Asthma and Invasive Pneumococcal Disease

描述（由申请人提供）：尽管美国和世界范围内哮喘的患病率增加，但哮喘与发生侵袭性肺炎球菌疾病风险之间的关系尚不清楚。目前的指南不建议哮喘患者常规接种肺炎球菌疫苗，尽管他们是否会因侵袭性肺炎球菌疾病而增加发病率和死亡率的风险尚不清楚。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负担的贡献程度尚不清楚。如果能够确定可作为疫苗接种对象的高危患者亚群，有效疫苗的可用性可能会在更大程度上降低侵袭性肺炎球菌疾病的发病率。这项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存在关联，将导致对这种关联机制的进一步研究，以及对哮喘和其他微生物感染之间可能关系的研究。 此外，最近的研究表明，这些细菌及其产物（例如，超抗原）或阴性（例如，卫生假说）影响哮喘的发展。然而，我们对哮喘或其他过敏性疾病如何影响对微生物感染的易感性的知识严重缺乏。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。本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。该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，该研究包括1964年至1983年明尼苏达州罗切斯特居民中估计的373例侵袭性肺炎球菌疾病病例和1：2出生日期和性别匹配的对照（746例）。从我们的初步工作中制定的具体研究目标是： 1.通过检验侵袭性肺炎球菌疾病患者中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疾病的易感性。 2.通过检验以下假设来确定哮喘患者中侵袭性肺炎球菌疾病的严重程度：在侵袭性肺炎球菌疾病患者中，哮喘患者因侵袭性肺炎球菌疾病住院的时间长于非哮喘患者。 我们的研究地点是进行拟议研究的理想地点，原因如下：（1）我们先前已经确定了1964年至1983年期间明尼苏达州罗切斯特的所有2499例儿童和成人哮喘发病病例;（2）这段时间内侵袭性肺炎球菌疾病的病例数将为实现我们的特定目标提供足够的把握度;和（3）研究将在肺炎球菌疫苗前时期进行，因此不会发生疫苗状态的混淆。

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.