Dysbiosis Impact on Lung Disease in HIV

NCT04155684 | Completed DMC

• 2 other identifiers: STUDY19060360R01HL138630
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the high burden of respiratory symptoms in the HIV+ population, causes of chronic obstructive pulmonary disease (COPD) in individuals with HIV are poorly understood. Microbial communities present in the lungs or gut could play an important role in COPD via their ability to stimulate inflammation and oxidative stress and by the interactions of microbial and host gene transcription. By exploring the impact of the structure and function of microbial communities on the host in HIV-associated COPD, this project could lead to discovery of novel therapeutics to treat and prevent COPD. Subjects will be 20 HIV+ individuals with COPD (FEV1/FVC \<0.70 and FEV1 and DLco\<80% predicted) and 20 HIV+ individuals with normal lung function (controls) and 10 HIV negative individuals recruited from our ongoing cohorts. Controls will be matched to the individuals with COPD based on age, gender, pack-years of smoking, ART use, HIV viral suppression, and history of illicit drug use. Bronchoscopy will be performed on all subjects. The investigator will uncover mechanisms that contribute to COPD in HIV+ individuals, which will lead to interventional therapies. For example, the investigators evaluate the impact of bacteria on lung epithelial cell gene expression and inflammation and test ability of anti-inflammatories to alter responses. Identification of other key pathways or microbes could also lead to testing of pro-biotics, post-biotics (bacterial metabolites), or therapy with bacteria genetically modified for desired function or metabolites.

Conditions

HIV Infections; COPD; Microbiome

Keywords

microbiome

Outcome Measures

Primary Outcomes (3)

• Comparison of Ig-bound and BAL bacteria

  Using 16S sequencing, we will compare unsorted bacteria from BAL to IgG- and IgM-bound and Ig-negative bacteria in HIV+ individuals with and without COPD.

  5 years

• AEC supernatant cytokines and cell gene expression

  Basolateral supernatant cytokines and MMPs will be measured by ELISA, and AEC cytokine and MMP gene expression by rtPCR. We will determine if IgG- or IgM-bound bacteria from HIV+ individuals with COPD generate a greater inflammatory response in co-culture than bacteria from HIV+ individuals without COPD and if this response can be decreased by anti-inflammatories.

  5 years

• AEC function

  Trans-epithelial electrical resistance (TEER) will be measured hourly during bacterial co-culture with ALI AECs in the various experimental conditions using an Ag/AgCl electrode106

  5 years

Study Arms (2)

HIV + with COPD

COPD will be defined as Subjects with FEV1/FVC\<0.70 or FEV1 and DLco \< 80% predicted

HIV+ normal

Normal PFT's

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

Men and women HIV positive or HIV negative who have participated in The HIV Lung Research group studies in the past.

You may qualify if:

• HIV-1 infection, documented in medical record at any time prior to study entry.
• HIV negative who have prior involvement in an HLRC study.
• Men and women age 18 to 80.
• Ability and willingness to complete all tests.
• Participant in HLRC studies,(PRO10060177, PRO09050521, PRO14070355, PRO08030011, PRO00606151, PRO13050229) MACS(Pitt Men's study), Women's Interagency Health Study, PACT or local HIV + clinics.
• COPD will be defined as Subjects with FEV1/FVC\<0.70 or FEV1 and DLco \< 80% predicted - this is the same criteria for the other HLRC studies listed in #5.

You may not qualify if:

• Pregnancy or breast-feeding. (urine pregnancy done on all females of child bearing potential-males and females who are at least 1 year post menopausal or surgically sterile will not be tested)
• 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.
• Acute cardiopulmonary issue in the past 4 months.
• 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.
• 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, for example; uncontrolled diabetes or uncontrolled hypertension.
• on antibiotics in the past 3 months for an acute infection (prophylaxis OK)
• FEV1 less than 30% predicted
• Allergy to any drug needed to perform testing and no alternative available (albuterol, atropine, lidocaine, fentanyl, versed, Demerol)

Sponsors & Collaborators

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

Study Sites (1)

University of Pittsburagh

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, oral samples, bronchial wash and stool will be stored in Dr. Morris's lab at the University of Pittsburgh indefinitely.

MeSH Terms

Conditions

HIV Infections; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alison J Morris, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Pulmonary, Allergy, and Critical Care Medicine

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 7, 2019
• Study Start: November 1, 2018
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: April 3, 2025

Record last verified: 2022-10

Locations

US (1)