Date Published: January 25, 2017
Publisher: Public Library of Science
Author(s): Matthew Triplette, Engi F. Attia, Kathleen M. Akgün, Guy W. Soo Hoo, Matthew S. Freiberg, Adeel A. Butt, Cherry Wongtrakool, Matthew Bidwell Goetz, Sheldon T. Brown, Christopher J. Graber, Laurence Huang, Kristina Crothers, Navneet K. Dhillon.
The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects.
We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD.
Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO).
A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.
The prevalence of emphysema and other chronic lung diseases is higher in HIV-infected (HIV+) compared to HIV-uninfected (HIV-) persons. [1–5] Although greater tobacco use accounts for much of this increase in risk, HIV infection is an independent risk factor for chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype. The link underlying the association of HIV and emphysema remains incompletely understood, but may be related to immune dysfunction, severity of immunocompromise induced by HIV infection, and HIV-related immune activation. [1,3]
The majority of the subjects were male (98%). The median age at baseline was 55 (IQR 49–59) years old. Most subjects were black (72%); 13% of subjects were white and 12% identified as Hispanic. Most were either current (63%) or former (21%) smokers. 71% of subjects were on ART at study entry; 66% had an undetectable viral load and 86% had a CD4 cell count ≥200 cells/μL.
In this study, we sought to determine whether a decreased CD4/CD8 ratio was associated with emphysema and other pulmonary function markers of COPD. In our cohort of 190 HIV+ subjects, we found that a low CD4/CD8 ratio was associated with semi-quantitative radiographic emphysema and this association was independent of potential confounding factors including smoking, age, other major chronic diseases, current and nadir CD4 cell count, and HIV viral load. This association was robust when modeling the CD4/CD8 ratio in different ways, as a continuous measure or in categories. We also found a significant trend towards higher severity of emphysema in those with lower CD4/CD8 ratios (Fig 1). Additionally, we found a statistically significant association between a low CD4/CD8 ratio with low DLCO, but no definitive association between a low CD4/CD8 ratio with airflow obstruction and FEV1. These findings reinforce that CD4/CD8 ratio is associated with emphysema, which is defined radiographically but is also characterized by–and correlated with–a low DLCO. [21,22]