Abstract

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