Evaluation of Eosinophil Phenotype in COPD Patients
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- STATUS
- Recruiting
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- participants needed
- 30
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- sponsor
- IRCCS San Raffaele
Summary
This is a pilot non pharmacological observational study. Aim of the study is to analyze the immunophenotype of circulating eosinophils in chronic obstructive pulmonary disease (COPD) patients, and to correlate results with clinical status of patients (stable versus exacerbated patients, response to therapy). In about 30% of COPD patients there is an increase in the number of circulating eosinophils, which associates with an increased risk for exacerbation. However, no data is available on the role of eosinophils in this disease, on their activation status and their response to chemotactic factors. By multicolor flow cytometry the investigators will analyze membrane molecules and intracellular cytokines associated to chemotaxis, degranulation and inflammation. The study will enroll 30 patients (15 stable and 15 with exacerbation). Results will be analyzed taking into account clinical status,disease progression and response to treatment.
Description
In about 30% of COPD patients there is an increased number of circulating eosinophils. On their membrane, eosinophils express several molecules, also related to their physiology, namely major histocompatibility complex (MHC) class II, needed for antigen presentation; CCR3, receptor for a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), monocyte chemotactict protein (MCP)-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5); cluster of differentiation (CD)125, which binds IL-5 and stimulates eosinophils proliferation; CD63, a marker that is upregulated after eosinophils degranulation; and CD294 (CRTH2) which is the prostaglandin D2 receptor, and is associated to allergy and inflammation . The hypothesis for the present trial is that different clinical phenotypes of COPD patients could be associated to different activation statuses of eosinophils, that can be evaluated analyzing by flow cytometry the membrane expression of the above mentioned molecules. In particular, the investigators hypothesize that membrane molecules may be modulated in different stages of the diseases, and may change after medical and rehabilitative therapies.
The investigators will analyze phenotype of eosinophils from blood samples of patients with COPD, admitted to the hospital after an episode of exacerbation, or for routine controls. In this way, the association between a particular pattern of molecules expressed on eosinophils membrane and the severity of COPD will be defined. Moreover, for hospitalized patients, eosinophils phenotype also on discharge day will be analyzed. In this way the effect of therapies on eosinophils activation will be assessed. Clinical status of patients will be assessed by standard tests such as St George Respiratory Questionnaire (SGRQ), BODE index, COPD Assessment Test (CAT), Six min. Walking Test (6'WT), Pulmonary Function Tests (PFT).
Eosinophils phenotype and in vitro cytokines production will be analyzed by multicolor flow cytometry. To minimize the effect of manipulation, staining of membrane molecules will be performed on whole blood samples, followed by lysis of erythrocytes. The following molecules will be analyzed: CD45, CD16, CD15, CD63, CCR3, CD125, CD294, Siglec-8. After in vitro stimulation with lipopolysaccharide (LPS) or CCL11, the production of interleukine (IL)-4, TGFbeta and IL-2 will be analyzed.
Details
| Condition | Chronic Obstructive Lung Disease, Chronic Obstructive Lung Disease, COPD Exacerbation |
|---|---|
| Age | 18years - 100years |
| Treatment | biomarker identification |
| Clinical Study Identifier | NCT04494308 |
| Sponsor | IRCCS San Raffaele |
| Last Modified on | 16 February 2024 |
How to participate?
Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.
Learn moreIf you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Learn moreComplete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.
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