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The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

Sarkoidoza je retka multisistemska granulomatozna bolest nepoznate etiologije. Karakteriše je stvaranje granuloma, koji se mogu javiti u bilo kom delu tela, a najčešće se javljaju u plućima i limfnim čvorovima. Pacijenti često pate od kašlja, nedostatka daha, bolova u grudima i izraženog umora i preti im rizik od razvoja fibroze pluća ili nepovratnog oštećenja drugih organa. Kod mnogih pacijenata bolest spontano prođe, često i bez kliničke dijagnoze, dok kod 10–30% slučajeva sarkoidoza postaje hronična i progresivna, i ponekad dovodi do smrti. Smrtnost je relativno mala, od 1-8%, zavisno od intenziteta bolesti, starosti pacijenta, pola i etničke pripadnosti. Prema brojnim studijama, vitamin D i sarkoidoza su u bliskoj vezi. Sarkoidoza se najčešće javlja u zimskim mesecima kada je nivo vitamina D nizak. Dalje, sarkoidoza je češća u oblastima koje su dalje od ekvatora. Nedostatak vitamina D i rizik od razvoja sarkoidoze je uobičajen kod tamno pigmentiranih pojedinaca i posebno je visok kod Afro-Amerikanaca koji žive na severnim geografskim širinama i koji imaju veću učestalost nedostatka vitamina D. Kod njih je sarkoidoza ozbiljna multisistemska bolest sa hroničnim tokom. Uloga molekularnih markera u deficijenciji vitamina D, odnosno varijanti u genima koji kodiraju za proteine uključene u metabolizam vitamina D, je nedovoljno istražena u etiologiji sarkoidoze. Smatra se da brojni proteini, među kojima su CYP2R1, DBP, CYP27B1 i VDR imaju ulogu u metabolizmu i signalnim putevima vitamina D. Naime, nakon primarne aktivacije vitmina D u koži, pro- vitamin podleže dvostrukoj hidroksilaciji. Prava se odigrava u jetri posredstvom enzima CYP2R1, a druga u bubrezima, posredstvom CYP27B1 enzima. Vitamin D-vezujući protein (DBP) je glavni nosač vitamina D, koji vezuje metabolite vitamina D i transportuje ih kroz cirkulaciju do ćelija. Receptor za vitamin D (VDR) pripada familiji nuklearnih receptora i nakon vezivanja liganda – aktivne forme vitamina D, stvara heterodimer sa ret, Sarcoidosis is a rare multisystem granulomatous disease of unknown etiology. It is characterized by the formation of granulomas, which can occur in any part of the body, most commonly occurring in the lungs and lymph nodes. Patients often suffer from coughing, shortness of breath, chest pain, and severe fatigue and are at risk of developing lung fibrosis or irreversible damage to other organs. In many patients, the disease resolves spontaneously, often without clinical diagnosis, while in 10-30% of cases, sarcoidosis becomes chronic and progressive, sometimes leading to death. Mortality is relatively low, from 1-8%, depending on the intensity of the disease, the patient’s age, gender and ethnicity. According to numerous studies, vitamin D and sarcoidosis are in close relationship. Sarcoidosis most commonly occurs in the winter months when vitamin D levels are low. Further, sarcoidosis is more common in areas beyond the equator. Vitamin D deficiency and the risk of sarcoidosis are common in dark pigmented individuals and are particularly high in African Americans living in northern latitudes and with a higher incidence of vitamin D. For those individuals sarcoidosis is a serious multisystemic disease with a chronic course. The role of molecular markers in vitamin D deficiency, that is, variants in genes encoding for proteins involved in vitamin D metabolism, has not been sufficiently investigated in the etiology of sarcoidosis. A number of proteins, including CYP2R1, DBP, CYP27B1, and VDR, are thought to play a role in the metabolism and signaling pathways of vitamin D. Namely, after primary activation of vitamin D in the skin, pro-vitamin D undergoes double hydroxylation. The first one is taking place in the liver by the CYP2R1 enzyme and the other one is in the kidney by the CYP27B1 enzyme. Vitamin D-binding protein (DBP) is a major carrier of vitamin D, which binds all vitamin D metabolites and transports them through the circulation to the cells. The vitamin D re

