National Center for Tuberculosis and Lung Disease

Pulmonary nodules are mostly solitary focal opacities typically round or oval in shape, with a diameter of less than 3 cm. They are surrounded by aerated lung parenchyma or located subpleurally, and are not associated with abnormalities, such as lymphadenopathy or atelectasis. Pulmonary nodules are found in up to one-third of computed tomography scans taken in adults, whereas they are significantly less common in children. In adult patients, incidentally detected pulmonary nodules are more frequently associated with neoplastic processes, while they are primarily related to congenital disorders or inflammatory conditions in paediatric populations. The identification of single or multiple pulmonary nodules should always prompt an attempt to determine the likely aetiology. The so-called idiopathic nodules, for which no definitive cause can be established, are a particular subgroup. Although the majority of these lesions are benign in children, some may represent an early stage of malignancy. Due to the lack of standardised management guidelines for the paediatric population, clinical decisions regarding follow-up and further diagnostic workup are often challenging. This literature review outlines the potential causes of incidentally detected paediatric pulmonary nodules, from malignant tumours to other diseases that can present in this form, and discusses methods for assessing the malignant risk of pulmonary nodules in paediatric patients. Finally, a management strategy is proposed for asymptomatic pulmonary nodules detected on imaging, computed tomography in particular.

Background:Little is known about the relationship between weight gain during treatment and the subsequent risk of cardiovascular and metabolic (cardiometabolic) diseases. We assessed the relationship between changes in body mass index (BMI) during TB treatment with prevalence post-TB metabolic syndrome, a strong predictor of cardiometabolic diseases.Methods:We enrolled a prospective cohort of individuals successfully treated for TB disease in Tbilisi, Georgia, from 2019 – 2022. Eligible participants were HIV-negative individuals aged ≥16 years with newly diagnosed and laboratory-confirmed pulmonary TB. Our study exposure was the relative change in BMI from treatment initiation to treatment completion, dichotomized using ≥5% relative increase cut-off. Our primary study outcome was prevalence post-TB metabolic syndrome (i.e., having ≥3 of the following: elevated blood pressure, elevated triglycerides, low high-density lipoprotein, elevated glycated hemoglobin [HbA1c], and abdominal obesity) at any study visits (including the end of, 6- and 12-months post-TB treatment). Multilevel models were used to estimate the effect of BMI change on post-TB metabolic syndrome.Results:Among 120 participants, the adjusted risk of having metabolic syndrome after TB treatment among those with ≥5% relative increase in BMI was 2.07 times (95% confidence interval [CI] 1.07–4.01) the risk of those with <5% relative increase in BMI during treatment. Additionally, the adjusted mean of post-TB HbA1c among those with ≥5% relative increase in BMI was 0.37 (95%CI 0.03–0.71) points higher compared to those with <5% relative increase in BMI.Conclusions:Our findings indicate that weight gain during TB treatment may influence the risk of cardiovascular/metabolic diseases after TB treatment.

BackgroundThis case report describes an uncommon Mycobacterium avium infection mimicking lymphoma in a dog.Case presentationA 1.5-year-old female Miniature Schnauzer presented with persistent lymphadenopathy, fever, and diarrhea, which were refractory to conventional therapy. Hematological and biochemical analyses revealed anemia, thrombocytopenia, elevated liver enzymes, creatine kinase, glutamate dehydrogenase, lactate dehydrogenase, hyperkalemia, low IgG levels, and euthyroid sick syndrome. Ultrasonography confirmed generalized visceral, retroperitoneal, and peripheral lymphadenopathy with concurrent inflammatory reactions, splenomegaly, and hepatomegaly characterized by heterogeneous parenchyma and multiple foci, further supporting the suspicion of lymphoma. However, cytological examination of an enlarged lymph node showed no evidence of lymphoma but revealed the presence of numerous bacilli suggestive of mycobacterial infection. Histopathological evaluation of a surgically excised lymph node similarly failed to confirm lymphoma. Mycobacterium avium was successfully cultured from the lymph node tissue and identified via the GenoType Mycobacterium CM test. Based on antimicrobial susceptibility testing, the initial therapeutic regimen of enrofloxacin, azithromycin, and rifampicin was modified to clarithromycin. Adjunctive treatments included blood transfusion, levothyroxine, prednisolone, omeprazole, sucralfate, parapoxvirus ovis, and soy phospholipids. Despite a temporary clinical improvement, the patient’s condition progressively worsened, and the dog succumbed to the disease after three months.ConclusionsThis case underscores the importance of including Mycobacterium avium in the differential diagnosis of generalized lymphadenopathy, particularly in Miniature Schnauzers. The findings support the routine use of Ziehl-Neelsen staining during cytological examinations to prevent misdiagnosis, especially in breeds predisposed to atypical infections. It also emphasizes the crucial role of targeted antimicrobial therapy in managing such cases, although the prognosis remains guarded.

