Search Results (704)

Background: This study aims to examine the level of awareness, attitudes (including stigma and discrimination), and behaviors related to tuberculosis among the population of the Republic of Kazakhstan to identify priorities for raising awareness and reducing stigma. Methods: The study interviewed 2400 people from six regions of Kazakhstan using stratified random sampling based on gender and age. Respondents were chosen from cities and villages, including RK citizens over 18 who could answer questions. Additionally, 400 people with HIV, 200 drug users, 200 internal migrants, and 500 health workers were interviewed. Recruitment was done through profile organizations and the snowball method, with all participants giving informed consent. Results: The study showed different levels of knowledge about tuberculosis (TB) in Kazakhstan. Radiography was the most commonly known detection method (71–91%). Awareness of sputum testing was highest among drug users (84%) and HIV patients (77%), but lower among internal migrants (39%). Internal migrants had the most uncertainty about TB tests (17%). Stigmatizing views of TB patients existed, with 28–38% believing most people reject them. Among healthcare workers, only 38. 8% correctly identified the G-Xpert test for TB and rifampicin resistance, and over one-third misunderstood the Mantoux test’s purpose. Conclusions: The findings show a need for focused educational efforts to boost TB awareness and lessen stigma, especially among internal migrants and the general public. Vulnerable groups, like PLHIV and PWUD, have higher awareness but still encounter major barriers. Improving healthcare workers’ knowledge about TB diagnostics is also crucial. Specific communication strategies and policies are needed to improve TB detection, reduce social stigma, and improve healthcare access for at-risk groups in Kazakhstan. Full article

Background: Cupriavidus is an aerobic Gram-negative bacterium and a rare conditional pathogen that mainly infects immunocompromised patients or those undergoing invasive procedures. Methods: We present the case of a 70-year-old male with diabetes mellitus who developed septic shock following influenza A virus (IAV) pneumonia. Cupriavidus gilardii (C. gilardii) was identified in his blood and sputum samples. Through a literature review, we identified 31 reported cases of Cupriavidus infections. Clinical data, including demographic information, clinical characteristics, comorbidities, laboratory results, Cupriavidus species, treatment, and clinical outcomes, were collected. Results: Among these 32 patients (including our patient), 23 were male (71.9%) and 9 were female (28.1%). The median patient age was 32.5 (2.12–70) years. Most patients had relevant risk factors or comorbidities before Cupriavidus infection, including exposure to polluted environments and recent invasive procedures (68.9%). Among these cases, Cupriavidus pauculus was the most common strain, accounting for 56.3% of cases. The mortality rate was the highest for Cupriavidus pauculus infections. Conclusions: Cupriavidus is a rare opportunistic pathogen in patients with compromised immune function. Early identification of pathogen and timely treatment are crucial. When traditional microbiological detection methods encounter difficulties, gene sequencing can be used as an auxiliary diagnostic tool and can further predict drug resistance. Targeted anti-infection treatment is effective in most cases, but some severe infection cases may lead to death due to serious complications. Full article

Introduction: Recombinant human deoxyribonuclease I (rhDNase) cleaves DNA in mucus, facilitating increased mucociliary clearance of purulent sputum. In cystic fibrosis (CF), rhDNase improves pulmonary function and decreases exacerbations. Conversely, rhDNase use in non-CF bronchiectasis (NCFB) patients has not yielded similarly effective results. We explored the safety and feasibility of rhDNase in patients with bronchiectasis due to primary ciliary dyskinesia (PCD). Methods: In this real-life pilot study, patients with PCD received rhDNase to treat viscous mucus. We compared pulmonary function tests and pulmonary exacerbations for these patients over six months of use of rhDNase. Results: Eight PCD patients with symptomatic bronchiectasis commenced use of rhDNase at variable dosing (ranging from at least twice weekly to a full 2.5 mg dose daily). Over a six-month period, pulmonary function tests, as measured by mean FVC and FEV₁, remained relatively stable compared to prior to commencing rhDNase. Mean pulmonary exacerbations decreased from 3.1 to 2.3 in the six-month period after commencing rhDNase, as compared to the six-month period prior to rhDNase. Conclusions: Use of rhDNase in PCD patients was safe and did not adversely impact lung function or increase pulmonary exacerbations, in contrast to earlier trial results in NCFB patients with heterogeneous etiologies. Further clinical data is required to identify the population of PCD patients who can benefit from rhDNase, as well as the appropriate dosing and timing. Full article

