CClinicalTrials.gg
RecruitingNCT06518655Updated Dec 24, 2025

Differentiation of Benign and Malignant Pulmonary Nodules by Volatile Organic Compounds in Human Exhaled Breath

An observational study in Pulmonary Nodules, Multiple, Pulmonary Nodules, Solitary and Lung Cancer, sponsored by ChromX Health. Recruiting at 15 sites in China. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-24.

Sponsored by ChromX Health · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
3,000
Ages
18 Years to 80 Years
Sex
All
01

Study summary

The goal of this observational study is to develop an advanced expiratory algorithm model utilizing exhaled breath volatile organic compound (VOC) markers. This model aims to accurately differentiate benign from malignant nodules in individuals harboring pulmonary nodules. The primary objectives it strives to accomplish are:

  1. To assess the diagnostic accuracy of an exhaled breath VOC-assisted diagnostic artificial intelligence (AI) model in distinguishing benign and malignant pulmonary nodules.
  2. To evaluate the diagnostic effectiveness of an AI model that employs exhaled breath VOC biomakers to identify specific types of malignant nodules, including lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer.
  3. To explore and identify key characteristic VOCs combinations that are associated with EGFR site mutations in malignant nodules, further modeling and evaluating the classification performance.

By utilizing this comprehensive approach, the study hopes to contribute significantly to early detection and accurate classification of pulmonary nodules, ultimately leading to improved patient care and treatment outcomes.

Read the detailed description

This is a prospective, cross-sectional, and observational cohort study aiming at recruiting 3000 participants with pulmonary nodules ranging from 5 to 30 mm in diameter. Prior to invasive surgery, exhaled breath samples will be collected from these participants and analyzed using Gas chromatography-mass spectrometry(GC-MS) and micro Gas Chromatography-photoionisation detector (μGC-PID) system. Following the acquisition of μGC-PID results, a comprehensive evaluation of the diagnostic performance of VOC biomakers distinguishing between benign and malignant pulmonary nodules will be conducted, leveraging histopathological findings, CT examination data, and clinical data.

02

Conditions studied

  • Pulmonary Nodules, Multiple
  • Pulmonary Nodules, Solitary
  • Lung Cancer

Keywords

  • Pulmonary Nodules
  • Lung Cancer
  • Volatile Organic Compounds
  • Human Exhaled Breath
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

People who have pulmonary nodules with a large diameter between 5 mm and 30 mm on a CT scan within six months.

Inclusion criteria

  • 18-80 years old;
  • Pulmonary nodules were detected through low-dose spiral CT, chest CT conventional scan, or high-resolution thin-layer CT examination, with a maximum diameter of 5-30 mm, including solid nodules and ground glass nodules;
  • Patients require pulmonary nodule resection to define the type of nodule pathology;
  • The Patients have not yet used any drugs for tumor treatment;
  • Patients and/or family members are able to understand the research protocol and are willing to participate in this study, providing written informed consent.

Exclusion criteria

Exclusion Criteria:

  • The maximum diameter of pulmonary nodules is greater than 30 mm;
  • Patients are unable to determine the pathological diagnosis of pulmonary nodules after surgical resection or biopsy;
  • Patients with recurrent lung cancer;
  • Patients who have undergone lung transplantation or lobectomy;
  • Individuals who currently or have a history of malignant tumors;
  • Patients in the acute phase of inflammation or in need of intensive care in the above selected disease groups;
  • Individuals with severe liver and kidney dysfunction;
  • Mental illness patients (such as severe dementia, schizophrenia, severe depression, manic depressive psychosis, etc.);
  • Confirmed HIV patients;
  • Pregnant or lactating women;
  • Patients or family members are unable to understand the conditions and objectives of this study.
  • The patient is unwilling or unable to personally sign the informed consent form.
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
3,000 participants (estimated)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • Pulmonary Nodules

    Pre-surgery adult patients with pulmonary nodule found by CT scan.

    Other: Gas chromatography-mass spectrometry(GC-MS) and micro Gas Chromatography-photoionisation detector (μGC-PID) system

Interventions

  • OtherGas chromatography-mass spectrometry(GC-MS) and micro Gas Chromatography-photoionisation detector (μGC-PID) system

    Detection of volatile organic compound molecules in human exhaled breath by GC-MS and μGC-PID

05

What researchers measure

Primary outcomes

  1. The diagnostic accuracy of an exhaled breath VOC-assisted diagnostic artificial intelligence (AI) model in distinguishing benign and malignant pulmonary nodules.

    The diagnostic performance of the exhaled breath VOC-assisted diagnostic artificial intelligence (AI) model will be compared with pathologic diagnosis and CT/LDCT data, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

    Time frame: 3 years

Secondary outcomes

  1. The diagnostic effectiveness of an AI model to identify specific types of malignant nodules, including lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer.

