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Original Research: COPD |

Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4Increased Risk of Radiographic Emphysema in HIV

Engi F. Attia, MD; Kathleen M. Akgün, MD; Cherry Wongtrakool, MD; Matthew Bidwell Goetz, MD; Maria C. Rodriguez-Barradas, MD; David Rimland, MD; Sheldon T. Brown, MD; Guy W. Soo Hoo, MD, FCCP; Joon Kim, MD; Patty J. Lee, MD; Lynn M. Schnapp, MD; Amir Sharafkhaneh, MD, PhD, FCCP; Amy C. Justice, MD, PhD; Kristina Crothers, MD
Author and Funding Information

From the Department of Medicine (Drs Attia, Schnapp, and Crothers), University of Washington, Seattle, WA; Department of Medicine (Drs Akgün and Justice), Veterans Affairs Connecticut Healthcare System, West Haven, CT; Department of Medicine (Drs Akgün, Lee, and Justice), Yale School of Medicine, New Haven, CT; Atlanta Veterans Affairs Medical Center (Drs Wongtrakool and Rimland), Atlanta, GA; Department of Medicine (Drs Wongtrakool and Rimland), Emory University School of Medicine, Atlanta, GA; Veterans Affairs Greater Los Angeles Healthcare System (Drs Goetz and Soo Hoo), Los Angeles, CA; Department of Medicine (Drs Goetz and Soo Hoo), David Geffen School of Medicine at UCLA, Los Angeles, CA; Michael E. DeBakey Veterans Affairs Medical Center (Drs Rodriguez-Barradas and Sharafkhaneh), Houston, TX; Department of Medicine (Drs Rodriguez-Barradas and Sharafkhaneh), Baylor College of Medicine, Houston, TX; Department of Medicine (Drs Brown and Kim), James J. Peters Veterans Affairs Medical Center, Bronx, NY; and Department of Medicine (Dr Brown), Icahn School of Medicine at Mt Sinai, New York, NY.

CORRESPONDENCE TO: Kristina Crothers, MD, Harborview Medical Center, 325 Ninth Ave, Campus Box 359762, Seattle, WA 98104; e-mail: crothk@uw.edu


Dr Schnapp is currently at the Medical University of South Carolina (Charleston, SC).

Part of this article has been presented in abstract form at Gairdner, UBC, and St. Paul’s Hospital 2013 Symposium on COPD, December 3-4, 2013, Vancouver, BC, Canada, and the Conference on Retroviruses and Opportunistic Infections, March 3-6, 2014, Boston, MA.

FUNDING/SUPPORT: This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [R21 HL120391 to Dr Schnapp and R01 HL090342 to Dr Crothers]. This research was funded in part by a 2012 developmental grant from the University of Washington Center for AIDS Research, an NIH-funded program under award number P30-AI-027757, which is supported by the following NIH institutes and centers: National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NHLBI, and National Institute on Aging.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(6):1543-1553. doi:10.1378/chest.14-0543
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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.

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