Environmental Pollutants in COPD and Lung Cancer
NCT Number: NCT06483490
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: COPD and Lung Cancer
Interventions: OTHER: This is a cross-sectional, non pharmacological study
Sponsor: University of Campania "Luigi Vanvitelli"
Collaborators: Cardarelli Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 200
Study Design: Observational Model: |Time Perspective: p
Start Date: 2023-05-01
Completion Date: 2026-05-01
Locations: Cardarelli Hospital, Napoli, 80131, Italy

Summary:
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.

Primary Outcome Measures: Immune checkpoints in COPD and lung cancer., Measurement of immune checkpoint PD-L1, PD-1, e CTLA-4 levels in all enrolled subjects. The relative expression will be calculated by Real-time PCR using the comparative cycle threshold method (Ct) (2 - ΔΔCt)., The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year|Mitochondrial activity in COPD and lung cancer., Measurement of mitochondrial dysfunction markers in all enrolled subjects. ATP levels will be measured by means of the 'ATP bioluminescence assay kit' and the factors 'PTEN-induced kinase 1 (PINK)-Parkin-mediated pathway' (marker of mitophagy) and sirtuins (marker of senescence) by ELISA assay, The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year.|Environmental pollutants in COPD and lung cancer., Measurement of pollutant concentrations in all enrolled subjects. A fraction of BAL and peripheral blood will be used for the analysis of pollutants deposited on the cell surface and in the supernatant by means of gas chromatography (GC) coupled to mass spectrometry (MS)., The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year.|G-quadruplex levels in all enrolled subjects., Measurement of G-quadruplex levels in all enrolled subjects. The BG4 antibody will be used to evaluate the formation of G-quadruplex structures. Laser scanning confocal microscopy will be performed with a laser scanning confocal microscope with a 400X objective and the signal analysed with Fiji software., The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year.