Sinusitis in Children and the Nasopharyngeal Microbiome

儿童鼻窦炎和鼻咽微生物组

• 批准号: 8216793
• 负责人: Ellen Wald
• 金额: $ 76.45万
• 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/8216793
• 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. PUBLIC HEALTH RELEVANCE: Acute bacterial sinusitis in children is a common and important clinical problem. This study will define the burden of acute sinusitis and identify children at greatest risk of developing sinusitis enabling the limitation of antimicrobial therapy. Ultimately, we will propose alternatives to antimicrobial agents in both prevention and treatment thereby decreasing antimicrobial resistance. These strategies will also impact on management of acute otitis media and acute bacterial pneumonia. Decreased antimicrobial use will provide a huge benefit to the public health.

描述（申请人提供）：儿童急性细菌性鼻窦炎是向初级保健医生提出的最常见的临床问题之一。在美国，一个鼻窦炎的诊断导致12岁以下儿童花费超过18亿美元，每年有超过2000万的抗生素处方。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，这已成为自前抗生素时代以来有效治疗的最严重障碍之一。尽管急性细菌性鼻窦炎的频率和重要性，其发病率和先前易感病毒感染的身份从未报道过。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来确定鼻咽微生物组和急性病毒感染在儿童急性细菌性鼻窦炎发展中的作用。为了实现这些目标，我们建议对获得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。在49至84月龄的儿童中，将确定引起URI的特定病毒制剂，并使用高分辨率、不依赖培养的方法以及常规微生物学技术在基线和在病毒性URI发病2至3天内对鼻咽微生物组（关于病原和共生微生物群）进行表征。将对儿童进行前瞻性随访，以确定哪些受试者会发展为急性细菌性鼻窦炎，哪些患者的URI会自行消退。我们的总体假设是，鼻咽微生物群是维持正常上呼吸道生理的主要因素，并强烈影响鼻窦炎和其他呼吸道细菌感染的风险。通过确定某些人口统计学特征（如年龄、性别、兄弟姐妹、日托就诊情况等）、鼻咽微生物群特征（特定病原菌和共生菌群的多样性、均匀性和相对丰度）和先前的病毒感染，我们将确定急性细菌性鼻窦炎发展的危险因素。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风险最高的人身上，从而限制抗生素的使用。检查健康时和病毒感染后鼻咽部微生物组的细菌多样性，将为先前有病毒感染的几种呼吸道继发性细菌感染（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，这些措施可能早在细菌感染演变之前就已制定。