Environmental Effects on Lung Function in Cystic Fibrosis Patients

描述（由申请人提供）：科学文献中有越来越多的证据表明，与当前标准范围内的环境空气污染水平相关的不利健康影响，特别是对患有慢性呼吸道疾病的人群。患有囊性纤维化（CF）的儿童和成人是环境空气污染对其健康影响的高危人群，此前从未对其进行过调查。确定囊性纤维化人群中肺部疾病进展的环境危险因素可能有助于更好地理解这种疾病的复杂异质性。我们的目的是评估和澄清美国CF患者中空气污染物与CF肺部健康和死亡率之间的关系。有关环境因素对囊性纤维化影响的信息有限。我们最近完成了一项初步队列研究，以评估空气污染物对囊性纤维化的影响。该研究包括1999年和2000年在囊性纤维化基金会国家患者登记处登记的6岁以上的患者。通过将空气计量信息检索系统中的空气污染值与患者的家庭邮政编码联系起来，对暴露进行了评估。我们发现，在调整混杂因素后，过程颗粒物（PM10）和细颗粒物（PM2.5）每增加10¿g/m3，两次或两次以上恶化的几率分别增加8% （95% CI 2-15%）和21% (7-33%)；臭氧浓度每上升10ppb，两次或两次以上恶化的几率就会增加10%（3-17%）。我们还发现，在调整混杂因素后，PM2.5每增加10¿g/m3, 1秒内强制呼气量（FEV1）就会相应下降24 ml（7 - 40）。鉴于这一发现，我们评估了长期暴露于环境空气污染对CF患者肺功能和死亡率的影响。我们发现，通过FEV1测量，环境空气污染与肺功能之间存在很强的关联。PM2.5和PM10升高与肺功能降低有关。考虑到这些数据，了解空气污染是否会影响CF患者的肺生长，以及肺功能与CF患者生存之间的关系是至关重要的。我们建议首先基于1994-2005年6-18岁囊性纤维化儿童FEV1和强迫肺活量（FVC）的混合效应多元回归模型来模拟CF患者的肺生长。然后，我们将评估环境空气污染（按年平均暴露量评估）对肺生长的影响。最后，我们建议评估不同暴露（环境空气污染）建模方法对CF中空气污染对肺生长影响的影响。随着CF研究人员寻找CF疾病的基因修饰因子，以更好地了解CF肺病的病理生理学并确定新的潜在治疗方法，了解环境暴露在疾病过程中的重要性至关重要。我们的建议工作可能有助于更好地了解环境因素对囊性纤维化（CF）结果和预后的作用，也可能增加关于空气污染物对易感和高危人群健康影响的证据。我们的建议也将增强我们对CF肺生长的理解，并代表了了解环境对CF肺部疾病影响的项目的初始阶段。

DESCRIPTION (provided by applicant): There is increasing evidence in the scientific literature that there are adverse health effects associated with levels of ambient air pollution that fall within the current standards, especially for populations with chronic respiratory diseases. Children and adults with cystic fibrosis (CF) are an at-risk population for which the health effects of ambient air pollution have not previously been investigated. Identifying environmental risk factors for the progression of pulmonary disease in the cystic fibrosis population may contribute to better understanding of this complex heterogeneous nature of this disease. Our objective is to assess and clarify the association between air pollutants and CF lung health and mortality among U.S. CF patients. Information concerning the impact of environmental factors on cystic fibrosis is limited. We recently completed a preliminary cohort study to assess the impact of air pollutants in cystic fibrosis. The study included patients over the age of 6 years enrolled in the Cystic Fibrosis Foundation National Patient Registry in 1999 and 2000. Exposure was assessed by linking air pollution values from the Aerometric Information Retrieval System with patients' home zip code. We found that after adjusting for confounders, a 10 ¿g/m3 rise in course particulate matter (PM10) and fine particulate matter (PM2.5) was associated with an 8% (95% CI 2-15%) and 21% (7-33%) increase in the odds of two or more exacerbations, respectively; a 10ppb rise in ozone was associated with a 10% (3-17%) increase in odds of two or more exacerbations. We also found that for every increase in PM2.5 of 10 ¿g/m3, there was an associated fall in forced expiratory volume in 1 second (FEV1) of 24 ml (7 - 40) after adjusting for confounders. Given this finding, we evaluating the impact of longer term exposure to ambient air pollution on lung function and mortality in CF. We found a strong association between ambient air pollution and lung function as measured by FEV1. Increased PM2.5 and PM10 was associated with lower lung function. Given this data, it is critical to understand whether air pollution affects lung growth in CF patients, given the relationship between lung function and survival in CF. We propose to first model lung growth in CF based on mixed effects multivariate regression models of FEV1 and forced vital capacity (FVC) in children ages 6-18 with cystic fibrosis from 1994-2005. We will then assess the impact of ambient air pollution (as assessed by average annual exposure) on lung growth. Lastly, we propose evaluating the impact of different methodologies of exposure (ambient air pollution) modeling on the impact of air pollution on lung growth in CF. As CF researchers search for gene modifiers in CF disease to better understand the pathophysiology of CF lung disease and identify new potential therapies, it is critical to understand how important environmental exposures are in the course of the disease. Our proposal work may contribute to a better understanding of the role of environmental factors on cystic fibrosis (CF) outcome and prognosis and also could add to the growing body of evidence regarding the health effects of air pollutants on susceptible and at risk populations. Our proposal will also enhance our understanding of lung growth in CF and represents the initial phase of a program to understand environmental effects on CF lung disease.