title: Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and is increasing, primarily among women. Underdiagnosis is common, and because of the heterogeneous disease characteristics, molecular markers of specific disease phenotypes and more efficacious treatment regimens are urgently needed.
  
  
  OBJECTIVE
  In this study the soluble proteome of bronchoalveolar lavage cells, primarily consisting of macrophages, was investigated with the aim of identifying phenotypic differences in early disease development.
  
  
  METHODS
  Two-dimensional difference gel electrophoresis was used for relative quantification of protein levels, and multivariate modeling was applied to identify proteins of interest that were subsequently identified by means of liquid chromatography-mass spectrometry.
  
  
  RESULTS
  Significant gender differences were unveiled, with numerous alterations in the bronchoalveolar lavage cell proteome occurring in female but not male patients with COPD. Specifically, a subset of 19 proteins provided classification of female healthy smokers from female patients with COPD with 78% predictive power. Subsequent pathway analyses linked the observed alterations to downregulation of the lysosomal pathway and upregulation of the oxidative phosphorylation pathway, possibly linking dysregulation of macroautophagy to a female-dominated COPD disease phenotype.
  
  
  CONCLUSIONS
  This investigation makes an important contribution to the elucidation of putative molecular mechanisms underlying gender-based differences in the pathophysiology of COPD, linking alterations of specific molecular pathways to previously observed gender differences in clinical COPD phenotypes. Furthermore, these results stress the importance of the gender-specific search for biomarkers, diagnosis, and treatment in COPD.
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet/University Hospital, Stockholm, Sweden. maxie.kohler@uni-koeln.de
authors.forename: Maxie
authors.initials: M
authors.lastname: Kohler
authors.forename: AnnSofi
authors.initials: A
authors.lastname: Sandberg
authors.forename: Sanela
authors.initials: S
authors.lastname: Kjellqvist
authors.forename: Andreas
authors.initials: A
authors.lastname: Thomas
authors.forename: Reza
authors.initials: R
authors.lastname: Karimi
authors.forename: Sven
authors.initials: S
authors.lastname: Nyrén
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
authors.forename: C Magnus
authors.initials: CM
authors.lastname: Sköld
authors.forename: Åsa M
authors.initials: ÅM
authors.lastname: Wheelock
mesh_terms: D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D012737:Sex Factors; D012907:Smoking / Q000378:metabolism*
chemical_list: D020543:Proteome