Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes

NCT02238327 | Completed

• 2 other identifiers: PRO140703551R01HL125049-01
• Study Type: observational
• Target: 232
• Locations: 1 country
• Sites: 1

Brief Summary

The overall hypotheses of this proposal are that discrete phenotypes of HIV Chronic Obstructive Pulmonary disease (COPD) differ in their trajectories, biomarkers, and risk factors and that persistent viral infection including residual HIV is linked to HIV COPD.

Conditions

Chronic Obstructive Pulmonary Disease; HIV; Emphysema

Keywords

Antiretroviral therapy; pulmonary function; biomarkers

Outcome Measures

Primary Outcomes (1)

• differences in the trajectory of FEV1 in clinical COPD phenotypes,

  PFT's at baseline, 18 months and 36months to determine modifying risk factors and relationship of phenotypes to mortality, and delineate the association of ART and lung dysfunction.

  36 months

Secondary Outcomes (1)

• will measure biomarkers of these phenotypes and ability to predict HIV COPD

  36 months

Study Arms (2)

HIV positive normal pulmonary function

HIV positive DLCO percent predicted \>=.80 FEV1/FVC percent predicted \>=0.70

Procedure: blood draw; Procedure: questionnaires; Procedure: Lung function testing; Procedure: Six-Minute walk test; Radiation: Quantitative CT scans; Procedure: Nasal secretion and cell collection; Procedure: Echocardiogram

HIV positive with pulmonary dysfuntion

HIV positive DLco percent predicted \<=0.80% FEV1/FVC percent predicted\<=0.70%

Procedure: blood draw; Procedure: questionnaires; Procedure: Lung function testing; Procedure: Six-Minute walk test; Radiation: Quantitative CT scans; Procedure: Nasal secretion and cell collection; Procedure: Echocardiogram

Interventions

blood draw PROCEDURE

Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

questionnaires PROCEDURE

The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

Lung function testing PROCEDURE

The routine lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured before and after bronchodilator administration (4 puffs of albuterol). The best of three reproducible forced expiratory attempts is used in analysis. Percent- predicted spirometric values are based on age, height, gender, and ethnicity. DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms to ATS standards. DLco will be adjusted for hemoglobin and carboxyhemoglobin.

Also known as: Spirometry

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

Six-Minute walk test PROCEDURE

Six-minute walk tests are performed in a 100 foot (30.48 m) segment of straight hallway marked at 10 foot (3 m) intervals. In addition to the usual ATS protocol, the patient is monitored, when available, with Bluetooth wireless pulse oximetry and the time and distance recorded after six minutes and if they desaturate to \<88%. Dyspnea (Borg 0-10) and perceived exertion (Borg 6-20) scales are completed at the beginning and the end of test.

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

Quantitative CT scans RADIATION

Subjects will undergo a standard chest CT. The CT scans will use a phantom shipped between sites to standardize results and 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 be performed during a breath-hold at end-inspiration. We 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.

Also known as: CT scan of the chest

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

Nasal secretion and cell collection PROCEDURE

Participants will be instructed to blow their nose to remove accumulated mucus. Two sprays of commercially available nasal saline will be instilled in each nostril. The participant will then be ask to exhale through the rinsed nostril into a specimen cup. We will repeat this up to 5 times on each side depending on the participants' tolerance to the procedure. Using an otoscope, a small curette will then be used to collect 3 to 5 samples of nasal cells from each nostril. These samples will be used immediately for analysis or banked for future study.

Also known as: Nasal wash, Nasal scrapping

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

Echocardiogram PROCEDURE

The cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging.

Also known as: Echo

HIV positive normal pulmonary function; HIV positive with pulmonary dysfuntion

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population will be HIV positive subjects previously seen for other studies. There will be three centers enrolling, the University of Pittsburgh, the University of California San Francisco, and the University of California Los Angeles. Recruitment will occur from participants in ongoing lung studies at these sites.

You may qualify if:

• HIV-1 infection, documented in medical record at any time prior to study entry.
• Men and women age 18 to 80.
• Ability and willingness to complete all tests.
• Participant in HLRC studies, MACS, Women's Interagency Health Study, and local HIV clinics.
• For UCSF only, new ART initiators from Women's Interagency Health Study or the HIV clinic

You may not qualify if:

• Pregnancy or breast-feeding.
• Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
• Increasing respiratory symptoms or febrile (temperature \>100.40F \[380C\]) within 4 weeks of study entry.
• Hospitalization within 4 weeks prior to study entry (excluding mental health).
• Uncontrolled hypertension at screening visit (systolic \> 180 mm Hg or diastolic \> 100 mm Hg) from an average of two or more readings. Subject may return for screening after blood pressure is controlled.
• Active cancer requiring systemic chemotherapy or radiation.
• Active infection of lungs, brain, or abdomen.
• Intravenous drug use or alcohol use that will impair ability to complete study investigations in the opinion of the investigator

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• Drummond MB, Huang L, Diaz PT, Kirk GD, Kleerup EC, Morris A, Rom W, Weiden MD, Zhao E, Thompson B, Crothers K. Factors associated with abnormal spirometry among HIV-infected individuals. AIDS. 2015 Aug 24;29(13):1691-700. doi: 10.1097/QAD.0000000000000750.

  PMID: 26372280 BACKGROUND

• Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, Kingsley L, McMahon DK, Morris A. Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc. 2018 Feb;15(2):192-199. doi: 10.1513/AnnalsATS.201606-492OC.

  PMID: 29313714 BACKGROUND

• Qin S, Clausen E, Nouraie SM, Kingsley L, McMahon D, Kleerup E, Huang L, Ghedin E, Greenblatt RM, Morris A. Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One. 2018 Oct 4;13(10):e0205065. doi: 10.1371/journal.pone.0205065. eCollection 2018.

  PMID: 30286195 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, bronchial wash and cells

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema

Interventions

Blood Specimen Collection; Surveys and Questionnaires; Nasal Lavage; Caves

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Therapeutic Irrigation; Geological Phenomena; Physical Phenomena; Environment; Ecological and Environmental Phenomena; Biological Phenomena

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: September 12, 2014
• Study Start: September 1, 2014
• Primary Completion: March 2, 2020
• Study Completion: March 2, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

US (1)