[beta(2)-Sympathomimetics: risks for asthma therapy? Lessons from the SMART1 Study. A statement from the German Respiratory Tract League].
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Adrenergic beta-2 Receptor Agonists↗
Biomedical subjects
J C Virchow
Publications and source records attributed to J C Virchow.
[Hematothorax after sudden chest pain].
HISTORY: A 75-year-old woman was admitted to hospital because of the sudden onset of acute chest pain and dyspnea after defecation. INVESTIGATIONS: The initial working diagnosis was pulmonary embolism because of the clinical findings, laboratory results of elevated fibrin breakdown products and abnormal lung scintigraphy. However, persistent hemorrhagic pleural effusion on contrast enhanced computed tomography and magnetic resonance imaging subsequently revealed imminent rupture of the aorta from penetrating ulceration of the aorta with surrounding intramural hematoma. TREATMENT AND COURSE: Immediate implantation of an aortic stent-graft stopped leakage from the aorta and stabilized the patient's hemodynamic state. At follow up three months later the patient was without thoracic or cardiac symptoms. CONCLUSION: After exclusion of an acute coronary syndrome computed tomography imaging should always be performed in case of acute chest pain with no established cause. Interventional stent-graft placement can be an efficacious treatment option for emergency repair of imminent rupture in the descending aorta.
Acute Disease↗
Decrease of cytotoxic T cells in allergic asthma correlates with total serum immunglobulin E.
BACKGROUND: Allergic asthma has been linked to an increase in T-helper type 2-like cytokines and T cells, but there is growing evidence for a role of lymphocyte-mediated cytotoxic mechanisms in the pathogenesis of asthma. Therefore, we investigated the cytotoxic potential of different lymphocyte subpopulations in patients with allergic asthma. METHODS: Granzyme A, B, K, and perforin expression in peripheral blood lymphocytes was analyzed using flow cytometry. Soluble granzymes were measured in serum using specific enzyme-linked immunosorbent assays. RESULTS: Asthmatics had significantly decreased percentages of granzyme and perforin-positive CD4 T cells compared with non-atopic controls. In patients with asthma, the granzyme B and perforin-positive subset of CD8(+) T cells and natural killer T cells, which represent more differentiated cell populations, were significantly reduced, while this was not observed in the less differentiated granzyme K(+) subsets. In addition, the serum concentrations of granzyme B were significantly reduced in patients with asthma, while granzyme K concentrations were not different. Interestingly, there was a negative correlation between granzyme A, B and perforin expression in T cell subsets as well as serum granzyme B concentrations and total serum immunglobulin E. In CD3-negative natural killer cells, no differences in granzyme or perforin expression between patients with asthma and controls were detected. CONCLUSION: In allergic asthma, cytotoxic T lymphocyte subsets of a more differentiated phenotype are significantly decreased and this is correlated to serum immunglobulin E levels.
Adult↗
Excess mortality in patients with asthma on long-acting beta2-agonists.
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Adrenergic beta-Agonists↗
[Pneumological disease in pregnancy].
The age at manifestation of numerous diseases affecting the lungs is appreciably lower than the average age for other internistic diseases. 7-10% of women of child-bearing age suffer from asthma, and are in need of adequate management during their pregnancy. Other diseases affecting the lungs, such as pneumonia, occur as acute conditions and, despite their dramatic aspects, should be treated only with certain selected antibiotics, so as not to put the unborn child at risk. Apart from TB, cystic fibrosis, HIV and restrictive pulmonary illnesses, there are a number of less common pneumological diseases that require special attention during a pregnancy.
Female↗
[Asthma, allergic rhinitis, sinusitis. Concept of the "unified respiratory tracts"].
