Environmental Pollutants in COPD and Lung Cancer

Epidemiological studies describe a statistically significant correlation between hospitalization rate and exposure to environmental pollutants such as atmospheric particulates (PM10 and PM2.5) 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-1/PD-L1 immune check-points are essential in promoting the immune system homeostasis. Currently, although the role of environmental pollutants, mitochondrial dysfunction and the PD-1/PD-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.

Epidemiological studies describe a statistically significant correlation between hospitalization rate and exposure to environmental pollutants such as atmospheric particulates (PM10 and PM2.5). 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-1/PD-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-1/PD-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-1/PD-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.

Eligibility Criteria:
Inclusion Criteria:

* All patients of both sexes and over the age of 18 years
* Clinical diagnosis of suspected lung cancer

Exclusion Criteria:

* Patients with infectious diseases,
* Patients with interstitiopathy
* Patients with autoimmune diseases
* Patients with cancers not covered by the inclusion criteria
* subjects on glucocorticoid therapy
* subjects who cannot undergo bronchial biopsy
* subjects who will not sign informed consent.