title: Increased risk of radiographic emphysema in HIV is associated with elevated soluble CD14 and nadir CD4.
abstract: BACKGROUND
  The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema.
  
  
  METHODS
  We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semiquantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as > 10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection.
  
  
  RESULTS
  Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for > 10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/μL (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of > 10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV.
  
  
  CONCLUSIONS
  HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/μL and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema.
authors: Department of Medicine, University of Washington, Seattle, WA.
authors: Engi F
authors: EF
authors: Attia
authors: Department of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT; Department of Medicine, Yale School of Medicine, New Haven, CT.
authors: Kathleen M
authors: KM
authors: Akgün
authors: Atlanta Veterans Affairs Medical Center, Atlanta, GA; Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors: Cherry
authors: C
authors: Wongtrakool
authors: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Matthew Bidwell
authors: MB
authors: Goetz
authors: Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX; Department of Medicine, Baylor College of Medicine, Houston, TX.
authors: Maria C
authors: MC
authors: Rodriguez-Barradas
authors: Atlanta Veterans Affairs Medical Center, Atlanta, GA; Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors: David
authors: D
authors: Rimland
authors: Department of Medicine, James J. Peters Veterans Affairs Medical Center, Bronx, NY; Department of Medicine, Icahn School of Medicine at Mt Sinai, New York, NY.
authors: Sheldon T
authors: ST
authors: Brown
authors: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Guy W
authors: GW
authors: Soo Hoo
authors: Department of Medicine, Baylor College of Medicine, Houston, TX.
authors: Joon
authors: J
authors: Kim
authors: Department of Medicine, Yale School of Medicine, New Haven, CT.
authors: Patty J
authors: PJ
authors: Lee
authors: Department of Medicine, University of Washington, Seattle, WA.
authors: Lynn M
authors: LM
authors: Schnapp
authors: Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX; Department of Medicine, Baylor College of Medicine, Houston, TX.
authors: Amir
authors: A
authors: Sharafkhaneh
authors: Department of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT; Department of Medicine, Yale School of Medicine, New Haven, CT.
authors: Amy C
authors: AC
authors: Justice
authors: Department of Medicine, University of Washington, Seattle, WA. Electronic address: crothk@uw.edu.
authors: Kristina
authors: K
authors: Crothers
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000097:blood*; D015897:Comorbidity; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D011656:Pulmonary Emphysema / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology*; D011859:Radiography; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; D018950:Lipopolysaccharide Receptors