Breath Combined With CT for Diagnoses of Pulmonary Nodules

Assessment of the Efficacy of Breath Test Combined With Computed Tomography for Diagnoses of Pulmonary Nodules.

Pulmonary nodules diagnosis using breath test of volatile organic compound (VOC) is in its infancy. The accuracy of VOC analysis in diagnosing malignant pulmonary nodules varies cross the published studies. The diagnosis accuracy of VOC alone is generally poor. We speculate that the accuracy of diagnosing malignant pulmonary nodules will be improved by combining breath test with chest computed tomography (CT). This study aims to establish a predictive model of malignant pulmonary nodule using bio-markers from exhaled breath and image-markers from chest CT with retrospective data from multi centers. The sensitivity, specificity and accuracy of the model will be validated prospectively.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; Pulmonary Nodule, Multiple
• Intervention / Treatment: Diagnostic test: Pathological examinations as the golden diagnosis criteria; Diagnostic test: Breath test combined with computed tomography

Detailed Description

Endogenous volatile organic compounds (VOCs) can be derived from many different metabolic pathways. VOCs can be transported to the alveoli through the blood circulation and expelled by exhalation. Changes in VOCs production, clearance, and alterations in lung air-blood exchange functions can lead to aberrant VOCs profiles in the exhaled breath. Testing exhaled breath has the advantages of being completely non-invasive and easy to collect, and has been considered as a perfect approach for disease diagnoses and therapeutic monitoring. Many clinical studies have found that VOCs in exhaled breath are closely related to disease status. Specific VOCs alterations have been identified in many tumors, especially lung cancer. Pulmonary nodules diagnosis using breath test of volatile organic compound (VOC) is in its infancy. The accuracy of VOC analysis in diagnosing malignant pulmonary nodules varies cross the published studies. The diagnosis accuracy of VOC alone is generally poor. We speculate that the accuracy of diagnosing malignant pulmonary nodules will be improved by combining VOC analysis with chest computed tomography.

In this study, we use a highly sensitive mass spectrometry to detect exhaled VOCs of patients with pulmonary nodules. The chest CT will be used for detecting the imaging characteristics of pulmonary nodules. The pathological diagnosis of pulmonary nodules after surgical resections is selected as golden standard.

This study aims to establish a predictive model of malignant pulmonary nodule using bio-markers from breath test and image-markers from chest CT with retrospective data from multi centers. The sensitivity, specificity and accuracy of the model will be varied prospectively.

• Study Type: Observational
• Enrollment (Anticipated): 900

Contacts and Locations

• Study Contact: Name: Mantang Qiu, PhD; Phone Number: 13915973485; Email: qiumantang@163.com
• Study Contact Backup: Name: Peiyu Wang, MM; Email: 18339979852@163.com

Study Locations

• China
  • Beijing, China, 100044
    • Recruiting
    • Peking University People's Hospital
    • Contact: Mantang Qiu, PhD; Email: qiumantang@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

To establish pulmonary nodule diagnosis model of breath test combined with computed tomography, we reviewed the prospective database established during the study of NCT04419207 for participant recruitment. 200 participants with malignant pulmonary nodules and 200 patients with benign pulmonary nodules will be included for establishing the diagnosis model.

To validate the efficacy of the established model in distinguishing malignant pulmonary nodules from benign nodules, we will prospectively recruit 500 patients with pulmonary nodules in multi centers: Peking University People's Hospital (200 participants), The First Affiliated Hospital of Zhengzhou University (200 participants), and Beijing Haidian Hospital (100 participants).

Description

Inclusion Criteria:

1. Age > 18 years old;
2. Pulmonary nodules with planned surgical resection;
3. Signed informed consent and agreed to participate in this study.

Exclusion Criteria:

1. Preoperative radiotherapy, chemotherapy, targeted therapy or other anti-tumor therapy
2. The lack of chest computed tomography within two weeks before surgery
3. A history of malignant disease within 5 years.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Malignant pulmonary nodules; Patients with pulmonary nodule diagnosed as malignant cancer by pathological examinations after surgical resection.	Diagnostic test: Pathological examinations as the golden diagnosis criteria; Pathological diagnosis, as the golden standard for diagnosing pulmonary nodules, is achieved by two experienced pathologists and validated by the third senior pathologist.; Diagnostic test: Breath test combined with computed tomography; Exhaled breath of each participant will be collected with Tedlar bags. The volatile organic compounds will be detected by a high-resolution high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). The Imaging markers of pulmonary nodules, including the size, three-dimensional shape, and appearance characteristics, are derived from the chest computed tomography within 2 weeks before surgery resection.
Benign pulmonary nodules; Patients with pulmonary nodule diagnosed as benign disease by pathological examinations after surgical resection.	Diagnostic test: Pathological examinations as the golden diagnosis criteria; Pathological diagnosis, as the golden standard for diagnosing pulmonary nodules, is achieved by two experienced pathologists and validated by the third senior pathologist.; Diagnostic test: Breath test combined with computed tomography; Exhaled breath of each participant will be collected with Tedlar bags. The volatile organic compounds will be detected by a high-resolution high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). The Imaging markers of pulmonary nodules, including the size, three-dimensional shape, and appearance characteristics, are derived from the chest computed tomography within 2 weeks before surgery resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic sensitivity of breath test combined with computed tomography	Using pathological diagnosis of pulmonary nodule as gold standard, diagnostic specificity of breath test combined with computed tomography will be calculated	8 weeks
Diagnostic specificity of breath test combined with computed tomography	Using pathological diagnosis of pulmonary nodule as gold standard, diagnostic specificity of breath test combined with computed tomography will be calculated	8 weeks
Diagnostic accuracy of breath test combined with computed tomography	Using pathological diagnosis of pulmonary nodule as gold standard, diagnostic accuracy of breath test combined with computed tomography will be calculated	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive predictive value of breath test combined with computed tomography	Using pathological diagnosis of pulmonary nodule as gold standard, positive predictive value of breath test combined with computed tomography will be calculated	8 weeks
Negative predictive value of breath test combined with computed tomography	Using pathological diagnosis of pulmonary nodule as gold standard, negative predictive value of breath test combined with computed tomography will be calculated	8 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: The First Affiliated Hospital of Zhengzhou University; Jiangsu Cancer Institute & Hospital; Beijing Haidian Hospital; Beijing Breatha Biological Technology Co., Ltd, Beijing
• Investigators: Principal Investigator: Mantang Qiu, PhD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2021
• Primary Completion (Anticipated): October 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: predictive model; computed tomography; pulmonary nodules; volatile organic compound; HPPI-TOFMS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Multiple Pulmonary Nodules
• Other Study ID Numbers: 2021PHB150-001

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