Idiopatska plućna fibroza (IPF) ima zajedničke faktore rizika sa karcinomom pluća, posebno nesitnoćelijskim, kao i značajne sličnosti u svom patofizološkom procesu, pri čemu su oba oboljenja povezana sa lošim ishodom. Cilj ove studije bio je da se procene parametri inflamacije (C reaktivni protein - CRP, serum amiloid A1 - SAA1, ligand programirane ćelijske smrti 1 - PD-L1), oksidativnog stresa i lipidnog statusa, kao potencijalni dijagnostički i prognostički biomarkeri kod idiopatske plućne fibroze i karcinoma pluća, kao i da se uporede sličnosti i razlike između ove dve bolesti. Metode: Ovim istraživanjem obuhvaćeno je 30 pacijenata sa IPF i 115 pacijenata sa karcinomom pluća, lečenih na Klinici za pulmologiju, KCS. Pored kliničkih i parametara disajne funkcije (spirometrija, difuzija, telesna pletizmografija), određivani su serumski parametri inflamacije (CRP, SAA1, PD-L1), oksidativnog stresa i antioksidativne zaštite, lipidnog statusa, vitamin D. Rezultati: Pacijenti sa IPF imali su značajno niže koncentracije prooksidativno-antioksidativni balans (PAB) (P<0,001), O2-.i totalni oksidativni status (TOS) (P<0,01) u odnosu na obolele od karcinoma pluća. IPF imali su značajno višu koncentraciju CRP u odnosu na pacijente sa adenokarcinomom pluća, a značajno nižu u odnosu na skvamocelularni i mikrocelularni karcinom pluća. Koncentracija SAA1 je bila povišena pod obe ispitivane grupe pacijenata, ali bez značajne razlike između njih. Vrednosti sPD-L1 bile su značajno povišene i kod pacijenata sa IPF 297,5 ng/l (117,7-545,9 ng/l) i kod obolelih od karcinoma pluća 182,84 ng/L (100,7-303,4 ng/L), a koje su značajno veće u odnosu na zdravu kontrolnu grupu 89,9 ng/L (57,5–119,7ng/l), P <0,01. Pacijenti sa IPF imali su značajno više koncentracije PD-L1 u odnosu na adenokarcinom, dok se koncentracije nisu značajno razlikovale u odnosu na skvamocelularni i mikorocelularni karcinom pluća. Oboleli od IPF imali su tešku deficijenciju vitamina D (11,0 ng/m -ug/L,) uz značajno razl, diopathic pulmonary fibrosis (IPF) has common risk factors with lung cancer, in particular with non-small cell lung cancer (NSCLC), and significant similarities in its pathobiology process, both diseases associated having poor outcome. The aim of this study was to evaluate the parameters of inflammation (C reactive protein - CRP, serum amyloid A1 - SAA1, programmed death-ligand 1 - PD-L1), oxidative stress and lipid status, as potential diagnostic and prognostic biomarkers in idiopathic pulmonary fibrosis and lung cancer, along with evaluation of the relating similarities and differences between those two diseases. Methods: This study enrolled 30 patients with IPF and 115 patients with lung cancer, diagnosed and treated at the Pulmonology Clinic, Clinical Center of Serbia. In addition to clinical and respiratory function parameters (spirometry, diffusion, body plethysmography), serum parameters of inflammation (CRP, SAA1, PD-L1), oxidative stress and antioxidant protection, lipid status, vitamin D were determined. Results: IPF patients had significantly lower concentrations of pro-oxidant-antioxidant balance (PAB) (P <0.001), O2- and total oxidative status (TOS) (P <0.01) compared with lung cancer patients. They had a significantly higher CRP concentration compared to patients with lung adenocarcinoma, and significantly lower than squamous cell and small cell lung