To determine ex vivo neutrophil functions following exposure to therapeutic antibodies targeting inhibitory receptors expressed by neutrophils from RSV bronchiolitis patients. A secondary aim is to study soluble inhibitory receptors (such as LAIR-1…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Flow cytometry of peripheral blood will be used to determine expression of
inhibitory receptors in peripheral blood cells of patients. Neutrophil function
regulation by inhibitory receptors in tracheal aspirate cells will be studied.
ELISA will be used to determine levels of soluble inhibitory receptors and
other serum cytokines.
Secondary outcome
RSV staining of epithelial cells and qPCR on cell adhesion and
epithelium-mesenchymal transition (EMT) genes will be used to study interaction
between epithelium and leukocytes. In vitro culture of epithelial cells and
autologous blood neutrophil, macrophages or lymphocytes to study various
leukocyte functions.
Background summary
Respiratory syncytial virus bronchiolitis is the most frequent cause of
hospitalization during infancy. Tissue damage by neutrophils contributes to
disease severity. No effective treatment is available. In literature, is has
been suggested that disease is the consequence of lack of immune regulation of
tissue neutrophils. Our research group has special interest in the immune
inhibitory receptors. Our previous studies show that airway neutrophils of
mechanically ventilated RSV patients express various inhibitory receptors,
including LAIR-1, SIRL-1, Siglec-9 and SIRP-alpha. The hypothesis tested in
this study is that ex vivo neutrophil function in RSV bronchiolitis patients is
suppressed by agonistic antibodies of inhibitory receptors.
Study objective
To determine ex vivo neutrophil functions following exposure to therapeutic
antibodies targeting inhibitory receptors expressed by neutrophils from RSV
bronchiolitis patients. A secondary aim is to study soluble inhibitory
receptors (such as LAIR-1) and cytokines in blood, urine and respiratory tract
secretion as markers of disease severity. Study design: observational
case-control study
Study design
This will be a single-center observational case-control study
Study burden and risks
Once only; venous puncture of 4ml of blood (if possible combined with regular
blood withdrawal), removal of tracheal aspirate at time of inclusion and on day
3, 5 and before extubation (only in ventilated patient as part of routine
care), urine (using an urine bag, no catheter) and saliva suctioned from the
nose (as part of routine care). Twice a nasopharyngeal swab will be taken. No
additional hospital visits are needed. No additional physical examination is
performed. No questionnaires have to be completed.
Due to the type of study, observational, with non-invasive diagnostic
procedures as previously described, no adverse or serious adverse events are to
be expected.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
Group 1: RSV, mechanical ventilation (n<=35):
Age < 25 months
Respiratory insufficiency requiring mechanical ventilation due to proven RSV LRTI ;Group 2: RSV, no ventilation (n<=35):
Age < 25 months
Hospitalization for proven RSV LRTI (positive PCR or DIFF);Group 3: Non-ventilated hospitalized controls (n<=35):
Age < 25 months
No fever or other signs of infection, no respiratory symptoms, ;Group 4a: Ventilated controls without infection (n<=35)
Age < 25 months
Mechanical ventilation for non-infectious indication (e.g. status epilepticus, trauma);Group 4b: Ventilated controls with infection (n<=35)
Age < 25 months
Mechanical ventilation for non-RSV LRTI (e.g. bacterial pneumonia, sepsis)
Exclusion criteria
Severe comorbidity, such as any organ dysfunction except for cardiac malformalities or the presence of a trachea canulue.
Immune suppressed patients such as patient using immune suppressives or receiving chemotherapy.
Any severe congenital or acquired abnormality, such as Down syndrome
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 | NL58404.041.16 |