Levels of soluble triggering receptor expressed on myeloid cells 1 in infectious exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is an activating receptor on inflammatory cells upregulated by microbial products. Elevated levels of sTREM-1 have been associated with the diagnosis and prognosis of patients with sepsis, severe pneumonia and chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aim of this study was to define the role of sTREM-1 in acute exacerbations of COPD (AE-COPD) and to investigate the ability of sTREM-1 to differentiate between infectious triggers of AE-COPD. METHODS: Smokers without COPD (SM), patients with stable COPD (sCOPD) and patients with AE-COPD were prospectively recruited. sTREM-1 levels were determined by ELISA in serum. Potentially pathogenic bacteria were analyzed by sputum culture, and polymerase chain reaction was used to determine the presence of respiratory viruses. RESULTS: One hundred and ninety-five subjects were included: 64 sCOPD patients, 118 AE-COPD patients and 13 SM. In 62 (52.6%) AE-COPD patients, a respiratory pathogen was detected. Serum levels of sTREM-1 were barely detectable in SM but were significantly increased in patients with sCOPD [97.5 (interquartile value 76.6) pg/ml] and AE-COPD [110.9 (98.5) pg/ml; p<0.001]. There was no significant difference in sTREM-1 between sCOPD and AE-COPD (p=0.277). However, in AE-COPD, sTREM-1 was significantly lower in patients with virus detection [87.5 (97.3) pg/ml] compared to those without [120.3 (99.7) pg/ml; p=0.015]. No difference was found in AE-COPD patients with or without bacterial detection. CONCLUSIONS: The present study shows an increase in sTREM-1 in patients with COPD compared to SM but not in AE-COPD compared to sCOPD. Viral exacerbations showed significantly lower sTREM-1 levels than non-viral exacerbations.

Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers.

BACKGROUND: Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-gamma release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure. METHODS: In this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-gamma < 0.35 IU/ml and follow-up IFN-gamma > or = 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis. RESULTS: In total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (kappa = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-gamma response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years. CONCLUSIONS: The QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-gamma responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.

A fatal case of spinal tuberculosis mistaken for metastatic lung cancer: recalling ancient Pott's disease.

BACKGROUND: Tuberculous spondylitis (Pott's disease) is an ancient human disease. Because it is rare in high-income, tuberculosis (TB) low incidence countries, misdiagnoses occur as sufficient clinical experience is lacking. CASE PRESENTATION: We describe a fatal case of a patient with spinal TB, who was mistakenly irradiated for suspected metastatic lung cancer of the spine in the presence of a solitary pulmonary nodule of the left upper lobe. Subsequently, the patient progressed to central nervous system TB, and finally, disseminated TB before the accurate diagnosis was established. Isolation and antimycobacterial chemotherapy were initiated after an in-hospital course of approximately three months including numerous health care related contacts and procedures. CONCLUSION: The rapid diagnosis of spinal TB demands a high index of suspicion and expertise regarding the appropriate diagnostic procedures. Due to the devastating consequences of a missed diagnosis, Mycobacterium tuberculosis should be considered early in every case of spondylitis, intraspinal or paravertebral abscess. The presence of certain alarm signals like a prolonged history of progressive back pain, constitutional symptoms or pulmonary nodules on a chest radiograph, particularly in the upper lobes, may guide the clinical suspicion.

[The role of respiratory infections in chronic obstructive pulmonary disease]. / Die Rolle von Atemwegsinfektionen bei der chronisch-obstruktiven Lungenerkrankung.

Morbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy. Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future. The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Should asthma management include sojourns at high altitude?

Sojourns in the high mountains have been recommended by specialists for patients with asthma since many decades. An inquiry among physicians of the 'Davoser Arzteverein' revealed as early as 1906 that 133/143 patients with bronchial asthma had no or only few asthma attacks during their stay in Davos, and that 81% had a persistent improvement of their disease. These early observations about effects of the alpine climate were, of course, reported at a time, when the spectrum of pharmacotherapy was very limited. However, these observations were consistent and were therefore regarded as proof for the therapeutic value of sojourns under alpine conditions in bronchial asthma. In recent years, however, the indication for asthma treatment in high mountains is increasingly questioned, in particular by health insurance systems. Therefore it is the aim of this contribution to summarize the available data about the effects of a stay of asthmatic patients at 1,500-1,800 m above sea level. It is concluded that the available evidence suggests a significant beneficial effect of high altitude in bronchial asthma, in particular in steroid-dependent patients.

