Lung HIV Disease in a Large Cohort-Pitt

Specific Aim 1: To test the hypothesis that emphysema is more prevalent and progresses more
quickly in HIV+ subjects compared to HIV- controls: The investigators will characterize the
prevalence, nature, and progression of HIV-associated emphysema. Emphysema will be
determined in HIV+ and HIV- subjects by spirometry, diffusing capacity, and quantitative
computed tomography and/or EBCT. These studies will be repeated at 18 and 36 months after
baseline to assess differences in progression between HIV+ and HIV- subjects. Multifactorial
regression analyses will determine the contribution of various risk factors to presence and
progression of emphysema.

The investigators will perform pulmonary function testing at baseline and compare degree of
obstruction according to HIV status while adjusting for other clinical variables that
influence lung function. Assessment of degree of emphysema and its distribution can be
accomplished using quantitative CT morphometry density analysis. This technique measures
lung density by pixel analysis expressed in Hounsfield units (HU) or its inverse (ml of
gas/gram of tissue) which increases proportionately with the magnitude of emphysema. These
measurements have been histologically-verified and give quantitative, reproducible
measurements of percentage and distribution of lung considered normal, mildly emphysematous,
and severely emphysematous. The investigators will compare emphysema in the HIV+ and HIV-
subjects and compare progression over time.

Specific Aim 2: To establish a bank of saliva, sputum, serum, plasma, DNA, RNA, proteins and
cells from the biological samples of these subjects with a purpose of performing future
proteomic and genomic analyses of gene expression, genetic associations, disease
pathogenesis and markers of disease progression in subjects with HIV infection and lung
diseases:

2a) To test the role of low level infections with physiologic obstruction in HIV-infected
patients. The investigators will examine the role of co-infection with Pneumocystis and
other microbes in the pathogenesis of HIV-associated emphysema and the mechanism by which
they cause emphysema progression by examining induced sputum specimens at baseline, 18
months, and 36 months.

Specific Aim 3. To test the hypothesis that persistent, sub-clinical infection in HIV+
subjects augments the pulmonary inflammatory response and leads to emphysema.

3a. To test the hypothesis that pulmonary colonization is increased in subjects with
HIV-associated emphysema. The investigators will perform serial bronchoscopic alveolar
lavage (BAL) in four groups of HIV+ and HIV - subjects: smokers with emphysema, smokers
without emphysema, non-smokers with emphysema, and non-smokers without emphysema at the four
sub-study sites. The investigators will use culture and molecular techniques to test for
pathogens associated with emphysema and/or HIV and compare results between groups at
baseline and over time to test our hypothesis that HIV+ subjects with emphysema harbor
sub-clinical infection and that these infections accelerate lung damage and inflammation.
The investigators will also determine pulmonary HIV levels and their relationship to
emphysema and colonization.

3b. To test the hypothesis that local inflammatory responses and proteases are upregulated
in HIV+ subjects with emphysema. BAL cellular infiltration will be characterized by flow
cytometry to develop a quantitative and qualitative evaluation of cellular inflammatory
responses in the four patient groups in Aim 3a. Lymphocyte populations will be analyzed for
activation markers and intra-cellular cytokine production. The investigators will measure
cytokine expression and protease levels in BAL supernatant as well as macrophage protease
production. The investigators will compare results between groups and correlate with
infections and HIV BAL viral levels.

Inclusion Criteria:

- Age 18 years old or older

- By participant's report, s/he is:

- HIV positive OR

- HIV negative and at high risk

- Recruited via:

- Pitt Men's Study/MAC

- Women's Interagency Health Study

- Attendee of UPMC HIV/AIDS Program

Exclusion Criteria:

- Acute onset of shortness of breath, cough, fever or heart condition such as
tachycardia, angina or arrhythmias

- Pregnancy

- MI, CVA or cardiovascular event within last 3 months

- Eye or abdominal surgery with last 3 months

- Active TB by documentation or self-report

- Weight > 500 lbs.

- Exposure to > 10 rads in the previous 12 months (i.e., 2 CT or 4 cardiac cath…or
other fluoroscopic exams For bronchoscopy subjects only

- Subjects with an upper or lower respiratory tract infection

- Individuals with a Primary diagnosis of vocal cord dysfunction, or those with
significant or uncontrolled systemic diseases will be excluded

- 75 years of age or older