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      Efficacy of serum chitotriosidase activity in early treatment of patients with active tuberculosis and a negative sputum smear

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          The results of sputum culture for Mycobacterium tuberculosis must be awaited in most cases, which delays the start of treatment in patients with sputum smear-negative pulmonary tuberculosis. We investigated whether plasma chitotriosidase activity is a strong marker for early diagnosis of tuberculosis in patients for whom a bacillus smear is negative and tuberculosis culture is positive.


          Clinical, radiological, and laboratory features were evaluated in 75 patients, 17 of whom were diagnosed as having active tuberculosis by negative acid-fast bacillus smear and positive culture, 38 as having sequel tuberculosis which was radiologically and microbiologically negative, and 20 who served as healthy controls. Serum chitotriosidase activity levels were measured in both cases and controls.


          The mean age of the cases with active pulmonary tuberculosis, cases with sequel lesions, and controls was 23 ± 2.4 years, 22 ± 1.7 years, and 24 ± 2.1 years, respectively. Serum chitotriosidase levels were 68.05 ± 72.61 nmol/hour/mL in smear-negative, culture-positive pulmonary tuberculosis cases (Group A) and 29.73 ± 20.55 nmol/hour/mL in smear-negative, culture-negative sequel pulmonary tuberculosis cases (Group B). Serum chitotriosidase levels from patients in Group A were significantly higher than in Group B and Group C. There was no statistically significant difference in serum chitotriosidase levels between cases with sequel pulmonary tuberculosis (Group B, smear-negative, culture-negative) and healthy controls (Group C).


          In patients with active tuberculosis and a negative sputum smear for acid-fast bacillus, plasma chitotriosidase activity seems to be a strong marker for diagnosis of active disease which can be used while awaiting culture results.

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          Most cited references 12

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          Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease.

          Gaucher disease (GD; glucosylceramidosis) is caused by a deficient activity of the enzyme glucocerebrosidase (GC). Clinical manifestations are highly variable and cannot be predicted accurately on the basis of the properties of mutant GC. Analysis of secondary abnormalities, such as elevated plasma levels of some hydrolases, may help to increase insight into the complicated pathophysiology of the disease and could also provide useful disease markers. The recent availability of enzyme supplementation therapy for GD increases the need for markers as early predictors of the efficacy of treatment. We report the finding of a very marked increase in chitotrisidase activity in plasma of 30 of 32 symptomatic type 1 GD patients studied: the median activity being > 600 times the median value in plasma of healthy volunteers. In three GC-deficient individuals without clinical symptoms, only slight increases were noted. Chitotriosidase activity was absent in plasma of three control subjects and two patients. During enzyme supplementation therapy, chitotriosidase activity declined dramatically. We conclude that plasma chitotriosidase levels can serve as a new diagnostic hallmark of GD and should prove to be useful in assessing whether clinical manifestations of GD are present and for monitoring the efficacy of therapeutic intervention.
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            Synthesis, sorting, and processing into distinct isoforms of human macrophage chitotriosidase.

            Chitotriosidase, the human analogue of chitinases from non-vertebrate species, has recently been identified. The macrophage-derived enzyme is remarkably heterogeneous in molecular mass and isoelectric point. The synthesis and modification of the enzyme in cultured macrophages is reported. Chitotriosidase is synthesized as a 50-kDa protein with a pI of about 6.5 and 7.2. It is predominantly secreted, but in part processed into a 39-kDa form with a pI of 8.0 that accumulates in lysosomes. In the C-terminal extension of the 50-kDa chitotriosidase, sialic-acid containing O-linked glycans are present, causing its heterogeneous acidic isoelectric point. Chitotriosidase lacks N-linked glycans and the mechanism of routing to lysosomes proves to be distinct from that of soluble, N-glycosylated, lysosomal enzymes. It was observed that, in macrophages, alternative splicing generates a distinct chitotriosidase mRNA species, encoding a 40-kDa chitotriosidase that is C-terminally truncated. This enzyme is almost identical to the 39-kDa chitotriosidase formed from the 50-kDa precursor by proteolytic processing. It is concluded that the C-terminus present in the 50-kDa chitotriosidase, but absent in the 39-kDa isoform, was found to mediate tight binding to chitin. In the blood stream the secretory 50-kDa chitotriosidase occurs predominantly, whilst in tissues the 39-kDa form is also abundant. These findings are consistent with the data on the synthesis and processing of chitotriosidase in the cultured macrophage model.
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              Identifying pulmonary tuberculosis in patients with negative sputum smear results.

              Clinicians need to decide whether to begin empiric therapy for patients who are suspected of having tuberculosis (TB) but have negative sputum smear results. Culture results may take weeks, and delaying treatment may allow further transmission of disease. To identify the clinical, demographic, and radiographic characteristics that identify smear-negative patients who have TB, and to create a TB prediction rule. Retrospective chart review. University-affiliated public hospital in San Francisco, CA, between 1993 and 1998. Forty-seven patients with TB and 141 control patients who were hospitalized with a suspicion of pulmonary TB; all had negative sputum smear results. Demographic, clinical, and radiographic variables were determined by chart review. In multivariate analysis, a positive tuberculin skin test result (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.0 to 11.9) was independently associated with an increased risk of a positive TB culture finding. A radiographic pattern not typical of pulmonary tuberculosis (OR, 0.3; 95% CI, 0.1 to 0.7) and expectoration with cough (OR, 0.3; 95% CI, 0.1 to 0.6) were predictive of a decreased risk. An interaction between HIV seropositivity and mediastinal lymphadenopathy on the chest radiograph was also associated with a positive TB culture result (OR, 7.2; 95% CI, 1.4 to 36.0). The TB prediction score (TPS) was created with widely ranging likelihood ratios that could affect the posterior probability of TB by 30-fold. The TPS put into context with the overall prevalence of TB in a given area may help clinicians decide if a patient with negative sputum smear results should start empiric antituberculous therapy or wait for culture results. These results need prospective validation.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                27 August 2012
                : 8
                : 369-372
                [1 ]Department of Pulmonary Diseases, Gulhane Medical Faculty, Ankara
                [2 ]Department of Biochemistry, Gulhane Medical Faculty, Ankara
                [3 ]Department of Pulmonary Medicine, Dr Suat Seren Education and Research Hospital for Chest Diseases and Thoracic Surgery, Izmir
                [4 ]Istanbul Gulhane Medical Faculty, Department of Pulmonary Diseases, Istanbul, Turkey
                Author notes
                Correspondence: Canturk Tasci, Gülhane Askeri Tıp Akademisi, Göğüs, Hastalıkları AD, AAnkara, Türkiye, Tel +90 31 2304 4406, Email ctasci@ 123456gata.edu.tr
                © 2012 Tasci et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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