HIV-related Accelerated Aging of the Airway Epithelium
|HIV COPD Chronic Obstructive Pulmonary Disease Smoking|
|Study Design:||Observational Model: Case-Control
Time Perspective: Prospective
|Official Title:||HIV-related Accelerated Aging of the Airway Epithelium|
- Gene expression changes in airway epithelium [ Time Frame: One Year ]We examine the pathogenesis of the accelerated development of COPD in smokers with HIV infection and the premature biologic aging of the small airway epithelium (SAE) mediated by the effects of direct HIV infection of the SAE and/or through the interaction of HIV-infected T cells and/or alveolar macrophages (AM) with the SAE, resulting in the disordered biology of the SAE that is central to the pathogenesis of COPD.
Biospecimen Retention: Samples With DNA
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
While the epidemiologic data linking HIV infection to an increased risk for COPD is clear, the pathogenesis of the accelerated development of COPD in HIV infected smokers is not understood. We have focused on the SAE as the central target for the accelerated development of COPD in HIV infected smokers, as there is extensive data pointing to the SAE as the initial site of lung pathology in cigarette smokers and the small airways are the major site of airflow obstruction in COPD. Further, the emphysema associated with COPD begins in alveoli surrounding the SAE, and prior to the development of clinical evidence of lung disease, the SAE of smokers exhibit marked disordered biology, including changes in DNA methylation and gene expression, and disordered differentiation. Importantly, we have observed that HIV infection "ages" the SAE, with exaggerated shortening of SAE telomeres in individuals infected with HIV compared to HIV ‾ smokers.
We propose that the early events in the pathogenesis of the accelerated development of COPD in smokers with HIV infection results from the premature biologic aging of the small airway epithelium (SAE) mediated by the effects of direct HIV infection of the SAE and/or through the interaction of HIV-infected T cells and/or alveolar macrophages (AM) with the SAE, resulting in the disordered biology of the SAE that is central to the pathogenesis of COPD.
In cigarette smokers that are HIV+, one of the most common HIV-associated non-AIDS conditions is the accelerated development of chronic obstructive pulmonary disease (COPD), a disorder associated with significant morbidity and mortality. Based on the knowledge that COPD in smokers starts in the SAE, this proposal is focused on examining the hypothesis that the accelerated development of COPD associated with HIV infection results, in part, from an interaction of HIV directly on the small airway epithelium or through infection of cellular components of the immune system, with mediators released by these immune cells evoking premature biologic aging of the small airway epithelium. By identifying the early events in the pathogenesis of the HIV-associated accelerated COPD in smokers, we aim to identify biologic targets to which pharmacologic therapies could be addressed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01974219
|Contact: Grace Mammen, BA, CCRPemail@example.com|
|United States, New York|
|Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine||Recruiting|
|New York, New York, United States, 10065|
|Contact: Grace Mammen, BA, CCRP 646-962-2672 firstname.lastname@example.org|
|Sub-Investigator: Robert Kaner, MD|
|Sub-Investigator: Jason Mezey, PhD|
|Sub-Investigator: Renat Shaykhiev, MD, PhD|
|Sub-Investigator: Jacqueline Salit, MD|
|Sub-Investigator: Aileen Orpilla, BE|
|Sub-Investigator: Kimberly Berry, BA|
|Principal Investigator:||Ronald G Crystal, MD||Weill Medical College of Cornell University|