URBAN ENVIRONMENT AND CHILDHOOD ASTHMA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 城市环境与儿童哮喘（URECA） 产品描述： URECA研究是一项纵向出生队列研究，跟踪研究了3年内发生哮喘的高风险城市儿童。如果研究的初始阶段是成功的，并且可以获得资金，那么这些儿童将被跟踪到6岁，以评估真正的儿童哮喘的发展。 背景和依据： 即使考虑到种族和社会经济地位的差异，哮喘在市中心更普遍，可能更严重。这有力地表明，内城特有的环境因素可能会促进儿童早期哮喘的发展。虽然有其他的研究过敏原暴露在内城环境中，有关信息的早期生活暴露于病毒感染和压力在内城哮喘的发展是缺乏的。 此外，尽管有研究表明哮喘与免疫系统的异常发育和细胞因子分泌模式有关，但尚未对内城特有的环境暴露对免疫发育和哮喘发病率的影响进行前瞻性评估。 URECA研究将尝试回答以下问题： 1)先天免疫反应的失调，可能已经是 在出生时就存在，增加过敏原致敏（适应性免疫反应）和哮喘的风险，如果是这样，哪些细胞因子是这个过程的关键？ 2)婴儿期下呼吸道感染如何影响随后的风险 反复喘息和哮喘的可能性吗 3)内城儿童的免疫系统是否在出生时就已经异常， 独特的产前环境吗 4)在与内城环境相关的许多独特特征中， 哪些因素会对免疫系统发育产生不利影响，从而增加患哮喘的风险？ 5)市中心的环境（例如压力和污染的增加） 增加下呼吸道感染（LRI）的频率或严重程度，如果是这样，相关机制是什么（免疫调节与 肺特异性效应），以及 6)环境因素是否在关键时间点相互作用， 特定的喘息表型与未来的感染和/或暴露？ 研究设计和人群： URECA研究招募了患有过敏性疾病和哮喘的高风险儿童，这些儿童的父母有哮喘、过敏性鼻炎或特应性皮炎病史，并且居住在市中心。父母有过敏性疾病或哮喘阳性病史的家庭在出生前入选。产前评估产妇压力和其他环境暴露。每年都对儿童进行血细胞细胞因子反应和出生后环境影响（感染、过敏原和微生物暴露、压力、室内污染物）的评估，这些因素可能影响细胞因子反应的发展以及过敏和哮喘的临床表现（反复喘息）。研究人员还从研究参与者及其母亲身上获取DNA，以评估发生喘息性疾病和哮喘的遗传风险。 每年的门诊访视包括体格检查，以跟踪显著下呼吸道症状的发展和持续性。正在分析鼻咽粘液标本中是否存在病毒病原体。将在12、24和36个月时测量过敏原特异性IgE和IgG。正在进行家访，以进行环境评估和灰尘收集。与家属保持频繁的电话联系，以评估呼吸道感染、喘息、特应性疾病的出现、环境暴露的变化，并鼓励参与研究访视的安排和完成。 URECA研究中增加了一组没有哮喘或过敏家族史的儿童，以提供具有类似环境暴露的低风险人群中细胞因子反应的信息。了解家族史如何改变免疫发育，生活方式和早期生活环境暴露将是URECA研究的重要优势。 还邀请所有URECA参与者参加辅助URECA体重研究。URECA体重研究的目的是检查体重/组成、儿童期体重增加、哮喘发病率和炎症生物标志物之间的关系。 主要和次要结局指标 URECA研究的主要结局指标是反复喘息。在本研究中，反复喘息定义为在出生后的前三年内至少发生两次喘息，其中一次喘息发生在第三年。 还将评估一些次要结局变量，如下所示： 1)儿童哮喘预测的严格指标 图森儿童呼吸研究 2)特应性，定义为3岁时总IgE 60 KU/L，特应性 皮炎（医生诊断或工作人员观察）或一个或多个阳性 在三岁时进行空气过敏原皮肤测试。 3)使用抗炎药物治疗哮喘（皮质类固醇， 克罗埃西亚，孟鲁卡斯特）至少两个星期后，年龄2岁。 4)肺功能 5)由健康提供者诊断的哮喘

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Urban Environment and Childhood Asthma(URECA) Overview Description: The URECA study is a longitudinal birth cohort study, which is following inner-city children at high risk for developing asthma for 3 years. If the initial phases of the study are successful and funding can be secured, the children will be followed to the age of 6 to assess the development of bon fide childhood asthma. Background and Rationale: Asthma is more prevalent, and may be more severe, in the inner city, even after taking differences in ethnicity and socioeconomic status into account. This strongly suggests that environmental factors unique to the inner city may promote the development of asthma in early childhood. Although there are other studies of allergen exposure in the inner city environment, information relating early life exposures to viral infections and stress in the inner city to the development of asthma are lacking. Furthermore, despite studies which link asthma to abnormal development of the immune system and patterns of cytokine secretion, there has been no prospective evaluation of the effects of the environmental exposures unique to the inner city on immune development and the incidence of asthma. The URECA study will attempt to answer the following questions: 1) Does dysregulation of innate immune responses, which may already be present at birth, increase the risk of allergen sensitization (adaptive immune responses) and asthma, and if so, which cytokines are key in this process? 2) How do lower respiratory infections in infancy affect the subsequent risk of recurrent wheezing and asthma in inner city children? 3) Is the immune system of inner city children already abnormal at birth, due to a unique prenatal environment? 4) Of the many unique features associated with the inner city environment, which are the principal factors that adversely affect immune development, and thereby increase the risk of asthma? 