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.