Breathomics: May it Become an Affordable, New Tool for Early Diagnosis and Screening of Lung Cancer?

Breathomics: May it Become an Affordable, New Tool for Early Diagnosis and Screening of Lung Cancer? An Exploratory Study on a Cohort of 60 Patients

Breath analysis examining specific patterns of volatile organic compounds (VOCs) has been demonstrated to be able to discriminate lung cancer (LC) patients from healthy controls (HC). However, the existing technology uses complex, expensive, and low throughput analytical platforms to give an offline response, thus preventing its applicability for mass screening. The reliability of a new portable device to enable rapid, on-site LC diagnosis is tested.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Device: Portable GC device for brath analysis

Detailed Description

The breath of patients with histologically proven NSCLC and healthy controls was sampled into Tedlar bags through a Nafion filter and a one-way mouthpiece. The breath samples in the bags were then analyzed by an automated micro portable gas chromatography device developed in-house, which consisted of a thermal desorption tube, thermal injector, separation column, and photoionization detector, as well as other accessories such as pumps, valves, and a helium cartridge. The chromatograms were analyzed by chemometrics and machine learning techniques.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70121
    • Azienda Consorziale Ospedaliero-Universitaria Policlinico di Bari - Thoracic Surgery Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

A total of 60 patients undergoing surgery for histologically proven NSCLC and a comparative group of non-cancer controls who had negative findings on preoperative chest X-rays/chest CT scan were admitted to our Thoracic Surgery Unit between August 2021 and March 2022. Patients underwent breath collection during the pre-hospitalization analysis before surgery. The control group was recruited from patients undergoing surgery for benign extra-thoracic disease who had undergone chest X-rays/chest CT-scan, proved to be negative during preoperative evaluation.

Patients excluded from analysis were those who had any history of another type of cancer and those who had received neoadjuvant chemo/radiotherapy because of the possible unknown effects on cancer metabolism.

Description

Inclusion Criteria:

• NSCLC histologically proven (for LC group) at any stage of disease
• non-cancer controls who had negative findings on preoperative chest X-rays/chest CT scan (for HC groups)

Exclusion Criteria:

• Patients who had any history of another type of cancer
• who had received neoadjuvant chemo/radiotherapy because of the possible unknown effects on cancer metabolism
• pediatric patients.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lung Cancer Patients; patients undergoing surgery for histologically proven NSCLC	Device: Portable GC device for brath analysis; Patients were asked to orally exhale 1-2 L breath into a 5 L Tedlar bag via a one-way mouthpiece and Nafion filter for moisture removal, as shown in Figure 1B. The process usually takes about a few minutes. The breath analysis took place either in-situ immediately after the breath sample collection or within 24 h of breath collection. The Tedlar bags were stored under ambient condition until analyzed. During the breath analysis, the Tedlar bag was connected to the sampling port of the portable GC (Figure 1C). Approximately 350 mL of breath was pulled from the Tedlar bag into the GC for analysis. The GC operation was controlled using LabView via a laptop. The total assay time was 30 min, including 5 min of breath sampling time from the Tedlar bag at a flow rate of 70 mL/min (see the blue path in Figure 1A), 5 min of desorption/transfer time, 10 min of chromatographic separation time (see the orange path in Figure 1A), and 10 min of GC system cleaning time.
Healthy Control Patients; patients undergoing surgery for benign extra-thoracic disease who had undergone chest X-rays/chest CT-scan, proved to be negative during preoperative evaluation.	Device: Portable GC device for brath analysis; Patients were asked to orally exhale 1-2 L breath into a 5 L Tedlar bag via a one-way mouthpiece and Nafion filter for moisture removal, as shown in Figure 1B. The process usually takes about a few minutes. The breath analysis took place either in-situ immediately after the breath sample collection or within 24 h of breath collection. The Tedlar bags were stored under ambient condition until analyzed. During the breath analysis, the Tedlar bag was connected to the sampling port of the portable GC (Figure 1C). Approximately 350 mL of breath was pulled from the Tedlar bag into the GC for analysis. The GC operation was controlled using LabView via a laptop. The total assay time was 30 min, including 5 min of breath sampling time from the Tedlar bag at a flow rate of 70 mL/min (see the blue path in Figure 1A), 5 min of desorption/transfer time, 10 min of chromatographic separation time (see the orange path in Figure 1A), and 10 min of GC system cleaning time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in VOCs peaks in patients with lung cancer vs healthy patients	Identify biomarkers able to discriminate between lung cancer patients and healthy controls.	24 hours

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
• Collaborators: University of Michigan; Humanitas Hospital, Italy
• Investigators: Study Director: Giuseppe Marulli, MD, PhD, Humanitas Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; screening; volatile organic compounds; breathomic
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: 665139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: On request alla data will be available

Drug and device information, study documents

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