Investigating immune cells in the lungs of people with severe community-acquired pneumonia

ISRCTN	ISRCTN19920744
DOI	https://doi.org/10.1186/ISRCTN19920744
IRAS number	263517
Secondary identifying numbers	PID 14303, IRAS 263517

Submission date: 20/12/2019
Registration date: 06/01/2020
Last edited: 03/01/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Community-acquired pneumonia (CAP) is an infection of the lungs where the lungs become inflamed. Severe CAP requires admission to hospital in specialised areas with increased nursing care such as intensive care (ICU) and may require the temporary support of a breathing machine (mechanical ventilation). In England pneumonia is the most common infection-related cause for ICU admission and UK data indicates that up to a third of patients admitted to an ICU with pneumonia die. Additionally, there is a large economic cost and survivors are often left with significant reductions in their quality of life.
Immune responses in the lung need to balance identification and clearance of disease-causing microbes with the collateral damage of lung inflammation and injury. Of particular interest are local immune cells that play a crucial role in protecting the lung against bacteria and viruses. These specialised immune cells remain in the lung and cannot be detected in the circulating blood of patients, so samples of lung cells must be taken.
This study will investigate local immune cells in mechanically ventilated patients with severe CAP. Studying the local immune response to severe CAP offers insights into how this disease occurs, may help decide which patients are going to need to most support and may identify new treatment targets for this important condition.

Who can participate?
People admitted to intensive care at Oxford University Hospitals Foundation NHS Trust who require mechanical ventilation

What does the study involve?
Doctors use samples taken from lung fluid to detect infection. This study will use the excess samples to measure the levels of immune cells in the lung fluid. The lung fluid is collected using a process called bronchoalveolar lavage. This involves passing a tube from the patient's mouth or nose into the lung, squirting in some saline (salt solution) and then sucking it back up the tube so that any cells or substances in the lung fluid can be examined.

What are the possible benefits and risks of participating?
There are no specific benefits to participating in this study and taking part in this study will not affect participants' care in any way. The lung fluid samples would be taken anyway as part of routine medical care.

Where is the study run from?
The Kadoorie Centre for Critical Care Research (UK)

When is the study starting and how long is it expected to run for?
February 2019 to January 2021

Who is funding the study?
Oxford University (UK)

Who is the main contact?
Christopher Andersen, christopher.andersen@ndcn.ox.ac.uk

Contact information

Dr Christopher Andersen
Scientific

Kadoorie Centre for Critical Care Research
Level 3 John Radcliffe Hospital
Oxford University Hospitals Foundation NHS Trust
Headington
Oxford
OX3 9DU
United Kingdom

ORCID ID	0000-0002-9321-8660
Phone	+44 (0)1865 223101
Email	chris_andersen@gmp.usyd.edu.au

Study information

Study design	Cross-sectional observational study
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	Hospital
Study type	Other
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet.
Scientific title	ImmuneCAP: T-cell responses in severe community acquired pneumonia, a pilot observational study
Study acronym	ImmuneCAP
Study objectives	Community acquired pneumonia (CAP) is a pathogen-driven inflammatory process of the lung parenchyma characterised by an exudative infiltration of alveolae causing impairment of lung function. Our understanding of the underlying processes associated with this condition is incomplete. In this study we will study the local immune responses in pneumonia through analysis of bronchioalveolar lavage fluid.
Ethics approval(s)	Approved 30/10/2019, Yorkshire & The Humber – Leeds East Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ; +44 (0)207 1048 088), ref: 19/YH/0289
Health condition(s) or problem(s) studied	Community-acquired pneumonia
Intervention	This observational study will compare consented patients with severe acute pneumonia to consented patients with and without lung injury. Once enrolled in the study, the participant will have a bronchoalveolar lavage sample taken and will be followed up for 90 days or until hospital discharge.
Intervention type	Procedure/Surgery
Primary outcome measure	Quantity and phenotype of lung-derived T-cell populations measured using flow cytometry at a single timepoint within 72 h of the establishment of mechanical ventilation
Secondary outcome measures	Severity of respiratory failure and other organ failure using the sequential organ failure assessment (SOFA) score during the 90 days following admittance or the period from hospital admittance to discharge
Overall study start date	01/02/2019
Completion date	20/01/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	15
Key inclusion criteria	1. Admitted to a critical care setting in the Oxford University Hospital Trust 2. Mechanically ventilated for less than 72 h 3. Diagnosis of community acquired pneumonia has been made by the treating physicians based on the following criteria: 3.1. Symptoms and/or signs consistent with a lower respiratory tract infection 3.2. Radiological evidence of new onset consolidation on a chest x-ray or CT scan 4. Aged ≥16 years 5. Able to consent themselves or declaration obtained from a personal or professional consultee
Key exclusion criteria	1. Previously included in the study 2. Hospital admission in the past 30 days (prior to this current presentation) 3. Long-term resident of a nursing home or other residential care facility
Date of first enrolment	21/12/2019
Date of final enrolment	20/10/2020

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Oxford University Hospitals Foundation NHS Trust

Kadoorie Centre, Level 3
John Radcliffe Hospital
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

University of Oxford
University/education

Clinical Trials Research Group
Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
England
United Kingdom

Phone	+44 01865 616480
Email	ctrg@admin.ox.ac.uk
Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

University/education

Medical Sciences Division, University of Oxford

No information available

Results and Publications

Intention to publish date	01/06/2021
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	The results of this study will be published in a peer-reviewed journal and presented at local, national and international meetings. Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. The results of the study will be summarised on the Critical Care Research Group webpages: https://www.ndcn.ox.ac.uk/research/critical-care-research-group-kadooriecentre .
IPD sharing plan	The datasets generated and/or analysed during this study will be included in the subsequent results publication.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

02/01/2020: Trial's existence confirmed by Yorkshire & The Humber – Leeds East Research Ethics Committee.