Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes. Secondary objectives: 1. Investigate differences in microbiome composition and immunophenotyping…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Gene expression differences in sputum and nasal epithelium between eosinophilic
COPD exacerbations and other subtypes.
Secondary outcome
1. Microbiome composition and immunophenotyping profiles of the different
subtypes, i) eosinophilic, ii) viral, iii) bacterial, iv) pauci-inflammatory.
2. Course and duration of symptoms, measured by changes in peak flow and CAT
scores.
3. RNA sequencing in nasal epithelium and sputum, and immunophenotyping in
blood.
4. Differences in the sputum and nasal epithelial microbiome between COPD
exacerbation subtypes, both during stable state and exacerbations.
5. Per subtype: course and duration of symptoms (CAT questionnaire), and lung
function recovery after exacerbation, duration of hospital admission, risk of
2nd exacerbation during the follow-up.
Background summary
Acute COPD exacerbations are heterogeneous of nature and can be grouped into
specific biologic clusters. Moreover, there are unique microbial compositions
within these clusters of acute exacerbations of COPD. This suggests that each
COPD patient carries a unique microbiome composition and that this composition
drives an immunological response during an exacerbation through cross-talk with
the host. Meta-transcriptomic analyses of respiratory samples can
simultaneously assay microbial and host genomes to identify microbial
transcriptional changes and host gene expression responses. However, the exact
immunological response orchestrating the cross-talk between microbiome and host
response during an AECOPD remains elusive.
Study objective
Main objective: investigate gene expression differences in nasal epithelium and
sputum between eosinophilic COPD exacerbations and other subtypes.
Secondary objectives:
1. Investigate differences in microbiome composition and immunophenotyping
profiles in peripheral blood per subtype.
2. Assess for clinical differences between all COPD exacerbation subtypes.
3. Assess if and how baseline meta-transcriptomics either in nasal epithelium
or sputum and blood immunophenotyping can be utilized to predict COPD
exacerbation subtype.
4. Determine if the microbiome in sputum and nasal epithelial material are
comparable.
5. Determine if different subtypes of COPD exacerbations respond differently to
standard treatment with oral prednisolone (40 mg daily) with or without
antibiotics.
Study design
In this prospective observational study, data and samples will be collected
from 100 COPD patients at time of hospitalization for a severe COPD
exacerbation, and in stable state, 6-8 weeks after onset of the exacerbation.
If a second exacerbation occurs, more data and samples will be collected.
Moreover, subjects will be followed-up for the duration of one year after
inclusion to register symptoms by means of a telephone assessment. This is a
multicentre study.
Study burden and risks
There are several burdens for participants in this study. Participants will
have to visit the study hospital, fill in the questionnaires and take peak flow
measurements several times. Extra blood will be drawn (3x56.5ml) and nasal
brushes will be taken. When necessary, a subject will be asked to undergo a
sputum induction. These procedures cause several risks. Venipuncture may cause
a local hematoma, acquiring nasal brushes may cause a nose bleed, sputum
induction may lead to transient bronchospasm and dyspnea.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
- COPD patient admitted to the hospital for an acute exacerbation - A physician
diagnosed COPD according to the GOLD 2017 guidelines - Age >40 years -
Smoker or ex-smoker, >10 pack years of smoking
Exclusion criteria
- Current asthma or prior physician diagnosis of asthma without a symptom-free
interval of at least 10 years before the age of 40 - Use of systemic
corticosteroids >-4 days prior to hospital admission - Necessity (upon
hospitalization) for non-invasive ventilation or ICU admission - Pneumonia at
hospital admission, defined by the clincal presentation and the presence of a
lobar consolidation on radiographical imaging - Any other clinically relevant
lung disease deemed to interfere with the concept of the study design -
Pregnancy and lactation.
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 | NL75151.042.20 |