Emerging evidence suggests that air pollution may exacerbate obstructive sleep apnoea (OSA) however, findings are conflicting and studies limited to single countries. We aimed to investigate the association between long-term exposure to particulate matter (PM10) and OSA severity in different European cities. ESADA records of OSA patients were integrated with data of PM10 concentrations extracted from Copernicus Atmosphere Monitoring Service. The associations between 1-year daily moving average PM10 concentration and OSA severity indices were evaluated by regression models and adjusted for age, sex, body mass index (BMI), smoking, humidity and temperature, season. 19,325 patients were analysed: age 54.6 (13.2) years, 30% females, BMI 32.1 (6.8) kg/m2, apnoea hypopnea index (AHI) 33.2/h (26.1), oxygen saturation (SpO2) 92.5% (3.3) and time with SpO2 below 90% (T90) 48.2 minutes (79.5). A 1-unit increase in long-term PM10 exposure was associated with a 0.41 increase in AHI (95% Confidence Interval: 0.21 - 0.67), while no association was seen for SpO2 and T90. A centre-specific analysis showed significant regional differences in both intensity and impact of association. <fig><object-id>erj;66/suppl_69/PA5662/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>The findings of the present study support the association between long term PM10 exposure and OSA severity. However, such association does not appear to be homogeneous in the different centres suggesting regional disparities across Europe.

Tuberculosis (TB) remains as a most disseminated infectious disease resulting in different complications and lethal outcome. Studies conducted in last decades showed the increase frequency of pulmonary tuberculosis (PTB) in subjects suffered by diabetes mellitus type-2 (DMT2). The goal of the present investigation was to study the modulatory action of inflammatory cytokines (IL-1B, TNFα), vasoactive agents: epoxyeicosatrienoic acids (EETs), endothelin-1 (E-1), vascular endothelium growth factor (VEGF), resistin (R), lipid spectrum, catecholamines (noradrenaline, epinephrine) and endocrine factors – leptin and adiponectin plasma levels alterations in the formation and prognosis of PTB and PTB comorbid with DMT2. Observational study was carried out in 2023-2025 years period in Tbilisi National Center for Tuberculosis and Lung Diseases (Georgia). Recruiting male and female adult patients (18 and more years old, n=50) were divided into 3 groups: a) Healthy volunteers (HV)-n=10; b) Subjects with newly diagnosed PTB-n=20; c) Patients with PTB coincident with DMT2 (PTBDMT2)-n=20. All patients were involved in this study according inclusion and exclusion criteria. The existence of MTB along with clinical symptoms and X-rays examinations was confirmed by Gene Xpert MTB/RiF ULTRA Test. Plasma concentrations of abovementioned agents as well as glycemic control of fasting glucose, insulin and glycated hemoglobin - (HbA1C%) levels was performed by ELISA Kits method. Insulin resistance (IR) was calculated by HOMA-index using formula: [(fasting glucose (mmol/L X fasting insulin (micromole/L/22,5)]. Receiving results revealed in subjects suffered by PTBDMT2 significantly higher plasma level of cytokines IL-1 31,4 (4,2-60,0) pg/ml, P&lt;0,1534) and TNFα 76,2 (3,5-120,0) pg/ml, P&lt;0,0001), that more expressively positively correlated with elevated concentrations of vasoactive agents – E-1 10,3 (3,5-18,4) pg/ml, P&lt;0,0008), catecholamines, VEGF 917,44 (400,0-1495) pg/ml, P&lt;0,00054), R 43,8(14-259) pg/ml, P&lt;0,03846) and endocrine factor leptin 2,02 (0,34-5,8) pg/ml, P&lt;0,00001), providing marked negative relationship to EETs 6,9 (4,8-9,9) pg/ml and adiponectin 95,47 (18-305) pg/ml, P&lt;0,00694) as compared to the same values of PTB and especially HV groups of patients. Such events were associated with lipid spectrum disorders in PTB and PTBDMT2 patients. It is suggesting that cytokines, vasoactive and endocrine agents can be considered as potential biomarkers for early diagnostic and assessment of treatment effectiveness and outcome of PTB and PTBDMT2.

