Understanding Childhood Infection, Inflammation and Allergy
A Comprehensive, Long-term Integrated Programme to Study the Aetiology and Immunopathology of Childhood Infectious, Inflammatory and Allergic Disease, Using the Large Patient Base of Children Attending St Mary's Hospital, London
This proposal represents a unified programme supported by both clinical and academic staff in the Departments of Paediatrics at Imperial College and St Mary's Hospital, Southampton Hospital and John Radcliffe Hospital (Oxford). St Mary's Hospital is the hub of a paediatric network for West London, and forms part of the Paediatric Intensive Care Network for the London region, with potential access to a population of 3 million children.
We aim to improve diagnosis and understanding of children with infectious, inflammatory and allergic conditions. Our study will establish well-characterised cohorts of patients with defined conditions, in whom microbiological and patient samples will be used to understand the contribution of genetic background, differential gene expression, proteomics and the pathogen type to the disease process.
Unwell children coming to hospital through any route will be invited to join the study. Entering the study will entail the child having blood taken for research purposes in addition to the clinically indicated tests. We will also recruit well (control) children who are having blood tests performed for elective purposes, such as surgery.
In addition, children presenting with an illness that is likely to have an infectious aetiology will also have samples collected for microbiological diagnosis. Those samples taken for ordinary diagnostic purposes (such as blood, urine, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) fluid or nasal brushings for epithelial cell cultures) would also be used for state-of-the-art diagnostic techniques, in order to maximise the likelihood of confirming a microbiological diagnosis. Where healthy, uninfected children are having invasive procedures, such as lumbar punctures, we would aim to recruit these children as controls and collect biological samples such as CSF samples.
This bid addresses the need for translational research in paediatrics, by building on the world-class basic science and clinical paediatric base at Imperial College and St Mary's Hospital.
調査の概要
詳細な説明
There is currently little understanding of the mechanisms by which respiratory infections can cause severe illness and death. The emergence of Influenza A subtype (H1N1) as a major cause of childhood severe illness in 2009 permitted further study of how this virus triggers severe disease, and how the inflammatory response to H1N1 differs from other infections. It is likely that host-mediated inflammatory processes triggered by the infecting agent contributes to severe illness. In addition, viral infection induces profound changes in the innate immune response to common bacterial pathogens, with increased bacterial colonisation of normally sterile lower airway. Thus both host and bacterial factors may contribute to lung damage in severe respiratory infection.
This study was initiated to identify the aetiology and immunopathologic mechanisms of childhood respiratory infection (Immunopathology of Respiratory Infection Study - IRIS), recruiting children with suspected respiratory infection or respiratory failure (and controls). This dataset will provide a unique resource for further study of disease mechanisms in children with a range of infections including H1N1/09 infection, Respiratory Syncytial Virus (RSV), Rhinovirus, other common respiratory viruses and severe bacterial infections.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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London、イギリス、W2 1NY
- St Mary's Hospital, Paddington
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- children presenting via any means to Hospital
- children needing blood tests for any clinical reason
- children who have presented because of a condition consistent with an infectious, inflammatory or allergic process
Exclusion Criteria:
- aged 17 or older
- children re-presenting with the same condition
- concern that the study is not fully understood by the parent or guardian
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
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Infection, inflammation or allergy
Children presenting via any means to St Mary's Hospital; this would include the A&E department, the general and infectious disease wards and the paediatric intensive care unit. Children needing blood tests for any clinical reason Children who, in the clinical judgement of the doctor assessing them, have presented because of a condition consistent with an infectious, inflammatory or allergic process |
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controls
children who do not have an infectious, inflammatory or allergic condition, who anyway require blood tests for clinical reasons
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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What Are the Bacterial and Viral Causes of Acute Illness in Children Presenting to a UK General Hospital, Tertiary Paediatric Infectious Disease Unit and Paediatric Intensive Care Unit?
