Exhaled Breath Particles in Lung Cancer

Study Overview
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Brief Summary
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Lung cancer (CaP) is the leading cause of cancer related deaths on a global level. Early diagnosis is vital for survival and life quality of the affected patients, yet lung cancer is often diagnosed at advanced stages, causing poor five-year survival rates. Exhaled breath particles (EBP) and particle flow rate (PFR) collected by the particles in exhaled air (PExA) system is a safe and easily reproducible non-invasive method for gaining insight into the molecular environment of the distal airways. EBP and PFR have been found useful in detection of other airway diseases such as acute respiratory distress syndrome (ARDS), primary graft dysfunction (PGD) and bronchiolitis obliterans syndrome (BOS). It has been shown that particles found in EBP reflect the general composition of respiratory tract lining fluid (RTLF) and that biomarkers found in EBP correlate to proteins that can be found in both bronchoalveolar lavage fluid (BALF) and plasma. Particle flow rate (PFR) has been found to differ between patients with lung cancer compared to control patients. In the present study the investigators aim to collect EBP samples and measure PFR from patients with primary lung cancer and from control patients. EBPs are collected for molecular analysis. The investigators aim to identify biomarkers for diagnosing, predicting prognosis of and evaluating surgical treatment of non small cell lung cancer.

Detailed Description
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EBP samples and measurements of PFR will be collected from patients with primary non-small cell lung cancer (NSCLC) at Skåne University Hospital (SUS) Lund. Measurements will be done at 2 time points, before and after surgical resection for NSCLC. EBP samples will be collected at one time point from a matched (by age and smoking history) control cohort. Blood samples will be collected from both cohorts, at the same time points as the EBP/PFR measurements. Tumor tissue and healthy adjacent lung tissue will be collected from lung cancer patients with tumors greater than 3 cm in diameter on preoperative computed tomography. The purpose of this clinical trial is to identify non-invasive means of diagnosing NSCLC at earlier stages. The PExA method is not associated with any risks and has potential minimize hospitalization associated with more invasive methods that are in clinical practice today, such as bronchoscopy and biopsies.

Official Title
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Exhaled Breath Particles as Biomarkers for Diagnosing, Prognosticating and Evaluating of Non Small Cell Lung Cancer

Conditions
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Lung Cancer, Non-small Cell Lung Cancer, Lung Adenocarcinoma, Squamous Cell Lung Cancer

Intervention / Treatment
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* Other: EBPcollected using the PExA device.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary lung cancer with clinical Tumor, Node, Metastasis (TNM) up to cT3N1M0 according to TNM 7th edition Able to take instructions and perform the standardized breathing maneuver Exclusion Criteria: Dementia Severe neurological disease Drug abuse Heart failure New York Heart Association (NYHA) Classification, NYHA class III or IV Ejection fraction < 50 % S-creatinine > 140 µmol/L Poorly regulated diabetes mellitus

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 90 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 |
| --- | --- |
| Lung cancer<br>Patients with primary non small cell lung cancer listed for tumor resection. EBP, plasma and lung tumor tissue will be collected for protein profiling. Collection of EBP will be done at 2 time points before and after surgery. Collection of plasma will be done at 2 time points before and after surgery. Collection of lung/tumor tissue will be done at the time of surgery | Other: EBPcollected using the PExA device.<br>* The PExA device is a non invasive device that collect particles in exhaled air<br>|
| Control<br>Patients without lung cancer matched according to age and smoking history (control cohort) Collection of EBP will be done at one time point. Collection of plasma will be done at one time point. | Other: EBPcollected using the PExA device.<br>* The PExA device is a non invasive device that collect particles in exhaled air<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protein concentration in exhaled breath particles (EBP) | EBPs are collected on membranes and analyzed in regards to protein concentration and abundance | Before surgery for NSCLC | 
| Protein concentration in exhaled breath particles (EBP) | EBPs are collected on membranes and analyzed in regards to protein concentration and abundance | After surgery for NSCLC (2 weeks - 36 months) | 
| Protein concentration in exhaled breath particles (EBP) | EBPs are collected on membranes and analyzed in regards to protein concentration and abundance | In patients without NSCLC (control cohort). (0- 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Particle flow rate (PFR) expressed as particles/liter of exhaled air | Particle flow rate (PFR) has recently been shown to differ significantly between patients suffering from respiratory diseases such as bronchiolitis obliterans syndrome (BOS) and covid-19 compared to healthy controls. PFR will be measured from patients with primary lung cancer and control patients to investigate if PFR can be used to distinguish between the two groups and thus help diagnosing lung cancer in earlier stages. | Before surgery for NSCLC | 
| Particle flow rate (PFR) expressed as particles/liter of exhaled air | Particle flow rate (PFR) has recently been shown to differ significantly between patients suffering from respiratory diseases such as bronchiolitis obliterans syndrome (BOS) and covid-19 compared to healthy controls. PFR will be measured from patients with primary lung cancer and control patients to investigate if PFR can be used to distinguish between the two groups and thus help diagnosing lung cancer in earlier stages. | After surgery for NSCLC (2 weeks - 36 months) | 
| Particle flow rate (PFR) expressed as particles/liter of exhaled air | Particle flow rate (PFR) has recently been shown to differ significantly between patients suffering from respiratory diseases such as bronchiolitis obliterans syndrome (BOS) and covid-19 compared to healthy controls. PFR will be measured from patients with primary lung cancer and control patients to investigate if PFR can be used to distinguish between the two groups and thus help diagnosing lung cancer in earlier stages. | In patients without NSCLC (control cohort). (0- 2 weeks) | 
| Protein expression in plasma | Concentration and composition of proteins will be measured in plasma from lung cancer patients | Before surgery for NSCLC | 
| Protein expression in plasma | Concentration and composition of proteins will be measured in plasma from lung cancer patients | After surgery for NSCLC (2 weeks - 36 months) | 
| Protein expression in plasma | Concentration and composition of proteins will be measured in plasma from healthy control patients | In patients without NSCLC (control cohort). (0- 2 weeks) | 
| Protein expression in tissue | Concentration and composition of proteins will be measured in tumor tissue and the surrounding lung tissue. | During surgery for NSCLC. (0- 2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PExA, Exhaled Breath Particles, Lung cancer, Non-small cell lung cancer