cancer as well. The SAA1 concentration was elevated in both investigated patient groups (IPF, lung cancer), but without a significant difference between them. The sPD-L1 values were significantly increased in patients with IPF 297.5 ng/l (117.7-545.9 ng/l) and in patients with lung cancer 182.84 ng/L (100.7-303,4 ng/L), both significantly higher compared to a healthy control group of 89.9 ng/L (57.5-119.7ng/l), P <0.01. Patients with IPF had significantly higher levels of PD-L1 than adenocarcinoma, while concentrations did not differ significantly from squamous cell- and small cell lung cancer patients. Pa

Uvod/Cilj: Hronična opstruktivna bolest pluća (HOBP) predstavlja značajan javno zdravstveni problem u celom svetu jer su njena učestalost i posledice u stalnom porastu, naročito u zemljama sa značajnom populacijom pušača. Procene oboljevanja za 2010.godinu su ukazale na 384 miliona slučajeva HOBP uz godišnji mortalitet od 2,9 miliona ljudi [1-3]. Hronična opstruktivna bolest pluća (HOBP) se karakteriše ograničenjem protoka vazduha koje nije potpuno reverzibilno. Ograničenje protoka vazduha je obično progresivno i udruženo sa poremećenim inflamacijskim odgovorom pluća na štetne čestice ili gasove [4,5]. Pacijente obolele od HOBP odlikuje stanje pojačane inflamacije i oksidativnog stresa, pojačane proteolize ekstracelularnog matriksa i neravnoteže u proteaza/antiproteaza sistemu, uz prateće patomorfolološke promene u smislu destrukcije alveola i remodelovanje disajnih puteva. Multikomponentna priroda bolesti podrazumeva pored patoloških promena u disajnom stablu i plućima, i sistemske efekte sa zahvatanjem drugih organskih sistema: kardio-vaskularnog sistema, mišića i kostiju, metabolizma, kognitivnih svojstva i raspoloženja. Cij ovog istraživanja je bio da se ispitaju nivoi pokazatelja sistemske inflamacije i sistema proteaza/antiproteaza i utvrdi njihova povezanost sa pokazateljima plućne funkcije i kliničkim karakteristikama pacijenata sa hroničnom opstruktivnom bolesti pluća. Metod: Ovim istraživanjem su bili obuhvaćeni svi pacijenti sa dijagnozom hronične opstruktivne bolesti pluća koja je postavljena prema GOLD kriterijumima (engl. Global Initiative for Chronic Obstructive Disease - GOLD) [1]) i lečeni su u periodu od maja 2017.godine do januara 2018.godine na Odeljenje za astmu, HOBP i hroničnu respiracijsku insuficijenciju Klinike za pulmologiju KCS. Učestvovalo je ukupno 98 ispitanika, starijih od 40 godina, pušači i bivši pušači, u stabilnoj fazi bolesti, bez drugog respiratornog oboljenja. Kontrolnu grupu je činilo 47 zdravih ispitanika uparenih po polu i g, Introduction / Aim: Chronic Obstructive Pulmonary Disease (COPD) is a significant public health issue with a constant increase in disease incidence, especially in countries with a significant population of smokers. Predictions for year 2010 were 384 million cases of COPD with an annual mortality of 2.9 million people [1-3]. Chronic obstructive pulmonary disease (HOBP) is characterized by a limitation of airflow that is not completely reversible. The limitation of airflow is usually progressive and associated with an abnormal inflammatory response to the fumes or gases [4,5]. Patients with COPD are characterized by a state of increased inflammation and oxidative stress, enhanced extracellular matrix degradation and imbalance in the proteasis/antiproteasis system, with accompanying pathomorphologic changes of alveolar destruction and airway remodeling. Multicomponent nature of the disease includes pathological changes in the respiratory tract, as well as systemic effects with the involvement of other organ systems: cardio-vascular system, osteosceletal, metabolism, cognitive properties. The aim of this study was to asses