A longitudinal prospective study of active tuberculosis in a Western Europe setting: insights and findings.

PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

BACKGROUND: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. METHODS: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. RESULTS: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. CONCLUSIONS: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

Is the long-term mortality similar in COVID-19 and community-acquired pneumonia?

Introduction: There are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged. Methods: Retrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders. Results: The study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died (p = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862-1.591; PE = 0.774). Conclusion: COVID-19 and CAP have similar long-term mortality after adjusting for potential confounders.

Incidence of pulmonary embolism in patients with non-invasive respiratory support during COVID-19 outbreak.

While the incidence of thrombotic complications in critically ill patients is very high, in patients under non-invasive respiratory support (NIS) is still unknown. The specific incidence of thrombotic events in each of the clinical scenarios within the broad spectrum of severity of COVID-19, is not clearly established, and this has not allowed the implementation of thromboprophylaxis or anticoagulation for routine care in COVID-19. Patients admitted in a semi-critical unit treated initially with NIS, especially Continuous-Positive Airway Pressure (CPAP), were included in the study. The cumulative incidence of pulmonary embolism was analyzed and compared between patients with good response to NIS and patients with clinical deterioration that required orotracheal intubation. 93 patients were included and 16% required mechanical ventilation (MV) after the NIS. The crude cumulative incidence of the PE was 14% (95%, CI 8-22) for all group. In patients that required orotracheal intubation and MV, the cumulative incidence was significantly higher [33% (95%, CI 16-58)] compared to patients that continued with non-invasive support [11% (CI 5-18)] (Log-Rank, p = 0.013). Patients that required mechanical ventilation were at higher risk of PE for a HR of 4.3 (95%CI 1.2-16). In conclusion, cumulative incidence of PE is remarkably higher in critically patients with a potential impact in COVID-19 evolution. In this context, patients under NIS are a very high-risk group for developing PE without a clear strategy regarding thromboprophylaxis.

La fisioterapia respiratoria en el síndrome de Lady Windermere: ¿el eslabón perdido? / Respiratory physiotherapy in Lady Windermere Syndrome: the missing link?

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Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity.

BACKGROUND: For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. METHODS: In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire). RESULTS: We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0-319.6) vs. 273.4 (203.1-426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35-15.3) vs. 15.6 (2.0-29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients. CONCLUSIONS: Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

Micobacteriosis pulmonar en un paciente en tratamiento crónico con metotrexato / Pulmonary Mycobacteriosis in a Patient Receiving Chronic Methotrexate Treatment

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Inflammatory Events and Oxidant Production in the Diaphragm, Gastrocnemius, and Blood of Rats Exposed to Chronic Intermittent Hypoxia: Therapeutic Strategies.

We hypothesized that inflammatory events and reactive oxygen species (ROS) production may be differentially expressed in respiratory and limb muscles, and blood of a chronic intermittent hypoxia (CIH) experimental model and that antioxidants and TNF-alpha blockade may influence those events. In blood, diaphragm, and gastrocnemius of rats non-invasively exposed to CIH (10% hypoxia, 2 h/day, 14 consecutive days) with/without concomitant treatment with either anti-TNF-alpha antibody (infliximab) or N-acetyl cysteine (NAC), inflammatory cytokines, superoxide anion production, muscle structural abnormalities, and fiber-type composition were assessed. Compared to non-exposed controls, in CIH-exposed rats, body weight gain was reduced, TNF-alpha, IL-1beta, IL-6, and interferon-gamma levels were increased in diaphragm, TNF-alpha, and IL-1 beta plasma levels were greater, systemic and muscle superoxide anion production was higher, diaphragm and gastrocnemius inflammatory cells and internal nuclei were higher, and muscle fiber-type and morphometry remained unmodified. CIH rats treated with infliximab further increased TNF-alpha, IL-1beta, IL-6, and interferon-gamma diaphragm levels, whereas NAC induced a reduction only in TNF-alpha and IL-1beta levels in diaphragm and plasma. Infliximab and NAC elicited a significant decline in superoxide anion production in diaphragm, gastrocnemius, and plasma, while inducing a further increase in inflammatory cells and internal nuclei in both muscles. Proinflammatory cytokines are differentially expressed in respiratory and limb muscles and plasma of CIH-exposed rats, while superoxide anion production increased in both muscle types and blood. Infliximab and NAC exerted different effects. These findings may help understand the biology underlying CIH in skeletal muscles and blood of patients with chronic respiratory diseases. J. Cell. Physiol. 232: 1165-1175, 2017. © 2016 Wiley Periodicals, Inc.

