Exploring exhaled volatile organic compounds as potential biomarkers in anti-MDA5 antibody-positive interstitial lung disease

Abstract

Interstitial lung diseases (ILDs) are a group of pulmonary disorders characterized by fibrosis, inflammation, and lung tissue deterioration. Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5-ILD), a subtype, is associated with high mortality due to rapid progression and severe lung damage. Volatile organic compounds (VOCs) in exhaled breath, reflecting metabolic changes, have been identified as potential non-invasive biomarkers for various diseases, including respiratory conditions. However, their role in MDA5-ILD has not been extensively studied. This retrospective cohort study included 45 exhaled breath samples from 19 ILD patients, with 31 samples from 9 patients with MDA5-ILD and 10 samples from 7 patients with non-MDA5-ILD. VOCs were collected using thermal desorption tubes and analyzed via gas chromatography-mass spectrometry (GC-MS). Clinical data, including the APACHE II score, were integrated with VOC profiles. Two logistic regression models were developed: Model 1 based on 11 clinical indicators, and Model 2 integrating 11 clinical indicators with 5 VOC features. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis, sensitivity, specificity, and accuracy metrics. Five VOCs-N-(2-Aziridinyl)ethanamine, Cyclohexanone, Nonanal, Dodecamethylcyclohexasiloxane, and 4-Methyltetradecane-were identified as significant biomarkers distinguishing MDA5-ILD from non-MDA5-ILD. Model 2, which integrated VOC data, outperformed Model 1, achieving an area under the curve (AUC) of 0.93 compared to 0.70. Model 2 also demonstrated enhanced accuracy (84.6% vs. 76.9%), specificity (66.7% vs. 33.3%), precision (90.0% vs. 81.8%), and F1-score (90.0% vs. 85.7%). Additionally, 1,3-Pentadiene and 3-Methylundecane were identified as potential markers of disease severity, with 1,3-Pentadiene negatively correlating and 3-Methylundecane positively correlating with both APACHE II scores and creatinine levels. VOCs in exhaled breath significantly enhance the diagnostic sensitivity and accuracy for detecting MDA5-ILD. In addition, VOCs show promise as disease severity markers, potentially aiding in the assessment of disease severity and progression. While the integration of VOCs holds great potential for improving diagnostic performance, further validation through larger, multicenter studies is necessary.

Keywords: Biomarker; Exhaled breath analysis; ILD; MDA5; VOC.