the levels of systemic inflammation and the possible imbalance in protease / antiprotease system and to determine their relation to lung function parameters and clinical characteristics of patients with COPD. Method: This study included all patients diagnosed with COPD according to the Global Initiative for Chronic Obstructive Disease (GOLD) [1], and treated in the period from May 2017 to January 2018 in the Department of Asthma, COPD and chronic respiratory insufficiency in the Clinic for pulmonology, Clinical center of Serbia, Belgrade. Study included 98 subjects, aged 40 and over, smokers and former smokers, in a stable phase of COPD, with no other respiratory disease. Healthy control group included 47 subjects. All subjects completed pulmonary function testing (spirometry, diffusion capacity for carbon monoxide (CO), and body plethysmography), COP

Matrix metaloproteinases (MMPs) and their specific inhibitors - tissue inhibitors of matrix metalloproteinases (TIMPs) play an important role in pulmonary extracellular matrix destruction. Sarcoidosis is an inflammatory disease affecting multiple organs. It has been reported that MMP-9 and TIMP-1 levels were increased in bronchoalveolar lavage fluid and induced sputum of sarcoidosis patients. The aim of our study was to evaluate MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations and MMP-9/TIMP-1 ratio in sarcoidosis patients, their relationship with inflammatory markers and their ability do predict the existence of disease. We included 101 sarcoidosis patients and 50 healthy subjects. Serum samples were analyzed. Besides routine biochemical parameters, high-sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations were measured. MMP-9 (P lt 0.05), hsCRP, SAA and TIMP-1 (P lt 0.001) concentrations were significantly increased in patients whereas MMP-9/TIMP-1 complex was higher in patients, but with marginal significance. In sarcoidosis, TIMP-1 correlated significantly positively with inflammatory parameters (P lt 0.05). Uni-variate analysis showed that MMP-9, TIMP-1, hsCRP and SAA had the ability to predict the existence of sarcoidosis. In the model consisted of MMP- 9, TIMP-1, hsCRP and SAA, only SAA remained significant predictor of disease (P lt 0.01). Results showed the significance of MMP-9 and TIMP-1 in sarcoidosis., Matriks metaloproteinaze (MMP) i tkivni inhibitori matriks metaloproteinaza (TIMP) imaju značajnu ulogu u destrukciji plućnog ekstracelularnog matriksa. Sarkoidoza je inflamatorno oboljenje koje zahvata različite organe. Utvrđeno je da su koncentracije MMP-9 i TIMP-1 povećane u bronhoalveolarnom lavatu i sputumu pacijenata sa sarkoidozom. Cilj naše studije je bio da se odrede koncentracije MMP-9, TIMP-1 i MMP-9/TIMP-1 kompleksa, MMP- 9/TIMP-1 odnosa u sarkoidozi, njihova povezanost sa parametrima inflamacije, kao i njihov potencijal za predviđanje postojanja bolesti. Ispitivanjem su obuhvaćeni 101 pacijent sa sarkoidozom i 50 zdravih ispitanika. Analizirani su uzorci seruma. Pored rutinskih biohemijskih parametara, merene su koncentracije visoko-osetljivog C-reaktivnog proteina (hsCRP), serumskog amiloida A (SAA), MMP-9, TIMP-1 i MMP-9/TIMP-1 kompleksa. MMP-9 (P lt 0,05), hsCRP, SAA i TIMP-1 (P lt 0,001) su bili značajno veći kod pacijenata dok je koncentracija MMP-9/TIMP-1 kompleksa bila veća, ali sa graničnom značajnošću. U sarkoidozi, TIMP-1 je značajno pozitivno korelirao sa inflamatornim parametrima (P lt 0,05). Uni-varijantna analiza je pokazala da su MMP-9, TIMP-1, hsCRP i SAA imali značajan potencijal za predviđanje postojanja bolesti. U modelu koji je sadržao MMP-9, TIMP-1, hsCRP i SAA, samo SAA je ostao značajan u ovom predviđanju (P lt 0,01). Rezultati pokazuju značaj MMP-9 i TIMP-1 u sarkoidozi.

