MUcociliary Clearance IN Stroke

Study Overview
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Brief Summary
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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
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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.

Official Title
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MUcociliary Clearance IN Stroke

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Diagnostic Test: bronchoscopy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| stroke<br> | Diagnostic Test: bronchoscopy<br>* Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance<br>|
| control<br> | Diagnostic Test: bronchoscopy<br>* Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucociliary Clearance | - number of cilia (scanning electron microscopy) | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Mucociliary Clearance | - activity of cilia given as frequency (in-vivo optical coherence tomography) | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of stroke-associated pneumonia | Pneumonia is defined according to the consensus recommendations (Smith et al., Stroke 2015) | 7 days after stroke | 
| Activity of autonomous nervous system | Concentration of Cortisol, Adrenaline and Noradrenaline in blood and heart frequency variability | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Activity of immune System - Concentration of cytokines | Concentration of cytokines (IL-6, IL-13 and more) in blood | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Activity of immune System - Concentration of inflammatory markers | Concentration of inflammatory markers (PCT, CRP) in blood | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Activity of immune System - Expression of HLA-DR | Expression of Human Leukocyte Antigens (HLA)-DR on monocytes in antigens/cell | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Autophagy | Intensity of fluorescence of Light chain (LC) 3b protein, Aurora A and Human enhancer of filamentation (HEF)1 | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Apoptosis | Intensity of fluorescence of TUNEL | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 
| Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Increase of secretory cells | Expression levels of surfactant protein, Muc5a, SPDEF, Foxa3 | at time of bronchoscopy (within 2 weeks after acute ischemic stroke) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, Bronchoscopy