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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIV positive with normal PFT's | HIV positive with normal baseline DLco. Subjects with DLco>80% predicted after adjustments for Hgb and Co |
| |
| HIV positive with mild DLco impairment | HIV positive with mild DLco impairment DLco <80% predicted after adjustments for Hgb and Co. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PFT's (pulmonary function testing) | Diagnostic Test | The routine lung function endpoints of FVC(forced vital capacity), FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder before and after bronchodilator administration. The system is calibrated for body temperature and pressure of saturated gas and volumes, per American Thoracic Society (ATS) standards . DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms with ATS standards. |
| Measure | Description | Time Frame |
|---|---|---|
| Identify key causal molecular pathways of DLco impairment. | elucidating complex associations and causal relationships between clinical characteristics, the host inflammatory response, cellular metabolism, the microbiome, and miRNAs. | 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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18-80 year old men and women who are HIV positive. All will be pulled from previous HIV/Lung studies done by the same PI
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| Name | Affiliation | Role |
|---|---|---|
| Alison Morris, MD, MS | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh department of medicine division of Pulmonary, Allergy and Critical Care medicine | Pittsburgh | Pennsylvania | 15213 | United States |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D008171 | Lung Diseases |
| D004646 | Emphysema |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D012129 | Respiratory Function Tests |
| D000070857 | Walk Test |
| ID | Term |
|---|---|
| D003948 | Diagnostic Techniques, Respiratory System |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D005080 | Exercise Test |
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Whole blood, serum, saliva, oral wash, stool
|
|
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008173 | Lung Diseases, Obstructive |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |