PCT, a protein of 116 amino acids with a molecular weight of 13 kDa, was discovered 25 years ago as a prohormone of calcitonin produced by C-cells of the thyroid gland [
16]. Under normal physiological conditions, PCT is stable in human body [
17]. PCT is intracellularly cleaved by proteolytic enzymes to generate the active hormone. Circulating levels of PCT in healthy subjects are below detection limit. It was found in 1993 that the serum PCT level is elevated in patients with bacterial infection [
18]. Since then PCT has become an important protein in the detection and differential diagnostics of inflammatory states [
3‐
5]. In microbial infections and in various forms of inflammation, circulating levels of PCT increase to several thousand-fold of its normal level [
18,
19]. In this case, PCT is produced by other tissues, especially adherent monocytes and macrophage-activated adipocytes [
19]. This increase correlates significantly with the severity of the condition and with mortality. However, PCT level does not increase markedly in patients with autoimmune inflammation or virus infection [
3‐
5,
7]. PCT is released within four hours in the initial stages of infection, and peaks in eight hours. Then PCT level begins to decrease when the infection is under control. The half-life of PCT is between 20 and 24 hours [
17,
20]. The serum PCT level is interfered by hormone levels and can easily be detected in a short time [
21]. Small doses of intravenous lipid polysaccharide in healthy volunteers could induce the production of PCT [
21]. The serum PCT can be detected after two hours and the PCT level increased rapidly in the following six to eight hours [
21]. The PCT level reaches the peak l2 to 48 hours later and returns to normal in two to three days [
22]. Respiratory tract infections induce the acute attacks of asthma. Bacterial infection seems to just play a minor role in acute exacerbations of asthma, while virus infection plays a major role [
1,
23,
24]. So many patients with acute asthma don’t need antibiotics. Antibiotic therapy benefits those patients with bacterial infection by alleviating respiratory tract spasm and shortening the duration of acute exacerbation, while it harms patients without bacterial infection by worsening their condition and increasing the chance of selective bacterial resistance [
2,
23]. The physicians often determine whether patients suffer from respiratory tract bacterial infections on the basis of sputum characteristics, body temperature, WBC, CRP and other indicators. However, clinical signs and symptoms of bacterial infection and other non-bacterial infections are often indistinguishable, making it difficult for physicians to determine accurately in clinical practice whether there is a bacterial infection in respiratory tract of patients [
25]. In general, bacterial culture is much accurate for diagnosis. However, bacterial culture takes too long time and it is difficult to obtain accurate information on etiology from asthma patients. Therefore bacterial culture is not suitable for the emergent treatment of asthma. And the positive rate of bacterial culture was limited by the hospital medical standards, medical technicians operating experience and other factors, which makes bacterial culture a less effective measure. When there is no effective approach for physicians to determine accurately whether there is a bacterial infection, physicians are more likely to use antibiotic therapy for most acute asthma patients, leading to antibiotics abuse and subsequent bacterial resistance [
2]. Recent studies showed that serum PCT level has higher sensitivity in determining whether bacterial infection exist in community acquired pneumonia, ventilator associated pneumonia and acute exacerbation of chronic obstructive pulmonary disease and can guide the usage of antibiotics [
6,
8,
26]. The serum PCT level is also an early diagnostic index and can identify sepsis from systemic inflammatory response syndrome (SIRS) [
3,
7,
14]. PCT test can objectively determine the severity of sepsis and be closely related to the severity of multiple organ dysfunction syndrome (MODS) [
3,
7,
14]. Physicians can judge the direction of progression and evaluate the therapeutic effectiveness by continuously monitoring the serum PCT level [
27,
28].
In this study, we treated the patients with antibiotics according to PCT serum level. Antibiotics usage was strongly discouraged when the serum PCT concentration was below 0.1 μg/L; antibiotics usage was discouraged when the serum PCT concentration was between 0.1 μg/L and 0.25 μg/L; and antibiotics usage was encouraged when the serum PCT concentration was greater than 0.25 μg/L. The results showed that many patients in the PCT group did not need antibiotics. The antibiotic usage rate was lower than that of the control group and the outcome of treatment was not significantly affected, especially for patients with mild to moderate asthma. Patients with mild to moderate asthma in the control group did not need antibiotics, which implicated that PCT could play an important role in guiding the use of antibiotics. Although there was no significant statistical difference in the rate of antibiotics usage in patients with severe to critical asthma between the two groups, the trend of antibiotics usage in PCT group deceased in comparison with the control group. Accordingly, we believe that PCT is a serum marker for the appropriate selection of antibiotics in the treatment of acute attack of asthma. PCT can be quickly tested to help determine whether there is bacterial infection and whether antibiotics are needed for the emergency treatment of patients.
In this study, the serum PCT level and IL-6 level were correlated, while there is no correlation between the serum PCT level and levels of other inflammatory indicators, including hsCRP, TNF-α, and WBC. Cellular IL-6 level rises sharply after exposure to bacterial toxins, falls rapidly as time elapses and has a longer half-life than TNF-α [
29,
30]. As a critical mediator of survival following pulmonary infection and sepsis, it protects patients from death by augmenting neutrophil killing of bacteria, enhancing the release of adrenaline and cortisol, as well as selectively activating the coagulation system [
31,
32]. IL-6 has the best discriminative power in sepsis and non-infectious SIRS, with sensitivity above 80% and specificity above 70%, which is higher than conventional inflammatory markers including CRP and TNF-α [
33]. There are limitations in the sensitivity and specificity of hsCRP, TNF-α, and WBC in judging whether patients with asthma are also suffering from bacterial infection. Both PCT and IL-6 levels of patients with severe to critical asthma in the PCT group were higher than that of patients with mild to moderate asthma in the same group. It implicated that patients with severe to critical asthma may be more prone to bacterial infection than patients with mild to moderate asthma. Zhang et al. found that bacterial colonization of the lower airways was common in patients with chronic severe asthma and was linked to the duration of asthma and the exacerbations in past years [
34,
35]. Therefore, PCT test prevents antibiotics usage mostly in patients with mild to moderate asthma but without bacterial infection, while most patients with severe to critical asthma do suffer from bacterial infection and need to be treated with proper antibiotics.