Elsevier

Journal of Infection

Volume 52, Issue 3, March 2006, Pages 169-177
Journal of Infection

Procalcitonin and neopterin correlation with aetiology and severity of pneumonia

https://doi.org/10.1016/j.jinf.2005.05.019Get rights and content

Summary

Objective

Clinical outcome of pneumonia depends on a multifaceted treatment approach. Not only diagnostic methods but also early indicators of the degree of inflammatory response can aid in therapeutic decisions. The objective was to evaluate the usefulness of procalcitonin and neopterin in distinguishing among aetiologies as well as severity in patients with pneumonia.

Patients

A total of one hundred sixteen patients with clinical, radiographic and microbiological diagnosis of pneumonia were grouped by aetiology, pneumonia severity index, and by the presence of unilobar or multilobar radiographic pulmonary infiltrates. Procalcitonin and neopterin were measured by immunoassays.

Results

Patients with pneumococcal pneumonia presented elevated procalcitonin and neopterin levels, being higher in bacteraemic than in non-bacteraemic pneumonia. Patients with Legionella pneumonia presented elevated neopterin levels and slightly elevated procalcitonin levels. Patients with tuberculosis and Pneumocystis jirovecii pneumonia presented elevated neopterin and low or not detectable procalcitonin. Procalcitonin and neopterin levels were increased in high-risk classes of pneumonia severity index. Both parameters yielded significant correlation to the radiographic extent and also to young age.

Conclusions

Procalcitonin and neopterin levels vary depending on age, aetiology and severity of pneumonia. Together with clinical and microbiological data, combined measurement can help to identify patients who might benefit from additional therapies.

Introduction

Pneumonia is still the leading infectious disease cause of death.1 For early and effective treatment, consistent diagnosis is essential. Despite the availability of several diagnostic and therapeutic methods, a better and more specific prediction of sepsis is still needed. Even when a correct antibiotic treatment is set up, there are patients with a poor outcome. Not only anti-microbial but also immunomodulatory therapies can condition the clinical outcome and a multifaceted treatment approach is needed.2 Scoring systems primarily measure the physiological effect of the infection on the host, not the microbial and inflammatory mechanisms of the organ injury response. Early indicators of the degree of inflammatory response can aid in therapeutic decisions. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm.

Inflammatory response in lower respiratory tract is triggered by bacterial products as lipopolysaccharide or peptidoglican, which stimulate alveolar macrophages that produce cytokines, mainly IL-1, IL-6, IL-8 and TNF-α, as well as neutrophils recruitment.3, 4 The induced reactive nitrogen species as nitric oxide (NO) may play a role in the pathogenesis of acute lung injury.5 Cytokines have been tested with the purpose of measuring inflammatory response, but they are produced locally in the lung at the site of infection and they cannot be detected in serum in large amounts.6 This compartimentalized production of cytokines may explain why their serum detection is not useful as a diagnostic method. Only interleukin-6 can be found in serum in large amounts and it has been associated with pneumococcal pneumonia7, 8 and also as a prognostic factor in severe pneumonia.9 Nevertheless, cytokines undergo a fast down regulation in serum and interpretation of results is difficult. In addition, elevated plasma levels of several cytokines are found in different stages of acute respiratory distress syndrome.10, 11

Blood levels of acute phase proteins are thought to reflect closely the acute-phase protein synthesis by mediators of the local inflammatory process.12, 13, 14, 15, 16 Their increase in serum depends on cytokines stimulus, they have a longer half-life, they are more stable in vivo and ex vivo, and laboratory tests for their measurement are easy to perform. Procalcitonin (PCT), one of the calcitonin precursor peptides, has been reported as a sensitive marker of severe bacterial infection.12, 13 There is evidence to suggest that monocyte–macrophage system cells are capable of synthesizing PCT,14 as well as other non-thyroidal tissues, mostly parenchymal cells, under the stimulus of bacterial products.15 Neopterin is a 2-amino-4-OH-pteridine16 which is produced by monocytes/macrophages17 and monocyte-derived dendritic cells18 after induction by IFN-gamma that is secreted by T lymphocytes. It has been reported to act as a mediator of cell immunity against intracellular pathogens. Both parameters seem to be involved in regulation of inducible nitric oxide synthase (iNOS) during inflammation.19, 20, 21

The aim of our study was to evaluate the usefulness of procalcitonin (PCT) and neopterin in distinguishing among aetiologies as well as severity of inflammatory response in patients with pneumonia. Disease severity and organ injury were assessed by pneumonia severity index (PSI) and by the radiographic extent of the pneumonia.

Section snippets

Methods

The study population was adult patients admitted to Emergency Department presenting clinical signs of lower respiratory tract infection and a new infiltrate on the chest radiograph. The study was approved by the institutional ethics committee, and informed consent was signed by all the patients included. At the time of arrival to the Emergency, samples were collected for microbiological diagnosis: blood cultures, sputum or bronchial lavage specimens for culture, urine for antigen detection and

Results

Patients characteristics are described in Table 1. The mean age of the patients included in the study was 56.62 years (standard deviation 19.15, 95% confidence interval for mean 53.09–60.14).

Control group showed a mean PCT value of 0.35 ng/ml (standard deviation 0.048) and mean neopterin value of 0.28 (standard deviation 0.38). The distribution of the parameters in the different groups using median and 5–95 percentiles is described in Table 2. The values of PCT and neopterin in the different

Discussion

The aim of our study was to evaluate the usefulness of PCT and neopterin in distinguishing among aetiologies as well as severity in patients with pneumonia. The utility of PCT in the diagnosis of lower respiratory tract infection has been studied in prior reports, but its correlation with severity has been mostly evaluated in ventilator-associated pneumonia and acute respiratory distress syndrome. Fewer studies have assessed the value of the combined measurement of PCT and neopterin, and its

Acknowledgements

This study was supported by grant of ‘Sociedad Española de Neumología y Cirugía Torácica’ (SEPAR).

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