Exhaled Breath Analysis in Lymphangioleiomyomatosis by Real-Time Proton Mass Spectrometry

Area of Science:

• Pulmonary Medicine
• Biomarker Discovery
• Analytical Chemistry

Background:

• Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease in women of reproductive age.
• Current LAM diagnostics are expensive or lack specificity, necessitating novel non-invasive methods.
• Exhaled breath analysis offers a potential avenue for identifying disease-specific volatile organic compounds (VOCs).

Purpose of the Study:

• To investigate exhaled breath volatile organic compound (VOC) profiles for diagnosing LAM.
• To identify VOC biomarkers predictive of LAM complications.
• To evaluate the diagnostic accuracy of VOC signatures for LAM.

Main Methods:

• Cross-sectional study involving 51 LAM patients and 51 healthy controls.
• Real-time proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) for exhaled breath analysis.
• Machine learning models, including XGBoost, for feature selection and classification.

Main Results:

• Identified potential LAM biomarkers: lactic acid (m/z = 90.06) and m/z = 113.13.
• Identified VOCs predicting complications: methanethiol (m/z = 49.00), O-methylhydroxylamine (m/z = 48.04), and m/z = 129.07.
• Achieved high diagnostic accuracy (AUC = 0.922) using a classifier with identified biomarkers.

Conclusions:

• Exhaled breath VOC profiling is a promising non-invasive tool for LAM diagnosis.
• VOC signatures can predict LAM complications such as pneumothorax and ventilation disorders.
• Further validation in larger cohorts is needed to refine clinical applications.