Morphological Parameters of Blood Cell's Activation in Characterization and Prognosis in a COPD Patients Cohort

COPD Clinical Trial

Official title:

Morphological Parameters of Blood Cell's Activation in Characterization and Prognosis in a COPD Patients Cohort

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04923360
• Other study ID #: G95756334
• Status: Recruiting
• Start date: January 1, 2018
• Est. completion date: June 1, 2022

Study information

• Verified date: April 2021
• Source: Hospital Galdakao-Usansolo
• Contact: Cristobal Esteban, MD
• Phone: +34 94 400 7002
• Email: cristobal.est[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Though exacerbations in the COPD (Chronic Pulmonary Obstructive Disease) and specially the most severe cases (hospitalizations) are currently a fundamental outcome in the COPD due to its clinical and economic significance, there are many unanswered questions still today such as the very definition of exacerbation itself.

Research parameters like the CPD (Cell Population Data) are added to the basic blood count. The CPD of the XN analyzers (Sysmex Corporation, Kobe, Japan) provide quantitative information of the morphological and functional characteristics of the leukocytes: their volume, content of nucleic acids and structure of the cytoplasm. The CPD are numerical data which represent the morphology which characterizes the neutrophils, lymphocytes, monocytes, eosinophils and platelets classifying them as per their volume and shape, granularity and their content of nucleic acids. The approach is that such cheap and accessible technique can provide relevant information in the area of COPD exacerbations.

Therefore, this study proposes several objectives:

1. Establish the CPD values for each phenotype of COPD (both for those already established in the Spanish guide of COPD and in the potential phenotypes which may be established in this study based on the CPDs themselves).

2. Identify which, among the CPDs, are more relevant in relation to cellular activation (neutrophils, lymphocytes, eosinophils and platelets) both in the stage of clinical stability and during the severe exacerbation.

3. Establish different phenotypes of COPD (in stable phase) according to the CPD values.

4. Determine the existence of an association between the level of activation of these cells in stability phase of the COPD and the risk of exacerbation; establish the optimum cutoff points.

The study will include 500 patients with different levels of COPD in the OSI-Barrualde and OSI-Bilbao. Several clinical measurements will be carried out for their characterization. CPD measurements will be made both in clinical stability phase or during exacerbations.

Description:

One of the most analyzed outcomes in COPD (Chronic Pulmonary Obstructive Disease) are the exacerbations, specially the severe ones. There are two challenges in relation to severe exacerbations: one related to the high use of sanitary resources and costs; and the second one, related to the worsening of the pulmonary function and the quality of life.

Nowadays in the Spanish COPD guideline called GESEPOC (Guía Española de la Enfermedad Pulmonar Obstructiva Crónica), there is a COPD "exacerbator" phenotype. However, there are some limitations round the COPD exacerbation, like its definition or its predictors. In other words, there are no indicators that can help the investigators to define more precisely an exacerbation or the COPD exacerbator profile.

COPD is a chronic disease with low intensity, systemic and chronic inflammation. The matter is that it is not established which indicators the investigators have to use to determinate it. There are some indicators like C reactive protein, TNF-alpha, IL-6 (Interleukin 6), microalbumins and adiponectin; and there are also prognostic scores based on them. However, they cannot help the investigators to establish COPD phenotypes of patients that can suffer an exacerbation. The investigators neither have indicators in stable phase that say them the risk of an exacerbation. Moreover, it is said that there are different types of exacerbations and even it has been established indicators of these exacerbation phenotypes. However, nowadays it cannot be translated into daily clinical practice. If investigators would be able to do it, they could advance in the knowledge of the exacerbations and they could establish precision treatments.

The blood count is one of the most required laboratory test in clinical practice. It is cost-effective because of its low price and the huge quantity of information it brings. After adapting the flow cytometry in hematologic modern analyzers, a more detailed study of cells can be done. Moreover, morphological changes can be detected in response to different stimulus, like infections or the ones that are caused by inflammatory reactions.

In this project, CPD ("Cellular Popular Data") is added to the basis blood count. They are parameters that are under investigation nowadays. The CPD of the XN analyzers (Sysmex Corporation, Kobe, Japan) give quantitative information about morphological and functional characteristics of leukocytes: their volume, the quantity of nucleic acid they contain and the structure of the cytoplasm. The CPD are numeric data that represent the morphology of the neutrophils, lymphocytes, monocytes and eosinophils, and they classify them by their volume, form, granularity and nucleic acid content. The same technology allows to the analyzer to classify the platelets by their morphology, what is related to its thrombogenic activity.

The composition of the membrane of the activated cells is different from the one of cells that are at rest, because of the expression of the receptors and the surface signaling molecules, in response to the activation. This membrane is more sensitive to the reagents of the analyzer, and more quantity of fluorescent colorant can enter in the activated cell and link to the cytoplasmic organelles and nucleic acids. The optic signals are different, what allows to distinguish morphological changes, and they are directly related to the cell functionality.

The activated neutrophils and monocytes have more "deformability", mobility and more capacity to adhesion, granulation and liberation of cytokines.

