This analysis suggests that recent severe asthma exacerbations are a strong independent factor predicting future exacerbations and, as such, should be considered as part of the clinical assessment of patients with severe or difficult-to-treat asthma.

Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.

BackgroundWomen and men have diverse responses to many infectious diseases. These differences are amplified following menopause. However, despite extensive information regarding the effects of sex hormones on immune cells, our knowledge is limited regarding the effects of sex and gender on the function of the mucosal immune system. Sex differences also manifest in the prevalence of gut associated inflammatory and autoimmune disorders, including Crohn’s disease, ulcerative colitis and Celiac disease. It is thus hypothesized that a baseline sex-associated difference in immune activation may predispose women to inflammation-associated disease.MethodsPeripheral blood samples and small intestinal biopsies were obtained from 34 healthy men and women. Immunophenotypic analysis of isolated lymphocytes was performed by flow cytometry. Oligonucleotide analysis was used to study the transcriptional profile in the gut mucosal microenvironment while real-time PCR analysis was utilized to identify differential gene expression in isolated CD4+ T cells. Transcriptional analysis was confirmed by protein expression levels for genes of interest using fluorescent immunohistochemistry. Data was analyzed using the GraphPad software package.ResultsWomen had higher levels of immune activation and inflammation-associated gene expression in gut mucosal samples. CD4+ and CD8+ T cells had a significantly higher level of immune activation-associated phenotype in peripheral blood as well as in gut associated lymphoid tissue along with higher levels of proliferating T cells. CD4+ T cells that showed upregulation of IL1β as well as the TH17 pathway-associated genes contributed a large part of the inflammatory profile.ConclusionIn this study, we demonstrated an upregulation in gene expression related to immune function in the gut microenvironment of women compared to men, in the absence of disease or pathology. Upon closer investigation, CD4+ T cell activation levels were higher in the LPLs in women than in men. Sex differences in the mucosal immune system may predispose women to inflammation-associated diseases that are exacerbated following menopause. Our study highlights the need for more detailed analysis of the effects of sex differences in immune responses at mucosal effector sites.

The aim of the present study was to predict which patients with severe or difficult-totreat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management.Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline.Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index o35 kg?m -2 ; post-bronchodilator per cent predicted forced vital capacity ,70%;history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0-18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12-to 18-months follow-up among the same cohort (c-index: 0.77). The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.

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