Stroke, Ischemic
Conditions
Keywords
Acute Ischemic Stroke, Bronchoscopy
Brief summary
Stroke patients frequently suffer from stroke associated pneumonia. Pathophysiologically speaking, dysphagia and central nervous system (CNS)-injury induced immunosuppression largely contribute to the risk for pneumonia. In mouse models for stroke, the self-cleaning mechanisms of the lung are also affected by stroke, possibly further contributing to this risk. The investigators designed a pilot-study to examine the structural and functional integrity of the self-cleaning mechanisms of the lung in stroke patients.
Detailed description
Survival and functional outcome of stroke is strongly depending on the occurence of pneumonia (stroke-associated pneumonia, SAP). Early diagnose and treatment of SAP is paramount in the treatment of stroke patients. While dysphagia strongly contributes to its pathogenesis, recent years have also shown a strong risk-modulation by CNS injury induced immunosuppression, making stroke patients more susceptible to SAP. Additionally, murine models of stroke showed changes in mucociliary clearance as possible contributors to SAP. It remains unclear, whether structural integrity and mucociliary clearance of the respiratory epithel change in stroke patients, and whether these changes might contribute to the occurence of SAP. Therefore, the investigators designed this exploratory observational pilot-study to examine the structural and functional integrity of respiratory epithel in severely affected stroke patients and correlate these findings to immune phenotyping and occurence of SAP. The investigators will conduct bronchoscopy in severely affected stroke patients to collect histological samples in order to evaluate multiple tissue predictors, as well as perform optical coherence tomography to examine ciliary kinetics in-vivo. The investigators will furthermore perform serum and plasma immune phenotyping, record occuring pneumonias and correlate these data in order to identify possible predictors of pneumonia.
Interventions
DIAGNOSTIC_TESTbronchoscopy
Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance
Sponsors
NeuroCure Clinical Research Center, Charite, Berlin
Department of Infectiology and Pneumonology, Charite, Berlin
University of Giessen
University of Luebeck
Labor Berlin - Charité Vivantes GmbH
Charite University, Berlin, Germany
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Informed consent signed by patient or legal representatives * Acute ischemic stroke within the past 2 weeks (except the control group) * Indication for diagnostic or therapeutic bronchoscopy
Exclusion criteria
* Confirmed lung malignancies or specific inflammations of the lungs * Pneumonia (only control group) * Autoimmune diseases of respiratory system (only control group) * Chronic inflammatory diseases of respiratory system (only control group) * chronic obstructive pulmonary disease (COPD) and spastic diseases of respiratory system (only control group) * Patients being committed to psychiatric institutions or prisons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mucociliary Clearance | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | \- number of cilia (scanning electron microscopy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Autophagy | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Intensity of fluorescence of Light chain (LC) 3b protein, Aurora A and Human enhancer of filamentation (HEF)1 |
| Occurence of stroke-associated pneumonia | 7 days after stroke | Pneumonia is defined according to the consensus recommendations (Smith et al., Stroke 2015) |
| Activity of autonomous nervous system | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Concentration of Cortisol, Adrenaline and Noradrenaline in blood and heart frequency variability |
| Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Apoptosis | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Intensity of fluorescence of TUNEL |
| Activity of immune System - Concentration of inflammatory markers | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Concentration of inflammatory markers (PCT, CRP) in blood |
| Activity of immune System - Expression of HLA-DR | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Expression of Human Leukocyte Antigens (HLA)-DR on monocytes in antigens/cell |
| Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Increase of secretory cells | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Expression levels of surfactant protein, Muc5a, SPDEF, Foxa3 |
| Activity of immune System - Concentration of cytokines | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | Concentration of cytokines (IL-6, IL-13 and more) in blood |
Countries
Germany
Contacts
Primary ContactAndreas Meisel, Prof. Dr. med.
Backup ContactBenjamin Hotter, Dr. med.
Outcome results
None listed