Sinusitis in Children and the Nasopharyngeal Microbiome

儿童鼻窦炎和鼻咽微生物组

• 批准号: 8588286
• 负责人: Ellen Wald
• 金额: $ 71.9万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588286
• 关键词: 12 year old; Acute; Age; Age-Months; Antibiotics; Antimicrobial Resistance; Antiviral Agents; Bacterial Infections; Bacterial Pneumonia; Characteristics; Child; Childhood; Clinical; Complex; Complication; Development; Diagnosis; Diagnostic; Disease Resistance; Elements; Enrollment; Environment; Etiology; Exposure to; Frequencies; Gender; Goals; Haemophilus influenzae; Health; Health Expenditures; Immune response; Incidence; Infection; Inflammatory Response; Institutes; Invaded; Knowledge; Lead; Longitudinal Studies; Lower respiratory tract structure; Maintenance; Measures; Methods; Microbiological Techniques; Molecular; Moraxella (Branhamella) catarrhalis; Otitis Media; Outcome; Pathogenesis; Pharmaceutical Preparations; Physiology; Predisposition; Prevention; Prevention strategy; Primary Health Care; Public Health; Recovery; Relative (related person); Reporting; Resolution; Respiratory System; Respiratory Tract Infections; Respiratory tract structure; Rhinovirus; Risk; Risk Factors; Role; Sampling; Siblings; Sinus; Sinusitis; Streptococcus pneumoniae; Symptoms; Techniques; Therapeutic; Upper Respiratory Infections; Upper respiratory tract; Viral; Viral Vaccines; Virus Diseases; acute bacterial sinusitis; antimicrobial; antimicrobial drug; base; burden of illness; commensal microbes; density; design; effective therapy; high risk; innovative technologies; insight; microbial community; microbiome; novel; pathogen; respiratory; respiratory virus; secondary infection; theories

DESCRIPTION (provided by applicant): Acute bacterial sinusitis in children is one of the most common clinical problems presenting to the primary care practitioner. A diagnosis of sinusitis results in over $1.8 billion spent on children < 12 years of age and is responsible for over 20 million antibiotic prescriptions per year in the US. Equally important, overtreatment contributes in large part to the development of antimicrobial resistance which has become one of the most serious obstacles to effective therapy since the pre-antibiotic era. Despite the frequency and importance of acute bacterial sinusitis, its incidence and the identity of the antecedent predisposing viral infections has never been reported. The goals of this study are to determine the burden of acute bacterial sinusitis in children and use state-of- the-art molecular techniques to determine the role of the nasopharyngeal microbiome and antecedent acute viral infections on the development of acute bacterial sinusitis in children. To accomplish these goals, we propose to conduct a systematic longitudinal study of the nasopharyngeal environment of otherwise healthy children who acquire viral upper respiratory infections (URIs). The specific viral agents that cause URIs in children 49 to 84 months of age will be identified and the nasopharyngeal microbiome will be characterized (regarding sinopathogens and commensal microbiota) using high-resolution, culture-independent methods as well as conventional microbiologic techniques at baseline and again within 2 to 3 days of onset of the viral URI. Children will be followed prospectively to determine which subjects develop acute bacterial sinusitis and which resolve their URI spontaneously. It is our overall hypothesis that the nasopharyngeal microbiome is a major factor in the maintenance of normal upper respiratory tract physiology and strongly influences the risk of developing sinusitis and other bacterial infections of the respiratory tract. By identifying certain demographic features (e.g., age, gender, siblings, attendance at daycare, etc), the characteristics of the nasopharyngeal microbiome (diversity, evenness and relative abundance of specific sinopathogens and commensal microbiota) and the antecedent viral infection, we will determine risk factors for the development of acute bacterial sinusitis. Ultimately, this information will help us to focus treatment on those at highest risk to develop acute bacterial sinusitis thereby limiting exposure to antimicrobials. Examining the bacterial diversity of the nasopharyngeal microbiome in health and after viral infection will provide critical insights with regard to several secondary bacterial infections of the respiratory tract in which there is an antecedent viral infection (acute otitis media, acute bacterial pneumonia and acute bacterial sinusitis). Finally, defining the mechanisms by which respiratory viruses cause changes in the nasopharyngeal microbiome will lead to new preventative and therapeutic measures which may be instituted long before the bacterial infection evolves.

描述（由申请人提供）：儿童急性细菌性鼻窦炎是初级保健医生最常见的临床问题之一。在美国，鼻窦炎的诊断导致 12 岁以下儿童花费超过 18 亿美元，并且每年开出超过 2000 万张抗生素处方。同样重要的是，过度治疗在很大程度上导致了抗菌素耐药性的发展，这已成为自抗生素问世以来有效治疗的最严重障碍之一。尽管急性细菌性鼻窦炎很常见且很重要，但其发病率和先前诱发病毒感染的身份从未有过报道。 本研究的目的是确定儿童急性细菌性鼻窦炎的负担，并使用最先进的分子技术确定鼻咽微生物组和先前的急性病毒感染对儿童急性细菌性鼻窦炎发展的作用。为了实现这些目标，我们建议对感染病毒性上呼吸道感染（URI）的其他健康儿童的鼻咽环境进行系统的纵向研究。将确定导致 49 至 84 个月大的儿童 URI 的特定病毒因子，并在基线和病毒 URI 发病后 2 至 3 天内使用高分辨率、独立于培养的方法以及常规微生物学技术来表征鼻咽微生物组（关于中华病原体和共生微生物群）。将对儿童进行前瞻性随访，以确定哪些受试者会患上急性细菌性鼻窦炎，哪些受试者会自发缓解 URI。我们的总体假设是，鼻咽微生物组是维持正常上呼吸道生理的主要因素，并且强烈影响发生鼻窦炎和其他呼吸道细菌感染的风险。通过确定某些人口特征（例如年龄、性别、兄弟姐妹、日托护理等）、鼻咽微生物组的特征（特定鼻窦病原体和共生微生物群的多样性、均匀性和相对丰度）以及既往病毒感染，我们将确定发生急性细菌性鼻窦炎的危险因素。最终，这些信息将帮助我们将治疗重点放在那些患急性细菌性鼻窦炎的最高风险人群上，从而限制抗菌药物的接触。检查健康状态下和病毒感染后鼻咽微生物组的细菌多样性，将为了解先前存在病毒感染的几种呼吸道继发细菌感染（急性中耳炎、急性细菌性肺炎和急性细菌性鼻窦炎）提供重要见解。最后，确定呼吸道病毒引起鼻咽微生物组变化的机制将导致新的预防和治疗措施，这些措施可能在细菌感染发生之前很久就已制定。