Adiposity and Airway Inflammation in HIV-Associated Airway Disease
Condition: Asthma; HIV; Adiposity
MeSH terms: Obesity; Inflammation
Study type: Observational

Summary: 
      The goals of this study are to 1) examine the relationships among inflammation, obesity, and
      asthma in people with HIV and 2) to test if special subtypes of cells or markers are present
      in the blood and lungs of people with HIV with asthma compared to those without asthma.
    

Detailed description: 
      The proposed study involves the recruitment of participant population and the use of data
      from the existing research study cohorts that have been recruited and have provided informed
      consent for participation. Participants meet all inclusion/exclusion criteria will be
      enrolled into the study. Participants in the existing research study cohorts have pulmonary
      function testing, chest CT scans, and blood draws at each study visit which occurs every 18
      months for 3 visits. Some of the study procedures may not be repeated if they were done as
      part of other research projects.

        1. Main study visit

           The following research procedures may be performed over the course of one or more visits
           to accommodate scheduling needs. The study visit will take place at the Montefiore
           Clinical and Translational Research Center and the University of Pittsburgh Asthma
           Institute in the University of Pittsburgh Medical Center - Montefiore Hospital and may
           take up to 4 hours to complete.

             -  Informed consent

             -  Medical history review and demographics

             -  Review of inclusion/exclusion criteria

             -  Physical examination to include vital signs, weight and height, waist, hip, and
                thigh circumferences.

             -  Urine pregnancy test for female of childbearing potential

             -  Asthma-focused and quality of life questionnaire

             -  Exhaled Nitric Oxide (eNO) measurement

             -  Spirometry

             -  Methacholine challenge testing - will not need to be repeated if the participant
                had done this as part of another study in the past 6 months.

             -  Chest/Abdominal CT scans (If the participant has had the Chest CT scan done within
                6 months as part of other research study, they will not be repeated for study
                purposes. Only the Abdominal CT will be performed)

             -  Research blood sampling for biomarker analyses - some of this blood will also be
                used for pre-bronchoscopy testing in the case that the participant qualifies and is
                interested in undergoing part 2, the bronchoscopy visit.

             -  Adipose tissue biopsy (Fat Biopsy): performed on participants with a BMI≥25). This
                will be repeated if done previously because testing to be done on the fat will be
                different than what had been tested on the fat previously.

        2. Optional sub-study

      On a separate visit, only a subset of 60 selected participants will be asked to undergo the
      following procedures to obtain additional lung biological samples. This visit is optional for
      participants who are willing to participate in the bronchoscopy portion. The investigators
      will try to recruit an equal number (n=15 per group) of obese asthmatics, obese
      non-asthmatics, non-obese asthmatics, and non-obese non-asthmatics. The visit will take place
      in the Montefiore Clinical Translational Research Center (MUH-CTRC). The bronchoscopy
      procedure will take about 30-45 minutes, but the preparation and recovery time will usually
      make the visit about 4-8 hours total.

      Participants will be expected to fast for 8 hours prior to the bronchoscopy procedure and
      refrain from drinking any liquids the day of the procedure. Participants may take their usual
      medicines with sips of water.

      • Clinical laboratory testing to include complete blood count/differential/platelet count,
      prothrombin time/partial thromboplastin time, international Normalized Ratio, blood urea
      nitrogen, and creatinine prior to bronchoscopy. If the patient refuses the first blood draw,
      the sample is inadequate, or the labs were run more than 30 days prior to the bronchoscopy
      visit, a second blood sample of up to 1 tablespoon may be drawn prior to the bronchoscopy
      procedure to ensure the patient is healthy enough for the procedure.

      If Methacholine challenge was done more than 30 days prior to the visit two date, pulmonary
      function tests will be repeated.

        -  Oral Wash: participants will be asked to gargle with salt water for 1 minute and then
           spit into a container to provide a sample of approximately 10mls (2 teaspoons) at this
           study visit.

        -  Tongue Scraping: tongue blade or similar object will be used to scrape the participant's
           tongue. This sample will be used to determine what bacteria are on the participant's
           tongue. This procedure should only take minutes and is not painful.

