title: Altered sputum granzyme B and granzyme B/proteinase inhibitor-9 in patients with non-eosinophilic asthma.
abstract: OBJECTIVE
  The non-eosinophilic phenotype of asthma (NEA) is associated with chronic airway inflammation and airway neutrophilia. An accumulation of apoptotic airway epithelial cells, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, with the potential for inflammation of surrounding tissues. Apoptosis may occur via the T cell granzyme B pathway. The role of granzyme B in NEA is not known. The aim of this study was to investigate production of granzyme B and its inhibitor proteinase inhibitor (PI)-9 by T cells from induced sputum and compare expression between eosinophilic, NEA and healthy controls.
  
  
  METHODS
  We investigated T cell intracellular granzyme B and its inhibitor, PI-9, in sputum from healthy control subjects (n = 10), and patients with NEA (n = 22) or eosinophilic asthma (EA) (n = 15) using flow cytometry.
  
  
  RESULTS
  Granzyme B expression and the ratio of granzyme B to PI-9 positive cells were highest in those with NEA for both CD3+ and CD4+ T cells. The expression of granzyme B was not statistically different between patients with NEA and EA; however, the ratio of granzyme B to PI-9 positive cells for CD3+ T cells was significantly higher in those with NEA compared with EA.
  
  
  CONCLUSIONS
  Induced sputum provides a non-invasive tool for investigating T cell cytotoxic mediators in the various asthma subtypes. Granzyme B expression is increased in NEA and the contribution of granzyme B to chronic inflammation requires further study.
authors.affiliation: Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.|Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.affiliation: Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.|Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.|The Prince Charles Hospital, Brisbane, Queensland, Australia.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.|Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Upham
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: James
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.|Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.|Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
mesh_terms: D001249:Asthma / Q000201:enzymology* / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D011657:Pulmonary Eosinophilia; D013183:Sputum / Q000201:enzymology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D053804:Granzymes
keywords: asthma; granzyme B; lymphocyte; non-eosinophilic asthma; proteinase inhibitor-9