Pathophysiology of Chronic Bronchial Infection in Bronchiectasis

Bronchiectasis is a complex and heterogeneous disease. Its pathophysiology is poorly understood, but chronic bronchial infection plays an important role in its natural history, and is associated with poor quality of life, more exacerbations and increased mortality. Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus are the most common bacteria related to chronic bronchial infection. Non-tuberculous mycobacteria, fungi and respiratory viruses are also present during clinical stability, and may increase the risk of acute exacerbation. Chronic inflammation is present in bronchiectasis, especially neutrophilic inflammation. However, macrophages and eosinophils also play a key role in the disease. Finally, airway epithelium has innate mechanisms such as mucociliary clearance and antibacterial molecules like mucins and antimicrobial peptides that protect the airways from pathogens. This review addresses how the persistence of microorganisms in the airways and the imbalance of the immune system contribute to the development of chronic bronchial infection in bronchiectasis. (AU)

Pathophysiology of Chronic Bronchial Infection in Bronchiectasis.

Bronchiectasis is a complex and heterogeneous disease. Its pathophysiology is poorly understood, but chronic bronchial infection plays an important role in its natural history, and is associated with poor quality of life, more exacerbations and increased mortality. Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus are the most common bacteria related to chronic bronchial infection. Non-tuberculous mycobacteria, fungi and respiratory viruses are also present during clinical stability, and may increase the risk of acute exacerbation. Chronic inflammation is present in bronchiectasis, especially neutrophilic inflammation. However, macrophages and eosinophils also play a key role in the disease. Finally, airway epithelium has innate mechanisms such as mucociliary clearance and antibacterial molecules like mucins and antimicrobial peptides that protect the airways from pathogens. This review addresses how the persistence of microorganisms in the airways and the imbalance of the immune system contribute to the development of chronic bronchial infection in bronchiectasis.

EBUS-TBNA in Extrathoracic Malignancies: Diagnostic and Prognostic Implications.

PURPOSE: In patients with extrathoracic malignancies (EM) the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the assessment of abnormal mediastinal lymph nodes (MLN) is controversial. The aim of this study was to assess the diagnostic yield and prognostic significance of EBUS-TBNA in these patients. METHODS: Retrospective analysis of patients with EM and abnormal MLN detected by Computed Tomography (CT) and/or Positron Emission Tomography (PET). RESULTS: A total of 161 patients with EM and abnormal MLN were included (93 males, 58%). The most common EM was melanoma (19%) and gastrointestinal cancer (17%). Assessed lymph nodes were mediastinal in 70% of cases and hilar in 30%. The most frequently sampled lymph nodes were subcarinal (45%) and lower right paratracheal (21%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EBUS-TBNA for the diagnosis of malignancy were 88%, 100%, 100% and 87%, respectively. These values were similar regardless the type of EM except for head and neck tumors where the NPV was particularly low (67%). The diagnosis of neoplastic involvement by EBUS-TBNA implied a worse prognosis in terms of overall survival (p < 0.02) and cancer-specific survival (p < 0.001). CONCLUSIONS: In patients with EM and abnormal MLN, EBUS-TBNA has a high diagnostic yield. However, the NPV decrease in patients with head and neck tumors. Neoplastic MLN detected by EBUS-TBNA has prognostic implications in these patients.

Predicting Early Hospital Readmissions in COPD Patients Using an Electronic Nose

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Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge.

BACKGROUND: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. METHODS: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. RESULTS: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. CONCLUSIONS: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

Anticoagulation strategies and risk of bleeding events in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the rate of thrombosis, bleeding and mortality comparing anticoagulant doses in critically ill COVID-19 patients. DESIGN: Retrospective observational and analytical cohort study. SETTING: COVID-19 patients admitted to the intensive care unit of a tertiary hospital between March and April 2020. PATIENTS: 201 critically ill COVID-19 patients were included. Patients were categorized into three groups according to the highest anticoagulant dose received during hospitalization: prophylactic, intermediate and therapeutic. INTERVENTIONS: The incidence of venous thromboembolism (VTE), bleeding and mortality was compared between groups. We performed two logistic multivariable regressions to test the association between VTE and bleeding and the anticoagulant regimen. MAIN VARIABLES OF INTEREST: VTE, bleeding and mortality. RESULTS: 78 patients received prophylactic, 94 intermediate and 29 therapeutic doses. No differences in VTE and mortality were found, while bleeding events were more frequent in the therapeutic (31%) and intermediate (15%) dose group than in the prophylactic group (5%) (p<0.001 and p<0.05 respectively). The anticoagulant dose was the strongest determinant for bleeding (odds ratio 2.4, 95% confidence interval 1.26-4.58, p=0.008) but had no impact on VTE. CONCLUSIONS: Intermediate and therapeutic doses appear to have a higher risk of bleeding without a decrease of VTE events and mortality in critically ill COVID-19 patients.

Intoxicación aguda mortal por ingesta de disolvente con indicación emergente de oxigenación por membrana extracorpórea / Emergency extracorporeal membrane oxygenation in a case of fatal acute poisoning by solvent intake

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