Methods: Sputum was induced [Thorax 61:1037; 2006] and 203 proteins identified by tandem mass spectrometry [J Proteome Res 6:4615; 2007]. Redundant proteins were consolidated by their gene of origin. Many immunoglobulins were assigned to gene clusters for light, heavy, constant and variable regions. Proteins present once or twice were deleted. The geometric means for numbers of mass spectra for each of the remaining 70 proteins were compared between the 24 gold0 and 25 GOLD+ by ANOVA and Pearson’s correlations used to assess patterns of protein expression.
Results: The gold0 smokers had higher serous (polymeric Ig receptor [PIGR], Iysozyme [LYZ], SLPI), epithelial (proline rich protein 4 [PRR4], Clara cell protein [SCGB1A1] and mucosal plasma cell (IgA) and possibly apoptosis markers. Goblet cell MUC5AC was highly expressed and negatively correlated with mucous gland MUC5B. At least 4 independent sets of correlated proteins suggested differential regulation of protein expression. In contrast, GOLD+ sputum contained markers of vascular permeability (albumin, IgG1) that were positively correlated with serous cell LPLUNC1, but negatively correlated with LYS, PIGR, and SLPI. A distinct subset of GOLD+ subjects showed correlated neutrophil (lipocalin 2 [NGAL]), epithelial (DEFA1), histone, and plasma markers.
Conclusions: The gold0 group had more mucus markers than the 2 subsets of GOLD+ smokers. This indicates that the phenotypic and mechanistic systems may be more versatile for assessing lung diseases and severity than those based on airflow obstruction.