    The diagnostic performance of the exhaled breath VOC-assisted diagnostic artificial intelligence (AI) model will be compared with pathologic diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

    Time frame: 3 years

Other outcomes

  1. Establish an exhaled breath VOC model for predicting EGFR mutations in malignant pulmonary nodules.

    Establish an exhaled breath VOC model for predicting EGFR mutations in pathologically confirmed malignant pulmonary nodules. And evaluate the prediction accuracy by comparing the results of EGFR gene testing.

    Time frame: 3 years

06

Study locations

15 of 15 sites recruiting
  • Peking Union Medical College Hospital
    Beijing, Beijing Municipality, China
    • Qian Wang, MD · Contact
    Recruiting
  • First People's Hospital of Foshan
    Foshan, Guangdong 528000, China
    • Zhuxing Chen · Contact
    Recruiting
  • The First Affiliated Hospital of Guangzhou Medical University
    Guangzhou, Guangdong 510140, China
    Recruiting
  • Liwan District Central Hospital
    Guangzhou, Guangdong 510175, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Guangzhou Development Zone Hospital
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Huangpu District Chinese Medicine Hospital
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Huangpu District Hongshan Street Community Health Service Center
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Huangpu District Jiufo Street Community Health Service Center
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Huangpu District Lianhe Street Second Community Health Service Center
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Huangpu District Xinlong Town Central Hospital
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Huangpu District Yonghe Street Community Health Service Center
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • The Fifth Affiliated Hospital of Guangzhou Medical University
    Guangzhou, Guangdong, China
    • Hengrui Liang, MD · Contact
    Recruiting
  • Renmin Hospital of Wuhan University
    Wuhan, Hubei, China
    • Huiqing Lin, MD · Contact
    Recruiting
  • Shanghai Chest Hospital
    Shanghai, Shanghai Municipality, China
    • Yanwei Zhang, MD · Contact
    Recruiting
  • Sichuan Cancer Hospital
    Chengdu, Sichuan 610042, China
    • Bo Tian, MD · Contact · +86 18980053101
    Recruiting
07

