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

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.