Chest

Chest

Volume 146, Issue 6, December 2014, Pages 1543-1553
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Original Research: COPD
Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4

https://doi.org/10.1378/chest.14-0543Get rights and content

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.

Section snippets

Study Design and Cohort

We performed a cross-sectional analysis of data from 114 participants with HIV infection and 89 participants without HIV infection enrolled from 2009 to 2012 in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, a substudy of the Veterans Aging Cohort Study.21 Enrollment was stratified by HIV and smoking status. All participants signed written informed consent. This study was approved by all appropriate institutional review boards. Methodologic details regarding the cohort, data

Baseline Characteristics

Most participants were black men, and those with HIV infection were slightly older (Table 2). Although there was no significant difference in cigarette smoking, marijuana and injection drug use, prior bacterial pneumonia and TB were significantly more common in participants with HIV infection. Most with HIV infection were receiving ART, had undetectable HIV RNA, and had recent CD4 ≥ 200 cells/μL, although more than one-half had nadir CD4 < 200 cells/μL. sCD14 and IL-6 levels were significantly

Discussion

We found that radiographic emphysema severity was overall significantly greater in individuals with HIV infection than in those without HIV infection and that HIV infection was an independent risk factor for emphysema defined by > 10% emphysema on chest CT scan using semiquantitative methods. In the present cohort, the upper lung zone was involved in nearly all participants with emphysema. Interestingly, we found that individuals with HIV infection may be more likely to have diffuse emphysema

Acknowledgments

Author contributions:E. F. A. and K. C. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. E. F. A. and K. C. contributed to the study concept and design, data analysis and interpretation, and drafting and review of the manuscript for important intellectual content; K. M. A., C. W., M. B. G., M. C. R.-B., S. T. B., G. W. S. H., J. K., and A. C. J. contributed to the data analysis and interpretation and

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

    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.

    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.

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

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