Ignite Creation Date:
2024-07-17 @ 11:06 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06483490
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-06-19
Brief Title:
Environmental Pollutants in COPD and Lung Cancer
Sponsor:
University of Campania Luigi Vanvitelli
Organization:
University of Campania Luigi Vanvitelli
Study Overview
Official Title:
Mitochondrial Dysfunction and Immune Checkpoints in Chronic Obstructive Pulmonary Disease COPD and Lung Cancer the Role of Environmental Pollutants
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Epidemiological studies describe a statistically significant correlation between hospitalization rate and exposure to environmental pollutants such as atmospheric particulates PM10 and PM25 and polycyclic aromatic hydrocarbons PAH Indeed they induced the release of inflammation mediators and oxidative stress involved in remodeling and destruction of the alveolar parenchyma in turn associated with the respiratory disease onset and progression such as asthma COPD pulmonary fibrosis and lung cancer Interestingly oxidative stress associated with environmental pollutants could also induce DNA damage by affecting the stability of G-quadruplex G4 sequences Given the role of G4 in physiological and pathological processes and their presence in mitochondrial DNA telomeres and proto-oncogene promoters it is interesting to investigate the potential involvement in cellular mechanisms of response to oxidative stress associated with pollutants Moreover it is known that pollutant-induced oxidative stress has the ability to alter mitochondrial integrity leading to mitochondrial dysfunction The mitochondria involvement in the innate and adaptive immune response regulation corroborates the role of pollutants in respiratory diseases pathogenesis Indeed mitochondrial function and integrity are critical for both the effector and memory stages of differentiation of T cells which play a primary role in respiratory diseases In this context the PD-1PD-L1 immune check-points are essential in promoting the immune system homeostasis Currently although the role of environmental pollutants mitochondrial dysfunction and the PD-1PD-L1 axis in the pathogenesis of many respiratory diseases is recognized it is useful to further clarify the underlying molecular interconnections and the mechanisms by which pollutants could affect mitochondrial integrity and immune checkpoints
Detailed Description:
Epidemiological studies describe a statistically significant correlation between hospitalization rate and exposure to environmental pollutants such as atmospheric particulates PM10 and PM25 The harmfulness to human health depends on both the chemical composition and the particle size Chronic exposure to particulate matter contributes to the risk of developing respiratory and cardiovascular diseases as well as may increase the risk of lung cancer In fact particulate matter is universally recognized as a Class 1 carcinogen The fine particulates are harmful for human health by the ability to carry other pollutants such as polycyclic aromatic hydrocarbons PAHs to the lungs Notably the PAHs cause lung damage due to their ability to induce the release of inflammatory mediators and oxidative stress These events result in remodeling and destruction of the alveolar parenchyma both involved in respiratory disease onset and progression such as asthma COPD pulmonary fibrosis and lung cancer Therefore the involvement of environmental pollutants in the predisposition and exacerbation of lung diseases in the development of respiratory infections and in the process of carcinogenesis is evident Moreover in addition oxidative stress associated with environmental pollutants could induce DNA damage Recently unconventional DNA structures have been identified recognized as G-quadruplex G4 which are particularly susceptible to oxidative stress In fact it is known that guanine-rich DNA sequences are more reactive with hydroxyl radicals than guanine residues scattered throughout the genome and that oxidative damage 8-oxo-dg formation at the G4 level reduces its thermal stability Given the role of G4 in physiological and pathological processes and their presence in mitochondrial DNA telomeres and proto-promoters oncogenes it is interesting to investigate the potential involvement in cellular mechanisms of response to oxidative stress associated with pollutants It is known that pollutant-induced oxidative stress has the ability to alter mitochondrial integrity leading to mitochondrial dysfunction Recent evidence points to innate immunity apoptosis and metabolism being largely regulated by mitochondrial activities In turn normal mitochondrial activity can be affected by inflammatory processes infections tobacco smoking and environmental insults and could respond to such stimuli through structural alterations and protein expression resulting in dysfunction The mitochondria involvement in the innate and adaptive immune response regulation corroborates the role of pollutants in respiratory diseases pathogenesis Indeed mitochondrial function and integrity are critical for both the effector and memory stages of differentiation of T cells which play a primary role in respiratory diseases In this context the PD-1PD-L1 immune check-points are essential in promoting the immune system homeostasis Indeed they take part in self-tolerance and consist of a series of ligand-receptor interactions involved in coordinating an effective immune response while limiting collateral damage to organs and tissues The contribution of our research group in the study of the pathway PD-1PD-L1 in the context of respiratory diseases was relevant observing that this pathway is not only altered in lung cancer but also in chronic lung diseases such as COPD Currently although the role of environmental pollutants mitochondrial dysfunction and the PD-1PD-L1 axis in the pathogenesis of many respiratory diseases is recognized it is useful to further clarify the underlying molecular interconnections and the mechanisms by which pollutants could affect mitochondrial integrity and immune checkpoints
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None