Epidemiological studies indicate that allergic rhinoconjunctivitis (ARC) is an important risk factor for bronchial asthma. Both asthma and ARC have now been recognized as inflammatory diseases with similar manifestations in the mucous membranes of the upper (nose and paranasal sinuses) and lower respiratory tract (bronchi). Recent studies show that the deposition of allergen into the lower respiratory tract leads to increased inflammation of the upper respiratory tract, even if the patients are only suffering from ARC. These and other findings indicate that allergic diseases have a systemic component, which might be insufficiently targeted with local therapy. It is currently believed that the impaired function of the upper airways due to ARC causing nasal obstruction, retention of secretions, and disturbed conditioning of the inspired air plays an important role in the development of lower airway symptoms. Studies indicate that treatment of the upper respiratory tract inflammation not only reduces the manifestation of allergen-associated symptoms in the lower respiratory tract, but might also have preventive properties if applied early. ARC should no longer be viewed as a harmless disorder but as the early manifestation of a potentially progressive systemic disease and be treated as such.
Asthma↗
Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients.
BACKGROUND: The interaction of chemokines with their receptors strongly influences the migration of leucocytes. OBJECTIVE: In order to assess the contribution of these molecules to the local recruitment of T cells in bronchial asthma, we analysed the expression of 14 chemokine receptors on lung-derived T cells. METHODS: Chemokine-receptor expression by T cells derived from the peripheral blood, the bronchoalveolar lavage fluid and the bronchial mucosa was analysed by flow cytometry and immunohistochemistry. Expression profiles in healthy and mildly asthmatic individuals were compared, the latter prior and after segmental allergen provocation. RESULTS: Compared with peripheral blood, alveolar T cells expressed significantly more CCR2, CCR5, CCR6, CXCR3 and CCR4. However, no differences were observed between healthy controls and unchallenged asthmatics. In patients developing significant inflammatory responses following specific allergen challenge, a marked increase in the percentage of CCR4+ and CCR7+, and reduced numbers of CXCR3-bearing alveolar T cells were detected. Following specific allergen challenge, chemokine-receptor expression profiles of T cells from the alveolar space and the mucosa or the submucosa were similar, excluding a particular subcompartmentalization of the chemokine/chemokine-receptor system. CONCLUSION: The expression of certain chemokine receptors by lung T cells suggests a contribution to the physiological recruitment of T cells to the lungs, both in healthy controls and unchallenged mild asthmatics. However, strong allergen-induced airway responses were associated with a specific chemokine-receptor profile, suggesting the involvement of certain chemokine receptors in the pathogenesis of allergic bronchial inflammation.
Adult↗
Increase in killer-specific secretory protein of 37 kDa in bronchoalveolar lavage fluid of allergen-challenged patients with atopic asthma.
BACKGROUND: Atopic asthma is linked to a T-helper type 2 dominated pathogenesis, but there is increasing evidence of Th1/Tc1-mediated processes in the aetiopathology of asthma. Killer-specific secretory protein of 37 kDa (Ksp37) is expressed in cytotoxic lymphocytes, selectively in the effector subsets of CD8+- and CD4+ T lymphocytes and in CD16+/CD56dim natural killer cells and gamma/delta T cells. This effector cell-specific expression of Ksp37 and its coexpression with perforin suggest that Ksp37 might be involved in processes mediated by cytotoxic cells. OBJECTIVE: We hypothesize that Ksp37 could indicate the involvement of cytotoxic lymphocytes in the pathogenesis of atopic asthma, and investigated Ksp37 concentration in bronchoalveolar lavage fluid (BALF) collected 10 min, 18, 42 or 162 h after segmental allergen provocation and in serum of patients with atopic asthma (n=25). METHODS: Ksp37 concentrations in BALF and serum were detected by ELISA. Flow cytometric analysis was used to assess numbers and cell subsets in BALF. RESULTS: Ksp37 increased significantly in BALF 10 min, 18 and 42 h, but not 162 h after allergen challenge compared with saline-challenged controls, while Ksp37 serum levels did not change significantly at all time-points. In addition, the increase in Ksp37 concentrations in BALF correlated with the corresponding numbers of lymphocytes. CONCLUSIONS: We conclude that Ksp37 level increased in BALF 10 min, 18 and 42 h after allergen challenge but not in peripheral blood. Our findings suggest that segmental allergen challenge in asthma is associated with an increase in Ksp37 concentrations in BALF and an influx of potentially cytotoxic T lymphocytes into the lungs.
