title: Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects.
abstract: 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.
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: bjorn.titz@pmi.com.
authors: Bjoern
authors: B
authors: Titz
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Alain
authors: A
authors: Sewer
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Thomas
authors: T
authors: Schneider
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Ashraf
authors: A
authors: Elamin
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Florian
authors: F
authors: Martin
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Sophie
authors: S
authors: Dijon
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Karsta
authors: K
authors: Luettich
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Emmanuel
authors: E
authors: Guedj
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Gregory
authors: G
authors: Vuillaume
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Nikolai V
authors: NV
authors: Ivanov
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Michael J
authors: MJ
authors: Peck
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Nveed I
authors: NI
authors: Chaudhary
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Julia
authors: J
authors: Hoeng
authors: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors: Manuel C
authors: MC
authors: Peitsch
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015984:Causality; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D020543:Proteome / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012907:Smoking / Q000453:epidemiology* / Q000378:metabolism*; D016540:Smoking Cessation / Q000706:statistics & numerical data; D000074606:Smoking Prevention; D013183:Sputum / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D020543:Proteome; D014157:Transcription Factors
keywords: COPD; Quantitative proteomics; Smoking; Sputum; Systems toxicology