Understanding Childhood Infection, Inflammation and Allergy

Inflammation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01022268
• Other study ID #: CRO1330
• Status: Completed
• Start date: July 20, 2009
• Est. completion date: June 11, 2019

Study information

• Verified date: April 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 902
• Est. completion date: June 11, 2019
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Allergy
• Children
• Hypersensitivity
• Infection
• Infections
• Inflammation

Locations

Country	Name	City	State
United Kingdom	St Mary's Hospital, Paddington	London

Sponsors (3)

Lead Sponsor	Collaborator
Imperial College London	Oxford University Hospitals NHS Trust, University Hospital Southampton NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

Cebey-López M, Herberg J, Pardo-Seco J, Gómez-Carballa A, Martinón-Torres N, Salas A, Martinón-Sánchez JM, Gormley S, Sumner E, Fink C, Martinón-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. — View Citation

Cebey-López M, Herberg J, Pardo-Seco J, Gómez-Carballa A, Martinón-Torres N, Salas A, Martinón-Sánchez JM, Justicia A, Rivero-Calle I, Sumner E, Fink C, Martinón-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. — View Citation

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): — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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, Glodé MP, Hibberd M, Kuijpers TW, Hoggart CJ, Burns JC, Levin M; Immunopathology of Res — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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?	number of participants with phenotype of definite bacterial or definite viral disease, based on culture or molecular investigations of samples from a sterile site	Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days