Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01974219 |
| Other study ID # |
1306013986 |
| Secondary ID |
5R01HL118857 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 23, 2013 |
| Est. completion date |
February 14, 2019 |
Study information
| Verified date |
June 2021 |
| Source |
Weill Medical College of Cornell University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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 small airway epithelium, this study 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.
Description:
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.
