Evolution of Risk Factors for Sinusitis in WTC Exposed Firefighters

描述（由申请人提供）：世界贸易中心（WTC）暴露导致所有暴露队列的上呼吸道和下呼吸道损伤。纽约消防局、纽约大学和西奈山医院之间的合作将研究wtc相关的上呼吸道损伤。虽然下气道损伤病例在2001年9月11日的几周内出现，但上呼吸道损伤的程度，如慢性鼻窦炎，需要几年的时间才能出现。在FDNY队列中，慢性鼻窦炎的发病率一直在上升。自2001年9月11日以来，通过鼻窦CT扫描确诊慢性鼻窦炎1821例；在这些病情最严重的患者中，有412人需要进行手术。由于迫切需要更好的预测工具来对这些患者进行风险分层，纽约大学/FDNY团队寻找鼻窦炎严重程度的生物标志物。我们最近报道，暴露后早期血液中中性粒细胞浓度的增加降低了随后鼻窦炎和鼻窦手术的风险（Cho等人，2013：一种气道：世界贸易中心暴露后保护上呼吸道和下呼吸道损伤的生物标志物）。目前的提议将验证一个假设，即暴露后早期全血细胞计数（CBC）中的白细胞浓度可以预测随后的鼻窦息肉和鼻窦手术的需要。由于CBC是WTC医学监测检查的常规部分，中性粒细胞和嗜酸性粒细胞浓度已经是所有WTC暴露队列纵向数据集的组成部分。因此，本建议建立的风险模型可以很容易地在所有世贸中心暴露人群中得到确认和应用。目的1：我们提出了一项回顾性队列研究，使用所有1540名暴露于世贸中心的FDNY消防员的数据，这些消防员都有早期CBC和随后的窦性CT扫描。我们将建立两个逻辑模型，以鼻窦手术和鼻窦息肉作为结果，以证实我们的初步数据，即早期中性粒细胞和嗜酸性粒细胞浓度预测这些结果。目的2：我们提出一项前瞻性巢式病例对照研究。我们将招募未被诊断为慢性鼻窦炎但有持续鼻窦症状的患者参加筛查问卷。结果是鼻窦息肉，因为这是一个客观的鼻窦炎严重程度的替代诊断，但持续症状组。我们将招募106名在世贸中心暴露后不久的低PMN浓度的消防员（病例）和106名高PMN浓度的消防员（低概率鼻窦息肉）（对照组）。我们将进行鼻窦CT，鼻腔冲洗和耳鼻喉科检查。我们将对鼻窦炎的严重程度和炎症进行客观测量，并通过非培养技术识别潜在的病原体。相对于对照组，我们预测病例将有更多的窦息肉、炎症和病原体。利用先前的CBCs信息对有鼻窦症状的WTC患者进行更好的分层可以指出更有效的诊断和治疗方法。低风险患者可以避免昂贵但不必要的检测。或者，高风险患者可以在这种新出现的致残性WTC相关疾病的早期接受更强化的治疗。

DESCRIPTION (provided by applicant): World Trade Center (WTC) exposure resulted in upper and lower airway injury in all exposed cohorts. This collaboration between the FDNY, NYU and Mt. Sinai will study WTC-related upper airway injury. While cases of lower airway injury presented within weeks of 9/11/2001, it took years longer for the extent of upper airway injury such as chronic sinusitis to emerge. In the FDNY cohort, the incidence of chronic sinusitis has been rising. Since 9/11/2001, 1,821 cases of chronic sinusitis have been confirmed by sinus CT scans; 412 of these patients with the most severe disease have required surgery. Because of the urgent need for better predictive tools to risk stratify these patients, the NYU/FDNY team sought biomarkers of sinusitis severity. We recently reported that increasing neutrophil concentration in blood early after exposure reduced the risk of subsequent sinusitis and sinus surgery (Cho et al., 2013: One airway: Biomarkers of protection from upper and lower airway injury after World Trade Center exposure). The current proposal will test the hypothesis that leukocyte concentration in the Complete Blood Count (CBC) early after exposure predicts subsequent sinus polyps and need for sinus surgery. Because the CBC is a routine part of the WTC medical monitoring exam, the neutrophil and eosinophil concentrations are already components of the longitudinal data sets for all WTC exposed cohorts. As a result, the risk models developed by this proposal can be readily confirmed in and applied to all WTC exposed cohorts. AIM 1: We propose a retrospective cohort study using data from all 1,540 WTC- exposed FDNY firefighters who have had an early CBC and subsequent sinus CT scan. We will develop two logistic models with sinus surgery and sinus polyps as outcomes to confirm our preliminary data that early neutrophil and eosinophil concentrations predict these outcomes. AIM 2: We propose a prospective nested case control study. We will enroll patients who have not been diagnosed with chronic sinusitis but who do have persistent sinus symptoms on screening questionnaires. The outcome is sinus polyps because this is an objective surrogate for sinusitis severity in this undiagnosed but persistently symptomatic group. We will recruit 106 firefighters with low PMN concentration soon after WTC exposure who have high probability for sinus polyps (cases) and 106 firefighters with high PMN who have low probability for sinus polyps (controls). We will obtain sinus CT, nasal lavage, and an ENT evaluation. We will perform objective measures of sinusitis severity and inflammation and identify potential pathogens by culture-independent techniques. Relative to controls, we predict that cases will have more sinus polyps, inflammation, and pathogens. A better stratification of WTC patients with sinus symptoms using information from prior CBCs could point to more effective diagnostic and therapeutic approaches. Low risk patients could avoid expensive but unnecessary testing. Alternately, high risk patients could receive more intensive treatment in early in the course of this emerging and disabling WTC related disease.