METHODS: We recruited adult subjects with moderate, severe or very severe but stable COPD from outpatient clinics. We also identified hospitalized patients with ARF due to COPD, CHF, and pneumonia (PNA) and enrolled them within 24 hours of NIPPV therapy. We excluded patients admitted with > 1 of the following diagnosis: COPD, CHF, PNA, patients with a history of both COPD and heart failure, and patients with obstructive sleep apnea, bronchial asthma, bronchiectasis or other obstructive lung disease. Serum and urine were collected from patients and metabolomics analysis was performed using nuclear magnetic resonance (NMR) in patient samples after adjustment for osmolality. Metabolites were identified and quantified with Chenomx software and the resulting profiles were analyzed for differences among patient groups with partial least squares discriminant analysis (PLS-DA).