HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium
Descripción general del estudio
Descripción detallada
The purpose of this study is to analyze biologic samples from the blood, airways and/or urine of HIV- and HIV+ smokers and non-smokers to better understand the etiology and pathogenesis of emphysema in association with HIV infection. The underlying hypothesis is that the combination of HIV infection and smoking creates chronic oxidant stress in the lower respiratory tract that promotes cellular loss and contributes to the progressive development of emphysema. Preliminary data strongly supports our hypothesis that the accelerated development of emphysema among HIV+ smokers is due in part to the interaction of HIV directly on the macrophage found in the pulmonary alveolus. The interaction causes a release of exaggerated amounts of oxidants in the lower respiratory tract and leads to increased levels of oxidized metabolites. HIV+ individuals with emphysema have high plasma levels of apoptotic pulmonary capillary-derived micro particles that contain oxidized metabolites. The increased release of micro particles is characteristic of an apoptotic process.
We will study this hypothesis by sampling HIV+ and HIV- subjects alveolar macrophages (AM), which are found on the epithelial surface of the lung, and epithelial lining fluid (ELF) found in the lower respiratory tract. We will also assess plasma pulmonary capillary-derived endothelial microparticles (EMPs) as a biomarker for pulmonary apoptosis. Using newly developed mass spectrometry methodologies, we will quantify the oxidant stress of AM, ELF and plasma EMPs, and identify specific oxidized metabolites within each of these compartments. Finally, we will examine the interaction in vitro to tease apart the contribution of each component (AM, ELF, and plasma EMPs) of the interaction.
To assess this concept, the following aims will be addressed:
Specific Aim 1 (n=160). To explore the extent of the oxidant stress in the lower respiratory tract in association with HIV infection and smoking.
Specific Aim 2 (n=160). To evaluate plasma levels of capillary apoptosis and oxidation state of HIV+ nonsmokers and smokers.
Specific Aim 3 (n=160). To examine the interaction of pulmonary capillary endothelium and various oxidant effector components to identify oxidant-vulnerable pathways relevant to the development of new treatment therapies.
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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New York
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New York, New York, Estados Unidos, 10021
- Department of Genetic Medicne
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
HEALTHY VOLUNTEER RESEARCH SUBJECTS
- All study subjects should be able to provide informed consent
- Males or females ages 18 years and older
- Must provide HIV informed consent
VOLUNTEER RESEARCH SUBJECTS WITH LUNG DISEASE
- Must provide informed consent
- Males and females age 18 years and older
- Lung disease proven by at least one of the following: symptoms consistent with pulmonary disease; (2) chest X-rays consistent with lung disease; (3) pulmonary function tests consistent with lung disease; (4) lung biopsy consistent with lung disease; (5) family history of lung disease; and/or (6) diseases of organs with known association with lung disease
- Must provide HIV informed consent
Exclusion Criteria:
HEALTHY VOLUNTEER RESEARCH SUBJECTS
- Individuals not deemed in good overall health by the investigator will not be accepted into the study.
- Habitual use of drugs and/or alcohol within the past six months (Acceptable: - Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria).
- Individuals with history of chronic lung disease, including asthma or with recurrent or recent (within three months) acute pulmonary disease will not be accepted into the study.
- Individuals with allergies to atropine or any local anesthetic will not be accepted into the study.
- Individuals with allergies to pilocarpine, isoproterenol, terbutaline, atropine or aminophylline will not be accepted into the study.
- Females who are pregnant or nursing will not be accepted into the study
VOLUNTEER RESEARCH SUBJECTS WITH LUNG DISEASE
- Any history of allergies to xylocaine, lidocaine, versed, valium, atropine, pilocarpine, isoproterenol, terbutaline, aminophylline, or any local anesthetic will not be included in the study.
- Habitual use of drugs and/or alcohol within the past six months (Acceptable: Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria)
- Females who are pregnant or nursing
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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HIV Negative Early COPD Smokers
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HIV Negative COPD Smokers
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HIV Negative Nonsmokers
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HIV Negative Smokers
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HIV Positive Smokers
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HIV Positive Nonsmokers
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HIV Positive COPD Smokers
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HIV Positive Early COPD Smokers
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Changes in oxidant stress in the lower respiratory tract in association with HIV infection and smoking
Periodo de tiempo: One year
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Using samples obtained from subjects the extent and nature of the HIV/smoking-induced oxidant burden of the lower respiratory tract will be assessed.
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One year
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 1307014135
- U01HL121828 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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