Acute respiratory infections are common worldwide, and in many countries constitute a major cause of mortality and morbidity. The underlying pathogenic agents behind acute respiratory infections vary geographically, but the clinical importance of early diagnosis is universal. Two major reasons for the importance of early diagnosis are firstly to minimize time from start of symptom until initiation of proper medical therapy to reduce risks of protracted infection, sepsis/mortality, and late sequelae. A second reason is to avoid improper use of antibiotics in cases where this is not indicated, emphasized by an increased universal problem with antibiotic resistance. Within a few years after the discovery of penicillin, resistance to penicillin was observed and today antibiotic resistance has become a substantial clinical problem. Bacterial infections have thus again reoccurred as a major threat to our health. To preserve the effectiveness of antibiotics it is important to use antibiotics more selectively and avoid unnecessary use. Biomarkers, which in early stage of an infection can distinguish between bacterial and viral infection could lead to a more selective use of antibiotics.

Since isolation of the disease-causing microorganism is usually too time consuming to be useful for early diagnosis, other biomarkers are used clinically to distinguish viral infections not requiring antibiotic treatment from bacterial infections in early phases of the infection. Such biomarkers usually include a combination of white blood cell count, neutrophil count, C-reactive protein, and less frequently procalcitonin (PCT), heparin binding protein (HBP) or calprotectin.

Procalcitonin (PCT) is a precursor to the hormone calcitonin, the latter being involved in calcium homeostasis. Together with CRP, white blood cells and neutrophils, procalcitonin is one of the markers most widely used to distinguish between bacterial and viral infections. Heparin binding protein (HBP) and calprotectin are expressed mainly in neutrophil granulocytes. HBP is stored in azurophil granules while calprotectin is stored in the cytosol. Both are used as markers of neutrophil activation. Calprotectin is one of the most abundant proteins in the cytosol of neutrophil granulocytes, where it accounts for 40–50% of the total protein content. Calprotectin is released upon activation and turnover of neutrophils and is recognized as an important marker for neutrophil mediated inflammation.

Bacterial and viral infections cause an acute phase response which will counterattack the infection and reduce the damage. The infection leads to an activation of the innate immune system which is an early defence mechanism. The major functions of the innate immunity include the recruitment of immune cells to the site of infection, activation of the complement cascade and activation of white blood cells to eliminate the microorganisms. This is a rapid process and the neutrophil is the first cell to reach the affected location14. Neutrophil activation markers will be released from the neutrophils upon activation. These activation markers are stored in granulae or cytoplasm and can be rapidly released from the neutrophils. As there is no need for de novo synthesis, a neutrophil marker should be an earlier marker of neutrophil activation caused by bacterial infections in comparison with formation of new white blood cells or synthesis of proteins.

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Journal of Clinical Chemistry and Laboratory Medicine