Isolated mediastinal lymphadenopathy - performance of EBUS-TBNA in clinical practice.

Background Isolated mediastinal lymphadenopathy is an increasingly common finding as a result of the increasing use of cross-sectional thoracic imaging. We investigated the performance of endobronchial ultrasoundguided transbronchial needle-aspiration (EBUS-TBNA) in establishing a pathological diagnosis in patients with isolated mediastinal lymphadenopathy. Methods We retrospectively analysed all consecutive EBUS-TBNA examinations performed over a 4-year period at a single tertiary referral centre. Final diagnoses were made using pathology reports, correlated with clinical features and the results of any other investigations. Results In total, 126 EBUS-TBNA examinations were performed to investigate isolated mediastinal lymphadenopathy. A positive pathological diagnosis was made following EBUSTBNA in 54 cases (43%). When the results of further investigations and variable radiological follow up were included, the final sensitivity of EBUS-TBNA for making a diagnosis in isolated mediastinal lymphadenopathy was 80% (95% CI 69%-89%). Conclusions This study confirms that EBUS-TBNA has acceptable sensitivity for detecting both benign and malignant pathologies underlying isolated mediastinal lymphadenopathy.

Is there still a role for mediastinoscopy as the first mediastinal staging procedure in lung cancer?

Lung cancer staging has evolved with the advent of endobronchial and endoscopic ultrasound (EBUS and EUS) as an alternative to mediastinoscopy and other surgical staging techniques. This has led to the debate now as to what the first-line staging investigation should be. Mr Waller makes the case that although EBUS and EUS are welcomed staging techniques, mediastinoscopy still has an important role as the first-line staging investigation in specific scenarios (when there is potentially surgically resectable mediastinal disease). Dr Skwarski argues that EBUS and EUS should be used in conjunction with CT-PET and considered as a complete alternative to mediastinoscopy.

Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin-layer cytology.

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.

Oxidative stress and airway inflammation in severe exacerbations of COPD.

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 (TNFalpha) 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-kappaB (NF-kappaB) 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-kappaB 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.

Endobronchial and endoscopic ultrasound-guided real-time fine-needle aspiration for mediastinal staging.

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 postero-inferior 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.

Randomized controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner. METHODS: Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment. RESULTS: Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group. CONCLUSIONS: This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.

Effects of hypoxia on renal hormonal balance in normal subjects and in patients with COPD.

There is a complex interaction between pulmonary haemodynamics, hormonal, and salt and water balance in patients with chronic obstructive pulmonary disease (COPD) and in normal subjects exposed to hypoxia or high altitude. This study aims to investigate the effects of hypoxia on renal hormonal balance in normal subjects and patients with COPD, particularly the role of urinary dopamine and atrial natriuretic peptide (ANP). Urinary dopamine output, ANP, and plasma renin activity (PRA) were measured in 12 normal subjects exposed to hypoxia (12% O2) and hyperoxia (40% O2) for 1 h and in 15 patients with exacerbations of COPD while breathing air or O2. These measurements were repeated in six of the patients with exacerbations of COPD when they were clinically stable. Hypoxia caused an increase in ANP levels (49 +/- 6-62 +/- 6 pg ml-1, P < 0.05) and a fall in urinary dopamine output (277 +/- 39-205 +/- 33 ng h-1, P < 0.002) in normal subjects. Hyperoxia was associated with a return of plasma ANP to the baseline values. In patients with exacerbations of COPD plasma ANP levels were higher (181 +/- 36 pg ml-1) than in normal subjects (49.5 +/- 6.5 pg ml-1, P < 0.001). Urinary dopamine output breathing air (175 +/- 34 ng h-1) was similar to the levels when normal subjects were made hypoxaemic and PRA was elevated in comparison to normal values. There was no change in their levels following the acute administration of oxygen in patients presenting with exacerbations of COPD, but oxygen improved urinary sodium excretion (P < 0.05). In six patients re-studied when clinically stable there was a fall in urinary dopamine output, plasma ANP and PRA when breathing air in comparison to the acute stage of the disease (P < 0.05). These data suggest presence of renal hormonal imbalance including endogenous urinary dopamine output during hypoxic exacerbation of COPD and in normal subjects exposed to hypoxia.

The adequacy of oxygenation in patients with hypoxic chronic obstructive pulmonary disease treated with long-term domiciliary oxygen.

Survival in patients with hypoxic chronic obstructive pulmonary disease (COPD) is improved by long-term oxygen therapy (LTOT). Such patients are known to desaturate during activity and at night. The aim of this study was to assess the adequacy of oxygenation in patients with COPD receiving LTOT. Oxygen saturation (SaO2) was measured at home over 24 h in 20 patients with hypoxic COPD receiving LTOT. Eleven had arterial oxygen partial pressure values (PaO2) > or = 8 kPa (Group 1) and nine had PaO2 < 8 kPa (Group 2), at rest, breathing oxygen. There was no difference in SaO2 during the day and night when breathing oxygen. In Group 1, SaO2 was > 90% for 78 +/- 24% of the 24-h period. Four patients spent between 75 and 90%, and three spent < 75% of the 24-h period with SaO2 > 90%. In Group 2, SaO2 was < 90% for 69 +/- 27% of the 24-h period (P = 0.02). Two patients spent between 75 and 90%, and four spent < 75% of the 24-h period with SaO2 > 90%. Measurements of SaO2 over 24 h in patients with hypoxic COPD, while breathing oxygen, add further information to arterial blood gas sampling on the adequacy of oxygenation, and reveal inadequate oxygenation in many patients.

The effects of cigarette smoking on pulmonary hemodynamics.

Neutrophils are delayed in transit in the pulmonary circulation during smoking which could reflect smoke-induced changes in local hemodynamics. The purpose of this study was to measure the changes in pulmonary hemodynamics during cigarette smoking in both healthy smokers and patients with COPD with and without pulmonary hypertension. In eight healthy smokers, cigarette smoking decreased the transit time of technetium-99m-labeled red blood cells, associated with an increase in cardiac output and a fall in the pulmonary blood volume index. In patients with COPD, the cardiac index also increased during smoking associated with a small increase in pulmonary arterial pressure only in those patients with pulmonary hypertension. However, pulmonary vascular resistance fell. These changes in pulmonary hemodynamics during cigarette smoking could not account for the increased neutrophil sequestration that has been observed previously in the lungs during smoking.