Chronic obstructive pulmonary disease (COPD) is a major contributor to global respiratory morbidity and exhibits substantial sex- and gender-related differences in incidence, phenotype, pathophysiology, and outcomes across the life course. Historically regarded as a predominantly male disease due to higher smoking rates, COPD is now increasingly recognized among women, reflecting changing exposure patterns and enhanced diagnostic attention. Moreover, evidence indicates that women may be more biologically susceptible to the harmful effects of tobacco smoke and often develop COPD at younger ages. Clinical manifestations also differ, with women more frequently reporting dyspnea, anxiety, and depression, whereas men may exhibit more cough and sputum production. Imaging studies suggest that airway-predominant disease is more common in women, while men are more likely to demonstrate emphysema-predominant patterns. Furthermore, women face an increased risk of exacerbation, yet they are more likely to experience underdiagnosis or misdiagnosis. Treatment responses and comorbidity patterns also show sex- and gender-related variations. Despite these differences, most clinical guidelines and therapeutic strategies do not differentiate by sex and gender, highlighting a gap in personalized COPD management. Overall, growing evidence underscores the importance of incorporating sex and gender as biological and sociocultural variables in COPD research, diagnosis, and treatment. Recognizing sex/gender-specific risk profiles, symptom patterns, and disease phenotypes may improve early detection and enable more targeted, effective interventions. This narrative synthesis, derived from a meticulous search in PubMed and the critical selection of 74 articles from the 448 identified originally, integrates evidence from guideline statements, registry studies, mechanistic and preclinical research, imaging and physiology investigations, systematic reviews, and randomized controlled trials that report sex- and gender-disaggregated data. Full article

Alterations in glutathione and its metabolism contribute to oxidative stress in COPD, but the role of S-glutathionylation (PSSG) and its major regulator glutaredoxin 1 (Grx1) remains unclear. This study investigated the Grx1/PSSG axis in sputum of COPD patients and its associations with lung function and inflammation, as well as Grx1 secretion in mouse models and in cell culture. In patients with an acute exacerbation, PSSG levels were significantly decreased in sputum, while Grx1 protein and total Grx activity were increased compared to stable COPD. No differences were observed between healthy smokers and stable patients. PSSG levels correlated negatively with sputum neutrophils, IL-8 and IL-1β, but positively with lung function parameters, whereas Grx1 showed the opposite pattern. Enhanced Grx1 levels were also detected in bronchoalveolar lavage fluid from mice exposed to cigarette smoke or chronic pulmonary inflammation. Moreover, epithelial cells and macrophages secreted Grx1 in response to pro-inflammatory mediators, and Grx1 modulated expression of MMPs by macrophages in vitro and in vivo. In conclusion, this study identifies the Grx1/PSSG redox axis as a potential important factor in COPD pathogenesis, especially during exacerbations. Further research should examine in more detail the intricate relation of extracellular Grx1 with lung function and inflammation. Full article

Pulmonary histoplasmosis is often misdiagnosed as or coinfected with pulmonary tuberculosis (TB). This study aims to analyze the misdiagnosis or co-occurrence of published cases of pulmonary TB and pulmonary histoplasmosis. Cases of histoplasmosis with dissemination were excluded, as it affects other organs. Systematic research was conducted using PubMed, EBSCOhost, ProQuest, BioRxiv, and MedRxiv databases. Twenty-seven articles were included, covering a total of 51 cases. Males were predominantly affected, with a median age of 54 years. Exposure to caves and farming occupations were identified as the primary sources of infection (61.9%). The most common clinical symptoms were fever (80%) and cough (82.5%). Laboratory tests revealed culture positivity in 77.1% of cases, with sputum being the most frequently used specimens. In proven pulmonary histoplasmosis, antibody tests were positive in 18 out of 24 cases. Chest X-rays commonly showed cavities, infiltrates, and nodules, with an increase in nodular pattern in recent cases. The number of pulmonary nodules detected was higher on chest computed tomography (CT). Radiologic abnormality could occur in any lung region. This review suggests the potential for misdiagnosis and/or coinfection of pulmonary histoplasmosis and pulmonary TB. The combination of clinical suspicion, radiological findings, antibody and/or antigen testing could improve the diagnosis of pulmonary histoplasmosis. Full article

