Is Sputum Eosinophilia A Prognosis Factor for Occupational Asthma? A proof of Con

描述（由申请人提供）：职业性哮喘（OA）是最常见的职业性呼吸系统疾病之一。尽管有一些有效的计划可以使患有OA的工人尽早脱离暴露环境，但这些工人中有70%在脱离暴露环境数年后仍患有哮喘。目前还没有任何标志可以识别哪些工人在停止接触后可能面临哮喘进一步恶化的风险。最近的一项研究表明，哮喘反应的发生没有嗜酸性粒细胞炎症后，暴露于致病剂可能是哮喘预后不良的一个指标。本研究的主要目的是确定暴露于有害职业因子后气道嗜酸性粒细胞炎症的缺乏是否是OA工人哮喘预后不良的标志。具体目标是：1。比较诊断时特异性吸入挑战（SIC）后（Eos+）和无痰嗜酸性粒细胞增多（Eos-）的工人的临床、功能和炎症特征；2. 评估非嗜酸性表型是否表现为痰中性粒细胞增加（bbb60 %）。3. 比较Eos+和Eos-工人诊断后5年及以上的临床、功能和炎症特征。4. 比较Eos+组和Eos-组气道重构的相关指标；5. 评价Eos+组和Eos-组诊断前后5年的医疗资源利用情况。方法：我们将对2000年至2005年间诊断为OA的受试者进行横断面队列研究。我们将确定2000年至2005年间在我们中心诊断为OA的所有受试者的图表，并在调查期间进行了痰鉴别细胞计数。这些受试者将被邀请参加随访。将进行肺活量测定、乙酰胆碱激发、痰诱导和呼出一氧化氮（eNO）测定。我们还将获得他们在诊断为OA前5年至随访期间使用医疗资源的数据（就诊、急诊和住院）。主要结果将是有和没有嗜酸性粒细胞炎症的受试者在诊断和随访期间非特异性气道反应性的变化。61名受试者的样本量将允许在具有6个预测因子的线性回归中具有80%的功率和5%的alpha误差，从而获得0.25的预期效应大小（r2）。确定一组有较差结果风险的受试者，可以让我们通过调整治疗方法和实施更密切的随访来改善对这些受试者的管理。

DESCRIPTION (provided by applicant): Occupational asthma (OA) is one of the most prevalent occupational respiratory diseases. In spite of efficient programs allowing the early removal from exposure of the workers with OA, seventy percent of these workers remain with asthma years after removal from exposure. There is no current marker allowing the identification of the workers who may be at risk of experiencing further deterioration of their asthma after removal from exposure. A recent study suggested that the occurrence of an asthmatic reaction without an eosinophilic inflammation after exposure to the offending agent may be an indicator of a poor asthma prognosis. The broad aim of this study is to determine whether or not the lack of airway eosinophilic inflammation following the exposure to their offending occupational agents is a marker of poor asthma prognosis in workers with OA. The specific objectives are : 1. To compare the clinical, functional and inflammatory characteristics of workers with (Eos+) and without sputum eosinophilia (Eos-) after specific inhalation challenges (SIC) at the time of the diagnosis; 2. To assess whether or not the non-eosinophilic phenotype shows an increase in sputum neutrophils (>60%). 3. To compare the clinical, functional and inflammatory characteristics of workers Eos+ and Eos- 5 years or more after the diagnosis. 4. To compare some markers of airway remodeling in the Eos+ and Eos- groups; 5. To assess the medical resource use 5 years before and after diagnosis in Eos+ and Eos- groups. Methods: We will conduct a cross-sectional cohort study of subjects diagnosed with OA between 2000 and 2005. We will identify the charts of all subjects who had a diagnosis of OA between 2000 and 2005 in our centre and who had sputum differential cell counts performed during the investigation. These subjects will be invited to attend a follow-up visit. Spirometry, methacholine challenge, sputum induction and measure of exhaled nitric oxide (eNO) will be performed. We will also obtain the data regarding their use of medical resources (visit to the physicians, visits to the emergency and hospitalizations) 5 years before the diagnosis of OA and until the follow-up visit. The primary outcome will be the change in non-specific airway responsiveness between the diagnosis and the follow-up visit in subjects with and without eosinophilic inflammation. A sample size of 61 subjects will allow having a power of 80% with an alpha error of 5% to obtain an anticipated effect size (r2) of 0.25 in the linear regression with 6 predictors. Identifying a group of subjects at risk to have a poorer outcome may allow us to improve the management of those subjects by modifying their treatment and implementing a closer follow-up. PUBLIC HEALTH RELEVANCE: This project is highly relevant for the workers as well as for the agencies responsible for the management of the workers with occupational asthma. Indeed, if we identify a specific type of airway inflammation as being associated with a poor prognosis of the disease, this will allow an early identification of the workers at risk of a further deterioration of their asthma. This will allow a closer follow-up of these workers along with an intensification of their asthma treatment after diagnosis.