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Biomedical subjects

Gerhard Schultze-Werninghaus

Publications and source records attributed to Gerhard Schultze-Werninghaus.

At least 19 recordsLinked to original sources
PubMed2006

Synergistically upregulated interleukin-10 production in cocultures of monocytes and T cells after stimulation with respiratory syncytial virus.

BACKGROUND: Respiratory syncytial virus (RSV) is known as a causal factor of severe bronchiolitis in young children. It has also been detected in patients with chronic obstructive pulmonary disease (COPD), a disease that is associated with an increased number of T cells in the bronchial mucosa. Here, we investigated the potential direct interaction between RSV and T cells and its impact on cytokine response. METHODS: Purified human peripheral blood T cells were stimulated with RSV in vitro and analyzed by flow cytometry and fluorescence microscopy. Cytokine expression and release were measured in T cell cultures and in cocultures with peripheral blood monocytes as well as with alveolar macrophages from bronchoalveolar lavage fluid by quantitative real-time PCR and ELISA. RESULTS: It was shown that RSV adhered to the surface of T cells. Stimulation of purified T cells with RSV led to a significant increase in interleukin (IL)-10 mRNA expression after 24 h. Moreover, in cocultures of T cells with monocytes or alveolar macrophages, IL-10 production was synergistically upregulated 24 h after stimulation with RSV. CONCLUSION: These results suggest that RSV can cause an excessive IL-10 response leading to downregulation of antiviral defense mechanisms and reduced elimination of respiratory pathogens when antigen-presenting cells and T cells are simultaneously present on the site of infection. This effect may possibly contribute to high frequencies of respiratory pathogens found in patients with chronic inflammatory airway diseases associated with increased local T cell influx such as COPD.

Bronchoalveolar Lavage Fluid↗
PubMed2006

[Improvement of cardiopulmonary exercise capacity in patients with obstructive sleep apnea syndrome under CPAP therapy].

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.

Adult↗
PubMed2006

Left ventricular geometry in patients with obstructive sleep apnea coexisting with treated systemic hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy is a common consequence of systemic hypertension (SH) and obstructive sleep apnea (OSA). However, little is known about the degree of LV involvement in patients with OSA coexisting with treated SH. OBJECTIVES: Our study was designed in order to assess the prevalence of distinct types of LV geometry in treated hypertensive OSA patients. METHODS PATIENTS: 183 patients with treated SH were enrolled to the study. Group 1 consisted of 38 patients with newly-diagnosed OSA and ineffectively treated SH. The remaining 145 patients with effectively treated SH were divided into three groups: group 2 - 70 patients with newly-diagnosed OSA, group 3 - 31 patients with OSA treated with continuous positive airway pressure (CPAP), and group 4 - 44 patients without OSA. Overnight sleep studies and M-mode echocardiography were performed. RESULTS: LV mass index did not differ between the study groups. Mean values of LV end-diastolic diameter (LVED) were 55.4 +/- 6.8 mm in group 1 and 53.6 +/- 6.9 mm in group 2 and were significantly increased in comparison to subjects treated with CPAP and controls (49.8 +/- 6.8 mm and 50.1 +/- 64.7 mm, respectively; p = 0.001). LVED correlated positively with the apnea-hypopnea index and desaturation index. LV eccentric hypertrophy was the commonest type of LV geometry in newly-diagnosed OSA patients. CONCLUSIONS: The major finding of our study is the predominance of LV eccentric hypertrophy in newly-diagnosed OSA patients. We suggest that a relatively moderate degree of LV involvement in hypertensive OSA patients may depend on the cardioprotective effect of concomitant antihypertensive therapy, ameliorating OSA-dependent neurohumoral abnormalities.

Antihypertensive Agents↗
PubMed2006

[Cardiac structure and function in patients with obstructive sleep apnea syndrome and co-prevalent arterial hypertension. Influence of CPAP therapy].

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.

Adult↗
PubMed2006

Vascular endothelial dysfunction in patients with mild obstructive sleep apnea syndrome.

BACKGROUND: We investigated endothelial dysfunction, an early manifestation of atherosclerosis, in patients with mild obstructive sleep apnea syndrome (OSAS) (5/h < AHI < 15/h). PATIENTS AND METHODS: Endothelium-dependent and -independent vasodilatory function was tested in 10 patients with mild OSAS, 12 healthy controls and 20 subjects with moderate to severe OSAS using the hand vein compliance technique. RESULTS: Maximum endothelium-dependent vasodilation to bradykinin (Emax) was significantly blunted in patients with mild OSAS (68.6 +/- 30.2 %) compared to healthy controls (94.8 +/- 9.5 %; p < 0.05; moderate to severe OSAS: 57.1 +/- 23.4 %; p = 0.33). Mean endothelium-independent venodilation was not altered. After 160.7 +/- 82.2 nights of CPAP therapy, mean Emax was significantly improved to 90.8 +/- 23.8 % (p < 0.01 vs. baseline; p = 0.7 vs. healthy controls) in 7 patients with mild OSAS. CONCLUSIONS: Systemic endothelium-dependent venodilation is markedly reduced in subjects with mild OSAS, which may imply adverse cardiovascular consequences. CPAP-treatment leads to a sustained restoration of endothelial dysfunction in these patients and is thus highly recommended.

