Proteomic biomarkers in plasma that differentiate rapid and slow decline in lung function in adult cigarette smokers with chronic obstructive pulmonary disease (COPD)

• Published in: Analytical and bioanalytical chemistry Vol. 397; no. 5; pp. 1809 - 1819
• Main Authors: Rana, Gaurav S. J. B, York, Timothy P, Edmiston, Jeffery S, Zedler, Barbara K, Pounds, Joel G, Adkins, Joshua N, Smith, Richard D, Liu, Zaigang, Li, Guoya, Webb, Bradley T, Murrelle, Edward L, Flora, Jason W
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-07-2010; Springer-Verlag; Springer
• Subjects: Adult; Adults; Amino acids/peptides; Analysis; Analytical Chemistry; Bioanalytical methods; Biochemistry; Biological and medical sciences; Biological markers; Biological samples; Biomarkers - blood; Blood Proteins - analysis; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Chromatographic methods and physical methods associated with chromatography; Chromatography, Liquid; Cigarettes; Clinical/biomedical analysis; Diverse techniques; Exact sciences and technology; Female; Food Science; Fundamental and applied biological sciences. Psychology; Genomics/proteomics; Health aspects; Humans; Laboratory Medicine; Lung - physiopathology; Lung diseases, Obstructive; Lungs; Male; Mass Spectrometry; Mathematical analysis; Middle Aged; Molecular and cellular biology; Monitoring/Environmental Analysis; Mortality; Original Paper; Other chromatographic methods; Peptides - blood; Prospective Studies; Proteins; Proteomics; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - physiopathology; Respiratory Function Tests; Smokers; Smoking; Smoking - adverse effects; Clinical/biomedical analysis; Amino acids/peptides; Bioanalytical methods; Biological samples; Genomics/proteomics; Plasma; High resolution; Fourier transform spectroscopy; Peptides; Lung; Biological marker; Time; Cigarette; Accuracy; Limitation; Database; Adult; Magnetic field; Human; Lung disease; Data analysis; Biochemical analysis; Mortality; Liquid chromatography; Method; Ion cyclotron resonance spectrometry; Protein; Biological compound; Volume; Aminoacid; Proteomics
• ISSN: 1618-2642; 1618-2650
• DOI: 10.1007/s00216-010-3742-4

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of morbidity and mortality in the United States and cigarette smoking is a primary determinant of the disease. COPD is characterized by chronic airflow limitation as measured by the forced expiratory volume in one second (FEV₁). In this study, the plasma proteomes of 38 middle-aged or older adult smokers with mild to moderate COPD, with FEV₁ decline characterized as either rapid (RPD, n = 20) or slow or absent (SLW, n = 18), were interrogated using a comprehensive high-throughput proteomic approach, the accurate mass and time (AMT) tag technology. This technology is based upon a putative mass and time tag database (PMT), high-resolution LC separations and high mass accuracy measurements using FT-ICR MS with a 9.4-T magnetic field. The peptide and protein data were analyzed using three statistical approaches to address ambiguities related to the high proportion of missing data inherent to proteomic analysis. The RPD and SLW groups were differentiated by 55 peptides which mapped to 33 unique proteins. Twelve of the proteins have known roles in the complement or coagulation cascade and, despite an inability to adjust for some factors known to affect lung function decline, suggest potential mechanistic biomarkers associated with the rate of lung function decline in COPD. Whether these proteins are the cause or result of accelerated decline will require further research.