Non-invasive Diagnosis of Pulmonary Embolism by Use of Biomarkers in Exhaled Breath Condensate

Study Overview
=================
Brief Summary
-----------------
In this study, a new, non-invasive method for diagnosis of pulmonary embolism (PE) will be tested. In pre-clinical studies, we have identified 151 putative biomarkers for pulmonary embolism in the exhaled breath condensate (EBC). These biomarkers needs validation/consolidation in a clinical setting before further test of this new diagnostic method.

Detailed Description
-----------------
The study will compare the protein profiles of EBC collected from patients admitted to the department of cardiology with suspected pulmonary embolism and controls with same age (within a range of 10 years) and gender from the outpatient clinic awaiting elective cardiovascular surgery. The main-outcome (i.e. means of the relative amounts of specific proteins in the EBC samples) will be compared by unpaired t-tests after assessment of normality and standard deviations within the three groups (PE confirmed, PE suspected but not confirmed and controls). Furthermore, sensitivity and specificity will be calculated for relevant proteins. The results from analysis of EBC samples from the patients and controls will be compared with results from the porcine model in order to confirm and reduce the number of putative biomarkers for PE. Blood samples (i.e. excess plasma from routine blood samples drawn as a part of routine diagnostic work-up) from the study participants will be stored for standardization of the putative markers and verification and supplementing analysis of the EBC markers. In order to qualify the most suitable markers and substrates for standardization, the analysis of the EBC samples must be completed before the blood samples can be analyzed. Only biochemical, no genetic analysis will be conducted.

Official Title
-----------------
Non-invasive Diagnosis of Pulmonary Embolism by Use of Biomarkers in Exhaled Breath Condensate

Conditions
-----------------
Pulmonary Embolism

Intervention / Treatment
-----------------
* Diagnostic Test: Test of biomarkers for PE in EBC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria - Suspected/confirmed PE patients: Admitted to the emergency department with initial diagnosis of PE, visited to the Department of Cardiology at Aalborg University Hospital. Are conscious and able to understand the given study information. Possess legal capacity. Age above 18 years. Informed, signed consent is obtained. Clinically stable, which is defined as patients with stable blood pressure and not in need for other treatments . No need for organ support, which comprises need for vasopressors or inotropes, mechanical ventilation, extra corporal circulation or renal replacement therapy. Inclusion Criteria - Controls: • Patients as the PE patients, but where the diagnosis of PE is rejected. The rest of the control persons will be recruited as described: Patients who are going to have elective procedures at the Department of Cardiology, Aalborg University Hospital. Same gender and age (within a 10-year range) as an included PE patient. Are conscious and able to understand the given study information. Possess legal capacity. Age above 18 years. Informed, signed consent is obtained. Exclusion Criteria: Active malignant disease (i.e. ongoing anti-cancer therapy or palliation). Current smokers

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PE confirmed<br>Patients admitted with confirmed pulmonary embolism. | Diagnostic Test: Test of biomarkers for PE in EBC<br>* New method for diagnosis of pulmonary embolism (PE) in order to validate/consolidate 151 putative identified biomarkers for PE in the exhaled breath condensate (EBC). The EBC will be collected by use of the RTube(R) system which has been used in previous studies of EBC. As the patient breathes through a mouth piece, the exhaled breath is led through a cooling chamber where the vaporous part of the exhaled breath condenses. We aim at collecting a total minimum of 3.0 mL EBC per study subject in order to have a sufficient amount of protein for the subsequent analysis. We aim at collecting exhaled breath condensate for 2*15 minutes with the possibility to stop the collection after less than 15 minutes if the volume is sufficient.<br>|
| PE suspected<br>Patients admitted with suspected, but not confirmed pulmonary embolism. | Diagnostic Test: Test of biomarkers for PE in EBC<br>* New method for diagnosis of pulmonary embolism (PE) in order to validate/consolidate 151 putative identified biomarkers for PE in the exhaled breath condensate (EBC). The EBC will be collected by use of the RTube(R) system which has been used in previous studies of EBC. As the patient breathes through a mouth piece, the exhaled breath is led through a cooling chamber where the vaporous part of the exhaled breath condenses. We aim at collecting a total minimum of 3.0 mL EBC per study subject in order to have a sufficient amount of protein for the subsequent analysis. We aim at collecting exhaled breath condensate for 2*15 minutes with the possibility to stop the collection after less than 15 minutes if the volume is sufficient.<br>|
| Controls<br>Healthy controls same gender and age (within af range of 10 years) as PE patients | Diagnostic Test: Test of biomarkers for PE in EBC<br>* New method for diagnosis of pulmonary embolism (PE) in order to validate/consolidate 151 putative identified biomarkers for PE in the exhaled breath condensate (EBC). The EBC will be collected by use of the RTube(R) system which has been used in previous studies of EBC. As the patient breathes through a mouth piece, the exhaled breath is led through a cooling chamber where the vaporous part of the exhaled breath condenses. We aim at collecting a total minimum of 3.0 mL EBC per study subject in order to have a sufficient amount of protein for the subsequent analysis. We aim at collecting exhaled breath condensate for 2*15 minutes with the possibility to stop the collection after less than 15 minutes if the volume is sufficient.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prediction of pulmonary embolism by use of biomarkers in the EBC | The primary outcome is prediction of pulmonary embolism by use of one or more novel biomarkers in the EBC. | 1-2 years |