The Effects of Cognitive Stress on Asthma Exacerbations among University Students

Introduction: Many asthmatics complain of worsening respiratory symptoms during periods of stress.This study evaluated the relationship among asthma symptoms, lung physiology, inflammatory parametersand perceived cognitive stress and quality of life in healthy adult students. This relationship was assessedat two time points: a time of normal activity and at a time of cognitive stress during academic examinations. Methods: Subjects attended the University of Alberta Hospital for a screening visit, which included aclinical exam, spirometry, methacholine challenge, allergen skin tests to assess atopy status and MiniInternational Neuropsychiatric Interview (MINI). Eligible subjects returned for a low stress visit (LSV) atleast 14 days prior to an exam and a high stress visit (HSV) within 24 hours of an exam. Spirometry, andmethacholine challenge were performed during both LSV and HSV along with the collection of urine (testedfor cortisol), and the administration of 4 questionnaires to assess perceived stress and quality of life. Results: Subjects showed no significant change in psychosocial or quality of life questionnaires betweenLSV and HSV. No significant change was noted in lung function or urine cortisol. There was an unexpectedhigh rate of pre-existing psychiatric comorbidities in this population (based on the MINI screen failure rate).Conclusion: We did not find a significant change in quality of life, psychosocial wellbeing or pulmonaryfunction or inflammation, measured by urine cortisol, during a high stress period. The high rate ofcomorbidities would be important to consider as part of evaluation used in clinical asthma studies in the future

A protease activated receptor-2 (PAR-2) activating peptide, tc-LIGRLO-NH(2), induces protease release from mast cells: role in TNF degradation

BACKGROUND: Mast cell (MC)-derived serine proteases have been implicated in a variety of inflammatory processes. We have previously shown that rat peritoneal MC (PMC) express mRNA for protease activated receptor 2 (PAR-2), a G-coupled receptor activated by trypsin-like proteases. Recent evidence also suggests that MC-induced inflammation can be mediated through PAR. Therefore, we hypothesized that specific PAR-2 agonist peptides (PAR-2ap) induce protease release from PMC. RESULTS: Western blot analysis of PMC supernatants revealed that a PAR-2ap, tc-LIGRLO (10 μM), stimulated the release of rat MC protease (RMCP)-1, RMCP-5 and carboxypeptidase-A. The release was evident by 20 min but further increased up to 8 h. To study the biological effects of protease release we tested supernatants from tc-LIGRLO, tc-OLRGIL (inactive control peptide) and antigen-activated PMC for proteolytic activity by seeding with TNF (150 pg/ml), incubating for 8 h at 37°C, and measuring TNF remaining in the supernatants. Supernatants from tc-LIGRLO-stimulated PMC degraded 44 % of seeded TNF (n = 5). Moreover, this TNF proteolysis was dependent on the concentration of tc-LIGRLO used to stimulate PMC, and was significantly inhibited (94 %) by soybean trypsin inhibitor. Antigen and tc-OLRGIL induced no significant release of such proteolytic activity. CONCLUSIONS: These data indicate that a PAR-2ap induces the release of proteases from mast cells, which may degrade extracellular cytokines and other substrates thus modulating the inflammatory response

Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

<p>Abstract</p> <p>Background</p> <p>Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant.</p> <p>Methods</p> <p>Cockroach extract (CE) was administered to mice intranasally (i.n.) daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR) was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate.</p> <p>Results</p> <p>Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol.</p> <p>Conclusions</p> <p>Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.</p