Utilidad de la punción aspirativa transbronquial guiada con ultrasonografía endobronquial en el diagnóstico de la tuberculosis mediastínica / Role of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal tuberculosis

Introducción: La tuberculosis (TBC) ganglionar mediastínica es rara y su presentación intratorácica es un reto diagnóstico. La punción aspirativa transbronquial guiada por ultrasonografía endobronquial (PATb-USEB) podría ser útil para su diagnóstico, pero no disponemos de estudios que evalúen su eficacia en nuestro medio. Métodos: Se analizaron retrospectivamente todos los pacientes con TBC ganglionar mediastínica aislada diagnosticados entre 2008 y 2014. Se identificaron los pacientes con diagnóstico definitivo a quienes se les realizó PATb-USEB. Resultados: Se identificaron 29 casos, siendo la PATb-USEB diagnóstica en 28 pacientes (96,6%). Los hallazgos citológicos confirmaron granulomas en el 93% de los casos. El cultivo fue positivo en 14 (48,2%) y la PCR para Mycobacterium tuberculosis, en el 30% de los casos en los que se realizó. El 84% de los pacientes eran inmigrantes y al compararlos con la población nativa se encontraron diferencias significativas en el estado inmunológico y el rendimiento del cultivo. No se registraron complicaciones derivadas del procedimiento. Conclusión: La PATb-USEB es una técnica de primera línea, efectiva y segura en el diagnóstico de pacientes con sospecha de TBC mediastínica (AU)

Introduction: Mediastinal tuberculosis (TB) is rare and a diagnostic challenge. Transbronchial needle aspiration guided by endoscopic ultrasonography (EBUS-TBNA) is an essential tool for staging and diagnosing patients with lung cancer but to date there are no studies in our environment evaluating its efficacy in mediastinal TB. Methods: Patients with a final diagnosis of isolated intrathoracic tuberculous lymphadenitis over a 6-year period were included. We analyzed the cases on whom EBUS-TBNA was performed. Results: Forty-six patients with mediastinal lymphadenopathy without pulmonary involvement were identified and 29 underwent EBUS-TBNA. In 28 of 29 patients (96.6%) EBUS-TBNA was diagnostic and cytological findings confirmed granulomas in 93% of cases. Microbiological investigation revealed positive TB culture in 14 (48.2%) and positive PCR for Mycobacterium tuberculosis in 30% of cases on whom it was carried out. Eighty-four per cent of the patients were immigrants and when compared with the native population we found statistical differences in immune status and culture yield. Conclusion: EBUS-TB (AU)

[Role of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal tuberculosis]. / Utilidad de la punción aspirativa transbronquial guiada con ultrasonografía endobronquial en el diagnóstico de la tuberculosis mediastínica.

INTRODUCTION: Mediastinal tuberculosis (TB) is rare and a diagnostic challenge. Transbronchial needle aspiration guided by endoscopic ultrasonography (EBUS-TBNA) is an essential tool for staging and diagnosing patients with lung cancer but to date there are no studies in our environment evaluating its efficacy in mediastinal TB. METHODS: Patients with a final diagnosis of isolated intrathoracic tuberculous lymphadenitis over a 6-year period were included. We analyzed the cases on whom EBUS-TBNA was performed. RESULTS: Forty-six patients with mediastinal lymphadenopathy without pulmonary involvement were identified and 29 underwent EBUS-TBNA. In 28 of 29 patients (96.6%) EBUS-TBNA was diagnostic and cytological findings confirmed granulomas in 93% of cases. Microbiological investigation revealed positive TB culture in 14 (48.2%) and positive PCR for Mycobacterium tuberculosis in 30% of cases on whom it was carried out. Eighty-four per cent of the patients were immigrants and when compared with the native population we found statistical differences in immune status and culture yield. CONCLUSION: EBUS-TBNA is a safe and effective technique in the diagnosis of patients with suspected mediastinal TB.

