Exhaled Breath Particles in Lung Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer; Lung Adenocarcinoma; Non-small Cell Lung Cancer; Squamous Cell Lung Cancer
• Intervention / Treatment: Other: EBPcollected using the PExA device.

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Sandra Lindstedt, MD, PhD; Phone Number: +46737220580; Email: sandra.lindstedt_ingemansson@med.lu.se

Study Locations

• Sweden
  • Skåne Län
    • Lund, Skåne Län, Sweden, 224 60
      • Recruiting
      • Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients diagnosed with primary lung cancer and listed for tumor resection. Patients without lung cancer.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lung cancer; 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.; The PExA device is a non invasive device that collect particles in exhaled air
Control; 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.; The PExA device is a non invasive device that collect particles in exhaled air

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Investigators: Principal Investigator: Sandra Lindstedt, MD, PhD, Region Skane, Lund University

Publications and helpful links

General Publications

• Stenlo M, Hyllen S, Silva IAN, Bolukbas DA, Pierre L, Hallgren O, Wagner DE, Lindstedt S. Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2020 Mar 1;318(3):L510-L517. doi: 10.1152/ajplung.00524.2019. Epub 2020 Jan 29.
• Broberg E, Hyllen S, Algotsson L, Wagner DE, Lindstedt S. Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction. Exp Clin Transplant. 2019 Dec;17(6):803-812. doi: 10.6002/ect.2019.0187. Epub 2019 Oct 11.
• Behndig AF, Mirgorodskaya E, Blomberg A, Olin AC. Surfactant Protein A in particles in exhaled air (PExA), bronchial lavage and bronchial wash - a methodological comparison. Respir Res. 2019 Sep 26;20(1):214. doi: 10.1186/s12931-019-1172-1.
• Broberg E, Andreasson J, Fakhro M, Olin AC, Wagner D, Hyllen S, Lindstedt S. Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients. ERJ Open Res. 2020 Feb 10;6(1):00198-2019. doi: 10.1183/23120541.00198-2019. eCollection 2020 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; Lung cancer; Exhaled Breath Particles; PExA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung
• Other Study ID Numbers: PExCaP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No