Adolescent↗
PubMed2006

Antihypertensive treatment and endothelium-dependent venodilation in sleep-disordered breathing.

Sleep-disordered breathing (SDB) is associated with nitric oxide-mediated endothelial dysfunction and increased risk and prevalence of cardiovascular disease, namely, arterial hypertension. A substantial number of patients do not comply with nasal continuous positive airway pressure (nCPAP) treatment. These individuals have a persisting increased cardiovascular risk. Antihypertensive drugs have shown to improve nitric oxide-mediated endothelial dysfunction. We therefore designed a study to test the hypothesis that antihypertensive drug treatment in hypertensive patients with SDB can have beneficial effects on nitric oxide-mediated endothelial function in the absence of treatment with nCPAP. Six patients with SDB and treated arterial hypertension, six normotensive patients with SDB, and six healthy controls received sleep studies and an assessment of venodilation using the dorsal hand vein technique. Polygraphic measures using standard overnight sleep studies and dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained. Maximum nitric-oxide-mediated dilation to bradykinin was significantly higher in patients with SDB who had received antihypertensive drug treatment compared to normotensive SDB patients. Nitric oxide-mediated dilation in hypertensive patients with SDB was similar to nitric oxide-mediated dilation in healthy controls. After treatment of normotensive patients with SDB using nCPAP, nitric oxide-mediated dilation in normotensive SDB patients was comparable to nitric oxide-mediated dilation in SDB patients with antihypertensive drug treatment and normal controls. Hypertensive patients with SDB present a normal nitric oxide-mediated endothelial function under antihypertensive treatment.

Aged↗
PubMed2006

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.

Air Pollution↗
PubMed2005

Radiological findings, pulmonary function and dyspnea in underground coal miners.

BACKGROUND: Respiratory disability induced by dust exposure in coal workers is assessed by pulmonary function tests and radiological evidence of pneumoconiosis. High-resolution computed tomography (HR-CT) improves the visibility of tissue changes, but the value of the findings for the clinical evaluation is controversial. OBJECTIVES: It was the aim of this study to evaluate the correlation between the International Labour Office (ILO) classification and the degree of emphysema in HR-CT with self-reported dyspnea and pulmonary function tests including diffusion capacity for CO (DL,CO). METHODS: We investigated 87 coal miners (aged 67+/-6 years), having worked underground for 26+/-9 years, with pulmonary function tests and HR-CT. Univariate associations were tested with correlation coefficients, and multivariable analyses used a stepwise forward regression model. RESULTS: No aspect of the ILO classification showed a univariate correlation with dyspnea or forced expiratory flow in 1 s (FEV1). Emphysema CT score was strongly associated with DL,CO (rs=-0.40; p<0.001) and FEV1/maximal vital capacity (r=-0.38; p<0.001) in univariate analysis, but not with the clinical grade of dyspnea (r=-0.14; p=0.256). CT emphysema score but not ILO classification was associated with FEV1 in multivariable analyses (rs=-0.37; p<0.001). Dyspnea was best approximated by DL,CO (r=-0.312; p=0.008). CONCLUSION: The clinical grade of breathlessness was best approximated by DL,CO. HR-CT showed a good association with expiratory flow limitation. ILO classification of the chest radiograph may be a marker of exposure but conveys little information about the degree of respiratory impairment.

Coal Mining↗
PubMed2005

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.

Aged↗
PubMed2005

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.

Adolescent↗
PubMed2005

[Early polysomnographic detection of congestive heart failure caused by aortic valve stenosis].

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.

Aged↗
PubMed2005

Polymorphisms in the interleukin-8 gene in patients with chronic obstructive pulmonary disease.

Airway inflammation is the main pathophysiological feature of patients with chronic obstructive pulmonary disease (COPD). Interleukin-8 (IL-8) is a potent chemoattractant for neutrophils and eosinophils. Increased IL-8 levels were observed in bronchoalveolar lavage (BAL) and induced sputum in patients with COPD. To evaluate the role of the IL-8 gene, we genotyped blood samples of 122 COPD-patients and 385 healthy controls for a known polymorphism in the promoter region (-251 A/T) of the IL-8 gene. Additionally, we screened the coding region for further polymorphisms by SSCP analyses. Comparison of the allele and genotype frequencies among each group revealed no significant differences between patients and controls. Although IL-8 plays an important role in the chemotaxis of inflammatory cells, the polymorphisms investigated here do not seem to be involved in the genetic predisposition to COPD.

Adult↗
PubMed2005

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.

Anthropometry↗
PubMed2005

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.

Administration, Oral↗
PubMed2005

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.

Aged↗