Background/Objectives: Pulmonary tuberculosis (TB) is accompanied by inflammation-driven hypercoagulability and increased venous thromboembolism risk. We investigated whether the natural anticoagulants protein C and free protein S are reduced in active TB and whether baseline levels are associated with bacillary burden, treatment response, CT evolution, and pulmonary embolism (PE). Methods: We conducted a prospective cohort study in Romania, including 63 adults with newly diagnosed, bacteriologically confirmed, drug-susceptible pulmonary TB and 30 TB-free controls (October 2024–December 2025). Venous blood was collected at baseline (before anti-TB therapy) and at 6 months to quantify inflammatory and coagulation parameters, protein C, and free protein S. Sputum AFB smear was assessed at baseline, 2 months, and 6 months; chest CT was performed at baseline and 6 months. Propensity score matching (age, sex, BMI, smoking) and multivariable regression were used to account for confounding. Logistic regression and ROC analyses evaluated the prediction of BK persistence. Results: Compared with controls, TB patients had substantially lower baseline protein C and free protein S levels, and higher D-dimer levels (all p < 0.001). In matched multivariable models, TB status remained independently associated with lower baseline natural anticoagulant levels. Lower baseline protein C and free protein S clustered with higher inflammatory markers and higher bacillary burden, and independently predicted BK persistence at 2 and 6 months (OR per 1%-point increase ~0.93–0.95 for protein C and ~0.92–0.94 for free protein S; all p < 0.001). Discrimination for BK persistence was high (AUCs ~0.88–0.89). Lower baseline levels of natural anticoagulants were also associated with greater residual CT abnormalities at 6 months. PE cases had significantly lower protein C and free protein S than PE-free patients. Conclusions: Active pulmonary TB is associated with marked depletion of protein C and free protein S. Baseline reductions identify patients with higher inflammatory/coagulation activation, higher bacillary burden, delayed microbiological clearance, more residual CT disease, and PE, supporting their potential role as adjunct risk-stratification biomarkers. Full article

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide, yet only a fraction of smokers develops the disease, suggesting protective mechanisms in resilient individuals. Identifying airway-localized molecular signatures may improve our understanding of disease pathomechanisms and support hypothesis generation for biomarker research. In this pilot study, induced sputum from smokers with COPD (n = 28) and smokers without COPD (n = 16; Global Initiative for Chronic Obstructive Lung Disease (GOLD)-defined pre-COPD) was analyzed by untargeted proteomics, metabolomics, and lipidomics. After quality control, 1180 proteins, 187 metabolites, and 1234 lipids were retained. Analyses included univariate models with false discovery rate adjustment and multivariate analyses (PCA, PLS-DA), followed by pathway enrichment and protein interaction network analysis. While few features remained significant after FDR correction, consistent cross-omics patterns were observed. COPD was characterized by ↑ glutathione, creatine, and L-arginine; ↓ CCDC88A and ↑ STAT3 and SYDE2; and broad lipid remodeling involving phosphatidylcholines, sphingolipids, and eicosanoids. Network analysis highlighted STAT3 as a highly connected node linking COPD-related genes. These findings suggest that the multi-omic profiling of induced sputum can capture coherent airway-localized molecular signatures such as oxidative stress, cytoskeletal remodeling, and Rho-family GTPase signaling. However, the results should be interpreted as exploratory and require validation in functional studies. Full article

