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Background: The therapeutic and economic benefits of continuous positive airway pressure (CPAP) for moderate to severe obstructive sleep apnoea (OSA) syndrome have been established in middle-aged people; however, the benefits in older people are unknown. This trial was designed to address this evidence gap. Methods: This 12-month, multicentre, randomised trial enrolled patients across 14 National Health Service sleep centres in the UK. Consecutive patients aged 65 years or older with newly diagnosed OSA syndrome were eligible to join the trial. Patients were randomly assigned (1:1) into parallel groups to receive either CPAP with best supportive care (BSC) or BSC alone for 12 months. Randomisation was done by the Medical Research Council Clinical Trials Unit with computer-generated randomisation. The main investigator at each centre was masked to the trial randomisation. Coprimary endpoints were Epworth sleepiness score (ESS) at 3 months and cost-effectiveness over the 12-month trial period. Secondary outcomes were subjective sleepiness at 12 months, plus objective sleepiness, quality of life, mood, functionality, nocturia, mobility, accidents, cognitive function, and cardiovascular risk factors and events at 3 months and 12 months. The analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN90464927. Findings: Between Feb 24, 2010, and May 30, 2012, 278 patients were randomly assigned to the trial, of whom 231 (83%) completed the trial. 140 patients were allocated to and received CPAP plus BSC and 138 were allocated to and received BSC only. CPAP reduced ESS by 2·1 points (95% CI -3·0 to -1·3; p

Pseudochylothorax (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion that is commonly associated with chronic inflammatory disorders such as tuberculosis or rheumatoid arthritis. Until now, there were only 15 published cases of arthritis-associated pseudochylothorax in the English language literature. Previous literature has suggested that pleural fluid cholesterol enrichment occurs in the context of grossly thickened (fibrotic) pleura over a prolonged period, usually > 5 years. We present six well-characterized cases of arthritis-associated pseudochylothorax, each notable due to their minimal pleural thickening. The median duration of symptoms (or arthritis, in the case of asymptomatic effusions) was 15 months. Such findings cast significant doubt on the conventional concepts of the pathogenesis of rheumatoid-associated pseudochylothorax. Clinicians should consider pseudochylothorax even in short-duration nonfibrotic pleural effusions.

Parapneumonic effusion is a common clinical problem, and those that go on to develop pleural infection have high morbidity and mortality. The process of pleural infection evolution involves changes in pleural physiology that are increasingly being elucidated and understood. The microbiology of pleural infection has changed over recent years, with clear differences emerging between hospital- and community-acquired infections. Using biochemical surrogates of infection, chest drainage can be undertaken rationally for those who do not respond to antibiotics alone. Recent data suggest that fibrinolytics do not influence outcomes in pleural infection. The optimal type and timing of surgery remain controversial.

Background Pleurodesis is important in the management of malignant pleural effusions, but no consensus exists on the optimal agent or methods of pleurodesis. How pleurodesis is practiced worldwide has not been studied. Objectives To identify variations in the clinical practice of pleurodesis in major English-speaking countries, and to quantify the experience of pulmonologists on the effectiveness and adverse effects of different pleurodesis agents worldwide. Methods Eight hundred fifty-nine pulmonologists practicing in the United States, United Kingdom, Canada, Australia, and New Zealand participated in a Web-based survey. Results The respondents collectively perform > 8,300 pleurodesis annually. Talc was the preferred agent by most respondents (slurry, 56%; poudrage, 12%), followed by tetracycline derivatives (26%), and bleomycin (7%). Differences were seen in pleurodesis practice patterns among practitioners among and within the surveyed countries. Physicians' overall satisfaction with the available pleurodesis agents was modest (5.0 out of 8), and the reported success rate averaged only 66%. Talc (both poudrage and slurry) was perceived as significantly more effective, but was associated with significantly more pain, nausea, and fever (p Conclusions Significant variations exist in how pleurodesis is performed worldwide. Pleurodesis agents currently available are perceived as suboptimal. Talc poudrage and slurry were perceived to be more effective, but were associated with more complications, including respiratory failure.

