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OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) accelerate the progressive impairment of lung function and general health. Together with maintenance therapy for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) and natural propolis have demonstrated pharmacological properties that address crucial pathophysiological processes underlying COPD and may prevent AECOPDs. This study aims at responding to dose-dependent efficacy and safety concerns regarding a propolis-NAC combination for the reduction of COPD exacerbation rates. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, phase IV trial with three treatment arms: Placebo and two active substance groups, one (AS-600) received 600 mg of NAC + 80 mg of propolis while the other (AS-1,200) received 1,200 mg of NAC + 160 mg of propolis. Following an AECOPD, frequent-exacerbation phenotype patients (n=46) were assigned a once-daily three-month therapy with the study drug and one year follow-up. The primary endpoint was the COPD exacerbation incidence rate during the follow-up period as a measure of dose-dependent efficacy of NAC-propolis combination compared to placebo. RESULTS: There was a statistically significant difference in the AECOPD incidence rate: 52.6% in patients that received placebo, 15.4% that received AS-600 and only 7.1% that received AS-1,200 (Fisher's exact test, p = 0.013). Compared to placebo, AECOPD frequency was significantly lower only in AS-1,200 (p=0.009). Compared to placebo, the relative risk for exacerbation was 0.29 in AS-600 and 0.13 in AS-1,200. No adverse events related to the treatment were reported. CONCLUSIONS: Oral combination of natural propolis with NAC confirmed formulation efficiency with a favorable safety profile. Our results need to be confirmed by larger clinical trials. [ABSTRACT FROM AUTHOR]

Introduction. COVID-19 is responsible for the current global pandemic. Globally, over 15 million people are currently infected, and just over 600,000 have died due to being infected. It is known that people with chronic illnesses and compromised immune systems can develop more severe clinical presentation. Tuberculosis (TB) is still one of the biggest epidemiological problems worldwide. Both of these diseases can be misdiagnosed and can manifest in a similar way. We will present a case study of a patient who was initially treated as a COVID-19 infection, with TB being diagnosed later on. The recovery began only after being treated for both diseases simultaneously. Case report. The patient is a 27-year-old male, non-smoker, with no history of any significant diseases. He presented with fever, fatigue and hemoptysis. Computed tomography pulmoangiography had shown massive consolidations and excavations, which could be caused by COVID-19. Despite being treated for COVID-19, there was no clinical improvement. On the follow-up chest X-ray, beside signs of COVID-19, there were also changes that could indicate TB. TB was detected in sputum, using PCR and Mycobacteria Growth Indicator Tube, and only after being treated for both diseases did his condition improve. Conclusion. There are a few reported cases of COVID-19 and TB coinfections, and we believe that there are many more patients with this coinfection being unrecognized

Sarcoidosis afflicts the central nervous system more frequently than previously believed. Neurological symptoms are present in roughly one-half of patients, and depend on the location in the central nervous system. The probability of spontaneous regression is significantly less when compared to other forms of sarcoidosis, which means that the proper diagnosis and treatment is paramount. Even when properly treated, functional defects are not uncommon. Majority of these patients require immunomodulating drugs and continuous follow-up. New immunomodulating drugs, especially biological agents, have shown to be significantly more effective, with fewer side effects, and are important when corticosteroids could not be applied. Less invasive methods, such as cerebrospinal analysis, help greatly in the diagnostics procedure, and require further research and improvement.

Introduction. COVID-19 pneumonia does not have a characteristic course and prognosis. Many facts still remain hidden, mainly why certain patients develop complications with serious tissue damage and whether it causes a permanent organ impairment. If and when will fibrosis develop in COVID-19 pneumonia requires further research, but a link between the amount of tissue afflicted and the development of fibrosis exists. Case outline. A previously healthy, non-smoker, woman with minor symptoms on admission had suddenly developed a serious respiratory insufficiency and whose radiographic finding on computed tomography scan had shown a serious progression with the development of fibrosis in a matter of days. The exact mechanism and correlation of this clinical course remains unknown; however, it is clear that the pulmonary fibrosis is caused by COVID-19 pneumonia. Follow-up computed tomography scan, performed 50 days after initial symptoms, had shown a partial regression of consolidations and post-inflammatory fibrosis. Conclusion. Pulmonary fibrosis is the most severe complication of COVID-19 infection on the respiratory system. Who, when or if a patient will develop any complication is still unclear, as well as whether these changes are reversible? Also, the number of recovered patients who later develop some chronic complications remains to be seen.

