Detection of mycobacterial pulmonary diseases via breath analysis in clinical practice

Abstract

Background Current clinical tests for mycobacterial pulmonary diseases (MPD), such as pulmonary tuberculosis (PTB) and non-tuberculous mycobacteria pulmonary diseases (NTM-PD), are inaccurate, time-consuming, sputum-dependent, and/or costly. We aimed to develop a simple, rapid and accurate breath test for screening and differential diagnosis of MPD patients in clinical settings. Methods Exhaled breath samples were collected from 142 PTB, 68 NTM-PD and 9 PTB&NTM-PD patients, 93 patients with other pulmonary diseases (OPD) and 181 healthy controls (HC), and tested using the online high-pressure photon ionisation time-of-flight mass spectrometer (HPPI-TOF-MS). Machine learning models were trained and blindly tested for the detection of MPD, PTB, NTM-PD, and the discrimination between PTB and NTM-PD, respectively. Diagnostic performance was evaluated by metrics of sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC). Results The breath PTB detection model achieved a sensitivity of 81.8%, a specificity of 94.3%, an accuracy of 90.7%, and an AUC of 0.957 in the blinded test set (n=150). The corresponding metrics for the NTM-PD detection model were 95.5%, 86.7%, 88.0% and 0.947, respectively. For distinguishing PTB from NTM-PD, the model also achieved good performance with sensitivity, specificity, accuracy, and AUC of 95.5%, 90.9%, 93.9% and 0.974, respectively. 24 potential breath biomarkers associated with MPD were putatively identified and discussed, which included 2-picoline, ethanol, 1-Pentene, etc. Conclusions The developed breathomics-based MPD detection method was demonstrated for the first time with good performance for potential screening and diagnosis of PTB and NTM-PD using a refined operating procedure on the HPPI-TOF-MS platform.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by Science and Technology Program of Guangzhou (2023A03J0991, 2023A03J0539), Guangzhou High Level Clinical Key Specialty - Tuberculosis, and Guangzhou Medical Key Disciplines - Tuberculosis (2021-2023).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Review Approval of Medical Ethics Committee of Guangzhou Chest Hospital (No. 2022-65): The ethics committee has reviewed the study protocol and found that it is in line with the relevant laws and regulations and the ethical requirements of medical research, and agreed to carry out the study. Patients should be properly informed and sign informed consent forms during project implementation, and patient information should be kept confidential. The Ethics Committee should be notified in a timely manner of any suspension/early termination of the project, and any changes to the implementation plan etc. during the study must be notified to the Ethics Committee in a timely manner for record or re-examined for approval before proceeding, and the Ethics Committee's final report or final summary must be submitted in a timely manner for record.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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