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

痰嗜酸性粒细胞增多是职业性哮喘的预后因素吗？

• 批准号: 8132357
• 负责人: Catherine Lemiere
• 金额: $ 4.8万
• 依托单位: SACRE COEUR MONTREAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8132357
• 关键词: Sputum; Eosinophilia; Prognosis; Factor; Occupational

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.

职业性哮喘（OA）是最常见的职业性呼吸道疾病之一。尽管有有效的方案允许早期从接触OA的工人中移除，但这些工人中的70%在移除接触后数年仍患有哮喘。目前还没有一种标志物可以用来识别那些在脱离接触后可能有哮喘进一步恶化风险的工人。最近的一项研究表明，在暴露于致敏剂后发生哮喘反应而无嗜酸性粒细胞炎症可能是哮喘预后不良的指标。本研究的主要目的是确定是否缺乏气道嗜酸性粒细胞炎症后，暴露于他们的犯罪职业代理人是一个标志，哮喘预后不良的工人与OA。具体目标是：1.比较痰嗜酸性粒细胞增多症（Eos+）和痰嗜酸性粒细胞增多症（Eos-）工人在诊断时特异性吸入激发（SIC）后的临床、功能和炎症特征; 2.评估非嗜酸性粒细胞表型是否显示痰中性粒细胞增加（>60%）。3.比较确诊后5年或更长时间内Eos+和Eos-工人的临床、功能和炎症特征。4.比较Eos+和Eos-组气道重塑的一些标志物; 5.评估Eos+和Eos-组诊断前后5年的医疗资源使用情况。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年在我们中心诊断为OA的所有受试者的图表，以及在研究期间进行痰细胞分类计数的受试者。将邀请这些受试者参加随访访视。将进行肺量测定、乙酰甲胆碱激发、痰诱导和呼出一氧化氮（eNO）测量。我们还将获得OA诊断前5年至随访访视期间的医疗资源使用数据（医生访视、急诊访视和住院）。主要结局将是有和无嗜酸性粒细胞炎症的受试者在诊断和随访访视之间非特异性气道反应性的变化。61例受试者的样本量将允许具有80%的把握度，α误差为5%，以在具有6个预测因子的线性回归中获得0.25的预期效应量（r2）。识别一组具有较差结局的风险受试者可能使我们能够通过修改其治疗和实施更密切的随访来改善对这些受试者的管理。 公共卫生关系：该项目与工人以及负责管理职业性哮喘工人的机构高度相关。事实上，如果我们确定一种特定类型的气道炎症与疾病的预后不良有关，这将允许早期识别处于哮喘进一步恶化风险中的工人。这将允许对这些工人进行更密切的随访沿着在诊断后加强哮喘治疗。

项目成果

Noneosinophilic responders with occupational asthma: a phenotype associated with a poor asthma prognosis.

患有职业性哮喘的非嗜酸性粒细胞反应者：与哮喘预后不良相关的表型。

• DOI: 10.1016/j.jaci.2013.09.005
• 发表时间: 2014
• 期刊: The Journal of allergy and clinical immunology
• 作者: Lemiere,Catherine;Chaboillez,Simone;Bohadana,Abraham;Blais,Lucie;Maghni,Karim
• 通讯作者: Maghni,Karim