Characteristics of Patients with Sarcoidosis with Emphasis on Acute vs. Chronic Forms-A Single Center Experience.

Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease.

Rethinking Aspergillosis in the Era of Microbiota and Mycobiota.

Aspergillosis encompasses a wide range of clinical conditions based on the interaction between Aspergillus and the host. It ranges from colonization to invasive aspergillosis. The human lung provides an entry door for Aspergillus. Aspergillus has virulence characteristics such as conidia, rapid growth at body temperature, and the production of specific proteins, carbohydrates, and secondary metabolites that allow A. fumigatus to infiltrate the lung's alveoli and cause invasive aspergillosis. Alveolar epithelial cells play an important role in both fungus clearance and immune cell recruitment via cytokine release. Although the innate immune system quickly clears conidia in immunocompetent hosts, A. fumigatus has evolved multiple virulence factors in order to escape immune response such as ROS detoxifying enzymes, the rodlet layer, DHN-melanin and toxins. Bacterial co-infections or interactions can alter the immune response, impact Aspergillus growth and virulence, enhance biofilm formation, confound diagnosis, and reduce treatment efficacy. The gut microbiome's makeup influences pulmonary immune responses generated by A. fumigatus infection and vice versa. The real-time PCR for Aspergillus DNA detection might be a particularly useful tool to diagnose pulmonary aspergillosis. Metagenomics analyses allow quick and easy detection and identification of a great variety of fungi in different clinical samples, although optimization is still required particularly for the use of NGS techniques. This review will analyze the current state of aspergillosis in light of recent discoveries in the microbiota and mycobiota.

Influence of Achalasia on the Spirometry Flow-Volume Curve and Peak Expiratory Flow.

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.

Phenotype and Clinicoradiological Differences in Multifocal and Focal Bronchiectasis.

Introduction: Bronchiectasis is a chronic progressive respiratory disease characterized by permanent dilatation of the bronchi. It is a complex condition with numerous different etiologies, co-morbidities, and a heterogeneous presentation. As we know, there is a lack of studies that describe the differences and compare the characteristics between focal and multifocal bronchiectasis. The aim of this study is to identify differences in clinical characteristics presentation, severity or distribution in focal and multifocal bronchiectasis, and prognostic implications. Methods: 126 patients with computed tomography (CT)-verified bronchiectasis were enrolled. Baseline characteristics that included age, sex, smoking history, and respiratory symptoms were recorded, with special attention paid to hemoptysis appearance, body mass index, and comorbidities. The type of bronchiectasis determined by CT scan and the modified Reiff scores indicating radiological severity were recorded. Patients were divided in two groups (I is focal and II is multifocal). Results: There were no statistically significant differences in age, smoking status, comorbidity, and BMI between the two groups. Multifocality was associated with a significantly higher proportion of females (p = 0.014), the rate of hemoptysis (p = 0.023), and the number of hospitalizations, but not of exacerbations and prevalence of immunodeficiency (p = 0.049). Significantly, a high number of subjects with multifocality had bronchiectasis of moderate severity, and post-infective and asthma-associated phenotypes were the dominant in this group. Unexpectedly, the cystic and varicose radiological phenotype (which need more time to develop) were more dominant in the focal group. The cylindrical phenotype was equally observed in the multifocal and focal groups. Conclusions: Our study suggests that multifocality is not related to age, number of exacerbations, or radiological phenotype, but it seems to be associated with the clinical post-infective phenotype, immunodeficiency, frequent hospitalizations, and severity. Thus, the presence of multifocal bronchiectasis may act as a biomarker of severity and poor outcomes in these patients.

Correlation between Radiological Characteristics, PET-CT and Histological Subtypes of Primary Lung Adenocarcinoma-A 102 Case Series Analysis.

