Background: A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)). Methods: BAL fluid cell numbers and levels of tumour necrosis factor (TNFa) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-kB (NF-kB) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples. Results: Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-kB DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p,0.001) but did not differ in COPD patients, whereas AP-1 DNA binding was significantly decreased during exacerbations of COPD. Conclusion: There is evidence of increased oxidative stress in the airways of patients with COPD that is increased further in severe and very severe exacerbations of the disease. This is associated with increased neutrophil influx and IL-8 levels during exacerbations.
Accurate staging of the mediastinum in lung cancer is essential for optimising treatment strategies. Conventional transbronchial needle aspiration (TBNA) is a blind procedure, reliant upon prior computed tomography (CT) or ultrasound imaging, but has low sensitivity. The current study reports the initial experience of using a prototype endobronchial ultrasound (EBUS) probe that allows TBNA under real-time imaging.In 20 patients selected by CT scanning, a linear-array ultrasound bronchoscope was used to visualise paratracheal and hilar lymph nodes, and TBNA was performed under direct ultrasonic control. In seven cases, sequential endoscopic ultrasound (EUS) was used to assess posteroinferior mediastinal lymph nodes. All procedures were performed under conscious sedation.EBUS-TBNA was undertaken in 18 out of 20 cases and EUS-guided fine-needle aspiration in six out of seven cases. Cytology showed node (N)2/N3 disease in 11 out of 18 EBUS-TBNA cases and provided a primary diagnosis for eight patients. EBUS-TBNA cytology was negative in six cases, which was confirmed by mediastinoscopy or clinical follow-up in four. EUS provided additional information in all cases. There were no procedural complications. Sensitivity, specificity and accuracy for EBUS-TBNA were 85%, 100% and 89%, respectively.In conclusion, endobronchial ultrasound with real-time transbronchial needle aspiration offers improved sensitivity and accuracy for staging of the middle mediastinum, and, combined with endoscopic ultrasound, should allow investigation of the majority of the mediastinum.
BackgroundThe assessment of medical trainees is becoming an increasingly prominent issue, with current methods having varying degrees of inherent subjectivity and bias. Cusum analysis is a technique used in quality control systems, and is starting to be employed in medical training. Endobronchial ultrasound (EBUS) is an established tool in the diagnosis and staging of lung cancer, although its use in the UK is currently restricted. As it becomes more widespread, there will be a need to assess trainees' competence accurately to ensure that those performing EBUS at new centres are appropriately skilled. Methods A retrospective review of clinical practice in tertiary referral centres in England, Scotland and Spain was carried out. The study group comprised 500 patients undergoing EBUS for the diagnosis and staging of lung cancer as part of a clinical service. Using cusum analysis, the first 100 cases from each of the five centres are presented. Each centre has one consultant physician as the primary EBUS operator, and all operators began using EBUS at their current centre (ie, no learning from prior experience). The data are presented as learning curves. Results It is evident that there is a wide range of time over which EBUS-guided transbronchial needle aspiration (TBNA) competence is attained. The pooled sensitivity was 67.4% (individual sensitivities 66.7, 70.7, 61.2, 80.3 and 59.7%). Conclusion Cusum analysis is well suited to the assessment of procedures with a binary outcome, but accurate and appropriate standards of practice must be determined prior to assessment to ensure correct identification of underperformance. This report suggests that the learning curve for EBUS is greater than previously reported using different methods, and that even experienced bronchoscopists vary in their speed of learning.
Background: Optimal management of patients with lung cancer requires accurate cell typing of tumours and staging at the time of diagnosis. Endobronchial ultrasound-guided lymph node aspiration as a method of diagnosing and staging lung cancer is a relatively new technique. Aim: To report the use of liquid-based-thin-layer cytology for the processing and reporting of these specimens. Methods: The specimens obtained from 80 patients were processed using the ThinPrep system, with the remainder of the samples being processed as a cell block. Results: 40 of the 81 procedures yielded malignant cells (30 non-small cell carcinoma, 8 small-cell carcinoma and 2 combined small-cell carcinoma/non-small-cell carcinoma). The cell blocks were found to contain sufficient material to allow the immunohistochemical characterisation of tumour cells with a range of antibodies. Conclusion:The use of liquid-based-thin-layer cytological techniques provides high-quality specimens for diagnostic purposes. When used in conjunction with cell blocks, sufficient material may be obtained to allow immunohistochemical studies to confirm the tumour cell type. Given the current move towards centralisation of pathology services, this approach gives the pathologist high-quality specimens without the need for direct onsite support at the time of the procedure.
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