Understanding Childhood Infection, Inflammation and Allergy
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 |
Outcome Measures
Primary Outcome Measures
- 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? [3y]
- What immunopathogenic mechanisms are involved in severe infection caused by specific bacterial and viral pathogens, and in inflammatory and allergic conditions? [5y]
Eligibility Criteria
Criteria
Inclusion Criteria:
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children presenting via any means to Hospital
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children needing blood tests for any clinical reason
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children who have presented because of a condition consistent with an infectious, inflammatory or allergic process
Exclusion Criteria:
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aged 17 or older
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children re-presenting with the same condition
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concern that the study is not fully understood by the parent or guardian
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St Mary's Hospital, Paddington | London | United Kingdom | W2 1NY |
Sponsors and Collaborators
- Imperial College London
Investigators
- Principal Investigator: Michael Levin, Imperial College London
Study Documents (Full-Text)
More Information
Publications
- 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, 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, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, Cebey-López 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, Martinón-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.
- CRO1330