Viral persistence & the microbiome in bronchiolitis and risk of recurrent wheeze

病毒持续存在

• 批准号: 9260759
• 负责人: Jonathan M Mansbach
• 金额: $ 70.83万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-14 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9260759
• 关键词: 3 year old; 6 year old; Address; African American; Age; Aspirate substance; Asthma; Bacteria; Blood; Bronchiolitis; Child; Childhood; Childhood Asthma; Cohort Studies; Collaborations; Consent; DNA; Data; Development; Diagnosis; Enrollment; Freezing; Funding; Gammaproteobacteria; Grant; Hispanics; Hospitalization; Immune response; Infant; Infection; Intensive Care Units; International; Interview; Knowledge; Lactobacillus; Lead; Lung diseases; Medical Records; Moraxella; Nose; Parents; Participant; Pathogenesis; Pattern; Play; Primary Prevention; Prospective cohort study; Recovery; Recurrence; Research; Research Personnel; Respiratory System; Respiratory syncytial virus; Respiratory tract structure; Rhinovirus; Ribosomal RNA; Risk; Risk Factors; Role; Site; Strategic Planning; Sum; Surveys; Swab; Testing; Time; United States National Institutes of Health; Viral; Virus; Virus Diseases; Wheezing; asthma prevention; clinically relevant; cohort; follow-up; high risk; high risk population; improved; indexing; microbiome; microbiota; multidisciplinary; novel; personalized medicine; prevent; primary outcome; public health relevance; respiratory; treatment strategy; ward

 DESCRIPTION (provided by applicant): Bronchiolitis is the #1 cause of infant hospitalization in the USA. Small cohort studies (n<210) suggest that ~50% of hospitalized infants with bronchiolitis will develop childhood asthma. Unfortunately, it remains unclear which infants will develop asthma and this knowledge gap has hindered primary prevention efforts. The 35th Multicenter Airway Research Collaboration (MARC-35) study (U01 AI-87881; Camargo, PI) is a 17-center prospective cohort study that completed enrollment of 926 infants hospitalized with bronchiolitis (85% ward, 15% intensive care unit) in April 2014. At start of the hospitalization, site investigators collected nasopharyngeal aspirates, nasal swabs, and blood, including items needed for the modified asthma predictive index (mAPI) and DNA. We also have extensive interview and medical records data. In an unfunded add-on study, site teams collected a nasal swab at hospitalization, and parents collected nasal swabs 3-weeks after the hospitalization and again over the summer when the child was healthy. There are extensive interview and survey data; and comprehensive medical records. Follow-up data include biannual parent interviews (~90% follow-up to date), and annual review of medical records. For timing reasons, the primary outcome of the 5- year U01 grant is recurrent wheezing by age 3 years. However, all participants were consented for follow-up to age 6 years to permit ascertainment of asthma. This revised R01 application includes preliminary data generated by testing nasal swabs from 102 participants at both hospitalization and 3 weeks later using 16S rRNA and real-time PCR and sequencing of respiratory syncytial virus and rhinovirus. Although these pilot data are underpowered, the statistically non-significant results suggest novel relations between the nasal microbiota, viral persistence, and recurrent wheezing. We found that increasing Gammaproteobacteria (e.g., Moraxella) was associated with an increased (OR 1.8, P=0.18), and increasing Lactobacillales (e.g., Lactobacillus) a decreased (OR 0.27, P=0.22), odds of recurrent wheezing by a median age of 2.2 years. Similarly, we found an increase in Gammaproteobacteria was associated with an increased (OR=1.9, P=0.19) and Lactobacillales with a decreased odds (OR=0.14, P=0.05) of viral persistence. Viral persistence is defined as having the same virus (delayed clearance) or a different virus (sequential infection) 3 weeks after hospitalization. And children with viral persistence had a non-significant increase in the odds of recurrent wheezing by a median age of 2.2 years (OR 1.8, P=0.21). Using the summer nasal swabs, we also examine if the dysbiosis present at hospitalization persists several months later. The R01 would provide funds to test the almost 2,000 nasal swabs from the entire MARC-35 cohort. We have >80% power in all Aims. The investigators are NIH-funded researchers with expertise in their fields. The study advances the primary prevention of asthma, and matches well with the 2009 NIH strategic plan for pediatric respiratory research.

 描述（由申请人提供）：细支气管炎是美国婴儿住院的第一大原因。小规模队列研究（n<210）表明，约 50% 的患有细支气管炎的住院婴儿会患上儿童哮喘。会发展为哮喘，这种知识差距阻碍了第 35 次多中心气道研究合作 (MARC-35) 研究 (U01 AI-87881； Camargo, PI）是一项 17 中心前瞻性队列研究，于 2014 年 4 月完成了 926 名因细支气管炎住院的婴儿（85% 为病房，15% 为重症监护室）的入组。在住院开始时，现场调查人员收集了鼻咽抽吸物、鼻拭子和血液，包括改良哮喘预测指数 (mAPI) 和 DNA 所需的项目。我们还拥有大量访谈和医疗记录数据。附加研究，现场团队在住院时收集了鼻拭子，家长在孩子住院后三周以及在孩子健康时再次收集了鼻拭子。有大量的访谈和调查数据以及全面的医疗记录。随访数据包括每年两次的家长访谈（迄今为止约 90% 的随访）和每年一次的病历审查。出于时间原因，5 年 U01 补助金的主要结果是 3 岁时反复喘息。参与者同意随访至 6 岁，以确定是否患有哮喘。修订后的 R01 应用程序包括通过使用 16S rRNA 和实时 PCR 以及测序测试 102 名参与者的鼻拭子生成的初步数据。尽管这些试点数据不够有力，但技术上不显着的结果表明，鼻腔微生物群、病毒持久性和反复喘息之间存在新的关系。伽玛变形菌（例如莫拉氏菌）与中位年龄 2.2 岁的复发性喘息几率增加相关（OR 1.8，P=0.18），而乳杆菌目（例如乳酸杆菌）增加与复发性喘息几率降低相关（OR 0.27，P=0.22）同样，我们发现伽马变形菌的增加与 . （OR=1.9，P=0.19）和病毒持续性几率降低（OR=0.14，P=0.05）的乳杆菌属病毒持续性定义为具有相同病毒（延迟清除）或不同病毒（连续感染）3。住院几周后，病毒持续存在的儿童复发喘息的几率中位年龄增加了 2.2 岁（OR 1.8， P=0.21）。我们还使用夏季鼻拭子检查住院时存在的菌群失调是否在几个月后持续存在。我们有超过 80% 的样本用于测试整个 MARC-35 队列中的近 2,000 份鼻拭子。研究人员是 NIH 资助的研究人员，他们在各自领域具有专业知识，并且与 2009 年 NIH 战略计划非常吻合。儿科呼吸研究。