Background/Objectives: An important diagnostic problem is to differentiate between active tuberculosis (TB) and latent TB infection (LTBI). Furthermore, the current biomarkers also offer minimal insight into disease pathogenesis to direct treatment. This triggered us to design a two-mode biomarker signature based on the multicohort analysis using a transcriptomic and stringent machine learning pipeline. Methods: When analyzing active TB, latent TB, and healthy control samples, a rigorous filter (ANOVA, p < 0.001) was used, followed by the selection of features with the help of Boruta-XGBoost and LASSO regression. This determined a small four-gene signature (TAP2, SORT1, WARS, and ANKRD22), which was selectively and highly upregulated in the active TB clinical state (p < 0.001). An ensemble staking classifier based on this signature (Random Forest and XGBoost) had a very high diagnostic performance (ROC-AUC = 0.991 (95% CI: 0.983–0.997)) in the stratification of infection phases, which was strongly confirmed in another cohort (GSE19444). Results: Importantly, the analysis of the functional pathways showed that all the genes are mapped to core dysregulated host pathways in active TB: antigen presentation (TAP2), lipid trafficking (SORT1), interferon response (WARS), and inflammasome signaling (ANKRD22). In such a way, the signature has a dual advantage: (1) high specificity, non-sputum transcriptional diagnostic of active TB, and (2) a mechanistic map of key host pathways, which describes targets of intervention. Conclusions: Thus, the signature provides a two-fold response: a biomarker panel aligned with WHO performance targets for TB triage and a mechanistic plan of therapy, which provides an easy way to implement transcriptomic discovery into clinical action against TB. Full article

Objective: Acute exacerbations (AECOPD) are primary determinants of clinical instability in chronic obstructive pulmonary disease (COPD), and the “frequent exacerbator” (≥2/year) phenotype markedly increases morbidity and healthcare utilization. In this study, we evaluated the association between the Systemic Immune-Inflammation Index (SII), calculated from routine hemogram parameters during the stable period, and the occurrence of frequent exacerbations within the subsequent 1 year, and aimed to define a clinically applicable SII threshold (cut-off). Materials and Methods: In this retrospective observational cohort study conducted at a tertiary care center, patients who attended the outpatient clinic between January 2020 and February 2025 and had COPD confirmed by post-bronchodilator spirometric criteria (FEV₁/FVC < 70%) were identified through electronic medical records. The index date was defined as a routine outpatient visit during stable COPD; patients were followed for AECOPD for 365 days after the index date. The stable period was defined as a visit occurring ≥4 weeks after the last exacerbation and without signs of acute infection. Patients with positive COVID-19 PCR results were excluded due to the uncertainty in distinguishing exacerbation from COVID-19. The primary endpoint was the development of frequent exacerbations (≥2 AECOPD) within 365 days. AECOPD was defined as an acute worsening of dyspnea, cough, and/or sputum requiring additional pharmacotherapy (systemic corticosteroids and/or antibiotics). SII, NLR, PLR, LMR, and PPN were calculated using hemogram parameters. Groups (<2 vs. ≥2 exacerbations) were compared; a ROC–Youden analysis was performed to determine cut-offs. After ROC-based dichotomization, univariate and multivariable logistic regression analyses were used to evaluate associations; multicollinearity was assessed using the VIF. To address potential optimism bias, diagnostic performance metrics (AUC, sensitivity, specificity) were internally validated using 1000 stratified bootstrap replicates. Results: A total of 159 patients were included. The cohort was predominantly male (91.2%). Demographic characteristics and most spirometric parameters were similar between groups; a trend toward lower absolute FVC was observed in the ≥2 exacerbation group (p = 0.051). Platelet counts were higher in the ≥2 exacerbation group (p = 0.029). In the ROC analysis, AUC values ranged from 0.505 to 0.591 across indices. For the SII, the AUC was 0.591 (95% CI: 0.500–0.677; p = 0.049), and the optimal cut-off was 1082.79. The LMR cut-off was 1.76; however, the LMR did not demonstrate statistically significant discriminatory performance in the ROC analysis (AUC 0.535; p = 0.448). In univariate analyses, SII > 1082.79 (OR = 3.028, 95% CI: 1.522–6.027; p = 0.002) was associated with frequent exacerbations. In a multivariable logistic regression adjusted for cardiovascular disease and overall comorbidity status, SII > 1082.79 remained independently associated (OR = 3.029, 95% CI: 1.485–6.179; p = 0.002). Other hemogram-derived indices did not retain independent prognostic significance in this outpatient cohort. Conclusion: SII measured during stable COPD was independently associated with frequent exacerbations over the subsequent 1 year. The SII > 1082.79 threshold may offer a practical risk stratification approach to flag “high-risk” patients in outpatient care. However, given the modest discriminative performance and the single-cohort derivation, this cut-off should be considered exploratory despite the use of bootstrap internal validation. Because this was a single-center study with a predominantly male cohort, the generalizability—particularly to female patients and other settings—requires prospective external validation. Full article

