Abstract

Background

Group III pulmonary hypertension (PH) is considered to be a delayed complication of various hypoxic lung diseases with a major burden of COPD cases. An increased morbidity and mortality of COPD associated PH (COPD-PH) is seen as compared to only COPD patients. Although COPD is an extensively studied clinical entity, not much is known about the pathophysiology ofCOPD-PH, since it often gets overshadowed by the symptoms of COPD.

Aim

This study is the first of its kind where we hypothesize that 1H nuclear magnetic resonance (NMR) based metabolomics may provide an insight into the pathophysiology of COPD-PH and may effectively differentiate it from COPD alone at a metabolic level.

Method

Serum samples were collected from patients with COPD (n=33) and COPD-PH (n=25). NMR spectra of the samples were acquired on 800 MHz BrukerAvance III spectrometer using CPMG pulse sequence program and subjected to chemometric analysis.

Result

OPLS-DA generated model reflected a distinct metabolic differentiation between COPD and COPD-PH. Values of R2Y (0.902) and Q2 (0.755) validate that the model fits well and has good predictive ability. Permutation test indicated a better predictive capability than 100 generated permuted models. The metabolites responsible for good discrimination were identified to be isoleucine, valine, L-leucine, acetic acid, glutamate, glucose, betaine, glycerol and creatinine.

Conclusion

These metabolites are majorly associated with glycolysis pathway, amino acid and lipid metabolism. The distinct metabolic signatures give us a preliminary idea about the pathophysiology of the disease, and also suggest that the two study groups are distinguishable from each other.