Chitotriosidase plays an important role in the innate and acquired immune response and its presence has been reported in many respiratory diseases like interstitial lung diseases, asthma, chronic obstructive lung disease, bronchopulmonary dysplasia, cystic fibrosis and pulmonary infections, including tuberculosis [11, 12]. Pulmonary infections present an emerging problem, with approximately 450 million people affected worldwide, with more than 4 million deaths every year, therefore need for additional tools in solving this problem seems to be reasonable [13]. Moreover, world population is aging, which is a growing risk factor for immunosuppression that can cause tuberculosis [14]. It has been shown that CHT activity is increased and correlates with the disease severity in pulmonary tuberculosis. It is known that chitotriosidase is released in serum from pulmonary granuloma. Activated M. tuberculosis and macrophages play an important role in granuloma formation. Macrophage activation brings to interferon delta and tumor necrosis factor alpha (TNFα) production, which both cause increased serum levels of chitotriosidase. Chitotriosidase serum level tends to decline accompanying with inflammation during standard six months treatment regimen as was shown in our results [15]. Among all respiratory diseases, CHT activity was first described in sarcoidosis [16]. In active phase of sarcoidosis, increased levels of CHT were noticed and correlate with the radiological stage of disease. Chitotriosidase level in sarcoidosis is nearly ten times higher than in healthy controls and six times greater than in tuberculosis [17], and was low at the time of remission while enhanced in time of chest X-ray worsening [18, 19]. According to the smear findings, previous papers reported that chitotriosidase level was significantly higher in smear negative and culture positive comparing with smear negative and culture negative patients [20]. Our results emphasizes that positive sputum smear for AFB were found in more than a half of our patients (91; 61.1%) which corresponds with positive solid cultures in 146 (98%). Chitotriosidase activity levels of both smear positive and smear negative patients decreased after 6 months treatment and approached normal levels [21] as was shown in our results. Moreover, significantly decrease of CHT activity was shown in treatment of new TB cases comparing with previously treated patients in line with findings in other published papers [20, 21]. CHT is expressed in various cells including neutrophils, lung macrophages, tissue macrophages and epithelial cells in the lungs and intestine. Neutrophils and macrophages release CHT after toll-like receptor (TLR) stimulation, while macrophages also release CHT after stimulation with interferon (IFNγ), (TNFα), granulocyte macrophage colony-stimulating factor (GM-CSF) [22].
Our results showed that CHT activity is associated with extension of radiographic patterns like cavitary lesions and spotted shadows. Majority of our patients manifested bilateral cavitary lesions (85%) conclusive for extensive tuberculosis, as shown before [21]. Although pleural effusion was found in 16 (11%) of our patients with elevated serum CHT level, pleural fluid CHT was not analyzed, but it is investigated in TB and non-TB pleural effusions [23]. Authors demonstrated that pleural fluid CHT level was significantly higher in tuberculosis than in non-TB pleural effusion. Positive correlation was found between pleural fluid CHT and adenosine deaminase (ADA), which was used as diagnostic marker for TB firstly. In other mycobacterial diseases like leprosy significantly higher level of CHT were also noticed [24]. On the contrary to chronic infections like pulmonary tuberculosis, in acute pulmonary infections such as those caused with Pseudomonas aeruginosa and Klebsiella pneumoniae, decrease level of CHT were observed because of neutrophil elastase presence and cleavage of CHT [25]. Recently published papers confirmed that lower level of chitinase protein at the beginning of TB treatment presents biomarker of unfavorable treatment outcome in tuberculosis connected with treatment failure, disease recurrence, adverse events or death which was not shown in our study group [26].
This study contributed to increasing overall knowledge and follow up studies can be conducted to understand the further associations. It provided important information for clinical management planning and future improvements of TB prevention and control. To the best of our knowledge, the present study is the first investigation of CHT activity in tuberculosis patients in the Serbia and among a few studies worldwide.