title: Clinical and Immunological Factors in Emphysema Progression. Five-Year Prospective Longitudinal Exacerbation Study of Chronic Obstructive Pulmonary Disease (LES-COPD).
abstract: BACKGROUND
  Cross-sectional studies of T-cell responses to self-antigens correlate with baseline emphysema severity.
  
  
  OBJECTIVE
  We investigated whether clinical and/or immunological factors could predict disease progression, such as emphysema, FEV1, and 6-minute-walk distance (6MWD), in former and active smokers in a 5-year prospective study.
  
  
  METHODS
  We recruited 224 ever smokers over 40 years of age and with greater than a 15 pack-year smoking history.
  
  
  RESULTS
  Repeated spirometry, 6MWD, and peripheral blood T-cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest computed tomography (CT) scans (34 to 65 mo apart) were used to quantify emphysema progression. Of the 141 ever-smokers with baseline and repeat CT scans, the mean (SD) annual rate of change in percent emphysema was +0.46 (0.92), ranging from -1.8 to +4.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (+0.15 per 5-unit decrease in BMI; 95% confidence interval, +0.03 to +0.29). In active smokers, increased IFN-γ and IL-6 T-cell responses had a positive association with the annual rate of emphysema progression. Male sex and IL-6 T-cell responses to elastin fragments were significantly associated with annual 6MWD decline, whereas IL-13 was associated with an increase in annual 6MWD.
  
  
  CONCLUSIONS
  The rate of emphysema progression quantified by CT scans among ever-smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells and low BMI may temporize progression of emphysema.
authors.affiliation: 1 Department of Medicine.
authors.forename: Sivasubramanium
authors.initials: S
authors.lastname: Bhavani
authors.affiliation: 2 Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|3 Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chu-Lin
authors.initials: CL
authors.lastname: Tsai
authors.affiliation: 1 Department of Medicine.
authors.forename: Sarah
authors.initials: S
authors.lastname: Perusich
authors.affiliation: 1 Department of Medicine.
authors.forename: Sean
authors.initials: S
authors.lastname: Hesselbacher
authors.affiliation: 4 Department of Radiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and.
authors.forename: Harvey
authors.initials: H
authors.lastname: Coxson
authors.affiliation: 1 Department of Medicine.|5 Michael E. DeBakey Veterans Affairs Center for Translational Research on Inflammatory Diseases, Houston Texas.
authors.forename: Lavannya
authors.initials: L
authors.lastname: Pandit
authors.affiliation: 1 Department of Medicine.|6 Department of Pathology and Immunology, and.|7 Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas.|5 Michael E. DeBakey Veterans Affairs Center for Translational Research on Inflammatory Diseases, Houston Texas.
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.affiliation: 1 Department of Medicine.|6 Department of Pathology and Immunology, and.|7 Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas.|5 Michael E. DeBakey Veterans Affairs Center for Translational Research on Inflammatory Diseases, Houston Texas.
authors.forename: Farrah
authors.identifier: http://orcid.org/0000-0001-5343-103X
authors.initials: F
authors.lastname: Kheradmand
mesh_terms: D000704:Analysis of Variance; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D018450:Disease Progression; D004646:Emphysema / Q000209:etiology*; D005080:Exercise Test; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: IFN-γ; IL-17; IL-6; T cells; emphysema progression