Abstract BACKGROUND AND OBJECTIVE&amp;#xD;Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) show high variability in&amp;#xD;individual susceptibility and promote disease progression; thus, accurate diagnosis and treatment is&amp;#xD;essential. Unravelling the molecular metabolic changes during AECOPD in breath could promote&amp;#xD;understanding of AECOPD and its treatment. Our objective was to investigate the metabolic breath&amp;#xD;profiles during AECOPD for biomarker detection.&amp;#xD;METHODS&amp;#xD;We conducted real-time breath analysis in patients with COPD during AECOPD and during&amp;#xD;subsequent stable phase. Molecular breath patterns were compared between AECOPD and stable&amp;#xD;phase by dimension reduction techniques and paired t-tests. Pathway enrichment analyses were&amp;#xD;performed to investigate underlying metabolic pathways. Partial least-squares discriminant analysis&amp;#xD;and XGboost were utilised to build a prediction model to differentiate AECOPD from stable state.&amp;#xD;RESULTS&amp;#xD;35 patients (60% male) with a mean age of 65 (10.2) years with AECOPD were included. AECOPD&amp;#xD;could be predicted with a high sensitivity of 82.5 % (95% confidence interval of 68.8 to 93.8 %) and&amp;#xD;an excellent discriminative power (AUC=0.86). Metabolic changes in the linoleate, tyrosine, and&amp;#xD;tryptophan pathways during AECOPD were predominant.&amp;#xD;CONCLUSION&amp;#xD;Significant metabolic changes occur during COPD exacerbations, predominantly in the linoleate,&amp;#xD;tyrosine, and tryptophan pathways, which are all linked to inflammation. Real-time exhaled breath&amp;#xD;analysis enables a good prediction of AECOPD compared to stable state and thus could enhance&amp;#xD;precision of AECOPD diagnosis and efficacy in clinical practice.&amp;#xD;CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05456009)&amp;#xD;SHORT TITLE: Molecular breath profile of AECOPD.

Molecular breath profile of acute COPD exacerbations