<![CDATA[Introduction: Rapid, non-invasive screening for drug-resistant tuberculosis (DR-TB) is urgently needed in high-burden settings such as Indonesia, where sputum-based diagnostics have practical limitations. Integrating exhaled breath volatile organic compounds (VOCs), which reflect host–pathogen metabolic interactions, with serum soluble intercellular adhesion molecule-1 (sICAM-1), a marker of endothelial activation and inflammation, may improve early detection. This study evaluated the combined potential of VOC profiling and sICAM-1 to distinguish drug-sensitive TB (DS-TB), DR-TB, and healthy controls. Methods: A prospective cross-sectional study was conducted in four TB referral hospitals in East Java, Indonesia. Eighty-eight participants were enrolled: DS-TB (n=32), DR-TB (n=30), and healthy controls (n=26). Exhaled breath VOC profiles were analyzed using a breath analyzer, and serum sICAM-1 levels were measured by enzyme-linked immunosorbent assay. Group comparisons used ANOVA or Kruskal–Wallis tests with post hoc analyses, and correlations were assessed using Pearson or Spearman tests. Results: Serum sICAM-1 levels were significantly higher in both TB groups than in controls (p<0.01) but did not differ between DS-TB and DR-TB (p=0.961). Several VOC components differed significantly, particularly formaldehyde, acetone, and methane (CH₄). CH₄ levels were significantly higher in DR-TB than in DS-TB and controls (p<0.05). A weak negative correlation between formaldehyde and sICAM-1 was observed in DS-TB (r = −0.355; p = 0.046). Conclusion: Integrating VOC profiling with sICAM-1 assessment offers a promising non-invasive strategy for TB screening. While sICAM-1 reflects inflammatory activity, methane-based VOC signatures may improve identification of DR-TB.]]>
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