Association of the ASP299GLY TLR4 polymorphism with COPD.

Bacterial infection and colonization plays an important role in COPD. The inflammatory response to these bacteria is mediated by Toll-like receptors. The Asp299Gly polymorphism of the Toll-like receptor-4 (TLR4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction resulting in impaired antimicrobial defense. Because altered TLR4 signalling may facilitate bacterial infection, we clinically phenotyped and genotyped 152 patients with COPD (including 24 non-smokers), and 444 healthy controls for the presence of the Asp299Gly polymorphism. Frequencies of the TLR4 Gly allele (4% vs. 8% in controls, odds ratio (OR) 2.24 (95% confidence interval (95%CI) 1.17-4.3)) as well as TLR4 Gly genotype (6% vs. 13% in controls, OR 2.39 (95%CI 1.20-4.79)) were significantly decreased among the patients with COPD. The TLR4 Gly allele was not detected at all in a subgroup of non-smoking patients (n=24). We conclude that the frequency of the Asp299Gly polymorphism is decreased in COPD patients. Unaltered LPS signal transduction by TLR4 may be important for the development of COPD.

[Cardiac structure and function in patients with obstructive sleep apnea syndrome and co-prevalent arterial hypertension. Influence of CPAP therapy]. / Kardiale Funktion bei Patienten mit obstruktivem Schlafapnoesyndrom und behandelter arterieller Hypertonie Vorteile durch CPAP-Therapie?

BACKGROUND AND PURPOSE: 30% of patients with arterial hypertension (AH) are supposed to have a co-prevalent obstructive sleep apnea syndrome (OSAS). Hence, the influence of CPAP (continuous positive airway pressure) therapy on cardiac structure and function was investigated in medically treated patients with AH and co-prevalent OSAS. PATIENTS AND METHODS: In all patients AH was treated for at least 5 years. Matched pairs concerning anthropometric data, medical therapy and duration of AH, and severity of OSAS were investigated: 20 patients with untreated OSAS were compared to 20 patients with CPAP therapy for at least 6 months. Further cardiopulmonary diseases were excluded. Cardiac structure and function were assessed echocardiographically. RESULTS: Patients under CPAP therapy had significantly better diastolic left ventricular function, a lower left ventricular mass index, and significantly less frequent signs of left ventricular (eccentric) hypertrophy than patients with untreated OSAS. Furthermore, differences were significant concerning right ventricular wall thickness and mean pulmonary artery pressure. CONCLUSION: CPAP therapy positively influences left and right cardial structure and function in addition to antihypertensive medication in patients with AH and co-prevalent OSAS.

[Improvement of cardiopulmonary exercise capacity in patients with obstructive sleep apnea syndrome under CPAP therapy]. / Verbesserung der kardiopulmonalen Leistungsfähigkeit bei Patienten mit obstruktivem Schlafapnoesyndrom unter CPAP-Langzeittherapie.

BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is regarded as a cardiovascular risk factor. Therefore, cardiopulmonary exercise capacity in patients with OSAS before and under treatment with continuous positive airway pressure (CPAP) was investigated. PATIENTS AND METHODS: Cardiopulmonary exercise capacity was investigated in 36 patients with untreated OSAS using spiroergometry. A follow-up after at least 6 months was performed in 17 of these patients being treated with CPAP and in eight CPAP-neglecting patients, who served as controls. RESULTS: Maximum oxygen uptake ( O(2max)) was significantly reduced in all 36 patients with untreated OSAS (17.68 +/- 6.1 ml/min/kg) compared with reference values (30.72 +/- 4.9 ml/min/kg; p < 0.001). After an average of 305.7 +/- 104.8 nights of CPAP therapy, O(2max) rose from 15.33 +/- 4.8 to 18.53 +/- 6.9 ml/min/kg, whereas O(2max) remained unchanged in controls. Further spirometric parameters of exercise capacity as well as arterial blood pressure were also significantly improved under CPAP therapy. CONCLUSION: Cardiopulmonary exercise capacity is markedly reduced in patients with OSAS. Long-term CPAP therapy leads to a significant improvement of reduced cardiopulmonary exercise capacity in these patients.

Evaluation of the toll-like receptor 6 Ser249Pro polymorphism in patients with asthma, atopic dermatitis and chronic obstructive pulmonary disease.