Study objectives: Pleural fluid cytology and non–image-guided Abrams or Cope biopsies have sensitivities of approximately 30% for detecting malignant mesothelioma, and thoracoscopic biopsy has a sensitivity of approximately 90%. The difference between these two probably relates to obtaining adequate tissue. The use of immunohistochemical stains allows a firm diagnosis to be made from relatively small samples. This study explores whether percutaneous image-guided cutting needle biopsy (CNB) combined with immunohistochemistry is accurate in diagnosing pleural thickening due to mesothelioma. Design: Retrospective review of image-guided CNB of pleural thickening performed on consecutive patients over 7 years by a single radiologist. Setting: Teaching hospital chest radiology department. Patients: Twenty-one adult patients with a final diagnosis of malignant mesothelioma were identified from 53 consecutive patients who underwent percutaneous image-guided CNB. All 21 patients had pleural thickening identified on contrast-enhanced CT, and all had a final histologic diagnosis of mesothelioma confirmed by postmortem examination or thoracoscopy. Interventions: Fourteen-gauge and 18-gauge cutting needles were used. Biopsy guidance was by ultrasound in 6 patients and by CT in 15 patients. Measurements and results: A correct histologic diagnosis of malignant mesothelioma was made by CNB in 18 patients (86% sensitivity and 100% specificity). Complications included one chest wall hematoma and a small hemoptysis. Four patients with a pleural thickness of < 5 mm underwent biopsy, and all specimens were diagnostic for mesothelioma. Conclusions: Image-guided percutaneous CNB of pleural thickening is a safe procedure, with 86% sensitivity for detecting malignant mesothelioma. Pleural thickening of < 5 mm may be successfully sampled. (CHEST 2001; 120:1798 –1802)

Patients with obstructive sleep apnoea (OSA) are reported to have an increased risk of road traffic accidents. This study examines the nature of the impairment during simulated steering in patients with OSA, compared to normal subjects following either sleep deprivation or alcohol ingestion. Twenty-six patients with OSA and 12 normal subjects, either deprived of one night's sleep or following alcohol ingestion [mean (SD) alcohol blood level 71.6 mg dl(-1) (19.6)], performed a simulated steering task for a total of 90 min. Performance was measured using the tendency to wander (SD), deterioration across the task, number of 'off-road' events and the reaction time to peripheral events. Control data for OSA, sleep deprivation and alcohol were obtained following treatment with nasal continuous positive airway pressure (nCPAP), after a normal night of sleep, and following no alcohol, respectively. Patients with untreated OSA, and sleep-deprived or alcohol-intoxicated normal subjects performed significantly less well, compared to their respective controls (P

Background: Recent studies have suggested that asthmatic patients may be more susceptible to the adverse effects of air pollutants, including diesel exhaust particles (DEP). The underlying mechanisms, however, are not clear. Methods: We cultured bronchial epithelial cells from bronchial biopsy specimens of well-characterized groups of nonatopic, nonasthmatic individuals and atopic patients with mild asthma and compared the ciliary beat frequency (CBF) and release of IL-8, GM-CSF, regulated on activation, normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells both before and after exposure for 24 hours to 10 to 100 μg/mL DEP in vitro. Results: The baseline CBF was not found to be significantly different in the bronchial epithelial cell cultures of nonasthmatic and asthmatic individuals. Incubation with DEP significantly attenuated the CBF of both the nonasthmatic and asthmatic bronchial epithelial cell cultures at all concentrations of DEP investigated and were maximal (55.5% and 45.2%, respectively) after incubation with 100 μg/mL DEP. The bronchial epithelial cell cultures of asthmatic patients constitutively released significantly greater amounts of IL-8, GM-CSF, and sICAM-1 than bronchial epithelial cell cultures of nonasthmatic subjects. The cultures of only asthmatic patients additionally released RANTES. Incubation of the asthmatic cultures with 10 μg/mL DEP significantly increased the release of IL-8 (from 102.0 to 167.8 pg/μg cellular protein; P < .01), GM-CSF (from 0.43 to 1.87 pg/μg cellular protein; P < .01), and sICAM-1 (from 14.7 to 38.1 pg/μg cellular protein; P < .02) after 24 hours. Incubation with 50 to 100 μg/mL DEP, however, significantly decreased the release of IL-8 and RANTES from these cultures. In contrast, only the higher concentrations of 50 to 100 μg/mL DEP significantly increased release of IL-8 (from 37.9 to 71.5 pg/μg cellular protein; P < .05) and GM-CSF (from 0.06 to 0.34 pg/μg cellular protein; P < .05) from the bronchial epithelial cells of nonasthmatic individuals. Conclusions: These results suggest that bronchial epithelial cells of asthmatic subjects are different from bronchial epithelial cells of nonasthmatic subjects with regard to the amounts and types of proinflammatory mediators they can release and that the increased sensitivity of bronchial epithelial cells of asthmatic subjects to DEP may possibly result in exacerbation of their disease symptoms. (J Allergy Clin Immunol 1998;102:771-82.)

