Breath Combined With CT for Diagnoses of Pulmonary Nodules

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non-small Cell Lung Cancer, Pulmonary Nodule, Multiple

Intervention / Treatment
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* Diagnostic Test: Pathological examinations as the golden diagnosis criteria
* Diagnostic Test: Breath test combined with computed tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old; Pulmonary nodules with planned surgical resection; Signed informed consent and agreed to participate in this study. Exclusion Criteria: Preoperative radiotherapy, chemotherapy, targeted therapy or other anti-tumor therapy The lack of chest computed tomography within two weeks before surgery A history of malignant disease within 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Malignant pulmonary nodules<br>Patients with pulmonary nodule diagnosed as malignant cancer by pathological examinations after surgical resection. | Diagnostic Test: Pathological examinations as the golden diagnosis criteria<br>* Pathological diagnosis, as the golden standard for diagnosing pulmonary nodules, is achieved by two experienced pathologists and validated by the third senior pathologist.<br>Diagnostic Test: Breath test combined with computed tomography<br>* 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.<br>|
| Benign pulmonary nodules<br>Patients with pulmonary nodule diagnosed as benign disease by pathological examinations after surgical resection. | Diagnostic Test: Pathological examinations as the golden diagnosis criteria<br>* Pathological diagnosis, as the golden standard for diagnosing pulmonary nodules, is achieved by two experienced pathologists and validated by the third senior pathologist.<br>Diagnostic Test: Breath test combined with computed tomography<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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volatile organic compound, pulmonary nodules, predictive model, computed tomography, HPPI-TOFMS