BACKGROUND: For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD). METHODS: Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion. RESULTS: We found a weak association of the 249Ser allele with childhood asthma (p = 0.03). Yet, significance was lost after Bonferroni correction. No association was evident for AD or COPD. CONCLUSION: Variation in TLR6 might play a role in the pathogenesis of childhood asthma.

Cost analyses of community-acquired pneumonia from the hospital perspective.

STUDY OBJECTIVES: Community-acquired pneumonia (CAP) is a widespread disease with important implications for health-care systems worldwide. This study investigated direct costs, treatment patterns, and outcomes associated with two patient cohorts hospitalized with CAP. DESIGN: The study design was naturalistic, prospective, and open. PATIENTS: The study enrolled 580 patients. Two hundred sixty-one patients were treated initially with IV moxifloxacin (45%, cohort M); the remaining 319 patients received nonstandardized treatment (cohort S). SETTING: Twenty-two hospitals in Germany. RESULTS: Clinical success rates were similar between treatment groups (cohort M, 242 of 256 patients, 95%; cohort S, 286 of 312 patients, 92%; p = 0.208). Mean +/- SD length of hospital stay was 10.8 +/- 5.2 days, with cohort M having a significantly shorter hospital stay (10.0 +/- 4 days) compared to cohort S (11.5 +/- 6 days; p < 0.001). Median of all direct costs was dollar 1,333 (minimum, dollar 127; maximum, dollar 9,488), with direct costs of dollar 1,250 in cohort M (minimum, dollar 372; maximum, dollar 9,488) and dollar 1,409 in cohort S (minimum, dollar 127; maximum, dollar 9,366) per treated episode of CAP (p = 0.066). CONCLUSIONS: Major determinants of costs were length of hospital stay and ICU admission, whereas costs for staff and hotel were major contributors to direct costs. Initial antibiotic therapy with moxifloxacin resulted in similar clinical efficacy and direct costs compared to nonstandardized therapy; however, patients treated with moxifloxacin benefited with an earlier hospital discharge.

Short-term effects of oral theophylline in addition to CPAP in mild to moderate OSAS.

Theophylline is effective in the treatment of central apneas and periodic breathing. In obstructive sleep apnea syndrome (OSAS), results of pharmacological monotherapy with theophylline are inconsistent. The present study investigates whether additional theophylline in patients with OSAS and continuous positive airway pressure (CPAP) therapy might improve ventilation, lower effective CPAP pressure levels or affect sleep architecture. Patients with mild to moderate OSAS (mean apnea index [AI] 12.8+/-11.7) and CPAP therapy (Autoset system; n=16, all male) received either 900 mg of oral sustained-release theophylline (T) or placebo (P) on two separate nights, 3 days apart, using a randomized double-blind crossover study design. There was no change in AI (T: 0.7+/-1.4 vs. P: 0.7+/-0.6/h; P=0.3) or apnea-hypopnea index (AHI; T: 4.3+/-3.3 vs. P: 4.5+/-3.7/h; P=0.84) when theophylline was added to CPAP therapy. We observed no difference in mean CPAP pressure (T: 6.9+/-2.1 vs. P: 6.7+/-1.9 cm H2O; P=0.7) or 95% pressure percentiles (T: 9.7+/-2.7 vs. P: 9.3+/-2.1cm H2O; P=0.3) when nights with theophylline were compared to placebo nights. Theophylline reduced significantly total sleep time (T: 290.6+/-58.9 vs. P: 338.0+/-40.1 min; P=0.02) and thus sleep efficiency (SE; T: 70.5+/-14.9%, P: 82.0+/-70.5%; P=0.005). Rapid eye movement and slow wave sleep were not affected. Oral theophylline did not show any additional effects on ventilation parameters or pressures in patients with mild to moderate OSAS once CPAP therapy has been successfully installed. SE was reduced with theophylline with unchanged sleep architecture. The role of oral theophylline may be in patients with predominately central apneas not eligible for ventilation therapy or severe cases.