Background and Objectives: Lung cancer is the second most common form of cancer in the world for both men and women as well as the most common cause of cancer-related deaths worldwide. The aim of this study is to summarize the radiological characteristics between primary lung adenocarcinoma subtypes and to correlate them with FDG uptake on PET-CT. Materials and Methods: This retrospective study included 102 patients with pathohistologically confirmed lung adenocarcinoma. A PET-CT examination was performed on some of the patients and the values of SUVmax were also correlated with the histological and morphological characteristics of the masses in the lungs. Results: The results of this analysis showed that the mean size of AIS-MIA (adenocarcinoma in situ and minimally invasive adenocarcinoma) cancer was significantly lower than for all other cancer types, while the mean size of the acinar cancer was smaller than in the solid type of cancer. Metastases were significantly more frequent in solid adenocarcinoma than in acinar, lepidic, and AIS-MIA cancer subtypes. The maximum standardized FDG uptake was significantly lower in AIS-MIA than in all other cancer types and in the acinar predominant subtype compared to solid cancer. Papillary predominant adenocarcinoma had higher odds of developing contralateral lymph node involvement compared to other types. Solid adenocarcinoma was associated with higher odds of having metastases and with higher SUVmax. AIS-MIA was associated with lower odds of one unit increase in tumor size and ipsilateral lymph node involvement. Conclusions: The correlation between histopathological and radiological findings is crucial for accurate diagnosis and staging. By integrating both sets of data, clinicians can enhance diagnostic accuracy and determine the optimal treatment plan.

The Effects of Six Weeks Pulmonary Rehabilitation on Functional and Psychological Outcomes in Long-COVID Patients: Preliminary Results from Serbian Single Center Study.

Background and Objectives: In this study, we aimed to evaluate the effects of six weeks of pulmonary rehabilitation on functional and psychological outcomes in long-COVID patients. Material and Methods: The prospective clinical study included 46 patients that were diagnosed with COVID-19. A respiratory rehabilitation program was implemented for six weeks. Further valuables were tested before the beginning of the rehabilitation program (admission) and six weeks after (discharge): SpO2, heart rate, respiratory rate, Visual Analogue Scale (VAS) score, Borg score, Sit-to-Stand (StS) test number of repetition, distance of 6-Minute Walking Test (6MWT), Patient Health Questionnaire (PHQ) 9 score and Generalized anxiety disorder (GAD) anxiety score. These parameters were tested before the rehabilitation program on admission and at discharge and after the rehabilitation program on admission and at discharge. The results were presented with standard descriptive and analytical methods. Differences between the continuous variables before and after physical rehabilitation intervention were tested using the Wilcoxon test. Graphical analysis is presented with a box plot. Results: On discharge, in comparison with admission, the values of SpO2 were significantly lower (p = 0.007) before the 6MWT, and VAS scores were significantly higher (p = 0.036), while after the 6MWT, VAS scores were significantly lower (p < 0.001) as were Borg scores (p = 0.016). On discharge, in comparison with admission, the respiratory rate was significantly higher (p = 0.005) before the StS test, and Borg scores were significantly lower (p = 0.001), while after the StS test, SpO2 levels were significantly higher (p = 0.036) and VAS scores were significantly lower (p < 0.001), as were Borg scores (p = 0.008). After discharge, the values of the StS test were significantly higher (p = 0.011), PHQ9 scores were significantly lower (p < 0.001) and GAD anxiety scores were significantly lower as well (p = 0.005), while the distances measured in meters on the 6MWT were significantly increased (p < 0.001). Conclusions: A structured rehabilitation program in our study was shown to have beneficial effects on physiological, psychological and functional improvements in patients with long-COVID, and therefore it is advisable for these patients.

Effective Differences between 2D and 3D Planned Brachytherapy in Lung Cancer: An Institutional Retrospective Study.

Background and Objectives: Advanced lung cancer is usually manifested by endoluminal tumor propagation, resulting in central airway obstruction. The objective of this study is to compare the high dose rate brachytherapy treatment outcomes in non-small-cell lung cancer (NSCLC) depending on the treatment planning pattern-two-dimension (2D) or three-dimension (3D) treatment planning. Materials and Methods: The study was retrospective and two groups of patients were compared in it (a group of 101 patients who underwent 2D planned high-dose-rate endobronchial brachytherapy (HDR-EBBT) in 2017/18 and a group of 83 patients who underwent 3D planned HDR-EBBT between January 2021 and June 2023). Results: In the group of 3D planned brachytherapy patients, there was a significant improvement in terms of loss of symptoms of bronchial obstruction (p = 0.038), but no improvement in terms of ECOG PS (European Cooperative Oncology Group Performance Status) of the patient (p = 0.847) and loss of lung atelectasis (if there was any at the beginning of the disease) (p = 0.781). Two-year overall survival and time-to-progression periods were similar for both groups of patients (p = 0.110 and 0.154). Fewer treatment complications were observed, and 91.4% were in 3D planned brachytherapy (BT) patients. Conclusions: Three-dimensionally planned HDR-EBBT is a suggestive, effective palliative method for the disobstruction of large airways caused by endobronchial lung tumor growth. Independent or more often combined with other types of specific oncological treatment, it certainly leads to the loss of symptoms caused by bronchial obstruction and the improvement of the quality of life of patients with advanced NSCLC. Complications of the procedure with 3D planning are less compared to 2D planned HDR-EBBT.

