体目的4：验证与CLRS患者相比，WTC EHC合并ULRS患者合并症发生率增加的假设。这些患者的生理表现、炎症反应和合并症的特征有可能指导该人群降低药物风险的治疗，并将为其他环境诱发下呼吸道疾病或哮喘人群的未来调查提供线索。

DESCRIPTION (provided by applicant): Exposure to the dust and fumes of the World Trade Center (WTC) disaster resulted in adverse health effects with upper and lower respiratory symptoms (LRS) in populations of responders and community members. The Bellevue Hospital WTC Environmental Health Center (WTC EHC) is a treatment program started in 2005 to target community members, now called "Survivors," including local residents, local workers and clean-up workers with WTC dust and fume exposures. Lower respiratory symptoms (cough, wheeze, dyspnea, chest tightness) are prevalent in patients in this program. Despite treatment, eleven years after the destruction of the WTC towers, many patients in the WTC EHC report incomplete clinical response with continued lower respiratory symptoms. Patients with continued uncontrolled lower respiratory symptoms (LRS) remain on treatment with long-term high dose ICS often with additional LABA use, rendering them at risk for adverse health effects of long term ICS treatment. The persistence of symptoms, despite therapeutic interventions, necessitates a reevaluation and a search for causes of persistent symptoms. Our overall hypothesis is that WTC EHC patients with uncontrolled LRS despite aggressive medical therapy have increased rates of abnormal airway physiology, airway inflammation and co-morbid conditions when compared to those with controlled symptoms. Identifying these mechanisms for uncontrolled LRS is imperative to guide therapy with the important potential to reduce secondary adverse health outcomes. We will test this hypothesis using a prospective study with the following aims: Specific Aim 1: To test the hypothesis that despite aggressive treatment for lower respiratory tract symptoms there is a continued group of patients with uncontrolled lower respiratory symptoms (ULRS) that differ from those with controlled lower respiratory symptoms (CLRS). Specific Aim 2: To test the hypothesis that discrete measures of lung physiology are associated with patients in the WTC EHC with URLS compared to CLRS Specific Aim 3: To test the hypothesis that higher levels of inflammatory markers (FeNO, peripheral eosinophils, C-reactive protein, serum periostin) are associated with WTC EHC patients with ULRS compared to CLRS. Specific Aim 4: To test the hypothesis that increased rates of comorbid conditions are associated with WTC EHC patients with ULRS compared to those with CLRS. Characterization of the physiologic findings, inflammatory response and co-morbid conditions in these patients has the potential to guide treatment with reduced medication risk for this population and will provide clues for future investigations in other populations with environmental induced lower respiratory disease or asthma.