Long-term effects of nasal continuous positive airway pressure on vasodilatory endothelial function in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with a dysfunction of vascular endothelial cells. The aim of this study was to investigate long-term improvement of endothelial dysfunction in OSAS with nasal continuous positive airway pressure (nCPAP) treatment. We investigated endothelium-dependent and endothelium-independent vasodilatory function in patients with OSAS using the hand vein compliance technique. Dose-response curves to endothelium-dependent vasodilator bradykinin were obtained in 16 subjects with OSAS before and after 6 months of nCPAP therapy and in 12 control subjects without OSAS. Maximum dilation (Emax) to bradykinin, being impaired in all OSAS patients, was completely restored with nCPAP. Mean Emax to bradykinin rose from 54.9+/-18.5 to 108.2+/-28.7% with 164.4+/-90.0 nights of nCPAP therapy (p<0.0001; Emax healthy controls, 94.8+/-9.5%). At treatment follow-up, endothelium-dependent vasodilatory capacity was not significantly different in nCPAP-treated OSAS patients vs healthy controls. Mean vasodilation with endothelium independently acting nitroglycerin was not altered initially and did not change with nCPAP therapy indicating that nCPAP restored endothelial cell function and not unspecific, endothelium-independent factors. These results suggest that regular nocturnal nCPAP treatment leads to a sustained restoration of OSAS-induced impaired endothelium-dependent nitric oxide-mediated vasodilation, suggesting an improvement of systemic endothelial dysfunction in patients studied.

[Early polysomnographic detection of congestive heart failure caused by aortic valve stenosis]. / Polysomnographische Früherkennung einer kardialen Dekompensation infolge hochgradiger Aortenklappenstenose.

BACKGROUND: Obstructive sleep apnea (OSAS) is assumed to be an independent cardiovascular risk factor, whereas central sleep apnea with Cheyne-Stokes breathing occurs in congestive heart failure and has a prognostic value. CASE REPORT: The case of a 74-year-old man with long-term continuous positive airway pressure treatment due to OSAS is reported. In a routine polysomnography central apneas and Cheyne-Stokes breathing without any clinical signs of heart failure were seen. Further investigations revealed a newly diagnosed aortic valve stenosis with good left ventricular function. Clinical signs of congestive heart failure came up 2 weeks after first diagnosed Cheyne-Stokes breathing. CONCLUSION: Cheyne-Stokes breathing can be observed in acute heart failure before occurrence of any clinical signs of congestive heart failure and should always lead to further investigations. The current understanding of pathophysiological pathways in Cheyne-Stokes breathing is reviewed.

Increased IgE-antibodies to Staphylococcus aureus enterotoxins in patients with COPD.

Recent evidence suggests that Staphylococcus aureus enterotoxins (SAEs) could modify airway disease by acting as superantigens, an immune response that can be monitored by detection of IgE antibodies to SAEs. We studied the expression of total IgE and specific IgE to SAEs using the Uni-CAP system in healthy controls, smokers without COPD and COPD patients. Only 1/10 controls (10%) and 1/16 smokers (6.3%) had IgE to SAEs compared to 7/18 patients with stable COPD (38.9%) and 21/54 patients with exacerbated COPD (38.9%). The IgE levels to SAEs of the patients with stable COPD (0.18 [0.05-26.2]kUA/l) and the patients with exacerbated COPD (0.09 [0.05-18.6]kUA/l) were significantly higher than those of smokers (n = 16; 0.05 [0.05-0.82]kUA/l) and controls (n = 11; 0.05 [0.05 0.9]kUA/l, P<0.05). IgE to SAEs decreased significantly in the exacerbated patients during hospitalization (0.13 [0.05-18.3] vs. 0.05 [0.05-11]kUA/l, P<0.001) going along with a significant increase in FEV1 (38.1 [16.9-79.5] vs. 51.6 [15-80]%predicted, P<0.001). Similarly to severe asthma, we found significantly elevated IgE to SAE in COPD patients. Our data for the first time suggest differences between healthy subjects, smokers and patients with established COPD regarding the role of bacterial products and point to a possible disease modifying role of SAEs.

Comparison of driving simulator performance and neuropsychological testing in narcolepsy.

