Immune Checkpoints in COPD (CP-COPD)

Predictive Role of Immune Checkpoints in COPD Evolution Towards Lung Cancer

The aim of this study is to investigate the mechanisms underlying the complex interaction between Chronic obstructive pulmonary disease (COPD) and lung cancer. Therefore, in order to identify a possible role of immune checkpoints not only in the susceptibility to COPD development but also in its evolution towards lung cancer, will be evaluate the correlation between PD-L1 expression and cigarette smoke exposure in COPD patients.

Although there are many epidemiological studies highlighting the interconnections between COPD and lung cancer and the influence of cigarette smoke, the molecular bases of this association are less well defined. Initially they were thought to be driven just by innate inflammation, however, recent studies have also demonstrated the influence of the adaptive immune system. Despite this, the role of immune checkpoints in chronic lung inflammatory diseases such as COPD is less well understood. COPD is currently the 4th leading cause of death worldwide but is assessed to be the 3rd by the end of 2020 resulting in an economic and social burden that is in continuous progression.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Lung Cancer; Copd; Severe ARDS
• Intervention / Treatment: Other: check immune check points

Detailed Description

The aim of this study is to investigate the mechanisms underlying the complex interaction between Chronic obstructive pulmonary disease (COPD) and lung cancer. Therefore, in order to identify a possible role of immune checkpoints not only in the susceptibility to COPD development but also in its evolution towards lung cancer, will be evaluate the correlation between PD-L1 expression and cigarette smoke exposure in COPD patients.

Although there are many epidemiological studies highlighting the interconnections between COPD and lung cancer and the influence of cigarette smoke, the molecular bases of this association are less well defined. Initially they were thought to be driven just by innate inflammation, however, recent studies have also demonstrated the influence of the adaptive immune system. Despite this, the role of immune checkpoints in chronic lung inflammatory diseases such as COPD is less well understood. COPD is currently the 4th leading cause of death worldwide but is assessed to be the 3rd by the end of 2020 resulting in an economic and social burden that is in continuous progression.

Patients will be recruited from from the outpatient clinics of the Pulmonary and Critical Care Medicine department of "Mauro Scarlato" Hospital in Scafati, Italy in collaboration with the Operational Unit of Clinical Pharmacology and Pharmacovigilance of Catanzaro University.

171 patients will be divided according to the results of the anatomopathological examinations into four groups:

• Healthy never smokers
• Smokers with normal lung
• Cancer
• COPD (COPD group was divided in two subgroups: GOLD 1-2 group and GOLD 3-4 group).

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Luca Gallelli, MD; Phone Number: 3339245656; Email: gallelli@unicz.it

Study Locations

• Italy
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Recruiting
      • Luca Gallelli
      • Contact: Luca Gallelli, MD; Phone Number: +39 0961712322; Email: gallelli@unicz.it
  • Italia
    • Catanzaro, Italia, Italy, 88100
      • Recruiting
      • AO Materdomini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The levels of PD-1, PD-L1 and CTLA-4 will be evaluated by immunofluorescence and by RT-PCR on biopsy samples, which will be taken according to normal clinical practice. The checkpoint levels will be assessed before and after exposure after a medium of smoke also in the macrophages extracted from the BAL, which will be collected according to normal clinical practice, by RT-PCR.

The aforementioned experiments will be carried out at the Pharmacology Section of the Department of Experimental Medicine, University of Campania Luigi Vanvitelli, their cost will not be borne by the NHS but will be fully borne by the aforementioned University.

Description

Inclusion Criteria:

• • over 18 years of age with suspected diagnosis of pulmonary neoplasia

  • signed the informed consent

Exclusion Criteria:

• • infected diseases

  • interstitiopathy
  • asthma,
  • autoimmune diseases,
  • neoplasia other than inclusion criteria
  • subjects on glucocorticoid therapy
  • alcohol consumption (>3 alcoholic beverages daily)
  • substance abuse
  • inability to give written informed consent
  • those who will not sign the consent to the processing of personal data

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy never smokers; Clinical evaluation of immune check points expression. A prospective study	Other: check immune check points; we will evaluate the expression of immune check points
Smokers with normal lung function; evaluation of immune check points expression	Other: check immune check points; we will evaluate the expression of immune check points
Lung cancer; evaluation of immune check points expression	Other: check immune check points; we will evaluate the expression of immune check points
COPD; evaluation of immune check points expression	Other: check immune check points; we will evaluate the expression of immune check points

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD-L1 in bronchoalveolar lavage fluid	to evaluate the expression of PD-L1	1 month
CTLA-4 in bronchoalveolar lavage fluid	to evaluate the expression of CTLA-4	1 month
mucin-domain containing-3 (TIM-3)	to evaluate the expression of mucin-domain containing-3 (TIM-3) in bronchoalveolar lavage fluid	1 month
PD-1 in bronchoalveolar lavage fluid	to evaluate the expression of PD-1	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
check point and smoke	to evaluate the correlation between PD-L1 expression and cigarette smoke exposure in COPD patients.	1 month

Collaborators and Investigators

• Sponsor: University of Catanzaro
• Collaborators: Azienda Sanitaria Provinciale Di Catanzaro; Azienda Ospedaliera Universitaria Mater Domini, Catanzaro

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Actual): November 30, 2020
• Study Completion (Anticipated): December 10, 2023

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: November 27, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: systemic diseases
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: 361/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: publication of the results
• IPD Sharing Time Frame: 12 months
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No