Introduction. Retroperitoneal hematoma may occur as a result of trauma, but also from rupture of arterial aneurysms (aortic or iliac), surgical complications, tumors or anticoagulation therapy. Case report. We presented a patient on permanent anticoagulation therapy. On the day of admission to our institution, the patient had the value of his INR 5.57 which required immediate suspension of the therapy. The main symptom in this patient was pain in the right inguinal canal with propagation along the right leg, which was indicated in clinical picture of spontaneous retroperitoneal haematoma. After three days the fall of hemoglobin occurred, so the additonal diagnostics was done. A computed tomography of the abdomen was performed showing well limited, large retroperitoneal hematoma (213 x 79 x 91 mm). Transfusion of concentrated red blood cells was performed twice with satisfactory correction of hemoglobin level, and four units of fresh frozen plasma. The patient was hemodynamically stabilized and discharged after a two-month long intensive care unit treatment, with the advice to use low-molecular weight heparin 2 x 0.4 mg subcutaneusly, due to persistent arrhythmia. Conclusion. In patients on anti-coagulation therapy regular monitoring of the anticoagulant status is extremely important, because of the possibility of fatal complications development, such as retroperitoneal hematoma.

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 response to tuberculosis. Calcitriol (1,25-dihydroxycholecalciferol), 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 vitamin D intake and particular VDR alleles. Vitamin D deficiency might predispose the individuals infected with Mycobacterium tuberculosis to develop tuberculosis. 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 TaqI vitamin D receptor polymorphism. On the contrary, slower sputum 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, clinical 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.

Background: Achalasia is an esophageal motor disorder characterized by aperistalsis and the failure of the relaxation of the lower esophageal sphincter. We want to find out whether external compression or recurrent micro-aspiration of undigested food has a functional effect on the airway., Methods: The aim of this research was to analyze the influence of achalasia on the peak expiratory flow and flow-volume curve. All of the 110 patients performed spirometry., Results: The mean diameter of the esophagus was 5.4 ± 2.1 cm, and nine of the patients had mega-esophagus. Seven patients had a plateau in the inspiratory part of the flow-volume curve, which coincides with the patients who had mega-esophagus. The rest of the patients had a plateau in the expiration part of the curve. The existence of a plateau in the diameter of the esophagus of more than 5 cm was significant ( p 0.003). Statistical significance between the existence of a plateau and a lowered PEF (PEF < 80) has been proven ( p 0.001). Also, a statistical significance between the subtype and diameter of more than 4 cm has been proved. There was no significant improvement in the PEF values after operation. In total, 20.9% of patients had a spirometry abnormality finding. The frequency of the improvement in the spirometry values after surgery did not differ significantly by achalasia subtype. The improvement in FEV1 was statistically significant compared to the FVC values., Conclusions: Awareness of the influence of achalasia on the pulmonary parameters is important because low values of PEF with a plateau on the spirometry loop can lead to misdiagnosis. The recognition of various patterns of the spirometry loop may help in identifying airway obstruction caused by another non-pulmonary disease such as achalasia.

Background and Objectives: induced sputum is used to assess different inflammatory phenotypes in asthma, but is not used routinely. We aimed to determine the proportion of inflammatory asthma phenotypes based on induced sputum, to find biomarkers that can discriminate between phenotypes, and to evaluate biomarkers in patients with and without biological therapy in different inflammatory asthma phenotypes., Materials and Methods: this cross-sectional study investigated clinical characteristics, asthma control tests, skin prick test, impulse oscillometry (IOS), spirometry, induced sputum, biomarkers (IgE, eosinophils, fractional exhaled nitric oxide (FeNO), serum periostin, IL-5, IL-6, IL-8, IL-17A, IL-33) in 80 asthmatics. A total of 17/80 patients were treated with biologics (10 with omalizumab, 7 with benralizumab)., Results: a total of 31% of patients had eosinophilic asthma (EA), 30% had mixed granulocytic asthma (MGA), 24% had paucigranulocytic asthma (PGA), and 15% had neutrophilic asthma (NA). The difference was found in blood eosinophils ( p = 0.002), the highest observed in EA. The cut-off ≥ 240/μL eosinophils, with 64% sensitivity and 72.7% specificity, identified EA (AUC = 0.743, p = 0.001). A higher IL-8 level was associated with NA ( p = 0.025). In 63 non-biologic asthma group, eosinophils were higher in EA than in NA, MGA, and PGA ( p = 0.012, p = 0.028, and p = 0.049, respectively). A higher IL-17A was associated with EA without biologics ( p = 0.004). A significantly higher IL-5 was found in EA treated with biologics, in comparison with EA without biologics ( p = 0.043). The number of leucocytes and neutrophils was higher in MGA without biologics ( p = 0.049, p = 0.019), while IL-5, IL-6, and IL-8 levels were higher in MGA treated with biologics ( p = 0.012, p = 0.032, p = 0.038, respectively)., Conclusions: EA and MGA were the most prevalent asthma phenotypes. Blood eosinophils can identify EA, both in patients with and without biologics. Apart from the clinical profile, a broad spectrum of biomarkers for assessing inflammatory phenotypes is necessary for an adequate therapy approach to patients with asthma.

