Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects

• Published in: Journal of proteomics Vol. 128; pp. 306 - 320
• Main Authors: Titz, Bjoern, Sewer, Alain, Schneider, Thomas, Elamin, Ashraf, Martin, Florian, Dijon, Sophie, Luettich, Karsta, Guedj, Emmanuel, Vuillaume, Gregory, Ivanov, Nikolai V., Peck, Michael J., Chaudhary, Nveed I., Hoeng, Julia, Peitsch, Manuel C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 14.10.2015
• Subjects: Adult; Aged; Biomarkers - blood; Biomarkers - metabolism; Causality; Comorbidity; COPD; Female; Humans; Male; Middle Aged; Prevalence; Proteome - metabolism; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - metabolism; Quantitative proteomics; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Smoking; Smoking - epidemiology; Smoking - metabolism; Smoking Cessation - statistics & numerical data; Smoking Prevention; Sputum; Sputum - metabolism; Systems toxicology; Transcription Factors - metabolism; Transcriptome; United Kingdom - epidemiology; Quantitative proteomics; Systems toxicology; Sputum; COPD; Smoking
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2015.08.009

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases. Cigarette smoking is the main risk factor for COPD. In this parallel-group clinical study we investigated to what extent the transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples. We selected 60 age- and gender-matched individuals for each of the four study groups: current asymptomatic smokers, smokers with early stage COPD, former smokers, and never smokers. The cell-free sputum supernatant was analyzed by quantitative proteomics and the cellular mRNA fraction by gene expression profiling. The sputum proteome of current smokers clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins and a prominent xenobiotic/oxidative stress response. The latter response also was observed in the transcriptome, which additionally demonstrated an immune-cell polarization change. The former smoker group showed nearly complete attenuation of these biological effects. Thirteen differentially abundant proteins between the COPD and the asymptomatic smoker group were identified including TIMP1, APOA1, C6orf58, and BPIFB1 (LPLUNC1). In summary, our study demonstrates that sputum profiling can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD. [Display omitted] •Clinical study with 240 subjects to assess effects of smoke exposure and COPD.•Combined quantitative assessment of sputum proteome and transcriptome.•Broad range of physiological smoke exposure effects captured.•Effects largely attenuated upon long-term smoking cessation.•Sputum demonstrates differences between COPD subjects and asymptomatic smokers.