Uvod: Sarkoidoza je multisistemska bolest nepoznate etiologije koja se karakteriše prisustvom nekazeifikujućih granuloma u tkivima i organima. Složena patogenetska osnova sarkoidoze uslovljava nepostojanje jedinstvenog dijagnostičkog testa za sarkoidozu. Neophodno je utrditi koja dijagnostička metoda i na koji način najbolje odražava tok bolesti, i koji bi od kliničkih parametara najbolje to mogli da predvide. Materijal i metode: Opservacijsko (deskriptivno) kliničko istraživanje (studija preseka) obavljeno je u Klinici za pulmologiju Kliničkog centra Srbije. Prospektivnom analizom je obuhvaćen uzorak od 571 bolesnika sa bronhoskopski i histološki verifikovanom sarkoidozom. Svim bolesnicima je uzeta detaljna anamneza sa procenom kliničkih simptoma, urađena radiografija grudnog koša i laboratorijske analize, kao i bronhoskopija sa biopsijom. Dobijeni rezultati su kodirani, uneti u bazu podataka i analizirana je statistička povezanost pojedinih varijabli laboratorijskih, kliničkih, radiografskih i endoskopskih karakteristika sarkoidoze. Cilj ispitivanja bio je utvrditi povezanost kliničkih, radiografskih i bronhoskopskih nalaza kod obolelih od sarkoidoze, u cilju procene kliničkog toka i aktivnosti bolesti. Rezultati: Bilo je više žena (66,1%) nego muškaraca (33,9%). Odnos polova iznosio je 1,94 u korist žena. Kod većine bolesnika sa plućnom sarkoidozom dominantni simptomi i znaci su bili: suv i uporan kašalj (501-88,2%), promene na koži (564-98,8%) Najveći broj bolesnika je bio u prvom stadijumu bolesti, a najmanje ih je bilo u trećem i četvrtom stadijumu. Kod muškaraca je registrovana statistički značajno veća aktivnost angiotenzin konvertujućeg enzima (ACE) i hitotriozidaze. Visoko je statistički značajna razlika u aktivnosti hitotriozidaze u serumu između bolesnika sa aktivnom i neaktivnom sarkoidozom..., Introduction. Sarcoidosis is a multisystemic disease of unknown aetiology which is characterized by presence of non-caseating granulomas in various tissues and organs. Complex pathogenetic basis of the sarcoidosis is causing non existence of unique diagnostic test for sarcoidosis. It is necessary to determine which diagnostic test and in what way reflects the course of the disease and which of the clinical parametars are the best in its prediction. Matherial and methods. Observational (descriptive) clinical study (crosssectional study) was performed in Clinic for Pulmonary Diseases of Clinical Center of Serbia. The prospective analysis included 571 patient with bronchoscopically and histopathologically verified sarcoidosis. In all patients, detailed anamnesis was taken, with assessment of clinical symptoms, then chest radiography and laboratory analyses, as well as bronchoscopy with biopsy. Results were coded, entered into database and statistical significance of correlation between variableslaboratory, clinical, radiographic and endoscopic findings-was analyzed with appropriate statistical tests. Results. There were more women (66.1%) then men (33.9%). Gender ratio was 1.94 in favor of women. In most patients with pulmonary sarcoidosis dominat symptoms and signs were: dry, persistent cough (in 501 patient-88.2%) and skin changes (in 564 patients-98.8%). Most of the patients were in the first stage of the disease and much less in the third and fourth stage. Statistically significantly higher activity of both angiotensine-converting enzyme (ACE) and chitotriosidase in serum was noticed in men. Highly statistically significant is the difference in serum chitotriosidase activity between patients with active and inactive sarcoidosis. Serum ACE activity is also statistically significantly different between patients with active and inactive disease. The highest chitotriosidase activity is verified in patients in the second radiographic stage of sarcoidosis...