Daytime sleepiness and cataplexy can increase automobile accident rates in narcolepsy. Several countries have produced guidelines for issuing a driving license. The aim of the study was to compare driving simulator performance and neuropsychological test results in narcolepsy in order to evaluate their predictive value regarding driving ability. Thirteen patients with narcolepsy (age: 41.5+/-12.9 years) and 10 healthy control patients (age: 55.1+/-7.8 years) were investigated. By computer-assisted neuropsychological testing, vigilance, alertness and divided attention were assessed. In a driving simulator patients and controls had to drive on a highway for 60 min (mean speed of 100 km/h). Different weather and daytime conditions and obstacles were presented. Epworth Sleepiness Scale-Scores were significantly raised (narcolepsy patients: 16.7+/-5.1, controls: 6.6+/-3.6, P < or = 0.001). The accident rate of the control patients increased (3.2+/-1.8 versus 1.3+/-1.5, P < or = 0.01). Significant differences in concentration lapses (e.g. tracking errors and deviation from speed limit) could not be revealed (9.8+/-3.5 versus 7.1+/-3.2, pns). Follow-up investigation in five patients after an optimising therapy could demonstrate the decrease in accidents due to concentration lapses (P < or = 0.05). Neuropsychological testing (expressed as percentage compared to a standardised control population) revealed deficits in alertness (32.3+/-28.6). Mean percentage scores of divided attention (56.9+/-25.4) and vigilance (58.7+/-26.8) were in a normal range. There was, however, a high inter-individual difference. There was no correlation between driving performance and neuropsychological test results or ESS Score. Neuropsychological test results did not significantly change in the follow-up. The difficulties encountered by the narcolepsy patient in remaining alert may account for sleep-related motor vehicle accidents. Driving simulator investigations are closely related to real traffic situations than isolated neuropsychological tests. At the present time the driving simulator seems to be a useful instrument judging driving ability especially in cases with ambiguous neuropsychological results.

Obstructive Sleep Apnea and Hypopnea Efficacy and Safety of a Long-Acting beta2-Agonist.

The effect of inhaled long-acting beta2-agonists in obstructive sleep apnea syndrome (OSAS) is unknown, although from the pharmacological point of view both therapeutic and adverse effects need to be considered. The purpose of this study was to obtain data on the efficacy and safety of salmeterol in patients with OSAS. In a randomized, double-blind, placebo-controlled, cross-over study, effects of salmeterol on respiration during sleep and sleep quality were investigated in 20 patients with OSAS. Of these, 4 patients were female, 16 male; the average age was 53.0 +/- 7.8 years, with average body mass index 28.0 +/- 3.0 kg small middle dot m(-2) and average apnea hypopnea index 35.6 +/- 17.8 h(-1). Patients with asthma, chronic obstructive pulmonary disease (COPD), and left heart failure were excluded. Placebo or verum (50 &mgr;g salmeterol) was administered at 7 pm by meter dose inhaler and spacer device. All patients underwent full polysomnography during baseline, placebo, and verum night. Statistical analysis was performed by StudentOs t-test (p > 0.05). Between the placebo and verum there were no differences in total sleep time, sleep stages, apnea index (AI), apnea hypopnea index (AHI), and nadir oxygen saturation. There was, however, 1) a significant deterioration of mean oxygen saturation (SaO2m; placebo 93.1 +/- 2.0 vs. verum 92.5 +/- 2.2%; p = 0.01), 2) of percent of time spent with an oxygen saturation (SaO2)

[Treatment of asthma in adults]. / Asthmatherapie im Erwachsenenalter.

The treatment of bronchial asthma comprises preventive measures, specific allergen immunotherapy and pharmacotherapy. The efficacy and cost-effectiveness of preventive measures such as avoidance of the offending allergens and abstinence from smoking so far have not been sufficiently evaluated. Indications for specific immunotherapy are relative and primarily refer to the symptoms caused by the respective allergens. For the most part, asthma therapy therefore relies on the available drugs that may be administered as either long-term or rescue medication. Inhaled glucocorticoids and long-acting beta 2 agonists are the mainstay of chronic treatment which is required for persistent asthma; substances applied if needed basically include short- and long-acting beta 2 agonists as well as systemic glucocorticoids for exacerbations of asthma. More recent guidelines can suitably be translated into the best treatment possible, especially with respect to the reduction of mucosal remodelling which aims at improving the patient's prognosis.

[Self-Management of Anti-Obstructive Therapy for Severe COPD with a Subcutaneous Terbutaline Pump]. / Einsatz eines subkutanen Terbutalin-Infusatsystems zur Selbstapplikation der Bedarfsmedikation bei schwerer chronisch-obstruktiver Atemwegserkrankung (COPD).