High-resolution metabolomics has shown promise for identifying blood-based biomarkers of tuberculosis (TB). We sought to discover a metabolic signature to detect pulmonary TB disease and monitor treatment response. Plasma from Ethiopian persons with pulmonary TB at diagnosis (n = 82) was compared to household contacts with TB symptoms (n = 104) and 2, 6, and 12 months after treatment initiation. Participants were divided into training and test sets for model building, with additional validation using independent cohorts from the countries of Georgia (n = 89) and South Africa (n = 85). Signatures were further evaluated in nonhuman primates infected with Mycobacterium tuberculosis (Mtb). Among the metabolites that most significantly differed in concentration, tryptophan (Trp) and retinol were significantly decreased in persons with TB disease (45.2 vs 62.5 μM and 4.1 vs 8.2 μM, respectively), while kynurenine (Kyn) was significantly increased (2.1 vs 1.6 μM; q < .0001 for all). A signature that included the Kyn/Trp ratio and retinol showed excellent classification for TB disease (area under the curve [AUC] = 0.97). The signature had an AUC of 0.97 in HIV-positive and 0.95 in HIV-negative persons with TB disease from South Africa and 0.93 in TB patients from Georgia. In Ethiopian participants, signature scores decreased after 2 months (0.85 to 0.42) and 6 months of TB treatment (0.42 to 0.18; P < .0001 for both) to similar levels as controls. Plasma retinol also declined in nonhuman primates infected with Mtb 15-16 weeks after infection (5.9 vs 3.6 μM; P < .001). The plasma Kyn/Trp ratio and retinol represents a promising metabolic signature that could advance TB diagnostics.

Tuberculosis (TB) remains a critical global public health challenge, and there is an urgent need to improve the diagnosis and management of post-TB lung disease (PTLD). We aimed to compare end of treatment prevalence of PTLD among participants with and without drug-resistant TB and to evaluate the association between plasma cytokines and matrix metalloproteinases with lung damage. We conducted a prospective cohort study among individuals with microbial cure status for drug-susceptible or multidrug-resistant pulmonary TB in Tbilisi, Georgia during 2020-2021. Eligible participants were ≥16 years without prior TB treatment history, microbiologically confirmed disease at baseline and who had a favourable treatment outcome (cured or completed treatment). The study outcome was the presence of PTLD defined as abnormalities on either chest CT, spirometry or Saint George's Respiratory Questionnaire. Among 123 participants, the prevalence of PTLD was 74% (n=91) with 53 participants meeting one criteria, 27 two criteria and 11 all three criteria. The prevalence of impaired respiratory health (47%) and lung damage on imaging (46%) was higher than abnormal lung function (21%). PTLD was not associated with drug resistance (adjusted OR 0.91, 95% CI 0.42 to 1.99). Persistent cavitary disease at the end of treatment was associated with higher matrix metalloproteinase 8 and lower matrix metalloproteinase 2, interleukin-17A and interleukin-1ß. Using comprehensive criteria, we found nearly three in four individuals with microbial cure status for TB disease had prevalent PTLD regardless of drug resistance status. Persistent cavitary disease was associated with serum markers of inflammation and lung tissue remodelling.