Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment. The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status. Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD. Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD. Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems. It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism.MethodsIn the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group). After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species. Later, the comparisons of individual lipids were performed between controls and patients with COPD. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers. Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated.ResultsOur results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD. Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change. In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers. Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity. Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years.ConclusionUsing lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD. Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD.

Highlights

  • Chronic obstructive pulmonary disease (COPD) is a chronic lung disease, which is characterized by irreversible airflow obstruction, mucus hypersecretion, and chronic airway inflammation

  • Subject characteristics Previous data demonstrated that patients with COPD exhibit systematic dysregulation in lipid metabolism, in which sphingolipid pathway is higher in smokers with COPD compared with smokers without COPD [15]

  • Other study indicated that sphingomyelins are strongly associated with emphysema and glycosphingolipids are associated with COPD exacerbations [19]

Read more

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease, which is characterized by irreversible airflow obstruction, mucus hypersecretion, and chronic airway inflammation. It is the third leading cause of death worldwide, and it was ranked second as disability-adjusted life-years (DALY) from 1990 to 2010 [1,2,3]. Clinical evidence indicates that spirometry can neither predict the disease activity or the severity nor differentiate the subtypes of disease Symptoms such as bronchial hyper-responsiveness and frequent exacerbations are used as indicators of COPD disease progression. It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call