Lung HIV Disease in a Large Cohort-Pitt
Condition: Pulmonary Disease; HIV; Emphysema
MeSH terms: Lung Diseases; Pulmonary Emphysema; Emphysema
Study type: Observational

Summary: 
      HIV-infected patients have an increased incidence of emphysema compared to non-HIV-infected
      patients, and it has been hypothesized that this accelerated disease progression is the
      result of one or more latent infections that amplifies the pulmonary inflammatory response.
      The investigators will examine the prevalence and progression of emphysema in subjects with
      and without HIV and determine risk factors for emphysema in this population.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        primary clinic for Pittsburghs Mens Aids Clinic Study(MACS)
      
Biospecimen description: 
      blood, sputum, oral wash, bronchial washes
    
Keywords: HIV; Pulmonary disease; emphysema; COPD