Adolescent↗
Regulation of brain-derived neurotrophic factor (BDNF) during sleep apnoea treatment.
BACKGROUND: Patients with obstructive sleep apnoea syndrome (OSAS) often display persistent cognitive dysfunction despite effective treatment with continuous positive airway pressure (CPAP). Brain-derived neurotrophic factor (BDNF) is a key mediator of memory and cognition, but its regulation in OSAS and during CPAP treatment is unknown. METHODS: Serum and plasma BDNF concentrations, BDNF secretion by peripheral blood mononuclear cells, and overnight polysomnography were evaluated in 17 men with newly diagnosed OSAS (as defined by a respiratory disturbance index of >10/hour with >70% obstructive events and corresponding daytime symptoms) and 12 healthy control men. In the patients all the parameters were monitored after 1 night and 3 months of CPAP treatment. RESULTS: There was no significant difference in baseline serum BDNF, plasma BDNF, or spontaneous BDNF secretion by peripheral blood mononuclear cells between untreated patients and controls. After 1 night of CPAP treatment there was a steep fall in median serum BDNF (from 18.0 ng/ml to 4.1 ng/ml) and plasma BDNF (from 58.7 pg/ml to 22.0 pg/ml) concentrations. Following 3 months of treatment BDNF concentrations did not return to baseline. In contrast, BDNF secretion was not suppressed by CPAP treatment. CONCLUSIONS: Patients with untreated OSAS have normal serum and plasma BDNF levels. CPAP treatment is associated with a rapid decrease in serum and plasma BDNF levels which may reflect enhanced neuronal demand for BDNF in this condition.
Biomarkers↗
Interleukin-5 receptors on human lung eosinophils after segmental allergen challenge.
BACKGROUND: IL-5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge. OBJECTIVE: The action of IL-5 is mediated via the specific IL-5 receptor-alpha (IL-5Ralpha). Although in vitro data suggest that IL-5R expression is regulated by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its kinetics following allergen provocation are incompletely understood. METHODS: We investigated IL-5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL-5Ralpha was measured by flow cytometry and IL-5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA. RESULTS: IL-5Ralpha expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure. CONCLUSIONS: Although there was no correlation between IL-5 concentrations and IL-5Ralpha expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL-5 concentrations and IL-5Ralpha expression on eosinophils.
Adult↗
Increase in granzyme B+ lymphocytes and soluble granzyme B in bronchoalveolar lavage of allergen challenged patients with atopic asthma.
Asthma has been linked to a chronic, T-cell-mediated bronchial inflammation. Because other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with elevated granzyme B (grB) expression we tested the hypothesis that atopic asthma might be associated with elevated grB levels in the bronchoalveolar compartment. Therefore we performed intracellular grB staining in lymphocytes from bronchoalveolar lavage (BAL) collected 42 h after segmental allergen provocation (SAP) in allergic patients with bronchial asthma. There was a significant increase in CD3(+), CD8(+), and CD16/56(+) lymphocytes expressing grB in BAL 42 h after SAP as compared to saline challenged controls. However, compared to peripheral blood the percentages of these lymphocyte subsets detected as grB(+) in BAL remained significantly lower. Measurement of extracellular grB in BAL fluids by a particle immunoassay revealed significantly elevated grB levels in the allergen challenged bronchoalveolar compartment 42 h following SAP in six of the eight patients (range, <1.0-348.1 pg/ml) as compared to saline challenged controls (range, <1.0-70.5 pg/ml). We conclude that total cell numbers of grB(+) lymphocyte subsets increase 42 h after SAP in the lower respiratory tract. In addition there is evidence to suggest that grB is released into the airways of asthmatic patients. This suggests a role for grB in the pathophysiological processes following SAP but its definitive role in allergic bronchial asthma needs to be established.
Adolescent↗
Increase in Ksp37-positive peripheral blood lymphocytes in mild extrinsic asthma.
