Clinical trial NCT04654104: Immune Checkpoints in COPD
Official title: Predictive Role of Immune Checkpoints in COPD Evolution Towards Lung Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lung Cancer
Severe ARDS
Asthma
Copd
Keywords: systemic diseases
Lead sponsor: University of Catanzaro
Sponsor class: OTHER
Collaborators: name: Azienda Sanitaria Provinciale Di Catanzaro
name: Azienda Ospedaliera Universitaria Mater Domini, Catanzaro
First posted: 2020-12-04
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: PD-L1 in bronchoalveolar lavage fluid
timeFrame: 1 month
measure: CTLA-4 in bronchoalveolar lavage fluid
timeFrame: 1 month
measure: mucin-domain containing-3 (TIM-3)
timeFrame: 1 month
measure: PD-1 in bronchoalveolar lavage fluid
timeFrame: 1 month
Secondary outcomes:
measure: check point and smoke
timeFrame: 1 month
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Luca Gallelli
state: CZ
city: Catanzaro
country: Italy
facility: AO Materdomini
state: Italia
Study officials:
References: