New Morphological Parameters of the Leukocyte (PCDs) as Prognostic Markers in Community Acquired Pneumonia (CAP)

Community-acquired pneumonia (CAP) has a high incidence of 2-8 cases per 1000 inhabitants per year and a mortality rate of around 5%. Mortality in admitted patients is10-25%, and is much higher in those requiring admission to intensive care (ICU). Most patients hospitalized for CAP respond satisfactorily to treatment, but 10-15% experience therapeutic failure and 6% may develop a rapid and progressive deterioration that can be life-threatening. Mortality from CAP occurs mainly in patients with therapeutic failure. The prognostic factors of mortality have been related to the germ-host binomial. Despite the emergence of antibiotic resistance, there are studies that show that mortality is more associated with patient-dependent factors than with germ resistance. For the management of CAP, it is essential to improve the microbiological diagnosis and the assessment of its severity, which will allow the choice of antimicrobial agents, establish the need for hospital admission, monitoring and care during admission, the appropriate time for hospital discharge, as well as post-discharge management. Determining the etiologic agent of CAP remains problematic, due to failure to detect the microorganism with the usual diagnostic methods. To establish the severity of CAP, severity scales have been created that allow predicting the patient's evolution. The best known are: PSI, CURB-65, SCAP score, and ATS / IDSA. The objectives of stratifying patients with CAP are multiple: defining which patients can be managed out-of-hospital, establishing the patients who require greater monitoring in intermediate respiratory care units (ICUs) or ICUs, establishing severity models to select patients for whom perform new diagnostic tests or therapeutic trials. The prognostic scales measure the physiological effect of the infection on the host but not the inflammatory response mechanisms against the microorganism.

A better understanding of the early inflammatory response may have clinical significance determined by greater therapeutic efficacy in patients with more severe CAP. Microbial invasion of lung tissue causes an inflammatory response aimed at limiting the progression of the infection and destroying the microorganism. The objective of this response is to facilitate the arrival of leukocytes and other inflammatory biomarkers to exercise their defense function. Among the biomarkers we can highlight C-reactive Protein (CRP), studied for the diagnosis and monitoring of inflammatory processes, and with which a certain relationship has been established with the severity of CAP. PCT, referred to as a sensitive marker of severity in bacterial infection and sepsis, and as a guide to adjust antibiotic treatment in patients with CAP. Pro-adrenomodulin (ProADM) has been associated with a prognostic marker in patients with sepsis and as a useful marker in the risk stratification of patients with CAP. Plasma levels of inflammatory mediators appear to correlate with the severity of sepsis or pneumonia.

The correct diagnosis of infections by the clinic, biochemical and microbiological markers can be expensive and time consuming. It is important to look for new and low-cost alternatives to evaluate this condition, with the aim of making an early and timely diagnosis and evaluation and instituting the best therapeutic strategy and follow-up. Among these new alternatives, the "Cellular Popular Data" (CPD) stand out, which are morphological parameters of different types of leukocytes. The CPDs of the XN analyzers (Sysmex Corporation, Kobe, Japan) report quantitative information on the morphological and functional characteristics of leukocytes. They are morphological parameters that characterize neutrophils, lymphocytes, and monocytes and classify them according to their volume, shape, granularity, and their nucleic acid content. The composition of activated cell membranes is different from that of resting cells, due to the expression of receptors and signaling molecules on their surface, in response to activation. This membrane is more sensitive to analyzer reagents, and more fluorescent dye can penetrate the activated cell, and bind to the cytoplasmic organelles and nucleic acids. The optical signals are different, which makes it possible to distinguish the morphological changes produced and that are directly related to the functionality of the cell. Activated neutrophils and monocytes are characterized by increased "deformability", mobility, and their ability to adhere, granulate, and release cytokines.

The CPD values reflect the morphological and functional transformation of these activated cells, offering very valuable information on the state of the cell and the patient at the time of obtaining the sample. Recent studies have shown that these parameters are valuable for the detection and control of infections and inflammation. Neutrophil structural parameters NE-SSC, (NEUT GI granularity index) and NE-SFL (NEUT RI reactivity index) could predict the appearance of later-stage infection markers, such as the presence of immature granulocytes, suggesting that they can be used to detect bacterial infections very early. It has been shown to be useful in acute bacterial infection, particularly in the differentiation of bacterial infection and early detection of sepsis. The mean volume of the neutrophil and its variability are more sensitive indicators of bacteremia than the leukocyte count and the percentage of neutrophils. Neutrophils in sepsis are larger and their volumes more heterogeneous than in the healthy population; the same happens to monocytes, larger and more heterogeneous than in localized infections, and in the ROC analysis they had the highest sensitivity for detection of sepsis. Lymphocyte CPDs show specific changes in viral infection, providing potential for differential diagnosis between viral and bacterial infection. Together, the CPDs support the differentiation between viral and bacterial infections, or between acute or evolving infections, and if there is an inflammatory condition without infection, with better diagnostic performance, especially in postsurgical bacterial infection, than the conventional parameters.

The available literature has focused on the potential usefulness of CPD in diagnosis, but we do not have data on prognostic value or its applicability to pneumonia. The classical inflammatory biomarkers are expensive and often not accessible in clinical practice, while the evaluation of new leukocyte markers through hematimetry analysis, cheaper and more accessible in clinical practice, can help to monitor the inflammatory response and recognize to patients who may have poor evolution. No study, to date, has related all these parameters (CPDs) together with the severe evolution of pneumonia or mortality, nor have clear cut-off points been established for each of them. We propose an observational study, in which these markers are related to the severity and prognosis of CAP, and a comparison between them, in addition to incorporating these biomarkers into the prognostic rules currently in use and seeing how their predictive capacity is modified.