Background: Recent studies have suggested that airway epithelial cells of atopic and nonatopic individuals may differ in their ability to produce proinflammatory cytokines. Methods : We have cultured human nasal epithelial cells (NECs) as confluent explant cultures from nasal biopsy specimens of well-characterized nonatopic normal volunteers without rhinitis ( n =8), atopic volunteers without rhinitis ( n =9), and atopic patient volunteers with rhinitis ( n =10) and measured the amounts of IL-1β, IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and RANTES released spontaneously into the culture medium by these cells in vitro. NECs from patients with allergic rhinitis were cultured from biopsy specimens obtained on two different occasions, during and after the pollen season. Results : In general, NECs from atopic individuals released significantly greater amounts ofIL-1β, IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and RANTES than NECs from nonatopic individuals. IL-8 was released in greatest quantity and IL-1β in lowest quantity, regardless of whether the NECs were derived from atopic or nonatopic volunteers. Of the atopic individuals, NECs of atopic patients with rhinitis naturally exposed to pollen released greater quantities of all these cytokines, compared with NECs of atopic patients with rhinitis and atopic patients without rhinitis who were not exposed to allergen. Conclusions : These results suggest that NECs of atopic individuals, who are geneticallypredisposed to upper airway disease, release increased amounts of proinflammatory cytokines and that natural exposure to allergen enhances the release of these cytokines, exacerbating the symptoms of allergic disease.

We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte macrophage colony-stimulating factor, "regulated on activation, normal T expressed and secreted," IL-1 beta, and tumor necrosis factor-alpha, increased eosinophil chemotaxis and eosinophil adhesion to cultured human endothelial cells. The chemotaxis and increased adhesion were blocked in the presence of nedocromil sodium. The drug also abrogated the epithelial cell dysfunction (assessed as ciliary beat frequency) induced by the presence of activated eosinophils and blocked the release of eosinophil cationic protein from the eosinophils. We also conducted a double-blind placebo-controlled study of the effects of regular albuterol 200 micrograms or nedocromil sodium 4 mg, both given four times daily for 16 weeks, on inflammatory cell numbers in bronchial biopsy and bronchoalveolar lavage samples. Assessed in terms of total and activated eosinophils in biopsy samples, inflammation decreased with nedocromil sodium and was significantly different from a deterioration with albuterol, although neither of these changes was significantly different from that with placebo treatment. Levels of eosinophil cationic protein in bronchoalveolar lavage samples showed a similar trend.

Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.

We have measured blood pressure continuously with a digital artery blood pressure monitor in eight patients with severe obstructive sleep apnea (OSA) during 30 min each of wakefulness, OSA, OSA with added oxygen to keep saturation above 96 percent at all times (OSA+O2), and nasal continuous positive airway pressure (CPAP) therapy. Mean blood pressures were not different between wakefulness, OSA, OSA+O2, and CPAP, although the variability in blood pressure was significantly greater during OSA and OSA+O2 than during wakefulness and CPAP. The addition of oxygen did not attenuate the variability in blood pressure. Using multiple linear regression modeling to further dissect out the principal variables determining the postapneic blood pressure rise, we found that only apnea length (r2 = 0.28, p less than 0.0001) and pulse rate changes (r2 = 0.15, p less than 0.0001) remained significantly related to SBPmax, while hypoxemia did not. We found the same trends in the other variables SBPten, DBPmax, and DBPten. Hypoxemia made a small contribution to the size of DBPmax, although this was small by comparison with apnea length. We conclude that CPAP treatment of OSA does not lower mean blood pressure acutely, although it significantly reduces the large oscillations in blood pressure seen in patients with untreated OSA. The rise in blood pressure following each apnea is not primarily due to arterial desaturation but is related to apnea length and may be caused by increased sympathetic activity secondary to arousal.