A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

Abstract

ObjectivesThe 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.MethodsWe 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.ResultsMild 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).ConclusionsA 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.

Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV

“…The median VACS Index was 29 in PLWH compared to [18][19][20][21][22][23][24][25][26][27] in the uninfected (p<0.001). There was a trend towards higher pack years of smoking in PLWH.…”

“…[50] PLWH may also experience an accelerated decline in pulmonary function. [51][52][53] We have previously shown that emphysema is associated with increased immune activation and inflammation, [25,54] and increased functional limitation in PLWH. [26] Our study adds to this literature by establishing that multiple markers of COPD and the emphysema subtype are associated with increased mortality among PLWH.…”

“…[24] Methods This study utilizes the Examinations of HIV-Associated Lung Emphysema (EXHALE) Study, a pulmonary substudy of VACS described in detail elsewhere. [25,26] VACS subjects were enrolled into EXHALE at 4 Veterans Affairs (VA) Medical Centers (VAMCs) between 2009-2012. PLWH and uninfected subjects were recruited matched on smoking status.…”

“…[30] CT scans were performed at baseline using a protocol described in detail previously. [25] These scans were interpreted by a thoracic radiologist blinded to clinical data to determine semi-quantitative emphysema scoring, which was dichotomized at the overall median of > or ≤10% involvement. Scans also underwent quantitative emphysema analysis using University of Pittsburgh software for lung segmentation followed by density mask technique to quantify percentage of low attenuation areas (Hounsfield units ≤ -950, %LAA) consistent with emphysema.…”

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients

“…[16, 23] Scans underwent a clinical read by an onsite radiologist, abstracted by a study investigator blinded to patient information to determine nodule presence and characteristics. Nodules were considered positive if they were ≥4mm and non-calcified (hereafter referred to as NCN), per NLST criteria.…”