Long-Term Pollen Monitoring in the Benelux: Evaluation of Allergenic Pollen Levels and Temporal Variations of Pollen Seasons.

Airborne pollen is a major cause of allergic rhinitis, affecting between 10 and 30% of the population in Belgium, the Netherlands, and Luxembourg (Benelux). Allergenic pollen is produced by wind pollinating plants and released in relatively low to massive amounts. Current climate changes, in combination with increasing urbanization, are likely to affect the presence of airborne allergenic pollen with respect to exposure intensity, timing as well as duration. Detailed analysis of long-term temporal trends at supranational scale may provide more comprehensive insight into these phenomena. To this end, the Spearman correlation was used to statistically compare the temporal trends in airborne pollen concentration monitored at the aerobiological stations which gathered the longest time-series (30-44 years) in the Benelux with a focus on the allergenic pollen taxa: Alnus, Corylus, Betula, Fraxinus, Quercus, Platanus, Poaceae, and Artemisia. Most arboreal species showed an overall trend toward an increase in the annual pollen integral and peak values and an overall trend toward an earlier start and end of the pollen season, which for Betula resulted in a significant decrease in season length. For the herbaceous species (Poaceae and Artemisia), the annual pollen integral and peak values showed a decreasing trend. The season timing of Poaceae showed a trend toward earlier starts and longer seasons in all locations. In all, these results show that temporal variations in pollen levels almost always follow a common trend in the Benelux, suggesting a similar force of climate change-driven factors, especially for Betula where a clear positive correlation was found between changes in temperature and pollen release over time. However, some trends were more local-specific indicating the influence of other environmental factors, e.g., the increasing urbanization in the surroundings of these monitoring locations. The dynamics in the observed trends can impact allergic patients by increasing the severity of symptoms, upsetting the habit of timing of the season, complicating diagnosis due to overlapping pollen seasons and the emergence of new symptoms due allergens that were weak at first.

Host and Environmental Factors Influencing Individual Human Cytokine Responses.

Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies. PAPERCLIP.

[Hyponatraemia]. / Hyponatriëmie.

Because hyponatraemia can be caused by many disorders, the diagnostic approach to hyponatraemia can be challenging for physicians. Causes of hyponatraemia can be classified according to a combination of laboratory parameters (e.g. sodium levels and osmolality in serum and urine) and clinical parameters (e.g. volume status, medication). Based on the description of two patient cases, the differential diagnosis of hyponatraemia is discussed by combining these parameters.

The analytic impact of a reduced centrifugation step on chemistry and immunochemistry assays: an evaluation of the Modular Pre-Analytics.

BACKGROUND: The COBAS 6000 system can be completed by a Modular Pre-Analytics (MPA), an integrated laboratory automation system that streamlines preanalysis. For an optimal throughput, the MPA centrifuges blood collection tubes for 5 min at 1885 × g - a centrifugation time that is not in concordance with the World Health Organization guidelines which suggest centrifugation for 10/15 min at 2000-3000 × g. METHODS: In this study, the analytical outcome of 50 serum and 50 plasma samples centrifuged for 5 or 10 min at 1885 × g was investigated. The study included routine chemistry and immunochemistry assays on the COBAS 6000 and the Minicap capillary electrophoresis. RESULTS: Deming-fit and Bland-Altman plots of the 5-min and 10-min centrifugation steps indicated a significant correlation in serum samples. The lipaemia index in plasma samples centrifuged for 5 min displayed a statistically significant variation when compared with the 10-min centrifugation. CONCLUSIONS: Preanalytical centrifugation can be successfully down-scaled to a duration of 5 min for most routine chemistry and immunochemistry assays in serum and plasma samples. To prevent inaccurate results in plasma samples with an increased lipaemia index from being reported, the laboratory information system was programmed to withhold results above certain lipaemia indices. The presented data support the use of a 5-min centrifugation step to improve turnaround times, thereby meeting one of the desires of the requesting clinicians.

High plasma mid-regional pro-adrenomedullin levels in children with severe dengue virus infections.

