Evolution of Risk Factors for Sinusitis in WTC Exposed Firefighters

描述（由申请方提供）：在所有暴露队列中，世界贸易中心（WTC）暴露均导致上呼吸道和下呼吸道损伤。FDNY，NYU和Mt之间的合作。西奈将研究WTC相关的上呼吸道损伤。虽然下呼吸道损伤的病例在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）需要数年才能出现。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，已有1,821例慢性鼻窦炎病例经鼻窦CT扫描确诊;其中412例病情最严重的患者需要手术治疗。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，NYU/FDNY团队寻求鼻窦炎严重程度的生物标志物。我们最近报道，在暴露后早期增加血液中的中性粒细胞浓度降低了随后的鼻窦炎和鼻窦手术的风险（Cho等人，2013年：一个气道：生物标志物的保护，从上，下气道损伤后，世界贸易中心曝光）。目前的建议将测试的假设，即白细胞浓度在全血细胞计数（CBC）暴露后早期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，因此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，本提案开发的风险模型可以很容易地在所有WTC暴露队列中得到确认并应用于所有WTC暴露队列。目标1：我们提出了一项回顾性队列研究，使用所有1,540名WTC暴露的FDNY消防员的数据，这些消防员进行了早期CBC和随后的鼻窦CT扫描。我们将建立两个以鼻窦手术和鼻窦息肉为结局的logistic模型，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可预测这些结局。目的2：我们提出一个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在筛选问卷中确实有持续鼻窦症状的患者。结果是鼻窦息肉，因为这是一个客观的替代鼻窦炎的严重程度，在这一未确诊，但持续的症状组。我们将招募106名在WTC暴露后不久具有低PMN浓度的消防员，他们有很高的鼻窦息肉概率（病例），以及106名具有高PMN浓度的消防员，他们有很低的鼻窦息肉概率（对照）。我们将进行鼻窦CT、鼻腔灌洗和耳鼻喉科评估。我们将对鼻窦炎的严重程度和炎症进行客观的测量，并通过非培养技术鉴定潜在的病原体。相对于对照组，我们预测病例将有更多的鼻窦息肉、炎症和病原体。使用既往CBC的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测试。另外，高风险患者可以在这种新兴和致残的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.