5) Does the inner city environment(e.g. increased stress and pollution) increase the frequency or severity of lower respiratory infections (LRI), and if so, what are the relevant mechanisms (immune modulation versus lung-specific effects), and 6) Do environmental factors interact at a critical time point to establish a particular wheezing phenotype with future infections and/or exposures? Study Design and Population: The URECA study has enrolled children who are at high risk for developing allergic diseases and asthma, on the basis of a parental history of asthma, allergic rhinitis or atopic dermatitis, and residence in the inner city. Families with a positive parental history of allergic diseases or asthma are enrolled prior to birth. Maternal stress and other environmental exposures are assessed prenatally. Children are being evaluated each year for blood cell cytokine responses and for postnatal environmental influences (infections, allergen and microbial exposure, stress, indoor pollutants) that could affect the development of cytokine responses and clinical manifestations of allergy and asthma (recurrent wheeze). DNA is also being obtained from study participants and their mothers to evaluate genetic risk for developing wheezing diseases and asthma. Yearly clinic visits include physical examinations to track the development and persistence of significant lower respiratory tract symptoms. Nasopharyngeal mucus specimens are being analyzed for the presence of viral pathogens. Measurement of allergen-specific IgE and IgG will be performed at 12, 24, and 36 months. Home visits for environmental assessment and dust collection are being performed. Frequent telephone contact is maintained with the families to assess the development of respiratory infections, wheeze, the appearance of atopic diseases, changes in environmental exposures and to encourage participation in the scheduling and completion of study visits. An ancillary group of children with no family history of asthma or allergies has been added to the URECA study to provide information on cytokine responses in a lower-risk population with similar environmental exposures. Knowing how family history alters immune development, lifestyle and early life environmental exposures will be an important advantage to the URECA study. All URECA participants are also invited to participate in an ancillary URECA weight study. The objective of the URECA weight study is to examine the relationship between the body weight/composition, childhood weight gain, asthma morbidity and biomarkers of inflammation. Primary and Secondary Outcome Measures The primary outcome measure of the URECA study is recurrent wheeze. For the purposes of the study, recurrent wheeze is defined as at least two episodes of wheezing in the first three years of life with one of these episodes of wheezing occurring during the third year. A number of secondary outcome variables will also be assessed as follows: 1) Stringent index for the prediction of childhood asthma from the Tucson Children's Respiratory Study 2) Atopy, defined as either a total IgE60KU/L at age three years, atopic dermatitis(doctor diagnosed or staff observed) or one or more positive skin tests to aeroallergens at age three years. 3) Use of an anti-inflammatory medication for asthma (Corticosteroids, Cromolyn, Montelukast) for at least two weeks after age two years. 4) Pulmonary Function 5) Asthma diagnosed by a health provider