BACKGROUND: Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is characterized by hemorrhage, plasma leakage and shock. Adrenomedullin and vasopressin are vaso-active hormones that mediate endothelial permeability, vascular tone and water balance and may therefore play a role during DHF/DSS. Adrenomedullin reduces endothelial permeability and has vasodilatory properties, while vasopressin is a potent vasoconstrictor with anti-diuretic effects. OBJECTIVES: To determine mid-regional pro-adrenomedullin (MR-proADM) and copeptin, which are reliable and stable markers for adrenomedullin and vasopressin response, respectively, and relate their plasma concentrations to outcome and markers of plasma leakage in Indonesian children with DHF and DSS. STUDY DESIGN: In this observational cohort study Indonesian children with DHF/DSS were enrolled. On study days 0 and 2, plasma MR-proADM and copeptin concentrations as well as parameters of plasma leakage were determined. Plasma MR-proADM and copeptin concentrations were compared to values of healthy controls. RESULTS: MR-proADM was increased in both DHF (n=43) and DSS (n=28) vs. controls (n=17), with median (IQR) values of 0.47 (0.40-0.68), 0.56 (0.44-1.00) vs. 0.22 (0.19-0.29) nmol/L, respectively. Additionally, MR-proADM correlated with signs of increased vascular leakage such as low albumin and increased pleural effusion. Copeptin concentrations showed no significant changes as compared to controls. CONCLUSIONS: MR-proADM concentrations are elevated in children with DHF and DSS and correlate with the severity of plasma leakage, in contrast to copeptin concentrations. We speculate that adrenomedullin has a functional role in limiting endothelial hyperpermeability during DHF/DSS. Finally, MR-proADM may be a candidate biomarker to predict development of DHF/DSS.

Fibrillin-1 staining anomalies are associated with increased staining for TGF-beta and elastic fibre degradation; new clues to the pathogenesis of emphysema.

We recently demonstrated aberrant staining of fibrillin-1 in lung tissue specimens with emphysematous lesions. In this study, we have extended this observation by an elaborate analysis of the elastic fibre. Using domain-specific antibodies to fibrillin-1, and to other elastin fibre-associated molecules, lung tissue derived from patients without obvious clinical emphysema, but harbouring various degrees of microscopical emphysematous lesions, was analysed. In addition, the fibrillin-regulated growth factor TGF-beta was studied. Electron microscopy and biochemical analysis of desmosine (a marker for elastin) were also performed. Results were compared with lung tissue derived from patients with clinical emphysema. Domain-specific antibodies recognizing the C-terminal, N-terminal, and middle part of fibrillin-1 showed aberrant staining patterns associated with increasing degrees of microscopical emphysema. Staining for elastin, emilin-1, and fibulin-2 was, however, not aberrant. TGF-beta staining was markedly increased. On the electron microscopic, but not light microscopical, level, initial elastic fibre degradation was noticed in specimens with microscopical emphysema. Lung specimens from patients with clinical emphysema also displayed fragmented fibrillin-1 staining and, in addition, displayed extensive degradation of the elastic fibre. The results suggest that fibrillin-1 anomalies and TGF-beta overexpression are associated with initial events occurring during the emphysematous process. Based on these and other data, a mechanism for emphysematogenesis is proposed.

Microscale mechanical properties of single elastic fibers: the role of fibrillin-microfibrils.

Micromechanical properties of single elastic fibers and fibrillin-microfibrils, isolated from equine ligamentum nuchae using chemical and enzymatic methods, were determined with atomic force microscopy (AFM). Young's moduli of single elastic fibers immersed in water, devoid of or containing fibrillin-microfibrils, were determined using bending tests. Bending freely suspended elastic fibers on a micro-channeled substrate by a tip-less AFM cantilever generated a force versus displacement curve from which Young's moduli were calculated. For single elastic fibers, Young's moduli in the range of 0.3-1.5 MPa were determined, values not significantly affected by the presence of fibrillin-microfibrils. To further understand the role of fibrillin-microfibrils in vertebrate elastic fibers, layers of fibrillin-microfibrils were subjected to nano-indentation tests. From the slope of the force versus indentation curves, Young's moduli ranging between 0.56 and 0.74 MPa were calculated. The results suggest that fibrillin-microfibrils are not essential for the mechanical properties of single vertebrate elastic fibers.

Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema.

Parenchymal destruction, airspace enlargement, and loss of elasticity are hallmarks of pulmonary emphysema. Although the basic mechanism is unknown, there is a consensus that malfunctioning of the extracellular matrix is a major contributor to the pathogenesis of emphysema. In this study, we analyzed the expression of the elastic fiber protein fibrillin-1 in a large number (n=69) of human lung specimens with early-onset emphysema. Specimens were morphologically characterized by the Destructive Index, the Mean Linear Intercept, and the Panel Grading. We observed a strong correlation (P<0.001) of aberrant fibrillin-1 staining with the degree of destruction of lung parenchyma (r=0.71), airspace enlargement (r=0.47), and emphysema-related morphological abnormalities (r=0.69). There were no obvious correlations with age and smoking behavior. Staining for three other extracellular matrix components (type I collagen, type IV collagen, and laminin) was not affected. The aberrant fibrillin-1 staining observed in this study is similar to that observed in Marfan syndrome, a syndrome caused by mutations in the gene encoding fibrillin-1. Strikingly, emphysema is noticed in a number of Marfan patients. This, together with the notion that disruption of the fibrillin-1 gene in mice results in emphysematous lesions, makes fibrillin-1 a strong candidate to be involved in the etiology and pathogenesis of emphysema.