Diferencias en los hallazgos clínicos en dos grupos de población inmigrante afecta de tuberculosis / Differences in clinical features of two immigrant populations with tuberculosis

Se realizó un estudio descriptivo para identificar posibles diferencias en la presentación clínica de la tuberculosis entre 2 grupos de población inmigrante. Se incluyeron 94 pacientes visitados en urgencias y que fueron diagnosticados de tuberculosis activa en el periodo 2006-12. Cuarenta y nueve pacientes era originarios de Asia Central (A) y 45 de Latinoamérica (LA). La edad media (años [DE]) fue de 35,3 (13) años en los procedentes de A por 33,9 (10) en los de LA. Existía un predominio de varones en asiáticos (40/49 vs. 25/45; p = 0,006). Los pacientes procedentes de LA tenían mayor porcentaje de tuberculosis pulmonar. Los pacientes de A vivían en condiciones de hacinamiento con mayor frecuencia. Los pacientes de LA tenían más antecedentes de seropositividad para el VIH. La mayoría recibió tratamiento cuádruple. Dos pacientes latinoamericanos eran resistentes a isoniazida

A study was performed to assess differences in the clinical presentation of tuberculosis between two groups of immigrants. Ninety-four patients seen in the emergency room for newly diagnosed tuberculosis between 2006 and 2012 were included. Forty-nine patients were from Asian countries and 45 from Latin America. Mean age [years (SD)] was 35.3 (13) in Asian patients and 33.9 (10) in Latin American patients. Asian subjects were predominantly male (40/49 vs 25/45; P=0.006). Patients from Latin American countries had a higher rate of pulmonary tuberculosis. A higher percentage of Asian patients lived in overcrowded conditions, whereas HIV infection was more frequent among Latin Americans. Most patients were treated with a quadruple regimen. Resistance to isoniazid was documented in two patients from Latin America

Differences in clinical features of two immigrant populations with tuberculosis.

A study was performed to assess differences in the clinical presentation of tuberculosis between two groups of immigrants. Ninety-four patients seen in the emergency room for newly diagnosed tuberculosis between 2006 and 2012 were included. Forty-nine patients were from Asian countries and 45 from Latin America. Mean age [years (SD)] was 35.3 (13) in Asian patients and 33.9 (10) in Latin American patients. Asian subjects were predominantly male (40/49 vs 25/45; P=0.006). Patients from Latin American countries had a higher rate of pulmonary tuberculosis. A higher percentage of Asian patients lived in overcrowded conditions, whereas HIV infection was more frequent among Latin Americans. Most patients were treated with a quadruple regimen. Resistance to isoniazid was documented in two patients from Latin America.

Molecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loading.

High-intensity exercise induces oxidative stress and inflammatory events in muscles. Tumor necrosis factor (TNF)-α may alter muscle protein metabolism or promote muscle regeneration. We hypothesized that a program of noninvasive chronic inspiratory loading of different intensities induces a differential pattern of physiological, molecular, and cellular events within rat diaphragms. Antioxidants and TNF-α blockade may influence those events. In the diaphragm, gastrocnemius, and blood of rats exposed to high-intensity inspiratory threshold loads (2 hour every 24 hours for 14 days), with and without treatment with N-acetyl cysteine or infliximab (anti-TNF-α antibody), inflammatory cells and cytokines, superoxide anion production, myogenesis markers, and muscle structure were explored. In all animals, maximum inspiratory pressure (MIP) and body weight were determined. High-intensity inspiratory loading for 2 weeks caused a decline in MIP and body weight, and in the diaphragm induced a reduction in fast-twitch fiber proportions and sizes, whereas inflammatory cells and cytokine levels, including TNF-α immunohistochemical expression, superoxide anion, internal nuclei counts, and markers of myogenesis were increased. Blockade of TNF-α improved respiratory muscle function and structure, and animal weight, and, in the diaphragm, reduced inflammatory cell numbers and superoxide anion production drastically while inducing larger increases in protein and messenger RNA levels and immunohistochemical expression of TNF-α, internal nuclei, and markers of muscle regeneration. Blunting of TNF-α also induced a reduction in blood inflammatory cytokines and superoxide anion production. We conclude that TNF-α synthesized by inflammatory cells or myofibers could have differential effects on muscle structure and function in response to chronic, noninvasive, high-intensity inspiratory threshold loading.