Environmental Pollutants in COPD and Lung Cancer

NCT06483490 | Recruiting DMC

• 1 other identifier: MITO2024
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COPD and Lung Cancer

Keywords

COPD; Lung cancer; Mitochondrial dysfunction; immune checkpoints; Environmental pollution; cross-sectional; non-pharmacological; multicenter study

Outcome Measures

Primary Outcomes (4)

• 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.

Interventions

This is a cross-sectional, non pharmacological study OTHER

Measurement of immune checkpoint levels, mitochondrial dysfunction, pollutant concentrations and G-quadruplex levels and their correlation in all enrolled subjects.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients belong to UOC Interventional Pulmonology- Hospital Cardarelli and subjected to bronchoscopy, BAL and routine blood sampling following the clinical routine. All participants must sign the informed consent for participation in the study. All analyses to be carried out in this study will not require more human samples than is required by normal clinical practice. The excess amount of biological samples will be destroyed.

You may qualify if:

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

You may not qualify if:

• Patients with infectious diseases,
• Patients with interstitiopathy
• Patients with autoimmune diseases
• subjects on glucocorticoid therapy
• subjects who cannot undergo bronchial biopsy
• subjects who will not sign informed consent.

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead
• Cardarelli Hospital: collaborator

Study Sites (1)

Cardarelli Hospital

Napoli, 80131, Italy

RECRUITING

Related Publications (5)

• Wilkinson 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 BACKGROUND

• Durham 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 BACKGROUND

• Wasen 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 BACKGROUND

• Prakash 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 BACKGROUND

• Sachdeva 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 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

biopsies, bronco-alveolar lavage (BAL) and blood samples

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Neoplasms; Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Bruno D'Agostino, MD, PhD

CONTACT

+393472601620; bruno.dagostino@unicampania.it

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: July 3, 2024
• Study Start: May 1, 2023
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)