Killer-specific secretory protein of 37 kDa (Ksp37), identified as a Th1/Tc1 specific secretory protein is expressed preferentially in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells and might be involved in essential processes of CTL-mediated immunity. Although extrinsic asthma is linked currently to a Th2-dominated pathogenesis, there is increasing evidence for Th1/Tc1-mediated processes in the aetiopathology of asthma. CTL from patients with asthma have been shown to express cytokines and effector molecules which were different from healthy controls. We hypothesized that Ksp37 could indicate the involvement of CTL in the pathogenesis of extrinsic asthma. We therefore investigated Ksp37 expression in PBMC from patients with mild extrinsic asthma (n = 7) and healthy controls (n = 7). Flow cytometric analysis was used to quantify Ksp37+ cells and to investigate cellular Ksp37 expression as relative mean fluorescence intensities (MFI). We found a significantly (P = 0.016) higher percentage of Ksp37+ cells within the total lymphocyte population obtained from patients with mild extrinsic asthma compared with healthy controls. Subdifferentiation revealed a significant difference limited exclusively to the CD8+ subset (P = 0.010). In addition, Ksp37 secretion from cultured peripheral blood mononuclear cells (PBMC) and MFI of Ksp37+ lymphocytes were increased in patients with asthma compared with healthy controls. We conclude that mild extrinsic asthma appears to be associated with an increased expression of the Tc1 related protein Ksp37. The functional role of Ksp37 in the pathogenesis of asthma remains to be elucidated.
Adult↗
[Gastroesophageal reflux disease (GERD) and asthma].
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Asthma↗
[Specific immunotherapy in allergic asthma].
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Allergens↗
Does interferon-gamma improve pulmonary function in idiopathic pulmonary fibrosis?
Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating deterioration of lung function and a fatal prognosis, despite aggressive therapeutic attempts, which, in the majority of cases are futile. Recently, a preliminary study of long-term treatment with interferon (IFN)-gamma1b and low-dose prednisolone in patients with IPF suggested that IFN-gamma1b treatment may improve lung function parameters of patients with IPF. Ever since, specialists in respiratory medicine who treat patients with IPF, are called by patients demanding treatment with IFN-gamma1b. Therefore, the authors here present another prospective investigation of IFN-gamma1b in five patients with IPF. According to the previously published design, patients received 200 microg IFN-gamma1b subcutaneously three-times per week and 10 mg prednisolone orally for 12 months. Two patients stopped IFN-gamma1b treatment after 4 months due to side-effects and further lung function deterioration and one patient died 3 months after commencement of therapy. In total, pulmonary function improved in only one patient during IFN-gamma1b treatment, while four patients deteriorated. To conclude, this small series of idiopathic pulmonary fibrosis cases treated with interferon-gamma1b and corticosteroids does not support previous data that this treatment improves pulmonary function or alters the natural course of idiopathic pulmonary fibrosis. Furthermore, in the authors' experience, side-effects of interferon-gamma1b treatment can significantly reduce patients' quality of life.
Aged↗
Normocapnia during nIPPV in chronic hypercapnic COPD reduces subsequent spontaneous PaCO2.
