Versican in inflammation and tissue remodelling: the impact on lung disorders.

Versican is a proteoglycan that has many different roles in tissue homeostasis and inflammation. The biochemical structure is comprised of four different types of the core protein with attached glycosaminoglycans that can be sulphated to various extents and has the capacity to regulate differentiation of different cell types, migration, cell adhesion, proliferation, tissue stabilization and inflammation. Versican's regulatory properties are of importance during both homeostasis and changes that lead to disease progression. The glycosaminoglycans that are attached to the core protein are of the chondroitin sulfate/dermatan sulfate type and are known to be important in inflammation through interactions with cytokines and growth factors. For a more complex understanding of versican it is of importance to study the tissue niche, where the wound healing process in both healthy and diseased conditions take place. In previous studies our group has identified changes in the amount of the multifaceted versican in chronic lung disorders such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome, which could be a result of pathologic, transforming growth factor β driven, on-going remodelling processes. Reversely, the context of versican in its niche is of great importance since versican has been reported to have a beneficial role in other contexts e.g. emphysema. Here we explore the vast mechanisms of versican in healthy lung and in lung disorders

Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions

Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix metalloproteinase (TIMP)-3. Results: In central airways we found increased percentage areas of versican and decorin in patients with uncontrolled asthma compared to both healthy controls and patients with controlled asthma. Percentage area of biglycan was significantly higher in both central airways and alveolar parenchyma of patients with uncontrolled compared to controlled asthma. Ratios of MMP-9/TIMP-3 were decreased in both uncontrolled and controlled asthma compared to healthy controls. In the alveolar parenchyma, patients with uncontrolled asthma had increased percentage areas of collagen, versican and decorin compared to patients with controlled asthma. Patients with uncontrolled asthma had significantly higher numbers of myofibroblasts in both central airways and alveolar parenchyma compared to patients with controlled asthma. Conclusions: Tissue composition differs, in both central and distal airways, between patients with uncontrolled and controlled asthma on equivalent doses of ICS. This altered structure and possible change in tissue elasticity may lead to abnormal mechanical properties, which could be a factor in the persistent symptoms for patients with uncontrolled asthma

Plasma proteome changes linked to late phase response after inhaled allergen challenge in asthmatics

Background: A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Methods: Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models. Results: Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Conclusions: Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma

Social stratification in the dissemination of statins after stroke in Sweden

PURPOSE: Since 2005, statins have been recommended to patients with ischaemic stroke. The objective of this study was to analyse how statin treatment has been disseminated in different patient groups (age, sex, socioeconomic status and country of birth) in Sweden between 2004 and 2009. METHODS: The Swedish Stroke Register (Riks-Stroke) has been linked to the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Approximately 85 % of stroke patients in Sweden are included in Riks-Stroke. Odds ratios for statin prescribing were calculated using a multivariable logistic regression model including age, sex, socioeconomic status and risk factors. RESULTS: During the study period, 108,950 ischaemic stroke patients were discharged alive from hospital. The proportion with statins at discharge increased from 32.9 % in 2004 to 60.1 % in 2009. Patients with secondary school or university education had slightly higher odds [odds ratio (OR) 1.07, 95 % confidence interval (CI) 1.04-1.11 and OR 1.05, 95 % CI 1.01-1.10 respectively] than patients with primary school education. Patients on a high income were prescribed more statins than those on a low income (OR 1.24, 95 % CI 1.19-1.28). Compared with patients born in Sweden, patients born in other countries were prescribed more statins (Nordic countries excepting Sweden: OR 1.07, 95 % CI 1.01-1.14; Europe: OR 1.31, 95 % CI 1.22-1.40; Outside Europe: OR 1.20, 95 % CI 1.08-1.34). CONCLUSIONS: Statin prescribing after ischaemic stroke has increased from 2004 to 2009. Our results also show a social stratification in the dissemination of statins, with patients having a higher income and patients with higher education receiving statins more often than those with a lower income and education, and patients born in Sweden receiving statins less often than those born outside of Sweden

Ethnic differences in psychological well-being in adolescence in the context of time spent in family activities

Background In Britain and elsewhere there is ethnic variation in mental health in adulthood but less is known about adolescence. Few studies examining the role of family life in adolescent mental well-being have been based on a multi-ethnic UK sample. We explored whether family activities explain ethnic differences in mental health among adolescents in London, UK. Method These analyses are based on 4,349 Black Caribbean, Black African, Indian, Pakistani and Bangladeshi and White UK boys and girls aged 11–13, in 51 schools. Psychological well-being was measured as the total difficulties score from Goodman’s strengths and difficulties questionnaire (increasing score represents increasing difficulties). Results Participation in family activities varied by ethnicity. Compared with the White UK group, all minority groups were more likely to visit friends and relatives and go other places as a family. Black Caribbeans and Nigerian/Ghanaians were less likely and South Asian groups more likely to eat a meal together as a family. In multivariate analyses all minority groups had better well-being scores compared to Whites, independent of family type and socio-economic status (SES). Although adjusting for family activities slightly attenuated the association for South Asians, the minority ethnic advantage in psychological well-being remained [regression coefficients for Black Caribbeans = −0.66 (95% CI = −1.13, −0.20); Nigerian/Ghanaians = −1.27 (−1.81, −0.74); Other Africans = −1.43 (−2.00, −0.86); Indians = −1.15 (−1.73, −0.58); Pakistani/Bangladeshis = −0.66 (−1.20, −0.12)]. In analyses based on the whole group, all activity variables were independent correlates of psychological well-being. Multivariate models, stratified by ethnicity, showed that ≤weekly compared to daily family meals was associated with poorer mental health for all groups, except Black Caribbeans, independent of family type and SES. Conclusion Despite ethnic patterning of the frequency of family activities, adjusting for differences in these variables did not account for the better psychological well-being of minorities. Family activities were, however, important independent correlates of psychological well-being for all groups in this sample