Clinical trial NCT05395611: Exhaled Breath Particles in Lung Cancer
Official title: Exhaled Breath Particles as Biomarkers for Diagnosing, Prognosticating and Evaluating of Non Small Cell Lung Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lung Cancer
Non-small Cell Lung Cancer
Lung Adenocarcinoma
Squamous Cell Lung Cancer
Keywords: Exhaled Breath Particles
PExA
Lung cancer
Non-small cell lung cancer
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2022-05-27
Enrollment: 300
Sex: ALL
Minimum age (years): 16
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients diagnosed with primary lung cancer and listed for tumor resection. Patients without lung cancer.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Protein concentration in exhaled breath particles (EBP)
timeFrame: Before surgery for NSCLC
measure: Protein concentration in exhaled breath particles (EBP)
timeFrame: After surgery for NSCLC (2 weeks - 36 months)
measure: Protein concentration in exhaled breath particles (EBP)
timeFrame: In patients without NSCLC (control cohort). (0- 2 weeks)
Secondary outcomes:
measure: Particle flow rate (PFR) expressed as particles/liter of exhaled air
timeFrame: Before surgery for NSCLC
measure: Particle flow rate (PFR) expressed as particles/liter of exhaled air
timeFrame: After surgery for NSCLC (2 weeks - 36 months)
measure: Particle flow rate (PFR) expressed as particles/liter of exhaled air
timeFrame: In patients without NSCLC (control cohort). (0- 2 weeks)
measure: Protein expression in plasma
timeFrame: Before surgery for NSCLC
measure: Protein expression in plasma
timeFrame: After surgery for NSCLC (2 weeks - 36 months)
measure: Protein expression in plasma
timeFrame: In patients without NSCLC (control cohort). (0- 2 weeks)
measure: Protein expression in tissue
timeFrame: During surgery for NSCLC. (0- 2 weeks)
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital
state: Skåne Län
Study officials:
affiliation: Region Skåne, Lund University
name: Sandra Lindstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.