Nicotine treatment improves Toll-like receptor 2 and Toll-like receptor 9 responsiveness in active pulmonary sarcoidosis.

BACKGROUND: New evidence links nicotine to the regulation of T cell-mediated inflammation via a 7 nicotinic cholinergic receptor activation, and chronic nicotine exposure (smoking) reduces the incidence of granulomatous diseases. We sought to determine whether nicotine treatment was well tolerated while effectively normalizing immune responses in patients with active pulmonary sarcoidosis. METHODS: Consenting adults with symptomatic sarcoidosis (n 5 13) were randomly assigned to receive 12 weeks of nicotine treatment plus conventional therapy or conventional therapy alone. Obtained blood cells were evaluated for their responsiveness to selected Toll-like receptor (TLR) and nucleotide oligomerization domain-like receptor ligands and T cell surface marker expression before and after nicotine treatment. Asymptomatic patients (n 5 6) and disease-free subjects (n 5 6) served as comparative control subjects. Adverse events were monitored for the duration of the study. RESULTS: Compared with the asymptomatic group, symptomatic patients had impaired peripheral responses to TLR2, TLR4, and TLR9 ligands (anergy) and reduced peripheral populations of CD4 1 FoxP3 1 regulatory T cells (Tregs). Nicotine treatment was associated with restoration of TLR2 and TLR9 responsiveness, and expansion of Tregs, including the CD4 1 CD25 2 FoxP3 1 phenotype. There were no serious adverse events or signs of nicotine dependency. CONCLUSIONS: Nicotine treatment in active pulmonary sarcoidosis was well tolerated and restored peripheral immune responsiveness to TLR2 and TLR9 agonists and expansion of FoxP3 1 Tregs, including a specific "preactivated" (CD25 2 ) phenotype. The immune phenotype of patients with symptomatic sarcoidosis treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.

Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity.

PURPOSE: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity. PATIENTS AND METHODS: Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR) up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay. RESULTS: We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFα) are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC(50) and IC(50) concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day. CONCLUSION: In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.

Screening for exercise-induced bronchoconstriction in college athletes.

OBJECTIVE: Previous studies have reported that the prevalence of exercise-induced bronchoconstriction (EIB) in athletes is higher than that of the general population. There is increasing evidence that athletes fail to recognize and report symptoms of EIB. As a result, there has been debate whether athletes should be screened for EIB, particularly in high-risk sports. METHODS: We prospectively studied 144 athletes from six different varsity sports at a large National Collegiate Athletic Association Division I collegiate athletic program. Baseline demographics and medical history were obtained and the presence of asthma symptoms during exercise was documented. Each athlete subsequently underwent a eucapnic voluntary hyperventilation (EVH) test to document the presence of EIB. Exhaled nitric oxide (eNO) quantification was performed immediately before EVH testing. EIB was defined as a ≥10% decline in forced expiratory volume in 1 second compared with baseline. RESULTS: Only 4 of 144 (2.7%) athletes were EIB-positive after EVH testing. The presence of symptoms was not predictive of EIB as only 2 of the 64 symptomatic athletes (3%) were EIB-positive based on EVH testing. Two of the four athletes who were found to be EIB-positive denied such symptoms. The mean baseline eNO in the four EIB-positive athletes was 13.25 parts per billion (ppb) and 24.5 ppb in the EIB-negative athletes. CONCLUSIONS: Our data argue that screening for EIB is not recommended given the surprisingly low prevalence of EIB in the population we studied. In addition, the presence or absence of symptoms was not predictive of EIB and eNO testing was not effective in predicting EIB.

Sources of happiness and stress for college students: a replication and comparison over 20 years.

The advancement of positive psychology is dependent upon measures of happiness, both globally and in specific contexts. Data are presented on two measures of sources of college students' happiness from two samples. Testing of the two cohorts (Ns=258, 68) was separated by 20 years. Measures for both samples had acceptable psychometric properties. There was an increase in college students' self-reported happiness across the 20-year period in the rankings of different sources of college happiness and general happiness. In a second study, a different group of students (N= 176) were given a list and asked to select the most important uplifts and hassles in their lives. In general, mean scores on affect measures were relatively stable across time, but transportation hassles were reported as a new source of negative affect in the present study.

Predicting travel attitudes among university faculty after 9/11.

The authors interviewed a random sample of 306 university faculty as part of an annual university poll. Items focused on air travel concerns following 9/11, positive aspects of travel, and future travel intentions. Demographic factors were not significant predictors for men or women faculty. Faculty expressed positive attitudes toward travel, for example agreeing that travel allows them to demonstrate competency. Concerns about missing connections and delays elicited a larger percent of negative reactions than concerns about hijackings or security. Gender differences were not observed on individual items, but in regression analyses a composite of self-reported travel risk factors was more predictive of future travel plans for women than for men, although women expected to travel as much in the future as men. The results are consistent with positive psychology and speak to applied aspects of travel and tourism.