Background: Pulmonary inflammation is a widely recognized characteristic of active tuberculosis (TB). Although standard TB treatment is effective, a substantial proportion of mycobacteriologically cured TB patients experience persistent pulmonary inflammation, which can lead to long-term lung impairment, post-tuberculosis lung disease (PTLD) and potentially TB recurrence. Methods: We conducted a case–control study to compare host serum biomarker profiles in individuals with minimal (TLG < 50 SUVbw*mL, n = 37) versus extensive (TLG ≥ 50 SUVbw*mL, n = 34) persistent lung inflammation following completion of standard drug-sensitive TB treatment. Lung inflammation was measured by 18F-FDG PET/CT scan using total lung glycolysis (TLG) as a surrogate marker. All participants had negative sputum cultures at four months of TB treatment, and blood samples were collected at treatment completion (month six). A Luminex^® multiplex assay performed on the Bio-Plex^® 200 platform was used to analyze 48 host serum biomarkers involved in cytokine/chemokine signaling. Results: Following multiple t-test analysis, fifteen biomarkers were significantly elevated (p < 0.05) in participants with extensive persistent lung inflammation compared to those with minimal inflammation. Among these, 14 demonstrated potential as discriminatory markers, with area under the curve (AUC) values ranging from 0.707 to 0.806, sensitivities ranging from 47.06% to 73.53%, and specificities ranging from 70.27% to 83.78%. Notably, 13 of these 16 candidate biomarkers significantly correlated with TLG values, further supporting their potential clinical utility. Conclusion: We report associations between serum inflammatory mediators and persistent pulmonary inflammation following mycobacterial clearance in TB patients, highlighting their potential as diagnostic biomarkers that could potentially meet the target product profile (TPP) criteria. Full article

Antimicrobial resistance constitutes a major global public health challenge, with Romania among the European countries affected. Acinetobacter baumannii and Pseudomonas aeruginosa was designated by the World Health Organization (WHO) as priority pathogens, are frequently implicated in healthcare-associated infections (HAIs), including pneumonia, surgical site infections, urinary tract infections, and bacteremia. We have narratively synthesized surveillance studies published in different regions of Romania, encompassing date whit the period 2001–2024. A total of 13 studies reporting data on P. aeruginosa (2003–2024) and 15 studies on A. baumannii (2001–2024) were included. The strains were isolated from various pathological products, including urine, sputum, tracheobronchial aspirate, blood, bronchoalveolar lavage, pus, peritoneal fluid, and cerebrospinal fluid, from hospitalized patients in different clinical departments. This review evaluated long-term trends in antimicrobial resistance profiles of A. baumannii and P. aeruginosa strains circulating in various regions of Romania. The findings revealed both temporal variability in resistance rates within comparable intervals and differences across distinct time periods. These long-term trends underscore the need for sustained national surveillance systems, harmonized reporting practices, and reinforced antimicrobial stewardship programs. Full article