Diagnosis of Chronic Pulmonary Aspergillosis: Clinical, Radiological or Laboratory?

Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40-50%. The disease is characterized by slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient's condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA.

Invasive Diagnostic Procedures from Bronchoscopy to Surgical Biopsy-Optimization of Non-Small Cell Lung Cancer Samples for Molecular Testing.

Background and Objectives: Treatment of advanced lung cancer (LC) has become increasingly personalized over the past decade due to an improved understanding of tumor molecular biology and antitumor immunity. The main task of a pulmonologist oncologist is to establish a tumor diagnosis and, ideally, to confirm the stage of the disease with the least invasive technique possible. Materials and Methods: The paper will summarize published reviews and original papers, as well as published clinical studies and case reports, which studied the role and compared the methods of invasive pulmonology diagnostics to obtain adequate tumor tissue samples for molecular analysis, thereby determining the most effective molecular treatments. Results: Bronchoscopy is often recommended as the initial diagnostic procedure for LC. If the tumor is endoscopically visible, the biopsy sample is susceptible to molecular testing, the same as tumor tissue samples obtained from surgical resection and mediastinoscopy. The use of new sampling methods, such as cryobiopsy for peripheral tumor lesions or cytoblock obtained by ultrasound-guided transbronchial needle aspiration (TBNA), enables obtaining adequate small biopsies and cytological samples for molecular testing, which have until recently been considered unsuitable for this type of analysis. During LC patients' treatment, resistance occurs due to changes in the mutational tumor status or pathohistological tumor type. Therefore, the repeated taking of liquid biopsies for molecular analysis or rebiopsy of tumor tissue for new pathohistological and molecular profiling has recently been mandated. Conclusions: In thoracic oncology, preference should be given to the least invasive diagnostic procedure providing a sample for histology rather than for cytology. However, there is increasing evidence that, when properly processed, cytology samples can be sufficient for both the cancer diagnosis and molecular analyses. A good knowledge of diagnostic procedures is essential for LC diagnosing and treatment in the personalized therapy era.

Knowledge is the most powerful tool in the fight against tuberculosis.

INTRODUCTION: In October 2022, after almost two years, tuberculosis reclaimed its first place as the world's deadliest infectious disease, replacing COVID-19. Since knowledge is the most powerful tool to combat any disease, the primary goal of our study was to assess patients' knowledge of tuberculosis and its relationship to their socio-demographic status. METHODOLOGY: This cross-sectional study included 1,067 respiratory patients who were surveyed between November 2021 and June 2022 at the Institute for Pulmonary Diseases of Vojvodina (Serbia). They completed a questionnaire designed for this study. RESULTS: The majority of patients (53.7%) were female; over two-thirds (70.8%) were ≥ 60 years; every fifth (23.2%) was either with or without primary school; every third (33.3%) was financially poor. Although the majority of patients (97.8%) were aware that tuberculosis is an infectious disease, only 44.2% knew the etiology. Around 3/4 (72.6%) were aware of a tuberculosis vaccine. Hospitalized patients had better knowledge that the vaccine helps prevent tuberculosis than ambulatory patients (p = 0.047). Only 16% of patients in both groups knew that tuberculosis incidence is decreasing in Serbia (p = 0.074). Good knowledge about tuberculosis was reported by 71.5%. Hospitalized patients showed better knowledge than ambulatory patients (p = 0.032). Patients with a higher level of education and higher monthly income were independent predictors of better knowledge of tuberculosis. CONCLUSIONS: The study underlines the need to promote knowledge about tuberculosis, particularly among chronic patients, socially vulnerable and refugees, especially in light of the pandemic and emerging economic problems in the region.

