Genetic /Environment Factors In Nonmalignant Resp Dis

有证据表明，在吸烟者和不吸烟者中，饮食因素可能在哮喘和慢性阻塞性肺疾病(COPD)的病因中起重要作用。然而，现有的关于饮食在哮喘和COPD病因中的作用的数据主要来自横断面研究。需要前瞻性数据来正确处理饮食在哮喘和慢性阻塞性肺疾病发展中的作用。空气污染显然会加剧现有的肺部疾病，但在成人哮喘和慢性阻塞性肺病的发病率中所起的作用尚未确定。要恰当地检验这种联系，前瞻性数据是必要的，但这样的数据很少。遗传因素可能在调节饮食、吸烟和环境空气污染对成人不良呼吸结果风险的影响方面发挥作用。遗传因素可能会影响食物中营养物质的新陈代谢，从而对健康产生影响。饮食和基因可能结合在一起，影响对空气污染不利影响的敏感性。空气污染对整个人口的平均影响可能很弱，确定易感因素将有助于澄清空气污染对健康的影响。 我正在建立两个高质量的人口资源，以前瞻性地研究饮食、吸烟、空气污染、遗传及其相互作用对成人哮喘和COPD的影响。第一个群体是新加坡的6.3万名华裔老年人。该队列是由NCI的外部资金建立的，目的是检查饮食和癌症之间的关系。我扩大了研究范围，将哮喘和慢性支气管炎的评估包括在内。慢性支气管炎是慢性阻塞性肺疾病的结果。现场工作人员开始重新联系受试者并审查记录，以验证哮喘的结果。由于风险因素数据的前瞻性收集，新加坡的华人队列尤其令人感兴趣。这项研究的另一个主要优势是高质量的饮食评估，这是专门为这一人群开发的，并在其中得到了验证。新加坡队列还遵循与现有成人呼吸系统研究中包括的西方人群截然不同的饮食模式。这项研究的其他优势是不吸烟者的比例很大，以及遗传样本的可用性。虽然目前新加坡研究的后续周期尚未完成，但我们已经开始制作手稿。我们已经确定了可溶纤维和大豆摄入量与慢性支气管炎风险之间有趣的联系。在当前的随访周期和哮喘验证完成后，我们将开始分析可能影响哮喘和慢性支气管炎风险并调节饮食和空气污染影响的基因多态。 第二项研究是与外部资助的队列合作，即社区动脉粥样硬化风险(ARIC)研究。我们将研究与交通相关的空气污染与随着时间的推移肺功能下降、成人哮喘和COPD之间的关系。ARIC的这项研究是在20世纪80年代末收集的16,000名成年人组成的队列--S，来自美国的四个社区。这是为数不多的纵向测量肺功能的大型研究之一。为了研究在ARIC研究中将与交通相关的空气污染作为健康后果的风险因素进行调查的可行性，我们已经开始了一项初步研究，以检查受试者住宅中与交通相关的空气污染的变化。如果试点研究显示交通密度的变化足够，我们将准备一份提案，对ARIC队列中与交通相关的空气污染进行全面调查。我们还寻求并获得了与ARIC研究合作的批准，以调查肥胖是否改变了吸烟对肺功能下降的影响。肥胖最近被认为是儿童和成人哮喘的一个危险因素，似乎与年龄相关的肺功能下降加剧有关。如果肥胖改变了人们所描述的吸烟的影响，那么肥胖也有可能改变空气污染的不利影响。

There is evidence that dietary factors may be important in the etiology of asthma and chronic obstructive pulmonary disease (COPD) in both smokers and nonsmokers. However, the existing data on the role of diet in the etiology of asthma and COPD come predominantly from cross-sectional studies. Prospective data are needed to properly address the role of diet in the development of asthma and COPD. Air pollution clearly exacerbates existing lung disease, but a role in the incidence of asthma and COPD in adults is not established. Prospective data are necessary to properly examine this association, but such data are few. Genetic factors are likely to play a role in modulating the effects of diet, smoking, and ambient air pollution on the risk of adverse respiratory outcomes in adults. Genetic factors may influence the metabolism of nutrients in food that are responsible for health effects. Both diet and genetics may combine to influence susceptibility to adverse effects of air pollution. Effects of air pollution are likely to be weak when averaged over whole populations and identification of susceptibility factors will help to clarify health consequences of air pollution. I am establishing two high-quality population resources to prospectively investigate effects of diet, smoking, air pollution, genetics and their interactions in relation to asthma and COPD in adults. The first population is a cohort of 63,000 older adults of Chinese ethnicity in Singapore. The cohort was established with NCI extramural funding to examine the relationship between diet and cancer. I have expanded the study to include the assessment of asthma and chronic bronchitis. Chronic bronchitis is a COPD outcome. Field staff are beginning to recontact subjects and review records to validate asthma outcomes. The Singapore Chinese cohort is of particular interest because of the prospective collection of risk factor data. Another major strength of the study is the high quality dietary assessment, which was developed specifically for, and validated in, this population. The Singapore cohort also follows dietary patterns quite distinct from the Western populations included in existing adult respiratory studies. Other strengths of the study are the large proportion of nonsmokers and the availability of genetic samples. Although the current follow-up cycle of the Singapore study is not yet complete, we have begun to produce manuscripts. We have identified interesting associations between soluble fiber and soy intake and the risk of chronic bronchitis. After the current follow-up cycle and asthma validation is complete, we will begin analyses of genetic polymorphisms that may influence risk of asthma and chronic bronchitis and modulate effects of diet and air pollution. The second study is a collaboration with an extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study. We will examine relationships between traffic-related air pollution and the decline in pulmonary function over time, asthma and COPD in adults. The ARIC study is a cohort of 16,000 adults assembled in the late 1980?s in four US communities. It is one of the few large studies with longitudinal measures of pulmonary function. To examine the feasibility of investigating traffic-related air pollution as a risk factor for health outcomes in the ARIC study, we have begun a pilot study to examine the variation in traffic related air pollution at the residences of subjects. If the pilot study shows the variation in traffic density to be sufficient, we will prepare a proposal to perform a full investigation of traffic-related air pollution in the ARIC cohort. We have also sought and obtained approval for a collaboration with the ARIC study to investigate whether obesity modifies the effect of smoking on decline in pulmonary function. Obesity has recently been appreciated to be a risk factor for asthma in children and adults and appears to be related to enhanced age-related decline in pulmonary function. If obesity modifies the well-described effect of smoking, then it is possible that obesity might modify the adverse effects of air pollution.