Cystic fibrosis (CF) is characterized by neutrophil-driven airway inflammation and acute respiratory events (AREs) that contribute to progressive lung damage. AREs are clinically heterogeneous and often occur without measurable changes in lung function. This study aimed to evaluate the utility of molecular airway inflammatory markers for detecting AREs in school-age children with CF. We performed a secondary analysis of a prospective observational study of children with CF (ages 6.7–16.8 years) followed for two years. Sputum samples were collected from 50 participants during stable visits and AREs. Concentrations of 14 inflammatory cytokines were measured using ELISA and multiplex assays. Associations with lung function (ppFEV₁ and lung clearance index [LCI]) and time to next ARE were assessed. A total of 179 sputum samples were analyzed, including 64 collected during AREs. Calprotectin, interleukin-8 (IL-8), and IL-1β were increased during AREs compared with stable visits, although concentrations frequently remained within ranges observed at stable visits. Other cytokines, including GM-CSF, IL-17A, IL-1α, TNF-α, and SPLUNC-1, were predictive of shorter time to subsequent AREs. No biomarker correlated with lung function measures. These findings indicate that airway inflammatory cytokine changes are associated with clinically diagnosed AREs but not with pulmonary function, supporting their potential role as complementary biomarkers in CF care. Full article

Introduction: Bronchiectasis is a chronic, heterogeneous airway disease characterised by irreversible bronchial dilatation, recurrent infections, and persistent inflammation, leading to progressive lung damage, frequent exacerbations, and impaired quality of life. Neutrophil-driven inflammation, largely mediated by excessive activity of neutrophil serine proteases such as neutrophil elastase, represents a central pathogenic mechanism and an important therapeutic target. Methods: Brensocatib, a first-in-class, selective, and reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), prevents the activation of neutrophil serine proteases during neutrophil maturation in the bone marrow. By reducing downstream protease activity, brensocatib modulates aberrant neutrophilic inflammation without broadly suppressing immune function. Results: Clinical studies, including the Phase-2 WILLOW trial and the Phase-3 ASPEN trial, have demonstrated that brensocatib significantly reduces exacerbation frequency, prolongs time to first exacerbation, and lowers sputum neutrophil protease activity, with a favourable safety profile. Importantly, these benefits were observed across multiple patient subgroups and in addition to standard-of-care therapies. Conclusions: As the first FDA-approved (12 August 2025) mechanism-based therapy for non–cystic fibrosis bronchiectasis, brensocatib represents a paradigm shift toward targeted, precision treatment of neutrophil-mediated airway disease. Its clinical efficacy, biomarker-driven rationale, and potential to reduce antibiotic dependence highlight brensocatib as a cornerstone therapy in bronchiectasis management and a promising strategy for other neutrophil-driven inflammatory conditions. Full article

Background/Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) is classified as an urgent-threat pathogen because of its resistance to nearly all available antibiotics, resulting in high morbidity and mortality rates. However, data on the molecular epidemiology of CRAB isolates in southern Thailand are limited. This study aimed to investigate the genomic epidemiology of CRAB isolates within a hospital network in lower southern Thailand. Methods: Whole-genome sequencing data of CRAB clinical isolates (n = 224) were obtained from a previous study. Additional isolates (n = 70) were included, for which genomic DNA was extracted and sequenced. In total, 294 isolates were collected from patients across seven hospitals in southern Thailand between 2019 and 2020. Their genomes were analyzed using several bioinformatic tools. Results: A high proportion of isolates were obtained from sputum samples of patients with CRAB infection or colonization. Sequence type (ST) 2 was the most frequent ST and was classified in the quadrant with high resistance and virulence. The Sankey diagram showed that ST2 was the dominant and most versatile CRAB lineage circulating across major hospitals, commonly associated with pneumonia, and that diverse resistance genes and plasmid combinations were dominated by bla_OXA-23. The core single-nucleotide polymorphism (SNP)-based phylogenetic tree revealed clades A1 (ST215), A2 (multiple STs), and B (ST2). Bloodstream, skin, and soft tissue infections were predominantly observed in clade B. Conclusions: Our analysis revealed widespread circulation of a high-risk ST2 CRAB lineage with enhanced resistance and virulence across hospital networks in the studied region, highlighting the importance of genomics-informed surveillance for controlling CRAB dissemination. Full article