Primary Objectives: 1.To obtain insight in the role of altered DNA methylation in blood leukocytes (monocytes and neutrophils) in innate immune responses and host defense in patients with CAP.2.To determine the composition and function of the gut…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main parameters of this study will be the alterations in leukocyte DNA
methylation and the composition and function of the intestinal and
nasopharyngeal microbiota in patients with CAP.
These data will be associated with several clinical parameters, including, but
not limited to:
• Patient demographics and medical history, at enrolment
• Date of hospital admission and discharge, transfer or death
• Date of high care unit/intensive care unit admission and discharge, transfer
or death, if applicable
• Clinical outcome: hospital discharge, transfer or in-hospital death
• Mortality at day 90
Secondary outcome
Secondary it will be evaluated whether microbiome derived signals are of
influence in differences found in methylation in these study groups.
Background summary
Community acquired pneumonia represents a major health care problem and
mortality and morbidity associated with severe pneumonia remains considerable,
despite state of the art care.
While the role of altered DNA methylation in cancer has been widely
studied, knowledge of its impact on antibacterial defense is highly limited. In
addition the gut microbiota contributes to host defense against bacterial
pneumonia.
This study aims to explore a completely novel research area linking the
extent of DNA methylation in blood leukocyte (monocytes and neutrophils) and
function of gut and nasopharyngeal microbiota on the influence of innate immune
responses to and host defense against community acquired pneumonia.
Study objective
Primary Objectives:
1.To obtain insight in the role of altered DNA methylation in blood leukocytes
(monocytes and neutrophils) in innate immune responses and host defense in
patients with CAP.
2.To determine the composition and function of the gut and nasopharyngeal
microbiota in patients with CAP.
Secondary Objective:
1.To assess the influence of the gut microbiota on leukocyte DNA methylation in
patients with CAP
2. To assess the influence of coagulation markers in innate immune responses
and host defense in patients with CAP.
3. To assess the influence of whole blood transcriptome profiles in patients
with CAP.
4. To compare the presence of gut epithelial integrity and bacterial
translocation in patients with CAP and healthy volunteers.
5. To compare differences within the host response and immune systems of
patients suffering from a COVID-19 CAP, regular CAP and healthy volunteers
Study design
Observational study among patients with CAP at the Emergency Department and
Internal Medicine Ward of the Academic Medical Center Amsterdam.
From above mentioned patients, blood (52.5ml) will be withdrawn at presentation
to analyze DNA methylation of purified monocytes and neutrophils which will be
linked with DNA methyltransferase and ten eleven translocation (TET) activity,
RNA expression and a selection of innate immune function tests. In addition, 2
rectal swabs and 1 nasopharyngeal swab will be obtained to investigate the
role of gut and nasopharyngeal microbiota composition and function
(metagenomics). Another blood sample (12.5ml), along with 2 rectal swabs and 1
nasopharyngeal swab, will be collected at day 2/3 of hospitalisation. More
patient material (47.5 ml of blood, 2 rectal swabs and 1 nasopharyngeal swab)
will be obtained upon day 90 (-7/+21 days), when patients will be seen at the
outpatient clinic of the AMC for follow up. Healthy volunteers will be
subjected to a single blood draw of 85 ml. Moreover, 2 rectal swabs and 1
nasopharyngeal swabs will be obtained.
Study burden and risks
Participating in this observational study will not directly benefit the
participant. The study will provide information about the influence of
leukocyte DNA methylation and the gut microbiota on host defense mechanisms
during CAP. The knowledge obtained in this study can potentially benefit CAP
patients in the future by providing alternative immune modulating treatment
options that modify the host response. The burden and risks for patients
participating in the ELDER-BIOME study is minimal. We will take a total of
112.5ml blood, 6 rectal swabs and 3 nasopharyngeal swabs upon inclusion up to
day 90. Healthy volunteers will be subjected to a 85ml blood draw, 2 rectal
swabs and 1 nasopharyngeal swabs at a single time point.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1) Age >= 18 y
2) Clinical suspicion of a new episode of acute respiratory tract infection
3) The presence of a new or increased infiltrate on chest radiography or
computed tomography (CT) or a positive SARS-CoV-2 PCR on nasopharyngeal swab
within 14 days prior to admission
4) Presence of two or more diagnostic clinical criteria:
- Cough
- Production of purulent sputum or a change in the character of sputum
- Temperature >38°C or <36.1°C
- Auscultatory findings consistent with pneumonia, including rales,
evidence of pulmonary consolidation (dullness on percussion, bronchial breath
sounds, or egophony), or both
- Leukocytosis (>10×109 white cells per liter or >15% bands)
- C-reactive protein level of more than 3 times the upper limit of the
normal range
- Dyspnea, tachypnea, or hypoxemia
Exclusion criteria
1) No informed consent is provided by patient
2) Patients who had recently been hospitalized (for >48 hours in the previous 2
weeks) or who resided in long-term care facilities
3) Patients with a colostomy
4) Patient is enrolled in an interventional clinical study of an anti-infective
or immunomodulatory therapy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL57847.018.16 |