The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy

Abstract

BackgroundWith the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown.MethodsThoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning.FindingsNearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction <.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype.InterpretationEmphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.

Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort

“…A number of studies in both the pre-ART and ART eras have demonstrated a link between HIV status and an increased risk of developing COPD/emphysema. 21,25,27,28,32,46,48,49 While evidence exists that this phenomenon may be related to an interaction between HIV infection and smoking, we did not find a significant correlation between CD4 cell count or HIV viral load and Perc950. Our findings are consistent with Samperiz and colleagues who reported no relation between quantitative assessment of emphysema on CT scan and either HIV viral load or CD4 count.…”

“…52 However, they reported that the Center for Disease Control HIV category C was a risk factor for quantitative emphysema and a modest emphysema prevalence (10.5%) using a low emphysema cutoff (greater than 1% of voxels with a value less than -950HU). Three recent studies of HIV-infected cohorts 46,48,52 observed that greater than 30% of the subjects had some evidence of emphysema by visual CT image assessment, which is somewhat higher than our findings of 25.1% by quantitative analysis. However, all three studies reported some significant relation between either nadir or current CD4 count and emphysema.…”

“…46,48-52 Furthermore, to our knowledge only two studies performed quantitative CT analyses. 27,52 A quantitative approach may be more sensitive to detect correlations between lung abnormalities on radiographic images and biological/physiological measures as well as to detect lung abnormalities at an earlier stage compared to subjective visual image review.…”

Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

“…For instance, St. George’s Respiratory Questionnaire (SGRQ) scores, which measure respiratory-related health status[6], can demonstrate significant impairment in HIV-infected subjects with otherwise normal spirometry[4]. Similarly, HIV patients with severe emphysema burdens as visualized on computed tomographic (CT) scanning can also have surprisingly well-preserved spirometry[7]. This stands in contrast to HIV-uninfected subjects in whom emphysema quantitation correlates strongly with forced expiratory volume in 1 second (FEV1) measurements[8].…”

“…In large, general population COPD cohorts, the presence of emphysema on CT imaging has been associated with increased dyspnea scores and reduced 6 minute walk distances[9], as well as with worse SGRQ scores[10], suggesting that emphysema may be a clinically meaningful marker of disease severity. In HIV-specific populations, the investigation of emphysema has been limited to cross-sectional, descriptive studies that have reported a range of emphysema prevalence from 26% to 53%[7, 11–14]. Longitudinal studies looking at the progression of emphysema over time and the risk factors associated with rapid emphysema progression in HIV have yet to be performed.…”