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Serum Procalcitonin Level as a Predictor of Bacterial Infection in Patients with COPD Exacerbation.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of mortality and morbidity throughout the world. Although the cause of COPD exacerbations can be bacterial or viral, use of antibiotics in exacerbations remains controversial. Procalcitonin serum level dramatically increases in bacterial infections, but not in viral or noninfectious febrile diseases. The aim of this study is to investigate whether the measurement of procalcitonin can be used to differentiate bacterial from non-bacterial causes of COPD exacerbations. Materials and Methods: Sixty-eight COPD patients admitted to the emergency department of Masih Daneshvari Hospital due to COPD exacerbation were studied. At admission and before prescribing antibiotics, we obtained sputum and blood samples for sputum gram staining and culture and measured serum C-reactive protein and procalcitonin. All results were analyzed by SPSS software version 22. Results: A total of 68 patients including 51 males and 17 females were studied. From 38.2% of patients a respiratory pathogen was isolated from their sputum and 23.5% of patients had elevated serum procalcitonin values. Using Fisher exact test, we found strong correlation between elevated procalcitonin levels above 0.5 ng/ml and sputum culture results (P < 0.01). We also found strong correlation between elevated procalcitonin levels above 0.5 ng/ml with abnormal C-reactive protein levels in a group of patients with positive sputum culture, using Fisher exact test (P <0.01) Conclusion: As sputum culture and microbiologic studies are time consuming and sometimes expensive, it seems that procalcitonin could be a reliable marker of bacterial infection in COPD exacerbation, although we recommend a larger study with larger sample to consolidate the finding of this study.


INTRODUCTION
Chronic Obstructive Pulmonary Disease (COPD), as it is currently defined, is a spectrum of lung abnormalities characterized physiologically by persistent airflow obstruction. COPD currently is the fourth leading cause of death in United States and is a major cause of mortality and morbidity throughout the world (1). It has been suggested that COPD will be the third cause of death in 2020 (2). More than 3 million people died of COPD in 2012 which accounts for 6% of all deaths globally (3). During the course of the disease there are periods of worsening symptoms called exacerbations. Exacerbations of COPD have major impact on disease control since they cause worsening of patient health, admission and readmission and disease progression (4). Exacerbations of COPD are complex events which are usually in correlation with increased airway inflammation, increased mucus and TANAFFOS Abedini,et al. 113 Tanaffos 2019; 18 (2): [112][113][114][115][116][117] worsening of airflow obstruction beside increasing cough and wheezing. Since COPD accompanies other comorbidities such as coronary heart disease, congestive heart failure, pneumonia and pulmonary embolism, it is imperative to differentiate these diseases from acute exacerbations (5). The Global Initiative for Obstructive Lung Disease states, "An exacerbation of COPD is an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication" (5,6).
COPD exacerbations are mostly due to respiratory viral infections, although bacterial infections and environmental factors such as air pollution and ambient temperature change can eventuate in worsening of symptoms (6).
Rhinovirus is the most common isolated viral pathogen and can be detected up to a week after an exacerbation onset (6,7). Exacerbations can be associated with increased sputum production and, if purulent, some studies showed increased bacteria in sputum (7,8).  (13,14).
Procalcitonin, precursor of hormone calcitonin, is produced by C cells in thyroid and also by neuroendocrine cells in lung and intestine and its normal serum levels in healthy individuals is less than 0.1 ng/ml (15).
Procalcitonin serum level dramatically increases in bacterial infections but not in viral or noninfectious febrile diseases (16,17). Several studies showed superiority of procalcitonin as a diagnostic marker of bacterial infection relative to other biomarkers such as ESR and C-reactive protein (16,18,19). Although procalcitonin levels of less than 0.5 ng/ml are contradicted with bacterial infections by most authors, evidence of infection has been seen with procalcitonin levels of less than 0.5 ng/ml (20).
The aim of this study was to investigate whether the measurement of procalcitonin can be used to differentiate bacterial from non-bacterial causes of COPD exacerbations, thus helping in treatment plan. Pseudomonas aeruginosa was the most common isolated pathogen with a prevalence of 13.2% and Escherichia coli (E.

MATERIALS AND METHODS
coli) was isolated from only one patient (Figure 1).    Because diagnosing bacterial infections are of great importance, procalcitonin seems an attractive test to diagnose bacterial infections since its serum levels are elevated as early as 3 to 4 hours after infection, which is much faster than other inflammatory markers such as ESR and C-reactive protein (27). For decades, guidelines recommend use of prophylactic antibiotic therapy in exacerbation of COPD based on Anthonisen criteria reported by patients and includes increased dyspnea, increased sputum volume or increased sputum purulence (28). Although prescribing antibiotics based on Anthonisen criteria is simple and practical, many authors believe that using these criteria results in antibiotic overuse without thorough microbiologic studies (12,29).