Asthma and Invasive Pneumococcal Disease

描述(由申请人提供)：尽管哮喘在美国和世界范围内的流行率不断上升，但哮喘与发展侵袭性肺炎球菌疾病的风险之间的关系尚不清楚。目前的指南不建议对哮喘患者进行常规肺炎球菌疫苗接种，尽管他们是否面临侵袭性肺炎球菌疾病的发病率和死亡率增加的风险尚不清楚。此外，在后七价肺炎球菌结合疫苗时代，哮喘患者在人群水平上对侵袭性肺炎球菌疾病的负担有多大程度的贡献尚不清楚。如果确定了可作为接种目标的高危患者亚群，有效疫苗的可获得性可能在更大程度上减少侵袭性肺炎球菌疾病的发病率。这项拟议的研究是为哮喘儿童和成人制定合理的肺炎球菌疫苗政策不可或缺的一步。如果发现哮喘和侵袭性肺炎球菌疾病之间的关联，将导致对这种关联的机制以及哮喘和其他微生物感染之间可能关系的进一步研究。 此外，最近的研究表明，这些细菌及其产物对哮喘的发展有积极的影响(如超级抗原)或消极的(如卫生假说)。然而，我们严重缺乏关于哮喘或其他过敏性疾病如何影响微生物感染易感性的知识。因此，我们的研究结果可能会影响目前理解微生物感染和哮喘之间因果关系的范式。这项研究的目的是确定哮喘和侵袭性肺炎球菌疾病之间的关系。这项研究将通过进行一项基于人群的病例对照研究来实现这一目标，该研究由1964至1983年间明尼苏达州罗切斯特居民中估计373例侵袭性肺炎球菌病例和1：2出生日期和性别匹配对照(746例)组成。根据前期工作制定的具体研究目标如下： 1.通过检验侵袭性肺炎球菌病患者哮喘发生率高于匹配对照组的假设，确定哮喘患者对侵袭性肺炎球菌病的易感性。 2.通过检验以下假设来确定哮喘患者中侵袭性肺炎球菌病的严重程度：在有侵袭性肺炎球菌病的人中，哮喘患者因侵袭性肺炎球菌病住院的时间比没有哮喘的人长。 我们的研究地点非常适合进行拟议的研究，原因如下：(1)我们之前已经确定了明尼苏达州罗切斯特市1964至1983年间所有2499例儿童和成人哮喘病例；(2)这段时间内侵袭性肺炎球菌疾病的病例数量将提供足够的力量来实现我们的特定目标；以及(3)研究将在肺炎球菌疫苗前时代进行，以避免因疫苗状况而引起的混乱。

DESCRIPTION (provided by applicant): Despite the increased prevalence of asthma in the United States and worldwide, the relationship between asthma and the risk of developing invasive pneumococcal disease is not known. Current guidelines do not recommend routine pneumococcal vaccination for asthmatic patients, although whether they are at an increased risk of morbidity and mortality from invasive pneumococcal disease is unknown. In addition, to what extent asthmatic patients contribute to the burden of invasive pneumococcal disease at a population-level in the post-heptavalent pneumococcal conjugate vaccine era is not known. Availability of effective vaccines is likely to reduce the incidence of invasive pneumococcal disease to a greater extent if subgroups of high-risk patients who can be targeted for vaccination are identified. The proposed study is an indispensable step toward formulating a rational pneumococcal vaccine policy for asthmatic children and adults. If an association between asthma and invasive pneumococcal disease is found, it will lead to further research into the mechanisms of such an association as well as studies of the possible relationship between asthma and other microbial infections. Furthermore, recent studies suggest those bacteria and their products positively (e.g., super antigens) or negatively (e.g., hygiene hypothesis) affect the development of asthma. However, our knowledge is severely lacking about how asthma or other allergic conditions influence the susceptibility to microbial infections. Therefore, our study findings may influence the current paradigm for understanding the causal relationship between microbial infections and asthma. The goal of this study is to determine the relationship between asthma and invasive pneumococcal disease. The study will accomplish this goal by conducting a population-based case-control study composed of an estimated 373 invasive pneumococcal disease cases and 1:2 dates of birth- and gender-matched controls (746) among the residents of Rochester, Minnesota, between 1964 and 1983. The specific study aims developed from our preliminary work are: 1. To determine the susceptibility of asthmatic patients to invasive pneumococcal disease by testing the hypothesis that the frequency of asthma is higher among patients with invasive pneumococcal disease than among matched controls. 2. To determine the severity of invasive pneumococcal disease among asthmatic patients by testing the hypothesis that among persons with invasive pneumococcal disease, asthmatic patients have longer duration of hospitalization for invasive pneumococcal disease than patients without asthma. Our study site is ideal for the proposed study for the following reasons: (1) we have previously identified all 2499 incident cases of asthma among children and adults in Rochester, Minnesota between 1964 and 1983; (2) the number of cases of invasive pneumococcal disease during this time period will provide sufficient power to accomplish our specific aims; and (3) the study will be performed during the pre-pneumococcal vaccine era so that confounding by vaccine status will not occur.