King's Sarcoidosis Questionnaire (KSQ) - Validation study in Serbian speaking population of sarcoidosis patients.

INTRODUCTION: Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England-King's Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment. OBJECTIVE: The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated. METHODS: A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ - new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale-MRC, Borg Dyspnea Scale and 15D as general questionnaire. RESULTS: KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.

The Predictive Value of Risk Factors and Prognostic Scores in Hospitalized COVID-19 Patients.

INTRODUCTION: Risk stratification in patients with COVID-19 is a challenging task. Early warning scores (EWSs) are commonly used tools in the initial assessment of critical patients. However, their utility in patients with COVID-19 is still undetermined. AIM: This study aimed to discover the most valuable predictive model among existing EWSs for ICU admissions and mortality in COVID-19 patients. MATERIALS AND METHODS: This was a single-center cohort study that included 3608 COVID-19 patients admitted to the University Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia, between 23 June 2020, and 14 April 2021. Various demographic, laboratory, and clinical data were collected to calculate several EWSs and determine their efficacy. For all 3608 patients, five EWSs were calculated (MEWS, NEWS, NEWS2, REMS, and qSOFA). Model discrimination performance was tested using sensitivity, specificity, and positive and negative predictive values. C statistic, representing the area under the receiver operating characteristic (ROC) curve, was used for the overall assessment of the predictive model. RESULTS: Among the evaluated prediction scores for 3068 patients with COVID-19, REMS demonstrated the highest diagnostic performance with the sensitivity, PPV, specificity, and NPV of 72.1%, 20.6%, 74.9%, and 96.8%, respectively. In the multivariate logistic regression analysis, aside from REMS, age (p < 0.001), higher CT score (p < 0.001), higher values of urea (p < 0.001), and the presence of bacterial superinfection (p < 0.001) were significant predictors of mortality. CONCLUSIONS: Among all evaluated EWSs to predict mortality and ICU admission in COVID-19 patients, the REMS score demonstrated the highest efficacy.

Hematological Indices Are Useful in Predicting Complications of Liver Cirrhosis.

BACKGROUND: Liver cirrhosis is the final stage of chronic liver disease. We aimed to evaluate non-invasive scores as predictors of complications and outcome in cirrhotic patients. METHODS: A total of 150 cirrhotic patients were included. Models for end-stage liver disease (MELD), albumin-bilirubin (ALBI) score, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MoLR), and neutrophil-lymphocyte-albumin ratio (NLA) scores were tested in relation to the development of complications and mortality using receiver operating characteristic (ROC) curves. RESULTS: The ROC curve analysis showed (area under the curve) AUC values of NLR, NLA, ALBI, and MELD of 0.711, 0.730, 0.627, and 0.684, respectively, for short-term mortality. MELD, ALBI, and NLA scores showed a statistically significant correlation with hepatic encephalopathy (p = 0.000 vs. 0.014 vs. 0.040, respectively), and the MELD cut-off value of 16 had a sensitivity of 70% and a specificity of 52% (AUC: 0.671, 95% CI (0.577-0.765)). For the assessment of the presence of ascites, the AUC values for NLA and MoLR were 0.583 and 0.658, respectively, with cut-offs of 11.38 and 0.44. CONCLUSIONS: MELD, ALBI, and NLA are reliable predictors of hepatic encephalopathy. NLA and MoLR showed a significant correlation with the presence of ascites, and MELD, ALBI, NLR, and NLA have prognostic value to predict 30-day mortality in cirrhotic patients.

What is the right moment for noninvasive ventilation in amyotrophic lateral sclerosis?