CPD values reflect morphological and functional transformation of these activated cells, and they give us very important information of the state of the cell and the state of the patient at the moment the sample is taken.

In addition, CPD support the differentiation between viral and bacterial infections or between acute and chronic infections, but also they say if there is an inflammatory condition without infection, with better diagnostic performance than conventional parameters, like total leukocytes, neutrophiles percentage and C reactive protein, that traditionally are used like acute infection markers.

Currently available literature speaks about the utility of CPD in the diagnosis, but there is no data about their possible prognostic value.

Respect from blood cells, previous COPD studies showed the relation between neutrophils/lymphocytes and platelets/lymphocytes as prognostic factors during severe exacerbations in COPD. Nowadays, it is emphasized the importance of eosinophils in COPD like predictor of exacerbation, like exacerbation severity marker and like response marker to the treatment in stable and in the exacerbation phase. It is thought that in this study the prognostic capacity of these new approaches can be better, becauseit is included the grade of activation of these cells like key parameter. This is a novel approach in the COPD field.

On the other hand, other inflammatory biomarkers (TNF-alpha, IL-6…) are expensive and less accessible in the daily clinical practice, while the evaluation of these new biomarkers of leukocytes are cheaper and more available in routine clinical practice by the blood count.

These new biomarkers could help the investigators confirming the inflammatory response and recognizing patients that could exacerbate. They also could determine the kind of their exacerbation and their prognosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• COPD diagnosis following American Thoracic Association (Am Rev Respir Dis 1987;136:225-244), FEV1/FVC < 70% (FEV1: forced expiratory volume in one second, FVC: forced vital capacity) post-bronchodilator. Acceptation to participate in the study by the informed consent.

Exclusion Criteria:

• Concomitant diseases that could interfere in the realization of the measures in the study (dementia, severe psychiatric disease, invalidating neurological diseases, important deafness, active neoplasms); patients with asthma as main diagnostic; patients with bronchiectasis as main disease or with extensive sequels of pulmonary tuberculosis; patients that in the beginning seem to be unable to follow the procedures of the study (questionnaires, pulmonary function test, 6 minutes walking test…); patients with difficulties to walk; patients with active infections or chronic inflammatory diseases; patients that reuse to participate in the study.

Related Conditions & MeSH terms

• COPD
• Pulmonary Disease, Chronic Obstructive

Locations

Country	Name	City	State
Spain	Hospital Galdakao Usansolo	Galdakao	Vizcaya

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Galdakao-Usansolo	Osakidetza

Country where clinical trial is conducted

Spain, 

References & Publications (25)

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Establish CPD (Cellular Popular Data) values for each phenotype of COPD.	CPD (Cellular Popular Data): morphological parameters measured in the blood count cells (neutrophils, lymphocytes, eosinophils and platelets).; Phenotypes of COPD described in Spanish COPD guideline (GesEPOC): No exacerbator: patient with 0-1 exacerbation per year, without admission; Exacerbator with emphysema: patient with emphysema and 2 or more exacerbations per year or 1 admission; Exacerbator with chronic bronchitis: patient with chronic bronchitis and 2 or more exacerbations per year or 1 admission; Mixed phenotype: asthma-COPD overlap: a patient with COPD and diagnostic criteria for asthma, or with a very positive bronchodilator test (increase in FEV1> 400ml and 15%) and / or peripheral blood eosinophilia greater than 300cells / mm3.	3 years
Secondary	Identify which, among the CPDs, are more relevant in relation to cellular activation (neutrophils, lymphocytes, eosinophils and platelets) both in the stage of clinical stability and during the severe exacerbation.	CPD (Cellular Popular Data): morphological parameters measured in the blood count cells (neutrophils, lymphocytes, eosinophils and platelets).; To define clinical status: Evaluation of dyspnea: mMRC (Modified Medical Research Council) scale Dyspnea only with strenuous exercise: 0 Dyspnea when hurrying or walking up a slight hill: 1 Walks slower than people of the same age because of dyspnea or has to stop for breath when walking at own pace: 2 Stops for breath after walking 100 yards (91 m) or after a few minutes: 3 Too dyspneic to leave house or breathless when dressing: 4; Functional respiratory examination (flow-volume curve, lung volumes, diffusing capacity of the lungs for carbon monoxide (DLCO).; Exercise capacity (6 minute walking test); Inflammation markers (C reactive protein, TNF-alpha, IL-6 (Interleukin 6), IL-1 (Interleukin 1), IL-8 (Interleukin 8), IGF-I and adiponectin).; Sputum culture.	3 years
Secondary	Establish new phenotypes of COPD	CPD (Cellular Popular Data): morphological parameters measured in the blood count cells (neutrophils, lymphocytes, eosinophils and platelets).; Clinical status is described in previous outcome.	3 years
Secondary	Determine the existence of an association between the level of activation of these cells in stability phase of COPD and the risk of exacerbation	CPD (Cellular Popular Data): morphological parameters measured in the blood count cells (neutrophils, lymphocytes, eosinophils and platelets).; Clinical status is described in previous outcome.	3 years