Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
| Status: | Recruiting |
|---|---|
| Conditions: | HIV / AIDS, HIV / AIDS, Pulmonary |
| Therapuetic Areas: | Immunology / Infectious Diseases, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 9/9/2018 |
| Start Date: | September 6, 2018 |
| End Date: | October 2022 |
| Contact: | Cathy J Kessinger, RN |
| Email: | kessingercj@pitt.edu |
| Phone: | 412-624-8330 |
Systems Biology of Diffusion Impairment in HIV--BoDI
Diffusing capacity for carbon monoxide (DLco) abnormalities are common in HIV+ individuals
and associated with significant morbidity and mortality. The complexity and the
individualized differences in causes of these abnormalities have been challenging to unravel
using traditional approaches. In this proposal, the investigators construct a systems'
modeling approach to identify novel molecular and clinical pathways contributing to DLco
impairment in HIV+ individuals and to determine predictive signatures of DLco decline in
order to develop strategies to treat and prevent abnormal lung function in this susceptible
population.
and associated with significant morbidity and mortality. The complexity and the
individualized differences in causes of these abnormalities have been challenging to unravel
using traditional approaches. In this proposal, the investigators construct a systems'
modeling approach to identify novel molecular and clinical pathways contributing to DLco
impairment in HIV+ individuals and to determine predictive signatures of DLco decline in
order to develop strategies to treat and prevent abnormal lung function in this susceptible
population.
Mechanisms of impairment of diffusing capacity for carbon monoxide (DLco), which affects over
50 percent of HIV+ individuals, are poorly understood. No therapies exist despite significant
impact on quality of life and mortality. Identifying molecular pathways of DLco impairment in
HIV+ individuals and developing ability to predict HIV+ individuals at risk of DLco
impairment is thus of utmost importance for improving care. In this proposal, the
investigators construct a systems' modeling approach to identify molecular and clinical
pathways contributing to DLco impairment in HIV+ individuals. The investigators collect
multiple parallel molecular datasets integrated with detailed pulmonary function,
radiographic, and echocardiographic measurements to build a comprehensive, systems level
model of DLco abnormalities in HIV and to develop predictive models of susceptibility to DLco
worsening. As our preliminary data suggest that certain micro ribonucleic acid (miRNAs), such
as the hypoxia-induced and metabolically active gene (miR-210), may play an important role in
DLco abnormalities in HIV, the investigators then perform hypothesis-testing experiments to
determine the impact of miRNAs on lung epithelial and endothelial cells. The investigators
will utilize a well phenotyped cohort of over 500 HIV+ individuals with associated
biospecimens to execute the aims.
Participants identified to already have specimens available will be scheduled to have PFT
testing, bronchoscopy including bronchial wash with brushes and blood collection.
50 percent of HIV+ individuals, are poorly understood. No therapies exist despite significant
impact on quality of life and mortality. Identifying molecular pathways of DLco impairment in
HIV+ individuals and developing ability to predict HIV+ individuals at risk of DLco
impairment is thus of utmost importance for improving care. In this proposal, the
investigators construct a systems' modeling approach to identify molecular and clinical
pathways contributing to DLco impairment in HIV+ individuals. The investigators collect
multiple parallel molecular datasets integrated with detailed pulmonary function,
radiographic, and echocardiographic measurements to build a comprehensive, systems level
model of DLco abnormalities in HIV and to develop predictive models of susceptibility to DLco
worsening. As our preliminary data suggest that certain micro ribonucleic acid (miRNAs), such
as the hypoxia-induced and metabolically active gene (miR-210), may play an important role in
DLco abnormalities in HIV, the investigators then perform hypothesis-testing experiments to
determine the impact of miRNAs on lung epithelial and endothelial cells. The investigators
will utilize a well phenotyped cohort of over 500 HIV+ individuals with associated
biospecimens to execute the aims.
Participants identified to already have specimens available will be scheduled to have PFT
testing, bronchoscopy including bronchial wash with brushes and blood collection.
Inclusion Criteria:
1. Men and women age 18 to 80
2. HIV positive and participated in previous HLRC(HIV Lung Research Center) study
(PRO10060177, PRO09050521, PRO14070355, PRO08030011, PRO00606151, PRO13050229,
PRO17060077).
3. Negative pregnancy test (for women of child barring capabilities).
4. Have undergone bronchoscopy with BAL(bronchial lavage) and/or brushing for AECs in
storage.
5. Receiving ART (Anti-Retroviral Therapy)and virally-suppressed for at least 6 months.
Exclusion Criteria:
1. 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)
2. Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery
within 3 months, recent myocardial infarction, etc.).
3. Increasing respiratory symptoms or febrile (temperature >100.40F [380C]) within 4
weeks of study entry.
4. Acute cardiopulmonary issue in the past 4 months.
5. 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.
6. Active cancer requiring systemic chemotherapy or radiation.
7. Active infection of lungs, brain, or abdomen.
8. Intravenous drug use or alcohol use that will impair ability to complete study
investigations in the opinion of the investigator.
9. subjects with an upper or lower respiratory tract infection
10. individuals receiving chronic or acute antibiotics in the prior 4 months.
We found this trial at
1
site
Pittsburgh, Pennsylvania 15213
Principal Investigator: Alison M Morris, MD,MS
Phone: 412-624-8330
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