Introduction: Sphingomonas paucimobilis can be found in air, water systems, dialysis fluid, nebulizers and laboratory instruments in hospitals. Despite its low pathogenicity, it can cause severe infections., Case Report: A 54-year-old man presented with fever, cough and pain in the right hemithorax. The laboratory results showed elevated inflammatory parameters. Chest radiography showed right upper lobe pneumonia. Empiric antibiotic therapy (cephalosporin) was prescribed. On control examination chest radiography showed incomplete regression. Chest computer tomography (CT) finding was bronchopneumonia in the right upper lobe. Bacteriological examination of fiberaspirate revealed Sphingomonas paucimobils. Trimethoprim-sulfamethoxazole was prescribed based on the antibiogram. After two weeks the control laboratory analysis was normal. The patient was fully recovered., Conclusions: Our patient had no comorbidities or malignancies, and no hospitalization in the recent past. He had a dental intervention 5 days prior to the onset of symptoms. We propose that it was an infection after the dental intervention., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Jelena Janković, Milija Gajić, Andrej Zečević, Ivan Milivojević, Ivana Buha.)

Three subtypes of achalasia have been defined using esophageal manometry. Several studies have reported that symptoms are experienced differently among men and women, regardless of subtype. All subtypes could have some impact on the appearance of respiratory symptoms and lung complications due to compression of the trachea or aspiration of undigested food. The aim of this research was to analyze the differences in respiratory symptoms and radiographic presentation of lung pathology depending on the diameter and achalasia types. One or more respiratory symptoms were reported in 48% of 114 patients, and all of them had two or more gastrointestinal symptoms. The symptom score (SS) is statistically significant for the prediction of subtype 1 (area under the curve = 0.318; p < 0.001, cut-off score of 6.5 had 95.2% sensitivity) and subtype 2 (area under the curve = 0.626; p = 0.020, cut-off score of 7.5 had 93.1% sensitivity). The most common type was subtype 2 (50.8%), and although only 14 patients had subtype 3, they had the largest esophageal diameter (mean 5.8 cm). The difference in esophageal diameter was significant between subtype 1 and 3 ( p = 0.011), subtype 2 and subtype 3 ( p = 0.011). Nine patients (6%) had mega-esophagus (four patients in type 1, three in type 2 and two in type 3). More than half of all patients (51.7%) had at least one parenchymal lung change on CT scan. Recurrent micro-aspirations led to changes in the structure of the airways and lung parenchyma such as ground glass (GGO) and nodular changes (12%) and fibrosis (14.5%), and they had higher esophageal diameters ( p < 0.001). Patients with chronic lung CT changes had significantly higher esophageal diameter than with acute changes ( p < 0.001). Awareness of the association of achalasia and lung disorders is important in early diagnosis and treatment. More than half (57.5%) of patients with achalasia had some clinical and/or structural pulmonary abnormalities. All three subtypes had similar respiratory symptoms, meaning they cannot be used to predict the subtype of achalasia; on the contrary, SS can predict the first two subtypes. A higher diameter of the esophagus is associated with chronic structural lung changes. Although unexpected, the pathological radiological findings and diameter were significantly different in subtype 3 patients, but those parameters cannot lead us to a specified subtype.

Objectives: Chronic obstructive pulmonary disease (COPD) is an irreversible disease and has influence on patients' quality of life. The aim is to investigate the influence of gender on the illness perception in COPD patients., Materials and Methods: This prospective study enrolled 151 COPD patients. For the evaluation of illness perception, we used Brief Illness Perception Questionnaire (BIPQ)., Results: Average FEV1 values were significantly different (p = 0.007) in favor of woman compared to men. There was a higher proportion of GOLD stage 3 and less stage 4 in women. We found a significant difference in total BIPQ scores between female and male patients (p = 0.008). Women gave a significantly higher score on question 6 and 8 (p = 0.003). We found a significant difference in total BIPQ scores between female and male patients. Women perceive COPD as a significantly more threatening disease and accept chronic course and long-term treatment., Conclusion: COPD is no longer a disease that predominantly affects men. BIPQ is a convenient tool for fast assessment of illness perception for COPD. Patients' perceptions of COPD is in correlation with gender and GOLD stadium. The results of this study have potential benefits in terms of health promotion and improvement of the quality of life and outcome (Fig. 4, Ref. 21).