        -  Participants will then rinse with 10cc's of Listerine. This is to assure that there are
           no bacteria left behind in the participant's mouth prior to the bronchoscopy.

        -  Bronchoscopy with bronchoalveolar lavage (BAL), endobronchial brushing and biopsy

      Under local anesthesia, participants will undergo bronchoscopy with BAL for microbiologic
      specimens. A light intravenous anesthetic will be titrated to provide participant comfort if
      necessary. Vitals signs will be monitored continuously before, during, and after the
      procedure. This procedure consists of 3 stages.

        1. Pulmonary Lavage: During pulmonary lavage, five 50 mL washes of sterile salt-water
           solution will be injected through the bronchoscope. Fluid will be collected with gentle
           suctioning for research studies.

        2. Bronchial Brushing: A small brush will be introduced through the bronchoscope and gently
           rubbed over a very small part of the surface of the lungs. Approximately 10 brushes will
           be performed to collect epithelial cells.

        3. Endobronchial Biopsy: While the bronchoscope is inserted, another small instrument will
           be passed through the bronchoscope to take small samples (biopsies) of tissue from the
           walls of the airways. Up to 5 samples may be taken during this procedure.

      Following the bronchoscopy procedure, participants will be closely monitored in the
      bronchoscopy recovery area or return to the CTRC. Rarely, the participant's asthma may worsen
      during or after the procedure. Appropriate medical treatments or overnight observation will
      be provided if needed. Participants will not be allowed to drive home after the bronchoscopy.
      This is because the sedatives used during the procedure may decrease driving ability. The
      investigators will ask for the contact name and number of the person that will pick up the
      participant after the bronchoscopy
    

Intervention name(s): Blood draw; Questionnaires; Spirometry; Methacholine challenge test; Quantitative CT scans; Urine pregnancy test; Adipose biopsy; Exhaled nitric oxide measurement
Intervention type(s): Procedure; Other; Procedure; Procedure; Radiation; Procedure; Procedure; Procedure
Intervention description(s): Blood will be drawn for plasma, serum, and peripheral blood mononuclear cells.; The following questionnaires are administered to participants by study personnel: Gingo Asthma Questionnaire (GAQ) and the Asthma Quality of Life questionnaire (AQL).; Spirometry is a simple breathing test that measures the amount of air in one's lungs and how well one can move that air by forcefully blowing 3 or more times into a mouthpiece. A series of these maneuvers will be performed under the instruction of a respiratory technician or respiratory therapist.; A methacholine challenge is a common test often used to support a diagnosis of asthma. The test consists of inhaling increasing doses of methacholine through a nebulizer to assess how quickly the participant's airways narrow.; There will be a standard chest CT and an abdominal CT. The CT scans capture contiguous volume scans acquired at slice thicknesses of 5.0 mm in the axial plane and reconstructed with 512 x 512 pixel matrices. CT examinations will encompass the entire thorax and the abdomen and will be performed during a breath-hold at end-inspiration. The investigators will measure % of lung tissue below a threshold for emphysema (i.e. -950 Hounsfield units). Measurements have been histologically-verified and give reproducible measurements. The data set is assembled and analyzed with the image data anonymized. If the participant has had a research chest CT scan done recently, only the abdomen CT will be done.; All female participants with childbearing potential will be asked to provide a urine sample for pregnancy testing. The result of the pregnancy test must be negative in order for her to be in this research study.; The doctor will obtain a sample of fat cells from the participant's abdomen. Numbing medicine will be applied. A needle is placed through the skin & into the fat pad under the skin. A blunt-tip hollow cannula is then used to aspirate fat tissue through the incision.; The investigators will measure concentrations of exhaled nitric oxide by asking the participant to inhale deeply, and then exhale very slowly into a mouthpiece for between 10-15 seconds.
Other intervention name(s): Lung function testing; Asthma Test; CT scan of the chest; CT scan of the abdomen; Fat pad biopsy; Fat biopsy; ENO measurement
Intervention MeSH terms: Nitric Oxide; Methacholine Chloride
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        HIV positive individuals in the Pittsburgh area
      
Biospecimen description: 
      Whole blood, serum, bronchial wash and cells
    
Keywords: HIV; Asthma; Adiposity; Lung disease; Weight; Fat; Obese