title: Protein networks in induced sputum from smokers and COPD patients.
abstract: BACKGROUND
  Subtypes of cigarette smoke-induced disease affect different lung structures and may have distinct pathophysiological mechanisms.
  
  
  OBJECTIVE
  To determine if proteomic classification of the cellular and vascular origins of sputum proteins can characterize these mechanisms and phenotypes.
  
  
  METHODS
  Individual sputum specimens from lifelong nonsmokers (n=7) and smokers with normal lung function (n=13), mucous hypersecretion with normal lung function (n=11), obstructed airflow without emphysema (n=15), and obstruction plus emphysema (n=10) were assessed with mass spectrometry. Data reduction, logarithmic transformation of spectral counts, and Cytoscape network-interaction analysis were performed. The original 203 proteins were reduced to the most informative 50. Sources were secretory dimeric IgA, submucosal gland serous and mucous cells, goblet and other epithelial cells, and vascular permeability.
  
  
  RESULTS
  Epithelial proteins discriminated nonsmokers from smokers. Mucin 5AC was elevated in healthy smokers and chronic bronchitis, suggesting a continuum with the severity of hypersecretion determined by mechanisms of goblet-cell hyperplasia. Obstructed airflow was correlated with glandular proteins and lower levels of Ig joining chain compared to other groups. Emphysema subjects' sputum was unique, with high plasma proteins and components of neutrophil extracellular traps, such as histones and defensins. In contrast, defensins were correlated with epithelial proteins in all other groups. Protein-network interactions were unique to each group.
  
  
  CONCLUSIONS
  The proteomes were interpreted as complex "biosignatures" that suggest distinct pathophysiological mechanisms for mucin 5AC hypersecretion, airflow obstruction, and inflammatory emphysema phenotypes. Proteomic phenotyping may improve genotyping studies by selecting more homogeneous study groups. Each phenotype may require its own mechanistically based diagnostic, risk-assessment, drug- and other treatment algorithms.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, USA.
authors.forename: James N
authors.initials: JN
authors.lastname: Baraniuk
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, USA.
authors.forename: Begona
authors.initials: B
authors.lastname: Casado
authors.affiliation: Proteomics and Mass Spectrometry Laboratory, Mitchell Cancer Center, University of South Alabama, Mobile, AL, USA.
authors.forename: Lewis K
authors.initials: LK
authors.lastname: Pannell
authors.affiliation: Innovation Center for Biomedical Informatics, Georgetown University, Washington, DC, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: McGarvey
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Boschetto
authors.affiliation: SC Pneumologia, Dipartimento Medicina Molecolare, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
authors.affiliation: Lazzaro Spallanzani Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Iadarola
mesh_terms: D000328:Adult; D000368:Aged; D029481:Bronchitis, Chronic / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000097:blood; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D011656:Pulmonary Emphysema / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism*
chemical_list: D007071:Immunoglobulin A, Secretory; D055271:Mucin 5AC
keywords: chronic bronchitis; cigarette smokers; emphysema; mucin 5AC; mucous hypersecretion; neutrophil extracellular nets; proteomics