Introduction: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity., Methodology: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB., Results: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups., Conclusions: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Ivana Buha, Vesna Skodric-Trifunovic, Marina Andelkovic, Sonja Pavlovic, Misa Vreca, Mihailo Stjepanovic, Jelena Milin-Lazovic, Marko Simic, Gordana Antonijevic, Vesna Spasovski.)

Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19., Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity., Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index ( p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) ( p < 0.0001). Serum concentrations of IgG ( p = 0.003) and IgA ( p = 0.032) were significantly lower in this group of patients. Higher total serum IgA ( p = 0.009) was associated with mortality, with no difference in serum IgG ( p = 0.115) or IgM ( p = 0.175). Lethal outcome was associated with lower complement C4 ( p = 0.013), while there was no difference in complement C3 concentration ( p = 0.135)., Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewers IJ and VC declared a shared affiliation with the authors MRS, MIS, SD-J, SP, IB, DJ, MS-L, IS, BB-N, RM, and SS to the handling editor at the time of review., (Copyright © 2022 Stjepanovic, Stojanovic, Stankovic, Cvejic, Dimic-Janjic, Popevic, Buha, Belic, Djurdjevic, Stjepanovic, Jovanovic, Stojkovic-Laloševic, Soldatovic, Bonaci-Nikolic and Miskovic.)

Background: Cough is frequent symptom in sarcoidosis and its impact on patient's quality of life (QoL) has not been adequately addressed so far., Objectives: The goal of this study was to determine the significant predictors of cough-specific and generic QoL in sarcoidosis patients., Methods: In the prospective study 275 sarcoidosis patients administered Patient Reported Outcomes instruments for measurement of dyspnea (Borg and MRC scales) and fatigue (Fatigue Assessment Scale (FAS) and Daily Activity List (DAL)), as well as patients' QoL (cough-specific Leicester Cough Questionnaire (LCQ) and generic tool - 15D). The LCQ contains 3 domains covering physical, psychological and social aspects of chronic cough. Pulmonary function tests (spirometry and diffusing capacity for carbon monoxide) and serum angiotensin converting enzyme (sACE) were also measured., Results: Dyspnea measured by Borg scale and impairment of daily activities determined by DAL instrument as well as sACE were the strongest predictors of all cough-specific QoL domains. Mental aspect of patients' fatigue was significantly correlated with all domains except with psychological LCQ domain. Regarding the generic QoL, the following significant predictors were: dyspnea measured by MRC scale, overall fatigue determined by FAS and physical domain of the LCQ., Conclusion: It is important to measure both cough-specific and generic QoL in sarcoidosis patients since they measure different health aspects and their predictors can be different. We demonstrated that physical domain of cough-specific QoL is significant predictor of generic QoL. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 158-168) ., Competing Interests: None of the authors disclosed any potential conflicts of interest, (Copyright: © 2020 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients., Methodology: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals., Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia., Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Ivana Buha, Vesna Skodric-Trifunovic, Tatjana Adzic-Vukicevic, Aleksandra Ilic, Ana Blanka-Protic, Mihailo Stjepanovic, Marina Andelkovic, Misa Vreca, Jelena Milin-Lazovic, Vesna Spasovski, Sonja Pavlovic.)

Currently, topical are studies that examine different reasons for delay of tuberculosis (TB) diagnosis and its impact on disease prognosis. The aim was to examine three time periods associated with treatment delay: patient related, health system related and total delay. This retrospective-prospective study included 100 consecutive patients hospitalized at Department of Pulmonology, Clinical Center of Serbia, in the period from March to December 2015. Study results showed median patient delay to be 92.5 days. Total delay was affected by patient related delay. Median healthcare delay was 18.5 days. Patients that reported excessive alcohol consumption were more likely to have prolonged time to seek medical help. Years of alcohol consumption yielded moderate positive correlation with patient related delay (r=0.362, p <0.001). Correlation between the number of cigarettes and patient delay was moderate, positive and statistically significant (r=0.314, p=0.001). Delay in seeking medical help was more likely in patients with negative family history of TB. There was no difference in the effect of the presence of symptoms on patient related delay (p>0.05). Clinical characteristics such as patient TB category and chest radiograph abnormalities were not associated with prolonged patient related delay (p>0.05). Study results point to the importance of health education and/or health intervention in the population group at a high risk of TB.