Mihailo Stjepanovic

Verifying Sarcoidosis Activity: Chitotriosidase Versus ACE in Sarcoidosis – A Case-Control Study

Summary Background: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme – ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. Methods: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. Results: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of 82.5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on 18F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P<0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ=0.272, P=0.001). Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

Assessment of health-related quality of life in end-stage chronic obstructive pulmonary disease and non-small-cell lung cancer patients in Serbia.

OBJECTIVE Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. METHOD This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. Georges Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. RESULTS The COPD group scored significantly lower compared to NSCLC patients in all SF-36 domains except for bodily pain. Additionally, a significantly higher level of depressive symptoms was observed in COPD patients. A worse physical QoL for COPD patients was independently associated with a longer duration of unemployment, a lack of wage earning, lower Karnofsky Performance Status (KPS) scores, and higher levels of depression. A worse mental QoL for COPD patients was related to a longer duration of disease, poorer KPS scores, and higher BDI scores. The independent variables significantly associated with worse physical and mental QoL of NSCLC patients were lower KPS and higher BDI scores. SIGNIFICANCE OF RESULTS A worse QoL, a significantly higher level of depressive symptoms, and adverse socioeconomic status in the COPD group imposes the need for development of more intensive psychosocial and community support for COPD patients during implementation of palliative care.

Utility of angiotensin-converting enzyme activity in aqueous humor in the diagnosis of ocular sarcoidosis

Purpose: Many studies include elevated activity of angiotensin-converting enzyme (ACE) in serum in sarcoidosis and in ocular sarcoidosis as well, but there are only a few analyzing ACE activities in aqueous humor. The aim of this study is to illuminate the diagnostic value of ACE in aqueous humor in patients with ocular sarcoidosis. Methods: We analyzed twenty patients with ocular sarcoidosis and 18 patients with nonocular involvement. All patients have biopsy-positive sarcoidosis of the lungs and/or mediastinal lymph nodes. Blood samples for ACE serum levels were obtained from all patients. Aqueous humor samples were taken by paracentesis with a 25-gauge needle in local anesthesia. With appropriate statistical tests, we compared ACE activity in serum and aqueous humor in patients with and without ocular sarcoidosis. Results: The majority of our patients with ocular sarcoidosis were female (12/20), also in the group with systemic sarcoidosis and without ocular involvement (12/6). Mean age of the whole analyzed group of sarcoidosis patients was 45 ± 6 years. There is no statistically significant difference in ACE activity in serum between two groups of patients (with and without ocular sarcoidosis). There is statistically significant difference in ACE activity in aqueous humor among patients with ocular and nonocular sarcoidosis. ACE activity in aqueous humor is significantly higher in patients with ocular sarcoidosis. Conclusion: Increased ACE activity in aqueous humor can point to a diagnosis of ocular sarcoidosis, without the need for ocular biopsy.

The Health Benefits of Vitamin D Relevant for Tuberculosis

Summary Vitamin D has an important role in numerous physiological functions. Vitamin D receptors are characterized by polymorphisms and presence in different tissues including a number of cells of the immune system. The role of vitamin D as a biological inhibitor of inflammatory hyperactivity is of particular importance. Hypovitaminosis D has been associated with many serious chronic diseases, such as autoimmune, infectious and cardiovascular diseases as well as some types of cancer. Vitamin D has an influence on the immune res ponse to tuberculosis. Calcitriol (1,25-dihydro xycholecalciferol), the major active form of vitamin D, has shown in vitro activity against Mycobacterium tuberculosis. It has been found that susceptibility to chronic mycobacterial infections is strongly correlated with a low vi tamin D intake and particular VDR alleles. Vitamin D deficiency might predispose the individuals infected with Myco bacterium tuberculosis to develop tu-ber culosis. Calcitriol binds to vitamin D receptors and modulates immune responses by regulating the transcription of genes responsive to vitamin D. Faster conversion of sputum mycobacterial culture in patients with pulmonary tuberculosis is associated with being a carrier of the t allele of the T a q I vitamin D receptor polymorphism. On the contrary, slower spu tum culture conversion in pulmonary tuberculosis has been found in the carriers of the f allele of the FokI vitamin D receptor polymorphism. The results of in vitro studies, clini-cal research and population studies indicated that vitamin D deficiency might be a strong risk factor for developing TB. Vitamin D is an inexpensive, easily accessible vitamin, relevant for the prevention of tuberculosis. In addition, vitamin D could contribute to the success of tuberculosis treatment.

Postponed diagnosis of alpha-1 antitrypsin deficiency

Milica Stojković-Lalošević1, Mihailo Stjepanović2, Nataša Čolović3,4, Jasmina Marić-Živković2, Violeta Mihailović-Vučinić2,3, Mirjana Stojković1,3 1Clinical Center of Serbia, Clinic of Gastroenterology and Hepatology, Belgrade, Serbia; 2Clinical Center of Serbia, Clinic of Pulmology, Belgrade, Serbia; 3University of Belgrade, School of Medicine, Belgrade, Serbia; 4Clinical Centre of Serbia, Clinic of Hematology, Belgrade, Serbia

Administering the Sarcoidosis Health Questionnaire to sarcoidosis patients in Serbia

Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.