時間枠：Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days
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number of participants with phenotype of definite bacterial or definite viral disease, based on culture or molecular investigations of samples from a sterile site
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Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Michael Levin、Imperial College London
出版物と役立つリンク
一般刊行物
- Cebey-Lopez M, Herberg J, Pardo-Seco J, Gomez-Carballa A, Martinon-Torres N, Salas A, Martinon-Sanchez JM, Gormley S, Sumner E, Fink C, Martinon-Torres F; GENDRES network. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections. PLoS One. 2015 Sep 2;10(9):e0136526. doi: 10.1371/journal.pone.0136526. eCollection 2015.
- Cebey-Lopez M, Herberg J, Pardo-Seco J, Gomez-Carballa A, Martinon-Torres N, Salas A, Martinon-Sanchez JM, Justicia A, Rivero-Calle I, Sumner E, Fink C, Martinon-Torres F; GENDRES network. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children? PLoS One. 2016 Apr 20;11(4):e0152481. doi: 10.1371/journal.pone.0152481. eCollection 2016.
- Kaforou M, Herberg JA, Wright VJ, Coin LJM, Levin M. Diagnosis of Bacterial Infection Using a 2-Transcript Host RNA Signature in Febrile Infants 60 Days or Younger. JAMA. 2017 Apr 18;317(15):1577-1578. doi: 10.1001/jama.2017.1365. No abstract available.
- Wang X, Nijman R, Camuzeaux S, Sands C, Jackson H, Kaforou M, Emonts M, Herberg JA, Maconochie I, Carrol ED, Paulus SC, Zenz W, Van der Flier M, de Groot R, Martinon-Torres F, Schlapbach LJ, Pollard AJ, Fink C, Kuijpers TT, Anderson S, Lewis MR, Levin M, McClure M; EUCLIDS consortium. Plasma lipid profiles discriminate bacterial from viral infection in febrile children. Sci Rep. 2019 Nov 27;9(1):17714. doi: 10.1038/s41598-019-53721-1.
- Herberg JA, Kaforou M, Gormley S, Sumner ER, Patel S, Jones KD, Paulus S, Fink C, Martinon-Torres F, Montana G, Wright VJ, Levin M. Transcriptomic profiling in childhood H1N1/09 influenza reveals reduced expression of protein synthesis genes. J Infect Dis. 2013 Nov 15;208(10):1664-8. doi: 10.1093/infdis/jit348. Epub 2013 Jul 29.
- Herberg JA, Jones KD, Paulus S, Gormley S, Muir D, Cooper M, Levin M. Comparison of pandemic and seasonal influenza reveals higher mortality and increased prevalence of shock in children with severe h1n1/09 infection. Pediatr Infect Dis J. 2011 May;30(5):438-40. doi: 10.1097/INF.0b013e3182040c90.
- Herberg JA, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, Cebey-Lopez M, Carter MJ, Janes VA, Gormley S, Shimizu C, Tremoulet AH, Barendregt AM, Salas A, Kanegaye J, Pollard AJ, Faust SN, Patel S, Kuijpers T, Martinon-Torres F, Burns JC, Coin LJ, Levin M; IRIS Consortium. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children. JAMA. 2016 Aug 23-30;316(8):835-45. doi: 10.1001/jama.2016.11236. Erratum In: JAMA. 2017 Feb 7;317(5):538.
- Wright VJ, Herberg JA, Kaforou M, Shimizu C, Eleftherohorinou H, Shailes H, Barendregt AM, Menikou S, Gormley S, Berk M, Hoang LT, Tremoulet AH, Kanegaye JT, Coin LJM, Glode MP, Hibberd M, Kuijpers TW, Hoggart CJ, Burns JC, Levin M; Immunopathology of Respiratory, Inflammatory and Infectious Disease Study (IRIS) Consortium and the Pediatric Emergency Medicine Kawasaki Disease Research Group (PEMKDRG). Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature. JAMA Pediatr. 2018 Oct 1;172(10):e182293. doi: 10.1001/jamapediatrics.2018.2293. Epub 2018 Oct 1.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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