• Frisk Smed posted an update 1 month, 3 weeks ago

    INTRODUCTION Since 2018, World Health Organization (WHO) recommended the Xpert MTB/RIF Ultra use for pulmonary and extrapulmonary TB diagnosis, and suggested that Xpert Ultra should be tested in various populations, with different geographical and epidemiological settings. METHODS Cross-sectional study with prospective data collection. Outpatients aged >18 years with respiratory symptoms suggestive of pulmonary TB were invited to participate. Sensitivity, specificity, positive and negative predictive values of the test were calculated and compared with the traditional Xpert MTB/RIF. RESULTS During the study period, 180 patients met the inclusion and were included in the analysis. Xpert MTB/RIF Ultra test was positive in 33 patients (18.3%), and RIF resistance was detected in 1 (3.1%) patient. Considering culture as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF Ultra were 100.0% (95% CI 85.2-100.0), 93.6% (95% CI 88.6-96.9), 69.7% (95% CI 55.8-80.7), and 100.0% (95% CI 87.2-100.0), respectively. The area under the ROC curve was 0.97 for the Xpert MTB/RIF Ultra test (95% CI 0.93 to 0.99; p  0.05). CONCLUSIONS This is the first study in Brazil to evaluate the accuracy of Xpert MTB/RIF Ultra in individuals with presumptive pulmonary TB. The test showed an excellent sensitivity and a high specificity, demonstrating that it is a useful tool for pulmonary TB diagnosis. BACKGROUND Some patients with asthma present with accelerated lung function decline. This phenomenon is mostly associated with severe exacerbations and with poor asthma control. OBJECTIVE Our aim was to detect the extent of FEV1 decline in patients with mild asthma and to discriminate clinical, functional and inflammatory factors associated with accelerated FEV1 decline. METHODS We recruited 50 patients with mild asthma for pulmonary function testing and induced sputum sampling 12-15 years after the initial diagnosis. In 33 patients, from whom sputum of a good quality was obtained, inflammatory cells were counted and concentrations of cytokines IL-2, IL-4, IL-5, IL-8, IL-10, IFN-γ, angiogenin and VEGF in the sputum were measured by cytometric bead array. RESULTS Eighteen of 33 patients presented with accelerated FEV1 decline of more than 30 ml/year, with a mean (SEM) of 43.2 (3.9) ml/year, compared to 15 control patients with a FEV1 decline of 14.4 (2.1) ml/year. In the accelerated FEV1 decline group, we found elevated sputum levels of IL5 with a median (IQR) of 1.8 (0.4-3.2) pg/ml vs. 0.2 (0.1-1.2) pg/ml, p = 0.04; IL8 with a mean (SEM) of 1503 (194) pg/ml vs. 938 (177) pg/ml, p = 0.04; and eosinophils with a median (IQR) of 223 (41-1020) cells/μl vs. 39 (1-190) cells/μl, p = 0.03. No significant differences in other measured parameters were detected between the two groups. CONCLUSION Elevated sputum eosinophils, IL5 and IL8, which have a potential to stimulate airway remodelling, might be a useful non-invasive biomarkers and therapeutic targets of accelerated FEV1 decline in asthma patients. BACKGROUND Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication. OBJECTIVE Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis. METHODS We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. Mitoquinone in vitro The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation. RESULTS The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 μg/ml. CONCLUSIONS Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa. BACKGROUND We should continually improve tools for evaluating asthma. The aim of this study was to evaluate whether the FEV1/FVC ratio in the lower range of normality is associated with worse outcomes in asthmatics without airway obstruction. METHODS We screened asthmatics at eight clinics. Subjects answered the Asthma Control Questionnaire and underwent spirometry. We assigned individuals without airway obstruction in three groups according to the post bronchodilator FEV1/FVC ratio lower range of normality, intermediary range of normality and upper range of normality. Asthma outcomes were hospital admission due to asthma during the preceding year, non-controlled asthma symptoms and moderate-high inhaled maintenance therapy need. RESULTS In subjects from six to 18 years old, the rate of hospital admission was higher in the group with FEV1/FVC ratio in the lower range of normality as compared with the other two groups but the frequency of non-controlled symptoms of asthma and moderate-high dose of inhaled maintenance therapy need was similar. From 19 to 59 years old, the rate of moderate-high inhaled maintenance therapy need was higher in the group with FEV1/FVC ratio in the lower range of normality as compared with the other two groups, but the frequency of hospital admissions and non-controlled symptoms of asthma was similar. Above 59 years old, there was no difference in clinical asthma outcomes between lung function groups. CONCLUSIONS FEV1/FVC ratio in the lower range of normality is a marker of worse clinical outcomes in asthmatics without airway obstruction.