Metabolomics of COPD Pulmonary Rehabilitation Outcomes via Exhaled Breath Condensate.

Chronic obstructive pulmonary disease (COPD) is characterized by different phenotypes and clinical presentations. Therefore, a single strategy of pulmonary rehabilitation (PR) does not always yield the expected clinical outcomes as some individuals respond excellently, others discreetly, or do not respond at all. Fifty consecutive COPD patients were enrolled. Of them, 35 starting a 5-week PR program were sampled at admission (T 0 ), after 2 (T 2W ) and 5 (T 5W ) weeks, while 15 controls not yet on PR were tested at T 0 and T 5W . Nuclear magnetic resonance (NMR) profiling of exhaled breath condensate (EBC) and multivariate statistical analysis were applied to investigate the relationship between biomarkers and clinical parameters. The model including the three classes correctly located T 2W between T 0 and T 5W , but 38.71% of samples partially overlapped with T 0 and 32.26% with T 5W , suggesting that for some patients PR is already beneficial at T 2W (32.26% overlapping with T 5W ), while for others (38.71% overlapping with T 0 ) more time is required. Rehabilitated patients presented several altered biomarkers. In particular, methanol from T 0 to T 5W decreased in parallel with dyspnea and fatigue, while the walk distance increased. Methanol could be ascribed to lung inflammation. We demonstrated that the metabolic COPD phenotype clearly evolves during PR, with a strict relationship between clinical and molecular parameters. Methanol, correlating with clinical parameters, represents a useful biomarker for monitoring personalized outcomes and establishing more targeted protocols.