References and documents

Publications

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PubMed 33538338 ↗
  • Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108. PubMed 35143424 ↗
  • Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016 Jul;66(4):271-89. doi: 10.3322/caac.21349. Epub 2016 Jun 2. PubMed 27253694 ↗
  • National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29. PubMed 21714641 ↗
  • Shlomi D, Abud M, Liran O, Bar J, Gai-Mor N, Ilouze M, Onn A, Ben-Nun A, Haick H, Peled N. Detection of Lung Cancer and EGFR Mutation by Electronic Nose System. J Thorac Oncol. 2017 Oct;12(10):1544-1551. doi: 10.1016/j.jtho.2017.06.073. Epub 2017 Jul 12. PubMed 28709937 ↗
  • van de Goor R, van Hooren M, Dingemans AM, Kremer B, Kross K. Training and Validating a Portable Electronic Nose for Lung Cancer Screening. J Thorac Oncol. 2018 May;13(5):676-681. doi: 10.1016/j.jtho.2018.01.024. Epub 2018 Feb 6. PubMed 29425703 ↗
  • Hanna GB, Boshier PR, Markar SR, Romano A. Accuracy and Methodologic Challenges of Volatile Organic Compound-Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis. JAMA Oncol. 2019 Jan 1;5(1):e182815. doi: 10.1001/jamaoncol.2018.2815. Epub 2019 Jan 10. PubMed 30128487 ↗
  • Horvath I, Lazar Z, Gyulai N, Kollai M, Losonczy G. Exhaled biomarkers in lung cancer. Eur Respir J. 2009 Jul;34(1):261-75. doi: 10.1183/09031936.00142508. PubMed 19567608 ↗
  • Mitsui T, Kondo T. Inadequacy of theoretical basis of breath methylated alkane contour for assessing oxidative stress. Clin Chim Acta. 2003 Jul 1;333(1):91; author reply 93-4. doi: 10.1016/s0009-8981(03)00173-6. No abstract available. PubMed 12809740 ↗
  • Stone BG, Besse TJ, Duane WC, Evans CD, DeMaster EG. Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men. Lipids. 1993 Aug;28(8):705-8. doi: 10.1007/BF02535990. PubMed 8377584 ↗
  • Nakhleh MK, Amal H, Jeries R, Broza YY, Aboud M, Gharra A, Ivgi H, Khatib S, Badarneh S, Har-Shai L, Glass-Marmor L, Lejbkowicz I, Miller A, Badarny S, Winer R, Finberg J, Cohen-Kaminsky S, Perros F, Montani D, Girerd B, Garcia G, Simonneau G, Nakhoul F, Baram S, Salim R, Hakim M, Gruber M, Ronen O, Marshak T, Doweck I, Nativ O, Bahouth Z, Shi DY, Zhang W, Hua QL, Pan YY, Tao L, Liu H, Karban A, Koifman E, Rainis T, Skapars R, Sivins A, Ancans G, Liepniece-Karele I, Kikuste I, Lasina I, Tolmanis I, Johnson D, Millstone SZ, Fulton J, Wells JW, Wilf LH, Humbert M, Leja M, Peled N, Haick H. Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules. ACS Nano. 2017 Jan 24;11(1):112-125. doi: 10.1021/acsnano.6b04930. Epub 2016 Dec 21. PubMed 28000444 ↗
  • Zhou J, Huang ZA, Kumar U, Chen DDY. Review of recent developments in determining volatile organic compounds in exhaled breath as biomarkers for lung cancer diagnosis. Anal Chim Acta. 2017 Dec 15;996:1-9. doi: 10.1016/j.aca.2017.09.021. Epub 2017 Sep 13. PubMed 29137702 ↗
  • Arasaradnam RP, Wicaksono A, O'Brien H, Kocher HM, Covington JA, Crnogorac-Jurcevic T. Noninvasive Diagnosis of Pancreatic Cancer Through Detection of Volatile Organic Compounds in Urine. Gastroenterology. 2018 Feb;154(3):485-487.e1. doi: 10.1053/j.gastro.2017.09.054. Epub 2017 Nov 10. No abstract available. PubMed 29129714 ↗
  • Chan DK, Zakko L, Visrodia KH, Leggett CL, Lutzke LS, Clemens MA, Allen JD, Anderson MA, Wang KK. Breath Testing for Barrett's Esophagus Using Exhaled Volatile Organic Compound Profiling With an Electronic Nose Device. Gastroenterology. 2017 Jan;152(1):24-26. doi: 10.1053/j.gastro.2016.11.001. Epub 2016 Nov 5. No abstract available. PubMed 27825962 ↗
  • Gordon SM, Szidon JP, Krotoszynski BK, Gibbons RD, O'Neill HJ. Volatile organic compounds in exhaled air from patients with lung cancer. Clin Chem. 1985 Aug;31(8):1278-82. PubMed 4017231 ↗
  • Corradi M, Pesci A, Casana R, Alinovi R, Goldoni M, Vettori MV, Cuomo A. Nitrate in exhaled breath condensate of patients with different airway diseases. Nitric Oxide. 2003 Feb;8(1):26-30. doi: 10.1016/s1089-8603(02)00128-3. PubMed 12586538 ↗
  • Bousamra M 2nd, Schumer E, Li M, Knipp RJ, Nantz MH, van Berkel V, Fu XA. Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease. J Thorac Cardiovasc Surg. 2014 Sep;148(3):1074-80; discussion 1080-1. doi: 10.1016/j.jtcvs.2014.06.006. Epub 2014 Jun 8. PubMed 25129599 ↗
  • Phillips M, Altorki N, Austin JH, Cameron RB, Cataneo RN, Greenberg J, Kloss R, Maxfield RA, Munawar MI, Pass HI, Rashid A, Rom WN, Schmitt P. Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomark. 2007;3(2):95-109. doi: 10.3233/cbm-2007-3204. PubMed 17522431 ↗
  • Phillips M, Bauer TL, Pass HI. A volatile biomarker in breath predicts lung cancer and pulmonary nodules. J Breath Res. 2019 Jun 19;13(3):036013. doi: 10.1088/1752-7163/ab21aa. PubMed 31085817 ↗
  • Phillips M, Cataneo RN, Greenberg J, Grodman R, Gunawardena R, Naidu A. Effect of oxygen on breath markers of oxidative stress. Eur Respir J. 2003 Jan;21(1):48-51. doi: 10.1183/09031936.02.00053402. PubMed 12570108 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06518655
Lead sponsor
ChromX Health
Collaborators
The First Affiliated Hospital of Guangzhou Medical University, First People's Hospital of Foshan, Sichuan Cancer Hospital and Research Institute, Liwan District Central Hospital, Shanghai Chest Hospital, Peking Union Medical College Hospital, Guangzhou Development Zone Hospital, Huangpu District Hongshan Street Community Health Service Center, Huangpu District Chinese Medicine Hospital, Fifth Affiliated Hospital of Guangzhou Medical University, Huangpu District Jiufo Street Community Health Service Center, Huangpu District Xinlong Town Central Hospital, Huangpu District Yonghe Street Community Health Service Center, Huangpu District Lianhe Street Second Community Health Service Center, Renmin Hospital of Wuhan University
Responsible party
Sponsor
First posted
Jul 24, 2024
Start date
Jun 30, 2024
Primary completion
Dec 30, 2026 (estimated)
Completion
Jun 30, 2027 (estimated)
Last update
Dec 24, 2025

Study contacts

Hengrui Liang, MD
Contact
hengrui_liang@163.com
+86 15625064712
Jianxing He, MD
study chair · The First Affiliated Hospital of Guangzhou Medical University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion