In HIV+ cigarette smokers, with no prior history of pulmonary infections, emphysema is often developed at an earlier age and is a significant cause of morbidity despite treatment with antiretroviral drugs. Preliminary data gathered from HIV+ individuals that smoke cigarettes strongly support the hypothesis that the combination of HIV infection and smoking creates increased stress in the lower respiratory tract. To examine the underlying factors that contribute to the accelerated development of emphysema in this cohort, samples from the lower respiratory tract will be provided by HIV+ and HIV- subjects. The samples collected will serve as biomarkers for assessing the onset of emphysema.

Population

New York Metropolitan area residents

Brief Title

HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium

Official Title

HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium

Brief Summary

In HIV+ cigarette smokers, with no prior history of pulmonary infections, emphysema is often <br /> developed at an earlier age and is a significant cause of morbidity despite treatment with <br /> antiretroviral drugs. Preliminary data gathered from HIV+ individuals that smoke cigarettes <br /> strongly support the hypothesis that the combination of HIV infection and smoking creates <br /> increased stress in the lower respiratory tract. To examine the underlying factors that <br /> contribute to the accelerated development of emphysema in this cohort, samples from the lower <br /> respiratory tract will be provided by HIV+ and HIV- subjects. The samples collected will <br /> serve as biomarkers for assessing the onset of emphysema.

Detailed Description

The purpose of this study is to analyze biologic samples from the blood, airways and/or urine
of HIV- and HIV+ smokers and non-smokers to better understand the etiology and pathogenesis
of emphysema in association with HIV infection. The underlying hypothesis is that the
combination of HIV infection and smoking creates chronic oxidant stress in the lower
respiratory tract that promotes cellular loss and contributes to the progressive development
of emphysema. Preliminary data strongly supports our hypothesis that the accelerated
development of emphysema among HIV+ smokers is due in part to the interaction of HIV directly
on the macrophage found in the pulmonary alveolus. The interaction causes a release of
exaggerated amounts of oxidants in the lower respiratory tract and leads to increased levels
of oxidized metabolites. HIV+ individuals with emphysema have high plasma levels of apoptotic
pulmonary capillary-derived micro particles that contain oxidized metabolites. The increased
release of micro particles is characteristic of an apoptotic process.

We will study this hypothesis by sampling HIV+ and HIV- subjects alveolar macrophages (AM),
which are found on the epithelial surface of the lung, and epithelial lining fluid (ELF)
found in the lower respiratory tract. We will also assess plasma pulmonary capillary-derived
endothelial microparticles (EMPs) as a biomarker for pulmonary apoptosis. Using newly
developed mass spectrometry methodologies, we will quantify the oxidant stress of AM, ELF and
plasma EMPs, and identify specific oxidized metabolites within each of these compartments.
Finally, we will examine the interaction in vitro to tease apart the contribution of each
component (AM, ELF, and plasma EMPs) of the interaction.

To assess this concept, the following aims will be addressed:

Specific Aim 1 (n=160). To explore the extent of the oxidant stress in the lower respiratory
tract in association with HIV infection and smoking.

Specific Aim 2 (n=160). To evaluate plasma levels of capillary apoptosis and oxidation state
of HIV+ nonsmokers and smokers.

Specific Aim 3 (n=160). To examine the interaction of pulmonary capillary endothelium and
various oxidant effector components to identify oxidant-vulnerable pathways relevant to the
development of new treatment therapies.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.