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Großhansdorf, Germany

Schneider A.,TU Munich | Faderl B.,TU Munich | Schwarzbach J.,TU Munich | Welker L.,LungenClinic Grosshansdorf | And 2 more authors.
Respiratory Medicine | Year: 2014

Objectives: To compare the prognostic value of FENO with bronchoprovocation testing when the clinical course within the first year after assessment was taken into account; to compare the prognostic values with respect to eosinophilic versus non-eosinophilic inflammatory pattern. Methods: Cross-sectional diagnostic study with a delayed-type reference standard in 393 patients attending a private practice of pneumologists with complaints suspicious of obstructive airway disease. Index test: FENO measurement. Reference standard: ratio FEV1/VC or airway resistance assessed by body plethysmography, with additional bronchoprovocation or bronchodilator testing, as well as spontaneous sputum (smear slides). This was combined with a follow-up evaluation by a structured interview after 12 months. Results: 302 (76.8%) patients were reached for follow-up. Regarding asthma diagnosis, the area under the curve (AUC) for FENO was 0.603 (95%CI 0.528-0.677) for the whole group. With eosinophilic asthma as target, AUC increased (0.819 (95%CI 0.703-0.934)) and exceeded that of bronchoprovocation (0.711 (95%CI 0.584-0.874)). FENO showed no diagnostic value in non-eosinophilic asthma. In patients reporting wheezing and allergic rhinitis at the initial assessment, its positive predictive value was 90.9% (95%CI 62.3%-98.4) at a cut-off of 45 ppb, and 100% (95%CI 56.6-100%) at 81 ppb. Conclusions: FENO bears limited information when measured non-specifically in primary care, but is useful for diagnosing eosinophilic asthma. If sputum is not available, information on wheezing and rhinitis can narrow down the range of patients in whom FENO is informative. Moreover, the evaluation of the clinical value of FENO benefits from taking into account follow-up data to confirm the diagnosis. © 2013 Elsevier Ltd. All rights reserved.

Kugler C.,LungenClinic Grosshansdorf | Stanzel F.,Lung Clinic Hemer
Thoracic Surgery Clinics | Year: 2014

Tracheomalacia is excessive collapsibility of the trachea, typically during expiration. Congenital forms are associated with severe symptoms. Milder forms often present after the neonatal period. Adult malacia is mostly associated with chronic obstructive pulmonary disease. Functional bronchoscopy is still not standardized. Dynamic airway CT is a promising tool for noninvasive diagnosis. Bronchoscopy and stent insertion lead to significant improvement, but with a high complication rate. Surgical lateropexia, tracheal resection, and surgical external stabilization are options. Tracheoplasty seems to be the best choice for selected cases of adult malacia. The most commonly performed surgery in children is aortopexy. © 2014 Elsevier Inc.

Spangenberg L.,University of Leipzig | Zenger M.,University of Leipzig | Zenger M.,Magdeburg Stendal University of Applied Sciences | Garcia-Torres F.,University of Cordoba, Spain | And 4 more authors.
Journal of Pain and Symptom Management | Year: 2016

