title: Induced sputum proteome in healthy subjects and asthmatic patients.
abstract: BACKGROUND
  Asthma is a heterogeneous disease characterized by abnormal airway pathophysiology and susceptibility to different stimuli, as exemplified by a subset of patients with exercise-induced bronchoconstriction. Induced sputum provides a noninvasive method to sample airway biofluids that are enriched in proteins.
  
  
  OBJECTIVE
  We hypothesized that novel mechanisms in the pathogenesis of asthma might be revealed by studying the patterns of protein expression in induced sputum.
  
  
  METHODS
  We used shotgun proteomics to analyze induced sputum from 5 healthy subjects and 10 asthmatic patients, including 5 with exercise-induced bronchoconstriction. Differential protein expression among asthmatic patients, asthma subphenotypes, and control subjects was determined by using spectral counting and computational methods.
  
  
  RESULTS
  Using Gene Ontology analysis, we defined the functional landscape of the induced sputum proteome and applied network analysis to construct a protein interaction map for this airway compartment. Shotgun proteomics analysis identified a number of proteins the differential enrichment or depletion of which robustly distinguished asthmatic patients from healthy control subjects and captured the effects of exercise on induced sputum proteome. Functional and network analysis identified key processes, including proteolytic activity, that are known contributors to airway remodeling. Importantly, this approach highlighted previously unrecognized roles for differentially expressed proteins in pathways implicated in asthma, such as modulation of phospholipase A(2) by secretoglobin, a putative role for S100A8/9 in human asthma, and selective upregulation of complement component 3a in response to exercise in asthmatic patients.
  
  
  CONCLUSIONS
  Computationally intensive analysis of induced sputum proteome is a powerful approach to understanding the pathophysiology of asthma and a promising methodology to investigating other diseases of the airways.
authors: Center for Lung Biology, University of Washington, Seattle, WA 98109, USA. sagharib@u.washington.edu
authors: Sina A
authors: SA
authors: Gharib
authors: Elizabeth V
authors: EV
authors: Nguyen
authors: Ying
authors: Y
authors: Lai
authors: Jessica D
authors: JD
authors: Plampin
authors: David R
authors: DR
authors: Goodlett
authors: Teal S
authors: TS
authors: Hallstrand
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D015153:Blotting, Western; D002853:Chromatography, Liquid; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis* / Q000378:metabolism*; D013183:Sputum / Q000737:chemistry* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D020543:Proteome