Introduction: The most common cause of death in patients with amyotrophic lateral sclerosis (ALS) is respiratory failure, often in the period of 2-5 years, with a small percentage of patients surviving up to 10 years or more. The aim of the study was to evaluate the significance of pulmonary function tests in prediction of mortality and definition of indications for noninvasive mechanical ventilation (NIMV). Material and methods: This retrospective-prospective study was performed at the Clinic of Pulmonology, Clinical Centre of Serbia in the period from January 2015 to December 2017. Patients with diagnosis of ALS established according to El Escorial criteria were included. Results: The study included 76 patients with ALS, 50 (65.85%) with spinal and 26 (34.2%) with bulbar form of disease. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were higher in spinal form of ALS, and the difference was statistically significant when compared to bulbar form. Form of disease, FVC < 70%, maximum inspiratory pressure (PImax) < 50 and maximum expiratory pressure (PEmax) < 50 were significant factors for survival. The patients with bulbar form of disease had 2.174 (95.0% CI: 1.261-3.747) higher risk for death. Conclusions: Our study points to the significance of timely application and early start of NIMV in patients with ALS as an important approach to defer functional impairment, which would mean that the criteria, in our country, for application of these devices must be changed, not only regarding the value of current functional diagnostic tests used in everyday practice in patients with ALS but also in regard to the introduction of new diagnostic tests, such as sniff nasal inspiratory pressure and/or polysomnographic testing.

The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity.

BACKGROUND: Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations. METHODS: In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed. RESULTS: COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV1, FEV1/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found. CONCLUSIONS: COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity.

Large-Vessel Giant Cell Arteritis following COVID-19-What Can HLA Typing Reveal?

Giant cell arteritis (GCA) is an immune-mediated vasculitis that affects large arteries. It has been hypothesized that viruses may trigger inflammation within the vessel walls. Genetic studies on human leukocyte antigens (HLAs) have previously reported HLA-DRB1*04 as a susceptible allele for GCA and HLA-DRB1*15 as a protective allele for GCA. Here, we discuss the clinical presentation, laboratory findings, HLA class I and class II analysis results, and management of patients with extracranial large-vessel (LV) GCA, detected at least six weeks after recovery from COVID-19. This case series encompassed three patients with LV-GCA (two males and a female with an age range of 63-69 years) whose leading clinical presentation included the presence of constitutional symptoms and significantly elevated inflammatory markers. The diagnosis of LV-GCA was confirmed by CT angiography and FDG-PET/CT, revealing inflammation in the large vessels. All were treated with corticosteroids, while two received adjunctive therapy. By analyzing HLA profiles, we found no presence of the susceptible HLA-DRB1*04 allele, while the HLA-DRB1*15 allele was detected in two patients. In conclusion, LV-GCA may be triggered by COVID-19. We highlight the importance of the early identification of LV-GCA following SARS-CoV-2 infection, which may be delayed due to the overlapping clinical features of GCA and COVID-19. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the role of specific HLA alleles in patients who developed GCA following COVID-19.

Diagnosis and treatment of adult asthma patients in Serbia: a 2022 experts group position statement.

INTRODUCTION: Asthma is the most common non-communicable chronic lung condition across all ages. Epidemiological data indicate that many asthma patients in Serbia remain undiagnosed and untreated. The implementation of recent global advances in asthma management is limited due to the lack of a systematic approach, drug availability and regulatory affairs. In addition, the global coronavirus disease pandemic has posed a significant challenge, particularly in resource-limited settings. AREAS COVERED: In this paper, we propose an algorithm for treating adult asthma patients in Serbia. We performed PubMed database search on published asthma clinical trials and guidelines from 1 January 2015 to 10 March 2020. The consensus process incorporated a modified Delphi method that included two rounds of e-mail questionnaires and three rounds of national asthma expert meetings. We focus on 1) objective diagnosis of asthma, 2) the implementation of up-to-date therapeutic options, and 3) the identification and referral of severe asthma patients to newly established severe asthma centers. EXPERT OPINION: Regional specificities and variations in healthcare systems require the adaptation of evidence-based knowledge. Practical, clinically oriented algorithms designed to overcome local barriers in healthcare delivery may facilitate timely and adequate asthma diagnosis and the local implementation of current advances in asthma management.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

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.

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

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.

Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population.

Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10-8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10-6) and severe COVID-19 (p = 6.88 × 10-7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 × 10-6), 5q11.2 (ESM1, p = 6.59 × 10-6), and 9p23 (TYRP1, LURAP1L, p = 8.69 × 10-6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.