Procalcitonin and Respiratory Tract Infections

Procalcitonin is a peptide biomarker used in the diagnosis of a number of infectious conditions. Detection of procalcitonin indicates the presence of inflammation, and is thus often used to diagnose respiratory tract infections.

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Procalcitonin structure and production

Made up of a protein structure containing 116 amino acids, procalcitonin acts as a substrate for production of calcitonin – a hormone responsible for producing C-cells of the thyroid gland and involved in maintaining calcium and phosphate homeostasis.

Procalcitonin is formed by the cleavage of pre-procalcitonin with the aid of an endopeptidase enzyme. The level of procalcitonin in the serum of a healthy individual is usually below 0.01 µg/L.

Other than playing a role in calcitonin production and its up/down-regulation, procalcitonin also responds to infectious stimuli. This makes the protein a candidate of interest for several clinical and diagnostic applications.

Procalcitonin as a biomarker

Scientists employ several biomarkers such as C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and differential white blood cell counts to confirm the diagnosis of several infectious diseases. In certain cases, symptoms and the laboratory results complement each other well, and physicians can confidently make the diagnosis.

Often, however, this is not the case due to the non-specificity of such biomarkers. The biochemical pathways in the human body can act differently depending on the situation, and one biomarker can be affected in multiple different conditions.

When symptoms are passive in nature, it becomes extremely difficult to diagnose the disease accurately. As such, an effective and timely management of the disease may not be easily met.

Additionally, as the results of these tests may take significant amount of time (ranging from several hours to a day) a need for a rapid diagnostic biomarker arises. Such need is filled in by procalcitonin.

Empirical studies have shown that procalcitonin levels in serum increase rapidly in response to bacterial infections and inflammations, while the same does not occur in casea of viral or non-infectious inflammations.

Apart from this, the latent response time of procalcitonin in a bacterial infection is much shorter. This makes procalcitonin a biomarker of choice in certain conditions, including sepsis, pneumonia, bloodstream infections, renal infections, and meningitis, among others.

Correlation of procalcitonin with respiratory tract infections

While the use of procalcitonin is relatively well-established for some conditions, it is under exploration for others. Respiratory tract infections are one of them.

Based on clinical observations in several patients that procalcitonin levels rise quickly in individuals with invasive bacterial infection such as community-acquired bacterial pneumonia, procalcitonin behavior has been examined.

It is generally believed by researchers that the procalcitonin level not only rises during the infection, but also rapidly declines when the patient is responding well to antibacterial treatment. This correlation, if validated, can be a boon not only for diagnosis, but also for understanding the prognosis of the disease in response to antimicrobial therapy.

It has been postulated that procalcitonin levels may guide the initiation and discontinuation of antibiotic treatments in respiratory infections. This, in turn, can be beneficial as the timely discontinuation of antibiotic therapy helps in reducing associated adverse effects and mortality. If proven reliable, the use of procalcitonin could reduce the ‘clinical judgment’ factor in the management of the respiratory tract infections.

Research and perspectives

Numerous clinical trials have been conducted in order to understand the behavior of procalcitonin in respiratory tract infections. While the results of some studies reinforced the hypothesis of correlation between serum procalcitonin level and bacterial infections, others yielded opposing outcomes.

The variability could be the result of several confounding covariates including, but not limited to, sample size, treatment setting (hospital, outpatient, or primary care), other coexisting conditions, concomitant medications, and age range of the subjects across the trials.

To get a bigger and conclusive picture, a systematic review was conducted for 26 randomized, controlled clinical trials across 12 different countries in 2017. The pooled data from 6,708 study subjects were analyzed for studying the patterns, if any, and for drawing a community-wide conclusion. The data revealed a clinically-significant decrease in the mortality in a procalcitonin-guided arm (8.6%) compared to the usual care arm (10%).

No significant difference was observed between both the arms in terms of treatment failures. It was also observed that the type of clinical setting was not a salient variable when studying procalcitonin behavior.

Additionally, the type of respiratory tract infection had less impact on the overall results. Antibiotic exposure, however, was found to be significantly lower in subjects in the procalcitonin-guided arm compared to the usual care arm (a mean reduction of 2.4 days of antibiotic exposure).

Even though not sufficiently conclusive, these results indicate some amount of benefit when using procalcitonin as a guide along with other clinical tools.