Metabolic Alterations in Pneumonia Assessed by Breath Analysis: A Paired Longitudinal Study Comparing Acute Infection and Post-Recovery States
Description
The diagnosis and monitoring of pneumonia remain a challenge due to its diverse etiology, overlapping clinical symptoms with other respiratory infections, and limitations in current diagnostic technologies for timely and accurate detection. We evaluated whether real-time secondary electrospray ionization–high‑resolution mass spectrometry (SESI‑HRMS) breathomics can capture disease‑associated metabolic signatures in a paired longitudinal cohort. Adults with clinically confirmed pneumonia (n = 47) were sampled during acute infection and again after recovery (median interval 85 days). After preprocessing, 3,635 mass‑spectral features were retained across ion modes, and 1,498 could be linked to at least one Human Metabolome Database (HMDB) entry by accurate‑mass matching (±1 ppm). Using a subject‑grouped, nested cross‑validated PLS‑DA framework, breath profiles discriminated pneumonia from post‑pneumonia with moderate performance (median balanced accuracy 0.72; median AUROC 0.80; Q² 0.24; two latent variables), with a permutation p value of 0.112. Paired differential analysis identified 104 recovery‑associated features (58 higher and 46 lower during pneumonia) meeting |mean log2 fold change| ≥ 1 and FDR q ≤ 0.05, mapping to 239 putative HMDB accessions. Together, these findings indicate that real‑time breathomics detects reproducible metabolic remodeling from pneumonia to convalescence and captures biochemical heterogeneity not reflected by standard clinical indices, motivating multicenter validation with tandem mass spectrometry (MS/MS)‑supported identification and longitudinal outcome linkage.