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may be difficult to stabilize with standard inhaled and oral medication. In those cases, outpatient care may even be impossible. Alternative therapeutic strategies, like subcutaneous self-application of terbutaline, could help to further improve health status. CASE REPORT: A 42-year old patient with severe COPD was admitted to the hospital. Despite maximal anti-obstructive therapy he required additional intravenous relief therapy and discharge was not possible. We treated this patient with a subcutaneous terbutaline pump for continuous and demand medication. We could show a significant decrease in additional intravenous medication, and the patient could leave the hospital. CONCLUSION: The use of terbutaline applied by a subcutaneous pump in addition to standard therapy may be helpful in severely ill patients suffering from COPD. This measure increased quality of life and shortened hospital stay.

[Prognosis, staging and therapy of malignant pleural mesothelioma]. / Prognose, Staging und Therapie des malignen Pleuramesothelioms.

PROGNOSIS: Prognosis of pleural mesothelioma remains dismal. Regardless of the modality employed median survival ranges between 6 and 12 months, only 20% of patients survive 1 year. In 1996 the International Mesothelioma Interest Group (IMIG) published a widely accepted staging system. So far there is no effective standard therapy. Even very aggressive therapies do not basically influence the course of the disease. THERAPEUTICAL STUDIES: Despite numerous single-agent and combination chemotherapy trials no standard regimen could be found. Few agents yield reproducible response rates above 20%. The majority of the trials are inconclusive according to statistical criteria, as subject numbers are insufficient to prove or deny effectiveness. It also remains obscure in which stage of the disease patients may benefit from chemotherapy because of a lack of analysis of response rates within different stages. Striking is the lack of sufficient studies analyzing patients' quality of life treated with often very toxic regimens. DRUG TREATMENT: Systemic administration of interferons alone or in combination with chemotherapeutic agents did not result in higher response rates or prolonged median survival. In very early stages of the disease patients may have limited benefit from intracavitary, local administration of gamma-interferon. MULTIMODALITY APPROACHES: Mere surgical procedures as extrapleural pneumonectomy or pleurectomy/decortication have been left in favor of multimodality approaches. Due to careful patient selection and improved operation techniques mortality could be reduced. Neither chemotherapy, radiotherapy nor photodynamic therapy can prevent local relapse which occurs in the majority of patients. RADIOTHERAPY: The effectiveness of primary radiation therapy remains controversial. Even very high doses of radiation cannot control tumor growth. It remains unclear whether radiation therapy may palliate tumor associated symptoms. Prophylactic radiation of puncture channels and thoracotomy scars is effective to prevent tumor growth caused by seeding of mesothelioma cells. PERSPECTIVES: Research of the biological behavior of mesothelioma resulted in first phase I gene therapy trials. The results of the few promising approaches tested in phase II and III trials with sufficient patient numbers have to be awaited until we have learned whether and in which stage of the disease patients may benefit from therapy.

[Improvement of health-related quality of life in patients with obstructive sleep apnea syndrome under CPAP therapy]. / Verbesserung der gesundheitsspezifischen Lebensqualität unter CPAP-Therapie bei Patienten mit obstruktivem Schlafapnoesyndrom.

BACKGROUND: Only poor data regarding changes in quality of life in patients with obstructive sleep apnea syndrome (OSAS) under continuous positive airway pressure (CPAP) therapy concerning long-term effects are available. PATIENTS AND METHODS: In this study, 85 patients were evaluated before and under CPAP therapy using the Visual Analog Scale (VAS) Quality of Life, the Nottingham Health Profile (NHP), and the Quality of Life Index (QL-Index). The results of patients with continuous usage of CPAP (n = 66) were compared with a control group of patients who discontinued CPAP therapy (n = 19). RESULTS: VAS (before CPAP 56.9 +/- 27.0, under CPAP 67.2 +/- 21.8 mm; p = 0.027) as well as the NHP dimensions "Energy" (before CPAP 44.2 +/- 39.5, under CPAP 25.0 +/- 34.2 points; p < 0.001), "Emotional reactions" (before CPAP 24.7 +/- 22.5, under CPAP 11.8 +/- 18.8 points; p < 0,001), and "Sleep problems" (before CPAP 32.0 + 30.0, under CPAP 21.5 + 27.2 points; p = 0.005) showed a significant improvement after 16 +/- 9-month follow-up. In the control group, none of the instruments displayed a significant change. A correlation between CPAP compliance (mask hours) and changes in quality of life was not detected. CONCLUSION: Thus, even suboptimal CPAP usage might bring benefit regarding quality of life. As not all health-related instruments or dimensions were able to display the effects on quality of life, there is a need to translate and validate disease-specific instruments into the German language.