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Bacterial lipopolysaccharide (LPS, endotoxin) is a ubiquitous component of dust and air pollution and is suspected to contribute after inhalation to an activation of eosinophils in bronchial tissues of asthmatic patients, provoking inflammatory and allergic processes. We were therefore interested in the interaction of eosinophil granulocytes with LPS and have examined the activation of and uptake to human peripheral blood eosinophils by LPS. Eosinophils IntroductionHuman eosinophils, like other granulocytes, are terminally differentiated effector cells that are recruited from the bloodstream into tissue sites during inflammatory, particularly allergic, reactions. 1 In asthmatic patients, the airways contain an increased number of eosinophils and the severity of their asthmatic symptoms correlates with the number of eosinophils in the bronchial tissue. 1-3 Eosinophils synthesize and release a number of substances, including leukotrienes, and a variety of granule-associated proteins such as eosinophil cationic protein (ECP). If released inappropriately, these substances contribute to tissue damage and to the pathogenesis of allergic diseases. [1][2][3][4] In addition to their capacity to release lipid mediators and cytotoxic granule proteins, eosinophils may contribute to the inflammatory process through expression and synthesis of cytokines including tumor necrosis factor alpha/beta (TGF-␣/␤), macrophage inflammatory protein 1 alpha (MIP-1␣), interleukin-1 (IL-1), IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-8, and TNF-␣. Furthermore, cytokines increase expression of ␤2 integrins on eosinophils, which are involved in the adhesion, transendothelial migration of eosinophils, and also in a variety of adherence-dependent functions. [5][6][7] Although stimuli such as calcium ionophore and ionomycin have been found capable of eliciting cytokine expression in eosinophils in vitro, 8,9 physiologic stimuli and the mechanisms that are involved in the regulation of eosinophil cytokine responses remain largely unknown. A potent candidate stimulus is lipopolysaccharide (LPS, endotoxin), the major constituent of the outer membrane of gram-negative bacteria. 10 LPS is present in the upper respiratory tract, 11 and its levels increase in the infected and inflamed state locally and systemically. Furthermore, LPS is a continuous ingredient of the environment, including air pollution. 12,13 In this context, LPS has been detected in a variety of dust extracts, and it has been suggested that chronically inhaled airborne endotoxin could contribute to the development or the enhancement of several chronic obstructive bronchial diseases, including asthma. 12,[14][15][16][17][18][19] Inhalation of low doses of endotoxins has been reported to contribute to bronchial constriction in asthmatic patients. [16][17][18] Hence, in addition to allergens, LPS inhalation could further activate myeloic cells, including eosinophils, thus exacerbating the ongoing inflammatory process.To our knowledge, the only eviden...

BackgroundThe aim of the study was to analyze the effect of preoperative patient characteristics on health outcomes 6 months after total hip replacement (THR), to support patient’s decision making in daily practice with predicted health states and satisfaction thresholds. By giving incremental effects for different patient subgroups, we support comparative effectiveness research (CER) on osteoarthritis interventions.MethodsIn 2012, 321 patients participated in health state evaluation before and 6 months after THR. Health-related quality of life (HRQoL) was measured with the EQ-5D questionnaire. Hip-specific pain, function, and mobility were measured with the WOMAC in a prospective observation of a cohort. The predictive capability of preoperative patient characteristics – classified according to socio-demographic factors, medical factors, and health state variables – for changes in health outcomes is tested by correlation analysis and multivariate linear regressions. Related satisfaction thresholds were calculated with the patient acceptable symptom state (PASS) concept.ResultsThe mean WOMAC and EQ-5D scores before operation were 52 and 60 respectively (0 worst, 100 best). At the 6-month follow-up, scores improved by 35 and 19 units. On average, patients reported satisfaction with the operation if postoperative (change) WOMAC scores were higher than 85 (32) and postoperative (change) EQ-5D scores were higher than 79 (14).ConclusionsChanges in WOMAC and EQ-5D scores can mainly be explained by preoperative scores. The lower the preoperative WOMAC or EQ-5D scores, the higher the change in the scores. Very good or very poor preoperative scores lower the probability of patient satisfaction with THR. Shared decision making using a personalized risk assessment approach provides predicted health states and satisfaction thresholds.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-014-0108-1) contains supplementary material, which is available to authorized users.