Context Hopelessness is a clinically important construct in patients with advanced illness. Objectives To evaluate the dimensionality, stability, and validity of the Beck Hopelessness Scale (BHS) in cancer patients receiving either curative or palliative treatment. Methods Following a longitudinal design, we assessed a sample of cancer patients receiving either curative or palliative treatment (N = 315) at baseline and at follow-up after 12 months (N = 158). In addition to hopelessness, we measured depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), and health-related quality of life (Short-Form Health Survey-8). We analyzed dimensionality, stability, and construct validity of the BHS using confirmatory factor analysis, exploratory factor analysis and correlational analysis. Results Independent of treatment intention, confirmatory factor analyses resulted in unsatisfactory model fits. Exploratory factor analysis yielded a two-factor solution in both groups receiving curative or palliative treatment. Factor 1 reflected pessimistic/resigned beliefs (Cronbach alpha ≥ 0.85), Factor 2 reflected positive beliefs toward the future (Cronbach alpha = 0.73). Both subscales showed significant associations with anxiety, depression, and decreased health-related quality of life. The factorial structure was partially replicated in patients being reexamined after 12 months (CMIN/DF = 2.130, Standardized Root Mean Square Residual = 0.0716, Comparative Fit Index = 0.904, Tucker-Lewis-Index = 0.883, Root Mean Square Error of Approximation = 0.085). Hopelessness scores were significantly higher in patients reporting suicidal ideation according to the Patient Health Questionnaire-9. Conclusion Our study demonstrates psychometric limitations of the BHS in patients receiving both curative and palliative treatment, suggesting reduced utility in cancer populations. Given the clinical importance of the construct, a cancer-specific approach to capture the unique meaning of hopelessness in patients with severe medical illness is recommended. © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Cagnoni E.F.,University of Sao Paulo | Ferreira D.S.,University of Sao Paulo | Ferraz Da Silva L.F.,University of Sao Paulo | Nicoletti Carvalho Petry A.L.,University of Sao Paulo | And 5 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Immune responses in asthmatic patients involve coordinated cellular responses in the airways and lymph nodes (LNs). However, no studies have described the composition of different cell populations in the bronchopulmonary LNs of asthmatic patients. Objective We sought to investigate the expression of dendritic cells (DCs) and costimulatory molecules, B cells, T cells, TH2-related cytokines, eosinophils, and vascular cell adhesion molecule in the bronchopulmonary LNs and large airways of asthmatic patients. Methods Using histochemistry, immunohistochemistry, and image analysis, we investigated the expression of Factor XIIIa+, CD1a+, CD83+, and CD207+ DCs; CD4+ and CD8+ T cells; CD20+ B cells; CD23+ (FcεRII) cells; IL-4; IL-5; eosinophils, and vascular cell adhesion molecule 1 in the large airways and bronchopulmonary LNs of 11 nonsmokers who died from an asthma exacerbation (fatal asthma [FA]) in comparison with 8 nonasthmatic control subjects. In selected cases of FA, we analyzed the coexpression of HLA-DR, CD40, and CD80 in lung and LN eosinophils. Results The LNs of asthmatic patients exhibited increased density of eosinophils. No other cells were expressed differently in the LNs of patients with FA. The large airways of patients with FA had increased expression of eosinophils in all layers and increased expression of Factor XIIIa+ cells, CD4+ and CD8+ T cells, CD20+ B cells, and CD23+ cells in the outer layer. There was colocalization of HLA-DR, CD40, and CD80 in the eosinophils at both sites. Conclusions FA is associated with the increased presence of eosinophils in the LNs and large airways, which express HLA-DR and costimulatory molecules. The expression of Factor XIIIa+ monocyte-derived DCs, CD4+ and CD8+ T cells, CD20+ B cells, and CD23+ cells was increased in the large airways without a corresponding increase in the expression of these cells in the bronchopulmonary LNs. These findings support the concept that eosinophils might act as antigen-presenting cells in patients with FA. © 2015 American Academy of Allergy, Asthma & Immunology.

Jager J.,TU Braunschweig | Marwitz S.,Research Center Borstel | Marwitz S.,Airway Research Center North | Tiefenau J.,TU Braunschweig | And 8 more authors.
Infection and Immunity | Year: 2014

Histological and clinical investigations describe late stages of Legionnaires' disease but cannot characterize early events of human infection. Cellular or rodent infection models lack the complexity of tissue or have nonhuman backgrounds. Therefore, we developed and applied a novel model for Legionella pneumophila infection comprising living human lung tissue. We stimulated lung explants with L. pneumophila strains and outer membrane vesicles (OMVs) to analyze tissue damage, bacterial replication, and localization as well as the transcriptional response of infected tissue. Interestingly, we found that extracellular adhesion of L. pneumophila to the entire alveolar lining precedes bacterial invasion and replication in recruited macrophages. In contrast, OMVs predominantly bound to alveolar macrophages. Specific damage to septa and epithelia increased over 48 h and was stronger in wild-type-infected and OMV-treated samples than in samples infected with the replication-deficient, type IVB secretiondeficient DotA- strain. Transcriptome analysis of lung tissue explants revealed a differential regulation of 2,499 genes after infection. The transcriptional response included the upregulation of uteroglobin and the downregulation of the macrophage receptor with collagenous structure (MARCO). Immunohistochemistry confirmed the downregulation of MARCO at sites of pathogen-induced tissue destruction. Neither host factor has ever been described in the context of L. pneumophila infections. This work demonstrates that the tissue explant model reproduces realistic features of Legionnaires' disease and reveals new functions for bacterial OMVs during infection. Our model allows us to characterize early steps of human infection which otherwise are not feasible for investigations. © 2014, American Society for Microbiology.

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