Hypercapnia has been accepted during nasal intermittent positive pressure ventilation (nIPPV) and during subsequent spontaneous breathing in patients with chronic hypercapnic respiratory failure (HRF) due to COPD. We tested the hypothesis that nIPPV aimed at normalizing PaCO2 will reduce PaCO2 during subsequent spontaneous breathing. For that purpose 14 consecutive inpatients (age 61.4 +/- 9.9 years) with chronic HRF due to COPD were established on passive pressure-controlled nIPPV in a stepwise approach. Assisted ventilation with supplemental oxygen to reach normoxemia was started followed by passive ventilation with a stepwise increment in the inspiratory pressure and finally by a stepwise increase in the respiratory rate to establish normocapnia. Baseline pulmonary function parameters were: FEV1 0.97 +/- 0.43 l, PaCO2 59.5 +/- 8.4 mmHg, PaO2 49.9 +/- 7.8 mmHg, HCO3- 35.6 +/- 5.2 mmol/l, pH 7.39 +/- 0.04. Normoxemia as well as normocapnia was thus established by decreasing PaCO2 by 19.5 +/- 7.0 mmHg during nIPPV within 8.8 +/- 3.8 days (P < 0.001) (inspiratory pressure 29.8 +/- 3.8 mmHg, respiratory rate 22.9 +/- 1.9 BPM). Spontaneous PaCO2 measured 4 h after cessation of nIPPV decreased to 46.0 +/- 5.5 mmHg (P < 0.001), and HCO3- decreased to 27.2 +/- 3.0 mmol/l (P < 0.001). At 6 months of follow-up, II patients continued nIPPV with stable blood gases and with a decrease of P0.1/Plmax from 9.4 +/- 4.3% to 5.9 +/- 2.0% (P < 0.005). In conclusion, normalization of PaCO2 by passive nIPPV in patients with HRF due to COPD is possible and leads to a significant reduction of PaCO2 during subsequent spontaneous breathing and is associated with improved parameters of respiratory muscle function.
Aged↗
[Epidemiology and costs of bronchial asthma and chronic bronchitis in Germany].
BACKGROUND AND OBJECTIVE: Asthma bronchiale (AB) and chronic bronchitis (CB) are common chronic disorders with high rates of prevalence. We performed a cost of illness study that aimed to assess the economic burden of these disorders in Germany. PATIENTS AND METHODS: Costs were estimated in 1996. In a retrospective analysis we calculated direct and indirect costs based on secondary data from governmental institutions as well as from the pharmaceutical industry. To the best of our knowledge, this is the first study which uses data for the Federal Republic of Germany following its reunification. RESULTS: Total estimated costs were DM 5.81 billion related to AB, and DM 20.17 billion related to CB. We did not include outpatient physician services in the calculation of direct costs due to a lack of adequate data. Therefore, direct costs represented only 33% and 22% of total estimated costs, respectively. The most important cost driver of direct costs were outpatient prescribed medicines, followed by hospitalization. Outpatient prescribed medicines accounted for 55% and 63% of the direct costs, respectively. Of the indirect costs of AB 43% were associated with early retirement. The largest single cost driver of indirect costs due to CB was by far loss of work, amounting to 75%. CONCLUSIONS: The data suggest that therapeutic progress and cessation of smoking can provide distinctive savings of direct costs and even more of indirect costs of AB and CB.
Adolescent↗
[Posterior uveitis: sarcoidosis or tuberculosis].
PURPOSE: To demonstrate the difficulties of the differential diagnosis between tuberculosis and sarcoidosis as the cause of posterior uveitis. CASE REPORTS: A 56-year-old woman suffered from bilateral anterior uveitis, snow-ball like infiltrates in the vitreous, and peripheral retinochoroidal granulomas with marked exudation shown in fluorescein angiography. Angiotensin-converting enzyme, as a marker of sarcoidosis, was elevated; the tuberculin test, however, was negative. Chest X-ray revealed an infiltrate and numerous smaller granulomas. The presumptive diagnosis was sarcoidosis. Surprisingly, in the biopsy of the pulmonal lesion tubercle bacilli were detected by Ziehl-Neelsen staining. Thus, a diagnosis of pulmonal and also retinochoroidal tuberculosis was made. After tuberculostatic therapy the choroidal lesions healed off. In a second case, a 30-year-old man suffered from bilateral panuveitis with candle wax exudates near the retinal vessels. Chest X-ray revealed lymphomas in the hilus, and the lymph node biopsy showed granulomas with epitheloid cells, indicating sarcoidosis. Detection of mycobacterium tuberculosis by culture or histological criteria was negative. Only in the PCR was mycobacterium tuberculosis DNA detectable. Tuberculostatic therapy had no benefit. Under therapy with steroids, however, pulmonal and ophthalmologic findings rapidly disappeared. CONCLUSION: The difficult differential diagnosis between sarcoidosis and tuberculosis cannot always be made by laboratory tests or diagnostic imaging alone. Clinical manifestations, including response to therapy, are essential.
Adult↗