Clinical trial · Observational
Environmental Pollutants in COPD and Lung Cancer
Mitochondrial Dysfunction and Immune Checkpoints in Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer: the Role of Environmental Pollutants
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| COPD and Lung Cancer | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| This is a cross-sectional, non pharmacological study | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (0)
[]Primary outcomes (4)
- measure
- Immune checkpoints in COPD and lung cancer.
- timeFrame
- The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year
- description
- 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).
- measure
- Mitochondrial activity in COPD and lung cancer.
- timeFrame
- The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year.
- description
- 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
- measure
- Environmental pollutants in COPD and lung cancer.
- timeFrame
- The outcome will be measured once for each included patient after the enrollment through study completion, an average of 3 year.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (5)
- BACKGROUNDWilkinson TMA. Immune checkpoints in chronic obstructive pulmonary disease. Eur Respir Rev. 2017 Jun 28;26(144):170045. doi: 10.1183/16000617.0045-2017. Print 2017 Jun 30. PMID 28659497
- BACKGROUNDDurham AL, Adcock IM. The relationship between COPD and lung cancer. Lung Cancer. 2015 Nov;90(2):121-7. doi: 10.1016/j.lungcan.2015.08.017. Epub 2015 Aug 29. PMID 26363803
- BACKGROUNDWasen C, Erlandsson MC, Bossios A, Ekerljung L, Malmhall C, Toyra Silfversward S, Pullerits R, Lundback B, Bokarewa MI. Smoking Is Associated With Low Levels of Soluble PD-L1 in Rheumatoid Arthritis. Front Immunol. 2018 Jul 27;9:1677. doi: 10.3389/fimmu.2018.01677. eCollection 2018. PMID 30140263
- BACKGROUNDPrakash YS, Pabelick CM, Sieck GC. Mitochondrial Dysfunction in Airway Disease. Chest. 2017 Sep;152(3):618-626. doi: 10.1016/j.chest.2017.03.020. Epub 2017 Mar 21. PMID 28336486
- BACKGROUNDSachdeva K, Do DC, Zhang Y, Hu X, Chen J, Gao P. Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence. Front Immunol. 2019 Nov 29;10:2787. doi: 10.3389/fimmu.2019.02787. eCollection 2019. PMID 31849968